Coreg is a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).

Coreg is used to treat heart failure and hypertension (high blood pressure).

Coreg is also used after a heart attack that has caused your heart not to pump as well.

Warnings

You should not take Coreg if you have asthma, bronchitis, emphysema, severe liver disease, or a serious heart condition such as heart block, “sick sinus syndrome,” or slow heart rate (unless you have a pacemaker).

Avoid drinking alcohol within 2 hours before or after taking extended-release Coreg CR capsules. Also avoid taking medicines or other products that might contain alcohol. Alcohol may cause the carvedilol in the controlled release (CR) capsule to be released too quickly into the body.

If you are being treated for high blood pressure, keep using Coreg even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your l

Before taking this medicine

You should not take Coreg if you are allergic to carvedilol, or if you have:

• asthma, bronchitis, emphysema;
• severe liver disease; or
• a serious heart condition such as severe heart failure, heart block, “sick sinus syndrome,” or slow heart rate (unless you have a pacemaker).

To make sure Coreg is safe for you, tell your doctor if you have:

• coronary artery disease (clogged arteries);
• slow heartbeats that have caused you to faint;
• fluid retention;
• asthma or other lung problems;
• angina (chest pain);
• diabetes (taking carvedilol can make it harder for you to tell when you have low blood sugar);
• a thyroid disorder;
• kidney disease;
• circulation problems (such as Raynaud’s syndrome); or
• pheochromocytoma (tumor of the adrenal gland).

Tell your doctor if you are pregnant or breastfeeding.

Coreg is not approved for use by anyone younger than 18 years old.

How should I take Coreg?

Take Coreg exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Coreg works best if you take it with food, at the same time every day.

Swallow the extended-release capsule whole and do not crush, chew, break, or open it.

If you cannot swallow a capsule whole, open it and sprinkle the medicine into a spoonful of cold applesauce. Swallow the mixture right away without chewing. Do not save it for later use.

If you are switched from the tablets to Coreg CR extended-release capsules, your daily total dose of this medicine may be higher or lower than before. Older adults may be more likely to become dizzy or feel faint when switching from tablets to extended-release capsules. Follow your doctor’s instructions.

Your blood pressure will need to be checked often.

If you need surgery (including cataract surgery), tell your surgeon you currently use this medicine. You may need to stop for a short time.

You should not stop using Coreg suddenly. Stopping suddenly may cause chest pain or a heart attack. Follow your doctor’s instructions about tapering your dose.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Coreg is only part of a complete treatment program that may also include diet, exercise, and weight control. Follow your doctor’s instructions very closely.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include uneven heartbeats, shortness of breath, bluish-colored fingernails, dizziness, weakness, fainting, and seizure (convulsions).

What to avoid

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Coreg side effects

Get emergency medical help if you have signs of an allergic reaction to Coreg: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• slow or uneven heartbeats;
• cold feeling or numbness in your fingers or toes;
• chest pain, dry cough, wheezing, chest tightness;
• heart problems – swelling, rapid weight gain, feeling short of breath; or
• high blood sugar – increased thirst, increased urination, dry mouth, fruity breath odor.

Common Coreg side effects may include:

• dizziness;
• slow heartbeats;
• diarrhea;
• weight gain;
• dry eyes; or
• problems wearing contact lenses.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect Coreg?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Other drugs may interact with carvedilol, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

What is clonidine?

Clonidine lowers blood pressure by decreasing the levels of certain chemicals in your blood. This allows your blood vessels to relax and your heart to beat more slowly and easily.

Clonidine (Catapres tablet/patch, Javadin) is used to treat hypertension (high blood pressure).

The Kapvay brand is an extended-release tablet used to treat attention deficit hyperactivity disorder (ADHD).

Onyda XR is an extended-release oral suspension used to treat ADHD in children 6 years and older.

Clonidine is sometimes given with other medications. Clonidine is also available as a transdermal patch worn on the skin. Do not use two forms of this medicine at the same time.

Warnings

Before you take clonidine, tell your doctor if you have heart disease or severe coronary artery disease, a heart rhythm disorder, slow heartbeats, low blood pressure, a history of heart attack or stroke, kidney disease, or if you have ever had an allergic reaction to a Catapres TTS transdermal skin patch.

Use only as directed. Tell your doctor if you use other medicines or have other medical conditions or allergies.

Before taking this medicine

You should not take this medicine if you are allergic to clonidine.

To make sure clonidine is safe for you, tell your doctor if you have:

• heart disease or severe coronary artery disease;
• a heart rhythm disorder, slow heartbeats;
• high or low blood pressure, or a history of fainting spells;
• a heart attack or stroke;
• pheochromocytoma (tumor of the adrenal gland);
• kidney disease; or
• if you have ever had an allergic reaction to a Catapres TTS transdermal skin patch.

It is not known if clonidine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of clonidine on the baby.

Clonidine may affect fertility in men or women. Pregnancy could be harder to achieve while either parent is using this medicine.

If you are breastfeeding, tell your doctor if you notice somnolence, tiredness, rapid breathing, and poor feeding in the nursing baby.

Catapres is not approved for use by anyone younger than 18 years old. Do not give Kapvay to a child younger than 6 years old.

How should I take clonidine?

Take clonidine exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Clonidine is usually taken in the morning and at bedtime. If you take different doses of this medicine at each dosing time, it may be best to take the larger dose at bedtime.

Clonidine may be taken with or without food.

Swallow the extended-release tablet whole and do not crush, chew, or break it.

Javadin oral solution is for adults with hypertension and can be taken with or without food.

Tell your doctor if you have a planned surgery.

You may have withdrawal symptoms if you stop using this medicine suddenly. Ask your doctor before stopping the medicine.

Call your doctor if you are sick with vomiting. This is especially important for a child taking clonidine.

If you have high blood pressure, keep using this medicine even if you feel well. High blood pressure often has no symptoms.

Store at room temperature away from moisture, heat, and light.

Dosing information

Usual Clonidine Adult Dose for Hypertension

Oral Tablets:

• Initial dose: 0.1 mg orally 2 times a day (morning and bedtime)
• Titration: Increments of 0.1 mg orally per day may be made at weekly intervals to desired response
• Maintenance dose: 0.2 to 0.6 mg orally per day in divided doses
• Maximum dose: 2.4 mg orally per day in divided doses

Comments:
Taking the larger portion of the oral daily dose at bedtime may minimize the transient adjustment effects of dry mouth and drowsiness

Transdermal patches:

• Initial dose: 0.1 mg/24 hr patch applied every 7 days
• Maintenance dose: If, after 1 to 2 weeks, the desired reduction in blood pressure is not achieved, increase the dosage by adding another 0.1 mg/24 hr patch or changing to a larger system
• Maximum dose: Doses above two 0.3 mg/24 hr patches applied every 7 days is usually not associated with additional efficacy

Comments:
-The transdermal patch should be applied to a hairless area of intact skin on the upper outer arm or chest.
-Each new patch should be applied on a different skin site from the previous location.
-If the patch loosens during 7-day wearing, the adhesive cover should be applied directly over the system to ensure good adhesion.
-There have been rare reports of the need for patch changes prior to 7 days to maintain blood pressure control.
-When substituting patches for the oral formulation or for other antihypertensive drugs, physicians should be aware that the antihypertensive effect of the patches may not commence until 2 to 3 days after initial application; therefore, gradual reduction of prior drug dosage is advised. Some or all previous antihypertensive treatment may have to be continued, particularly in patients with more severe forms of hypertension.
Use: For hypertension, alone or in combination with other antihypertensive agents

Javadin Oral Solution:

• Initial dose: 0.1 mg orally twice daily with or without food (morning and bedtime).
• Titrate in increments of 0.1 mg per day at weekly intervals if necessary until the desired response is achieved.
• Usual maintenance dose: 0.2 mg-0.6 mg per day, given in divided doses.

Comments: Store at 20°C to 25°C (68°F to 77°F). Discard unused portion 60 days after first opening. 

Usual Pediatric Dose for Attention Deficit Disorder

Kapvay Extended-release tablets:
6 years and older:
-Initial dose: 0.1 mg orally at bedtime
-Titration: Increase in 0.1 mg/day increments every 7 days until desired response; doses should be administered twice daily (either split equally or with the higher split dosage given at bedtime)
-Maximum dose: 0.4 mg/day in 2 divided doses

Comments:
-May be taken with or without food.
-If a dose is missed, that dose should be skipped and take the next dose as scheduled.
-Tablets should be swallowed whole, and not crushed, chewed, or broken to avoid increasing the rate of drug release.
-When discontinuing therapy, taper daily dose by no more than 0.1 mg every 3 to 7 days.

Use: For the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy or as adjunctive therapy to stimulant medications.

Onyda XR Extended-release oral suspension
–Children 6 years and older.
-Initial Onyda XR dose: 0.1 mg orally once daily at bedtime with or without food. Dosage may be increased in increments of 0.1 mg per day at weekly intervals.
-Maximum recommended dosage: 0.4 mg once daily at bedtime.
-Comments: Do not substitute Onyda XR for other clonidine products on a mg-per-mg basis because of differing pharmacokinetic profiles.
-When discontinuing: Taper the dose in decrements of no more than 0.1 mg every 3 to 7 days to avoid rebound hypertension.

What happens if I miss a dose?

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include feeling cold, irritable, weak, drowsy, or light-headed, or having weak reflexes, pinpoint pupils, slow heartbeats, shallow breathing, or a seizure.

What should I avoid while taking clonidine?

Avoid drinking alcohol. It may increase certain side effects of clonidine.

Avoid driving or hazardous activity until you know how clonidine will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

Avoid becoming overheated or dehydrated during exercise and in hot weather.

Clonidine side effects

Get emergency medical help if you have signs of an allergic reaction to clonidine: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe chest pain, shortness of breath, irregular heartbeats;
• a very slow heart rate; or
• a light-headed feeling, like you might pass out.

Common clonidine side effects may include:

• drowsiness, dizziness;
• feeling tired or irritable;
• dry mouth;
• constipation, loss of appetite; or
• sleep problems (insomnia), nightmares.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect clonidine?

Using clonidine with other drugs that make you drowsy can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.

Tell your doctor about all your other medicines, especially:

• other heart or blood pressure medications;
• an antidepressant; or
• any other medicine that contains clonidine.

This list is not complete. Other drugs may interact with clonidine, including prescription and over-the-counter medicines, vitamins, and herbal products. 

Chlorthalidone is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

Chlorthalidone treats fluid retention (edema) in people with congestive heart failure, cirrhosis of the liver, or kidney disorders, or edema caused by taking steroids or estrogen.

Chlorthalidone is also used to treat high blood pressure (hypertension).

Chlorthalidone may also be used for purposes not listed in this medication guide.

Chlorthalidone side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Chlorthalidone may cause serious side effects. Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• low sodium–headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• low potassium–leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
• low magnesium–dizziness, irregular heartbeats, feeling jittery, muscle cramps, muscle spasms, cough or choking feeling; or
• kidney problems–little or no urination, swelling in your feet or ankles, feeling tired or short of breath.

Common side effects of chlorthalidone may include:

• low blood pressure (feeling light-headed);
• kidney problems;
• dizziness; or
• an electrolyte imbalance (such as low levels of potassium, sodium, or magnesium in your blood).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Warnings

You should not use chlorthalidone if you are unable to urinate, or if you are allergic to sulfa drugs.

Before taking this medicine

You should not use chlorthalidone if you are allergic to it, or if:

• you are unable to urinate; or
• you are allergic to sulfa drugs.

Tell your doctor if you have ever had:

• kidney disease;
• heart failure;
• gout;
• high cholesterol or triglycerides;
• diabetes; or
• if you are on a low-salt diet.

Tell your doctor if you are pregnant or plan to become pregnant. Taking chlorthalidone during pregnancy may cause side effects in the newborn baby, such as jaundice (yellowing of the skin or eyes), bruising or bleeding, low blood sugar, or an electrolyte imbalance.

Do not start or stop taking chlorthalidone during pregnancy without your doctor’s advice. Although chlorthalidone may cause side effects in a newborn, having high blood pressure during pregnancy can cause complications such as diabetes or eclampsia (dangerously high blood pressure that can lead to medical problems in both mother and baby). The benefit of treating hypertension may outweigh any risks to the baby.

You should not breastfeed while using chlorthalidone.

How should I take chlorthalidone?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking chlorthalidone. This can lead to very low blood pressure, a serious electrolyte imbalance, or kidney failure.

Your blood pressure will need to be checked often. Your blood and urine may both be tested if you have been vomiting or are dehydrated.

chlorthalidone can affect the results of certain medical tests. Tell any doctor who treats you that you are using chlorthalidone.

If you need surgery, tell your surgeon you currently use this medicine.

If you have high blood pressure, keep using this medicine even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.

Store this medicine at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Chlorthalidone dosing information

Usual Adult Dose for Hypertension:

-Initial dose: 25 mg orally once a day
-Titration: Increase to 50 mg orally once a day if response is inadequate; if response is still inadequate, increase to 100 mg orally once a day, or a second antihypertensive drug (step 2 therapy) may be added
-Maintenance dose: 25 to 100 mg orally once a day
-Maximum dose: 100 mg orally once a day

Comments:
-Doses should be taken in the morning with food.
-Maintenance doses may be lower than initial doses and should be adjusted according to individual patient response.
-Effectiveness is well sustained during continued use.

Use: Hypertension (alone or with another antihypertensive drug)

Usual Adult Dose for Edema:

-Initial dose: 50 to 100 mg orally once a day, or 100 mg orally every other day; some patients may require 150 to 200 mg orally at these intervals
-Maximum dose: 200 mg orally once a day

Comments:
-Doses should be taken in the morning with food.
-Maintenance doses may be lower than initial doses and should be adjusted according to individual patient response.
-Effectiveness is well sustained during continued use.

Use: For edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include nausea, weakness, dizziness, drowsiness, extreme thirst, muscle pain, or rapid heartbeats.

What should I avoid while taking chlorthalidone?

Drinking alcohol with chlorthalidone can cause side effects.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Avoid becoming overheated or dehydrated during exercise, in hot weather, or by not drinking enough fluids. Follow your doctor’s instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

What other drugs will affect chlorthalidone?

Using chlorthalidone with other drugs that make you light-headed can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.

Tell your doctor about all your other medicines, especially:

• other blood pressure medications;
• lithium;
• digoxin, digitalis;
• insulin or oral diabetes medicine; or
• steroid medicine.

Carvedilol is a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).

Carvedilol is used to treat heart failure and hypertension (high blood pressure). It is also used after a heart attack that has caused your heart not to pump as well.

Carvedilol may also be used for purposes not listed in this medication guide.

Warnings

You should not take carvedilol if you have asthma, bronchitis, emphysema, severe liver disease, or a serious heart condition such as heart block, “sick sinus syndrome,” or slow heart rate (unless you have a pacemaker).

Avoid drinking alcohol within 2 hours before or after taking extended-release carvedilol (Coreg CR). Also avoid taking medicines or other products that might contain alcohol. Alcohol may cause the carvedilol in Coreg CR to be released too quickly into the body.

If you are being treated for high blood pressure, keep using carvedilol even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Before taking this medicine

You should not take carvedilol if you are allergic to it, or if you have:

• asthma, bronchitis, emphysema;
• severe liver disease; or
• a serious heart condition such as heart block, “sick sinus syndrome,” or slow heart rate (unless you have a pacemaker).

To make sure carvedilol is safe for you, tell your doctor if you have:

• diabetes (taking carvedilol can make it harder for you to tell when you have low blood sugar);
• angina (chest pain);
• liver or kidney disease;
• a thyroid disorder;
• pheochromocytoma (tumor of the adrenal gland);
• circulation problems (such as Raynaud’s syndrome); or
• a history of allergies.

FDA pregnancy category C. It is not known whether carvedilol will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether carvedilol passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking carvedilol.

How should I take carvedilol?

Take carvedilol exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Carvedilol works best if you take it with food.

You may open the carvedilol capsule and sprinkle the medicine into a spoonful of pudding or applesauce to make swallowing easier. Swallow right away without chewing. Do not save the mixture for later use. Discard the empty capsule.

Take carvedilol at the same time every day. Do not skip doses or stop taking carvedilol without first talking to your doctor. Stopping suddenly may make your condition worse.

If you are switched from carvedilol tablets to carvedilol extended-release capsules (Coreg CR), your daily total dose of this medicine may be higher or lower than before. Older adults may be more likely to become dizzy or feel faint when switching from tablets to extended-release capsules. Follow your doctor’s instructions.

Your blood pressure will need to be checked often.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

If you need surgery, tell the surgeon ahead of time that you are using carvedilol. You may need to stop using the medicine for a short time.

You should not stop using carvedilol suddenly. Stopping suddenly may make your condition worse.

Carvedilol can affect your pupils during cataract surgery. Tell your eye surgeon ahead of time that you are using this medication. Do not stop using carvedilol before surgery unless your surgeon tells you to.

Carvedilol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include uneven heartbeats, shortness of breath, bluish-colored fingernails, dizziness, weakness, fainting, and seizure (convulsions).

What to avoid

Carvedilol may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Drinking alcohol can further lower your blood pressure and may increase certain side effects of carvedilol. You should especially avoid drinking alcohol within 2 hours before or after taking extended-release carvedilol (Coreg CR).

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Carvedilol side effects

Get emergency medical help if you have any of these signs of an allergic reaction to carvedilol: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• a light-headed feeling, like you might pass out;
• slow or uneven heartbeats;
• swelling, rapid weight gain, feeling short of breath (even with mild exertion);
• cold feeling or numbness in your fingers or toes;
• chest pain, dry cough, wheezing, chest tightness, trouble breathing; or
• high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss).

Common carvedilol side effects may include:

• weakness, dizziness;
• diarrhea;
• dry eyes;
• tired feeling; or
• weight gain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect carvedilol?

Other drugs may interact with carvedilol, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Captopril is used in adults alone or in combination with other medications to treat high blood pressure (hypertension) and congestive heart failure.

Captopril is also used to improve survival and reduce the risk of heart failure after a heart attack in patients with a heart condition called left ventricular hypertrophy (enlargement of the walls of the left side of the heart). Captopril is also used to treat kidney disease (nephropathy) caused by diabetes in patients with type 1 diabetes and retinopathy (eye disease).

Captopril belongs to a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It decreases certain chemicals that tighten the blood vessels, so blood flows more smoothly and the heart can pump blood more efficiently.

Warnings

Do not use captopril if you are pregnant. Stop using captopril and tell your doctor right away if you become pregnant.

If you have diabetes, do not use captopril together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo).

Tell your doctor about all your other medicines. Some drugs should not be used with captopril.

Before taking this medicine

You should not use this medicine if you are allergic to captopril or to any other ACE (angiotensin converting enzyme) inhibitor such as benazepril, fosinopril, enalapril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.

If you have diabetes, do not take captopril with any medication that contains aliskiren (a blood pressure medicine).

Do not take captopril within 36 hours before or after taking medicine that contains sacubitril (such as Entresto).

To make sure captopril is safe for you, tell your doctor if you have ever had:

• heart failure, heart problems;
• severe allergic reaction such as angioedema;
• stomach pain;
• low blood pressure;
• low white blood cell counts;
• a connective tissue disease such as Marfan syndrome, Sjogren’s syndrome, lupus, scleroderma, or rheumatoid arthritis;
• if you are on a low-salt diet;
• to take medicines that weaken the immune system such as cancer medicine, steroids, and medicines to prevent organ transplant rejection;
• diabetes;
• liver disease; or
• kidney disease (or if you are on dialysis).

You may also need to avoid taking captopril with aliskiren if you have kidney disease.

Stop using this medicine and tell your doctor right away if you become pregnant. Captopril can cause injury or death to the unborn baby if you use the medicine during your second or third trimester.

Do not breastfeed.

How should I take captopril?

Take captopril exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Take on an empty stomach, at least 1 hour before a meal.

Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking captopril. This can lead to very low blood pressure, an electrolyte imbalance, or kidney failure.

Your blood pressure will need to be checked often, and you may need frequent blood tests.

captopril may cause false results on a urine test. Tell the laboratory staff that you use captopril.

Tell your doctor if you have a planned surgery.

If you have high blood pressure, keep using this medicine even if you feel well. High blood pressure often has no symptoms.

Store tightly closed at room temperature, away from moisture and heat.

Dosing information

Usual Adult Dose for Hypertension:

Initial dose: 25 mg orally 2 to 3 times a day one hour before meals

Maintenance dose: May increase every 1 to 2 weeks up to 50 mg orally three times a day. If blood pressure remains uncontrolled after 1 to 2 weeks at this dose, add a thiazide diuretic (loop diuretic if severe renal impairment exists) and titrate to its highest usual antihypertensive dose before further increases of captopril.

Maximum dose: 450 mg/day

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 25 mg orally three times a day (6.25 to 12.5 mg orally three times a day if hypotensive, hyponatremic, or hypovolemic)

Target maintenance dose: 50 mg orally three times a day for at least two weeks to ensure a satisfactory response

Maximum dose: 450 mg/day

Comments:
-Most patients experience satisfactory clinical improvement at 50 or 100 mg orally three times a day.
-Should generally be used in conjunction with other medicines, according to Guideline-directed medical therapy.

Usual Adult Dose for Left Ventricular Dysfunction:

Initial dose: 6.25 mg orally once as early as three days post-myocardial infarction, followed by 12.5 mg orally three times a day; increase to 25 mg orally three times a day over the next several days, and then increase to target dose over the next several weeks as tolerated.

Target maintenance dose: 50 mg orally three times a day

Use: To improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction of 40% or less and to reduce the incidence of overt heart failure and subsequent hospitalizations for congestive heart failure in these patients.

Usual Adult Dose for Diabetic Nephropathy:

25 mg orally three times a day

Comments: Other antihypertensives may be used in conjunction with this drug if additional blood pressure reduction is required.

Use: Treatment of diabetic nephropathy (proteinuria greater than 500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy.

Usual Adult Dose for Hypertensive Emergency:

25 mg orally 2 to 3 times a day; continue diuretic therapy and stop other antihypertensives upon initiation of this drug; may increase dose every 24 hours or less until satisfactory blood pressure or maximum dose is reached.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid while taking captopril?

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Do not take potassium supplements or use salt substitutes, unless your doctor has told you to.

Avoid becoming overheated or dehydrated during exercise, in hot weather, or by not drinking enough fluids. Follow your doctor’s instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

Avoid strenuous exercise if you are being treated for heart failure. Ask your doctor about your risk.

Captopril side effects

Get emergency medical help if you have signs of an allergic reaction to captopril: severe stomach pain, hives, difficult breathing, swelling of your face, lips, tongue, or throat.

Captopril may cause serious side effects. Call your doctor at once if you have:

• chest pain, fast, slow, or uneven heart rate;
• a light-headed feeling, like you might pass out;
• heart problems – swelling, rapid weight gain, feeling short of breath;
• kidney problems – swelling, urinating less, feeling tired or short of breath;
• signs of infection – fever, chills, sore throat, body aches, unusual tiredness, loss of appetite, bruising or bleeding;
• high blood potassium – nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement;
• low blood sodium – headache, confusion, problems with thinking or memory, weakness, feeling unsteady; or
• low white blood cell counts – fever, mouth sores, skin sores, sore throat, cough.

Common captopril side effects may include:

• cough;
• low blood pressure;
• flushing (sudden warmth, redness, or tingly feeling);
• low blood cell counts;
• decreased sense of taste; or
• mild skin itching or rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect captopril?

Captopril can harm your kidneys, especially if you also use certain medicines for infections, cancer, or osteoporosis.

Tell your doctor about all your other medicines, especially:

• a diuretic or “water pill” that may increase blood potassium such as spironolactone, triamterene, amiloride;
• NSAIDs (nonsteroidal anti-inflammatory drugs) – aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others;
• medicine to prevent organ transplant rejection such as temsirolimus, sirolimus, or everolimus; or
• heart or blood pressure medication.

Candesartan is an angiotensin II receptor blocker (sometimes called an ARB).

Candesartan is used to treat high blood pressure (hypertension) in adults and children who are at least 1 year old. Lowering blood pressure may lower your risk of a stroke or heart attack.

Candesartan is also used in adults to treat certain types of heart failure and lower your risk of death or needing to be hospitalized for heart damage.

Candesartan may also be used for purposes not listed in this medication guide.

Candesartan side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Candesartan may cause serious side effects. Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• little or no urination; or
• high potassium level–nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement.

Common side effects of candesartan may include:

• high potassium;
• headache, back pain;
• cold symptoms such as stuffy or runny nose, sneezing, sore throat;
• dizziness; or
• abnormal kidney test.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Warnings

Do not use if you are pregnant. Stop using candesartan and tell your doctor right away if you become pregnant.

If you have diabetes, do not take candesartan with any medication that contains aliskiren (a blood pressure medicine).

Before taking this medicine

You should not use this medication if you are allergic to candesartan.

If you have diabetes, do not take candesartan with any medication that contains aliskiren (a blood pressure medicine).

You may also need to avoid taking candesartan with aliskiren if you have kidney disease.

Tell your doctor if you have ever had:

• a heart condition other than one being treated with candesartan;
• kidney disease (or if you are on dialysis);
• liver disease; or
• if you are on a low-salt diet.

Do not use if you are pregnant. Stop using the medicine and tell your doctor right away if you become pregnant. Candesartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

If you plan to get pregnant, ask your doctor for a safer medicine to use before and during pregnancy. Having high blood pressure during pregnancy may cause complications in the mother and the baby.

You should not breastfeed while using candesartan.

How should I take candesartan?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

You may take candesartan with or without food.

For a child who cannot swallow a tablet whole, a pharmacist can mix the medicine into a liquid.

Shake the liquid before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Candesartan doses are based on weight in children and/or teenagers. Your child’s dose needs may change if the child gains or loses weight.

Your blood pressure will need to be checked often. Your kidney function may also need to be checked.

Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking candesartan.

It may take 2 to 4 weeks before your blood pressure is under control. Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms.

You may need to use blood pressure medicine for the rest of your life. Treatment may also include diet, exercise, lowering cholesterol, not smoking, and controlling diabetes.

If you need surgery, tell your surgeon you currently use this medicine. You may need to stop for a short time.

Store at room temperature away from moisture and heat.

Candesartan dosing information

Usual Adult Dose for Hypertension:

Initial dose: 16 mg orally once a day
Maintenance dose: 8 to 32 mg/day orally in 1 to 2 divided doses
Maximum dose: 32 mg/day

Comments:
-Consider administration of a lower initial dose in volume depleted patients.
-Most of the antihypertensive effect is present within 2 weeks; maximum blood pressure reduction at a given dose is generally observed within 4 to 6 weeks of starting that dose.

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 4 mg orally once a day; double dose every 2 weeks, as tolerated, to target dose of 32 mg orally once a day

Use: Treatment of New York Heart Association (NYHA) class II through IV heart failure

Usual Pediatric Dose for Hypertension:

1 TO LESS THAN 6 YEARS:
Initial dose: 0.2 mg/kg/day orally in 1 to 2 divided doses
Maintenance dose: 0.05 to 0.4 mg/kg/day orally in 1 to 2 divided doses

6 TO LESS THAN 17 YEARS:
Less than 50 kg:
-Initial dose: 4 to 8 mg/day orally in 1 to 2 divided doses
-Maintenance dose: 2 to 16 mg/day orally in 1 to 2 divided doses
Greater than 50 kg:
-Initial dose: 8 to 16 mg/day orally in 1 to 2 divided doses
-Maintenance dose: 4 to 32 mg/day orally in 1 to 2 divided doses

Comments:
-For patients with possible intravascular volume depletion (e.g., patients treated with diuretics, especially those with renal impairment), initiate this drug under close supervision and consider administration of a lower dose.
-Antihypertensive effect is present within 2 weeks; maximum blood pressure reduction at a given dose is generally observed within 4 weeks of starting that dose.
-For children unable to swallow tablets, an extemporaneous suspension may be used instead.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include dizziness, fast heartbeats, or fainting.

What should I avoid while taking candesartan?

Do not use potassium supplements or salt substitutes, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

What other drugs will affect candesartan?

Tell your doctor about all your other medicines, especially:

• any other heart or blood pressure medications;
• a diuretic or “water pill”;
• lithium; or
• NSAIDs (nonsteroidal anti-inflammatory drugs)–ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

What is Cabometyx?

Cabometyx is used to treat certain types of kidney cancer (renal cell carcinoma), liver cancer (hepatocellular carcinoma), differentiated thyroid cancer, and pancreatic and extra-pancreatic neuroendocrine tumors. It is an oral tablet taken once daily.

Cabometyx (cabozantinib) gained FDA approval on November 29, 2012. There is no generic.

FDA Approvals and Uses

Cabometyx (cabozantinib) is an oral kinase inhibitor approved to treat:

• Advanced renal cell carcinoma (RCC that has spread), as monotherapy
• Advanced RCC as first-line treatment in combination with nivolumab
• Hepatocellular carcinoma in patients previously treated with sorafenib
• Locally advanced or metastatic differentiated thyroid cancer (DTC) in adults and children 12 years and older that has progressed following VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.
• Previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) or extra-pancreatic neuroendocrine tumors (epNET) in adults and children 12 years and older

It is not known if Cabometyx is safe and effective in children younger than 12 years of age.

Side Effects

Common Side Effects

The most common side effects of Cabometyx are:

• Tiredness
• Nausea and vomiting
• Constipation
• Decreased appetite
• Weight decreased.

The most common side effects of Cabometyx when used in combination with nivolumab are:

• Tiredness
• Mouth sores
• Rash
• Low thyroid hormone levels (hypothyroidism)
• Pain in muscles, bones, and joints
• Decreased appetite
• Nausea
• Changes in the way things taste
• Stomach-area (abdominal) pain
• Cough
• Upper respiratory tract infection.

Cabometyx may cause fertility problems in females and males, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility.

Serious side effects and warnings

Cabometyx may cause the following serious side effects.

Bleeding (hemorrhage)

Cabometyx can cause severe bleeding that may lead to death. Tell your healthcare provider right away if you get any signs of bleeding during treatment with Cabometyx, including:

• Coughing up blood or blood clots
• Vomiting blood, or if your vomit looks like coffee grounds
• Red or black (looks like tar) stools
• Menstrual bleeding that is heavier than normal
• Any unusual or heavy bleeding

Perforations and fistulas

Cabometyx can cause a tear in your stomach or intestinal wall (perforation) or an abnormal connection between 2 parts of your body (fistula). Tell your healthcare provider right away if you get tenderness or pain in your stomacharea (abdomen) that is severe, or that does not go away.

Blood clots, stroke, heart attack, and chest pain

Cabometyx may affect the way your blood clots and increase the risk of blood clots, a stroke, heart attack, or chest pain. Get emergency help right away if you get:

• Swelling or pain in your arms or legs
• Shortness of breath
• Feel lightheaded or faint
• Sweating more than usual
• Numbness or weakness of your face, arm or leg, especially on one side of your body
• Sudden confusion, trouble speaking, or understanding
• Sudden trouble seeing in one or both eyes
• Sudden trouble walking
• Dizziness, loss of balance, or coordination
• A sudden severe headache.

High blood pressure (hypertension)

Hypertension is common with Cabometyx and sometimes can be severe. Your healthcare provider will check your blood pressure before starting Cabometyx and regularly during treatment. If needed, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you develop severe headaches, nose bleeds, tiredness or confusion, vision changes, chest pain, trouble breathing, irregular heartbeat, or blood in your urine.

Heart problems

Cabometyx can cause heart failure that may lead to death. Your healthcare provider may check your heart function before and during treatment with Cabometyx. Tell your healthcare provider right away if you get any of the following signs and symptoms:

• Feeling like your heart is pounding, racing, or beating irregularly
• Swelling of your ankles or feet
• Feeling lightheaded
• Shortness of breath
• Tiredness

Diarrhea

Diarrhea is common with Cabometyx and can be severe. If needed, your healthcare provider may prescribe medicine to treat your diarrhea. Tell your healthcare provider right away if you have frequent loose, watery bowel movements.

Hand-foot skin reaction

Hand-foot skin reactions are common with Cabometyx and can be severe. Tell your healthcare provider right away if you have rashes, redness, pain, swelling, or blisters on the palms of your hands or soles of your feet.

Liver problems

Liver problems may happen during treatment with Cabometyx. When Cabometyx is taken in combination with nivolumab, severe changes in liver function tests may happen more often than if you take Cabometyx alone. Your healthcare provider will do blood tests to check your liver function before and during treatment with Cabometyx. Tell your healthcare provider right away if you develop symptoms of liver problems, including yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach-area (abdomen), dark urine, bleeding, or bruising more easily than normal.

Adrenal gland problems

Your healthcare provider will monitor you for this problem. Your healthcare provider may prescribe hormone replacement therapy or corticosteroid medicines if needed. Tell your healthcare provider right away if you develop any of the following signs or symptoms: extreme tiredness, dizziness or fainting, weakness, nausea, or vomiting.

Protein in your urine and possible kidney problems

Symptoms may include swelling in your hands, arms, legs, or feet. Your healthcare provider will check you for this problem during treatment with Cabometyx.  

Severe jawbone problems (osteonecrosis)

Your healthcare provider should examine your mouth before you start and during treatment with Cabometyx. Tell your dentist that you are taking Cabometyx. It is important for you to practice good mouth care during treatment with Cabometyx. Tell your healthcare provider right away if you develop any symptoms of jaw problems, including: jaw pain, toothache, or sores on your gums.

Wound healing problems

Wound healing problems have happened in people who take Cabometyx. Tell your healthcare provider if you plan to have any surgery before or during treatment with Cabometyx.

• You should stop taking Cabometyx at least 3 weeks before planned surgery.
• Your healthcare provider should tell you when you may start taking Cabometyx again after surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

A condition called reversible posterior leukoencephalopathy syndrome can happen during treatment with Cabometyx. Tell your healthcare provider right away if you have headaches, seizures, confusion, changes in vision, or problems thinking.

Change in thyroid function

Cabometyx can cause changes in your thyroid function, including changes to thyroid hormone levels in your blood. Your healthcare provider will do blood tests to check your thyroid function before and during treatment with Cabometyx.

Decreased calcium level in your blood (hypocalcemia)

Cabometyx can cause you to have a decreased amount of calcium in your blood. Your healthcare provider will do blood tests to check you for this problem and give you calcium if needed. Tell your healthcare provider right away if you get any of the following signs or symptoms:

• Muscle stiffness or muscle spasms
• Sudden weight gain
• Numbness or tingling in your fingers, toes, or around your mouth
• Swelling of your arms, hands, legs, and ankles
• Seizures.

Notes:

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Cabometyx if you have certain side effects.

These are not all of the possible side effects of Cabometyx. Call your doctor for medical advice about side effects.

How does Cabometyx work?

Cabometyx (cabozantinib) works by blocking multiple tyrosine kinase enzymes, including MET, VEGFR, AXL, RET, and others. These enzymes regulate normal cell functions but also drive cancer-related processes like tumor growth, spread, blood vessel formation, drug resistance, and tumor microenvironment maintenance.

Cabometyx (cabozantinib) belongs to the drug class called multikinase inhibitors. It may also be called a VEGF/VEGFR inhibitor.

Before taking this medicine

Before you take Cabometyx, tell your healthcare provider about all of your medical conditions, including if you:

• Have had a liver problem other than liver cancer
• Have a recent history of bleeding, including coughing up or vomiting blood, or black tarry stools.
• Have an open or healing wound
• Have high blood pressure
• Have heart problems
• Have a low calcium level in your blood (hypocalcemia)
• Plan to have any surgery, dental procedure, or have had a recent surgery. You should stop taking Cabometyx at least 3 weeks before planned surgery
• Are pregnant, or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Pregnancy

Cabometyx can harm your unborn baby.

• If you can become pregnant, your healthcare provider will check your pregnancy status before you start treatment with Cabometyx.
• Females who can become pregnant should use effective birth control (contraception) during treatment and for 4 months after their last dose of Cabometyx.
• Talk to your healthcare provider about birth control methods that may be right for you.
• If you become pregnant or think you are pregnant, tell your healthcare provider right away.

Breastfeeding

It is not known if Cabometyx passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of Cabometyx.

How should I take Cabometyx?

• Take Cabometyx exactly as your healthcare provider tells you to take it.
• Do not take Cabometyx with food. Take Cabometyx on an empty stomach at least 1 hour before or at least 2 hours after eating.
• Swallow Cabometyx tablets whole.
• Do not crush, chew, or split Cabometyx tablets.

What happens if I miss a dose?

If you miss a dose and your next scheduled dose is in less than 12 hours, take your next dose at the normal time. Do not make up the missed dose.

What should I avoid while taking Cabometyx?

Avoid drinking grapefruit juice, eating grapefruit, or taking supplements that contain grapefruit or St. John’s wort during treatment with Cabometyx.

What other drugs will affect Cabometyx?

Tell your healthcare provider about all the medicines you take, including prescription or over-the-counter medicines, vitamins, and herbal supplements. Cabometyx and certain other medicines may affect each other, causing side effects.

Do NOT substitute Cabometyx tablets with cabozantinib capsules. 

Dosing information

• Administer on an empty stomach at least 1 hour before or at least 2 hours after eating.
• Stop treatment with Cabometyx at least 3 weeks before scheduled surgery, including dental surgery.

Adult Dose of Cabometyx for RCC

• Monotherapy: 60 mg orally once daily
• Combination therapy: 40 mg orally once daily with:
  • nivolumab 240 mg by intravenous infusion every 2 weeks

OR

• • nivolumab 480 mg by intravenous infusion every 4 weeks

OR

• • nivolumab 600 mg and hyaluronidase 10,000 units subcutaneously every 2 weeks

OR

• • nivolumab 1,200 mg and hyaluronidase 20,000 units subcutaneously every 4 weeks

Adult Dose of Cabometyx for HCC

• 60 mg orally once daily

Adult and Pediatric 12+ Dose of Cabometyx for DTC, pNET, epNET

• ≥40 kg: 60 mg orally once daily
• <40 kg: 40 mg orally once daily.

Storage

Store Cabometyx at room temperature between 68°F to 77°F (20°C to 25°C).

Keep out of the reach of children.

What are the ingredients in Cabometyx?

Active ingredient: cabozantinib

Inactive ingredients: microcrystalline cellulose, lactose anhydrous, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. The film coating contains hypromellose, titanium dioxide, triacetin, and iron oxide yellow.

Available as 20 mg, 40 mg, 60 mg, oral tablets.

Company

Cabometyx is manufactured for Exelixis, Inc. Alameda, CA 94502.

Bystolic belongs to a group of drugs called beta-blockers. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).

Bystolic is used to treat hypertension (high blood pressure). Lowering blood pressure may lower your risk of a stroke or heart attack.

Bystolic may also be used for other purposes not listed in this medication guide.

Warnings

Do not skip doses or stop taking Bystolic without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems such as severe chest pain or heart attack. You may need to use less and less before you stop the medication completely. If you need surgery, tell the surgeon ahead of time that you are using Bystolic.

Bystolic may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Bystolic is only part of a complete program of treatment that also includes diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Keep using Bystolic as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Before taking this medicine

To make sure you can safely take Bystolic, tell your doctor if you have any of these other conditions:

• severe liver disease; or
• a heart problem such as heart block, sick sinus syndrome, slow heart rate, or heart failure.

If you have any of these other conditions, you may need a Bystolic dose adjustment or special tests:

• asthma, bronchitis, emphysema;
• liver or kidney disease;
• diabetes;
• a thyroid disorder;
• a history of allergies;
• problems with circulation (such as Raynaud’s syndrome);
• pheochromocytoma (tumor of the adrenal gland); or
• if you have recently had a heart attack.

FDA pregnancy category C. It is not known whether Bystolic will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Bystolic. It is not known whether nebivolol passes into breast milk or if it could harm a nursing baby. Do not use Bystolic without telling your doctor if you are breast-feeding a baby.

How should I take Bystolic?

Take Bystolic exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take Bystolic at the same time every day. You may take the medication with or without food.

Do not skip doses or stop taking Bystolic without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems such as severe chest pain or heart attack. You may need to use less and less before you stop the medication completely.

Your blood pressure will need to be checked often. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using Bystolic.

Bystolic is only part of a complete program of treatment that also includes diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Keep using Bystolic as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store Bystolic at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include slow heart rate, dizziness, vomiting, trouble breathing, or feeling like you might pass out.

What should I avoid?

Bystolic may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Bystolic side effects

Get emergency medical help if you have any of these signs of an allergic reaction to Bystolic: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• feeling short of breath, even with mild exertion;
• swelling of your ankles or feet;
• slow or uneven heartbeats; or
• numbness or cold feeling in your hands and feet.

Less serious Bystolic side effects may include:

• headache;
• tired feeling;
• nausea, stomach pain;
• diarrhea; or
• sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect Bystolic?

Tell your doctor about all other medicines you use, especially:

• cimetidine (Tagamet);
• clonidine (Catapres);
• digitalis (digoxin, Lanoxin);
• isoniazid (for treating tuberculosis);
• methimazole (Tapazole);
• reserpine;
• ropinirole (Requip);
• ticlopidine (Ticlid);
• another beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others;
• an antibiotic such as terbinafine (Lamisil);
• an antidepressant such as clomipramine (Anafranil), desipramine (Norpramin), duloxetine (Cymbalta), fluoxetine (Prozac, Rapiflux, Sarafem, Selfemra, Symbyax), imipramine (Tofranil), paroxetine (Paxil, Pexeva), sertraline (Zoloft), or tranylcypromine (Parnate);
• anti-malaria medication such as chloroquine (Aralen) or pyrimethamine (Daraprim), or quinine (Qualaquin);
• heart or blood pressure medicine such as amlodipine (Norvasc, Caduet, Exforge, Lotrel, Tekamlo, Tribenzor, Twynsta, Amturnide), clonidine (Catapres, Clorpres, Kapvay, Nexiclon), diltiazem (Cardizem, Cartia, Dilacor, Diltia, Diltzac, Taztia, Tiazac), nicardipine (Cardene), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan, Tarka), and others;
• heart rhythm medicine such as amiodarone (Cordarone, Pacerone), quinidine (Quin-G), procainamide (Pronestyl), disopyramide (Norpace), flecaininde (Tambocor), mexiletine (Mexitil), propafenone, (Rythmol), and others;
• HIV or AIDS medicine such as delavirdine (Rescriptor) or ritonavir (Norvir, Kaletra); or
• medicine to treat psychiatric disorders, such as aripiprazole (Abilify), chlorpromazine (Thorazine), clozapine (Clozaril, FazaClo), fluphenazine (Permitil, Prolixin), haloperidol (Haldol), perphenazine (Trilafon), or thioridazine (Mellaril).

Bumex ®(bumetanide) is a loop diuretic available as 0.5 mg (light green), 1 mg (yellow) and 2 mg (peach) tablets for oral administration; each tablet also contains anhydrous lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch and talc, with the following dye systems: 0.5 mg—D&C Yellow No. 10 aluminum lake and FD&C Blue No. 1 aluminum lake; 1 mg—D&C Yellow No. 10 aluminum lake; 2 mg—red iron oxide.

Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white powder having a calculated molecular weight of 364.42, and the following structural formula:

FDA-approved impurity specifications differ from the USP.

Bumex – Clinical Pharmacology

Bumex is a loop diuretic with a rapid onset and short duration of action. Pharmacological and clinical studies have shown that 1 mg Bumex has a diuretic potency equivalent to approximately 40 mg furosemide. The major site of Bumex action is the ascending limb of the loop of Henle.

The mode of action has been determined through various clearance studies in both humans and experimental animals. Bumex inhibits sodium reabsorption in the ascending limb of the loop of Henle, as shown by marked reduction of free-water clearance (CH 2O) during hydration and tubular free-water reabsorption (T CH 2O) during hydropenia. Reabsorption of chloride in the ascending limb is also blocked by Bumex, and Bumex is somewhat more chloruretic than natriuretic.

Potassium excretion is also increased by Bumex, in a dose-related fashion.

Bumex may have an additional action in the proximal tubule. Since phosphate reabsorption takes place largely in the proximal tubule, phosphaturia during Bumex induced diuresis is indicative of this additional action. This is further supported by the reduction in the renal clearance of Bumex by probenecid, associated with diminution in the natriuretic response. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase. Bumex does not appear to have a noticeable action on the distal tubule.

Bumex decreases uric acid excretion and increases serum uric acid. Following oral administration of Bumex the onset of diuresis occurs in 30 to 60 minutes. Peak activity is reached between 1 and 2 hours. At usual doses (1 mg to 2 mg) diuresis is largely complete within 4 hours; with higher doses, the diuretic action lasts for 4 to 6 hours. Diuresis starts within minutes following an intravenous injection and reaches maximum levels within 15 to 30 minutes.

Several pharmacokinetic studies have shown that bumetanide, administered orally or parenterally, is eliminated rapidly in humans, with a half-life of between 1 and 1½ hours. Plasma protein-binding is in the range of 94% to 96%.

Oral administration of carbon-14 labeled Bumex to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Urinary and biliary metabolites identified in this study were formed by oxidation of the N-butyl side chain. Biliary excretion of Bumex amounted to only 2% of the administered dose.

Pediatric Pharmacology

Elimination of bumetanide appears to be considerably slower in neonatal patients compared with adults, possibly because of immature renal and hepatobiliary function in this population. Small pharmacokinetic studies of intravenous bumetanide in preterm and full-term neonates with respiratory disorders have reported an apparent half-life of approximately 6 hours, with a range up to 15 hours and a serum clearance ranging from 0.2 mL/min/kg to 1.1 mL/min/kg. In a population of neonates receiving bumetanide for volume overload, mean serum clearance rates were 2.2 mL/min/kg in patients less than 2 months of age and 3.8 mL/min/kg in patients aged 2 to 6 months. Mean serum half-life of bumetanide was 2.5 hours and 1.5 hours in patients aged less than 2 months and those aged 2 to 6 months, respectively. Elimination half-life decreased considerably during the first month of life, from a mean of approximately 6 hours at birth to approximately 2.4 hours at 1 month of age.

In preterm neonates, mean serum concentrations following a single 0.05 mg/kg dose ranged from 126 μg/L at 1 hour to 57 μg/L at 8 hours. In another study, mean serum concentrations following a single 0.05 mg/kg dose were 338 ng/mL at 30 minutes and 176 ng/mL after 4 hours. A single dose of 0.1 mg/kg produced mean serum levels of 314 ng/mL at 1 hour, and 195 ng/mL at 6 hours. Mean volume of distribution in neonates and infants has been reported to range from 0.26 L/kg to 0.39 L/kg.

The degree of protein binding of bumetanide in cord sera from healthy neonates was approximately 97%, suggesting the potential for bilirubin displacement. A study using pooled sera from critically ill neonates found that bumetanide at concentrations of 0.5 μg/mL to 50 μg/mL, but not 0.25 μg/mL, caused a linear increase in unbound bilirubin concentrations.

In 56 infants aged 4 days to 6 months, bumetanide doses ranging from 0.005 mg/kg to 0.1 mg/kg were studied for pharmacodynamic effect. Peak bumetanide excretion rates increased linearly with increasing doses of drug. Maximal diuretic effect was observed at a bumetanide excretion rate of about 7 μg/kg/h, corresponding to doses of 0.035 mg/kg to 0.040 mg/kg. Higher doses produced a higher bumetanide excretion rate but no increase in diuretic effect. Urine flow rate peaked during the first hour after drug administration in 80% of patients and by 3 hours in all patients.

Geriatric Pharmacology

In a group of ten geriatric subjects between the ages of 65 and 73 years, total bumetanide clearance was significantly lower (1.8 ± 0.3 mL/min·kg) compared with younger subjects (2.9 ± 0.2 mL/min·kg) after a single oral bumetanide 0.5 mg dose. Maximum plasma concentrations were higher in geriatric subjects (16.9 ± 1.8 ng/mL) compared with younger subjects (10.3 ± 1.5 ng/mL). Urine flow rate and total excretion of sodium and potassium were increased less in the geriatric subjects compared with younger subjects, although potassium excretion and fractional sodium excretion were similar between the two age groups. Nonrenal clearance, bioavailability, and volume of distribution were not significantly different between the two groups.

Indications and Usage for Bumex

Bumex tablets are indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome.

Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route.

Successful treatment with Bumex tablets following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.

Contraindications

Bumex is contraindicated in anuria. Although Bumex can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with Bumex. Bumex is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the condition is improved or corrected. Bumex is contraindicated in patients hypersensitive to this drug.

Warnings

Volume and Electrolyte Depletion

The dose of Bumex should be adjusted to the patient’s need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients.

Hypokalemia

Hypokalemia can occur as a consequence of Bumex administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, i.e., history of ventricular arrhythmias.

In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient’s clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients.

Ototoxicity

In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk.

Allergy to Sulfonamides

Patients allergic to sulfonamides may show hypersensitivity to Bumex.

Thrombocytopenia

Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.

Precautions

General

Serum potassium should be measured periodically and potassium supplements or potassium sparing diuretics added if necessary. Periodic determinations of other electrolytes are advised in patients treated with high doses or for prolonged periods, particularly in those on low-salt diets.

Hyperuricemia may occur; it has been asymptomatic in cases reported to date. Reversible elevations of the BUN and creatinine may also occur, especially in association with dehydration and particularly in patients with renal insufficiency. Bumex may increase urinary calcium excretion with resultant hypocalcemia.

Diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Laboratory Tests

Studies in normal subjects receiving Bumex revealed no adverse effects on glucose tolerance, plasma insulin, glucagon and growth hormone levels, but the possibility of an effect on glucose metabolism exists. Periodic determinations of blood sugar should be done, particularly in patients with diabetes or suspected latent diabetes.

Patients under treatment should be observed regularly for possible occurrence of blood dyscrasias, liver damage or idiosyncratic reactions, which have been reported occasionally in foreign marketing experience. The relationship of these occurrences to Bumex use is not certain.

Drug Interactions

Drugs with Ototoxic Potential 

Especially in the presence of impaired renal function, the use of parenterally administered bumetanide in patients to whom aminoglycoside antibiotics are also being given should be avoided, except in life-threatening conditions.

Drugs with Nephrotoxic Potential

There has been no experience with the concurrent use of Bumex with drugs known to have a nephrotoxic potential. Therefore, the simultaneous administration of these drugs should be avoided.

Lithium

Lithium should generally not be given with diuretics (such as Bumex) because they reduce its renal clearance and add a high risk of lithium toxicity.

Probenecid

Pretreatment with probenecid reduces both the natriuresis and hyperreninemia produced by Bumex. This antagonistic effect of probenecid on Bumex natriuresis is not due to a direct action on sodium excretion but is probably secondary to its inhibitory effect on renal tubular secretion of bumetanide. Thus, probenecid should not be administered concurrently with Bumex.

Indomethacin

Indomethacin blunts the increases in urine volume and sodium excretion seen during Bumex treatment and inhibits the bumetanide-induced increase in plasma renin activity. Concurrent therapy with Bumex is thus not recommended.

Antihypertensives

Bumex may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.

Digoxin

Interaction studies in humans have shown no effect on digoxin blood levels.

Anticoagulants

Interaction studies in humans have shown Bumex to have no effect on warfarin metabolism or on plasma prothrombin activity.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Bumex was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitrometabolic activation system. An 18-month study showed an increase in mammary adenomas of questionable significance in female rats receiving oral doses of 60 mg/kg/day (2000 times a 2-mg human dose). A repeat study at the same doses failed to duplicate this finding.

Reproduction studies were performed to evaluate general reproductive performance and fertility in rats at oral dose levels of 10, 30, 60 or 100 mg/kg/day. The pregnancy rate was slightly decreased in the treated animals; however, the differences were small and not statistically significant.

Pregnancy

Teratogenic Effects

Bumex is neither teratogenic nor embryocidal in mice when given in doses up to 3400 times the maximum human therapeutic dose.

Bumex has been shown to be nonteratogenic, but it has a slight embryocidal effect in rats when given in doses of 3400 times the maximum human therapeutic dose and in rabbits at doses of 3.4 times the maximum human therapeutic dose. In one study, moderate growth retardation and increased incidence of delayed ossification of sternebrae were observed in rats at oral doses of 100 mg/kg/day, 3400 times the maximum human therapeutic dose. These effects were associated with maternal weight reductions noted during dosing. No such adverse effects were observed at 30 mg/kg/day (1000 times the maximum human therapeutic dose). No fetotoxicity was observed at 1000 to 2000 times the human therapeutic dose.

In rabbits, a dose-related decrease in litter size and an increase in resorption rate were noted at oral doses of 0.1 mg/kg/day and 0.3 mg/kg/day (3.4 and 10 times the maximum human therapeutic dose). A slightly increased incidence of delayed ossification of sternebrae occurred at 0.3 mg/kg/day; however, no such adverse effects were observed at the dose of 0.03 mg/kg/day. The sensitivity of the rabbit to Bumex parallels the marked pharmacologic and toxicologic effects of the drug in this species.

Bumex was not teratogenic in the hamster at an oral dose of 0.5 mg/kg/day (17 times the maximum human therapeutic dose). Bumetanide was not teratogenic when given intravenously to mice and rats at doses up to 140 times the maximum human therapeutic dose.

There are no adequate and well-controlled studies in pregnant women. A small investigational experience in the and marketing experience in other countries to date have not indicated any evidence of adverse effects on the fetus, but these data do not rule out the possibility of harmful effects. Bumex should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while the patient is on Bumex since it may be excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 have not been established.

In vitrostudies using pooled sera from critically ill neonates have shown bumetanide to be a potent displacer of bilirubin . The administration of bumetanide could present a particular concern if given to critically ill or jaundiced neonates at risk for kernicterus.

Geriatric Use

Clinical studies of Bumex did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Adverse Reactions/Side Effects

The most frequent clinical adverse reactions considered probably or possibly related to Bumex are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with pre-existing liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with Bumex.

Serious skin reactions (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported in association with bumetanide use.

Less frequent clinical adverse reactions to Bumex are impaired hearing (0.5%), pruritus (0.4%), electrocardiogram changes (0.4%), weakness (0.2%), hives (0.2%), abdominal pain (0.2%), arthritic pain (0.2%), musculoskeletal pain (0.2%), rash (0.2%) and vomiting (0.2%). One or more of these adverse reactions have been reported in approximately 2.9% of patients treated with Bumex.

Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are vertigo, chest pain, ear discomfort, fatigue, dehydration, sweating, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, diarrhea, premature ejaculation and difficulty maintaining an erection.

Laboratory abnormalities reported have included hyperuricemia (in 18.4% of patients tested), hypochloremia (14.9%), hypokalemia (14.7%), azotemia (10.6%), hyponatremia (9.2%), increased serum creatinine (7.4%), hyperglycemia (6.6%), and variations in phosphorus (4.5%), CO content (4.3%), bicarbonate (3.1%) and calcium (2.4%). Although manifestations of the pharmacologic action of Bumex, these conditions may become more pronounced by intensive therapy.

Also reported have been thrombocytopenia (0.2%) and deviations in hemoglobin (0.8%), prothrombin time (0.8%), hematocrit (0.6%), WBC (0.3%) and differential counts (0.1%). There have been rare spontaneous reports of thrombocytopenia from postmarketing experience.

Diuresis induced by Bumex may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), SGOT (0.6%), SGPT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.

Overdosage

Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.

Bumex Dosage and Administration

Individualize dosage with careful monitoring of patient response.

Oral Administration

The usual total daily dosage of Bumex tablets is 0.5 mg to 2 mg and in most patients is given as a single dose.

If the diuretic response to an initial dose of Bumex tablets is not adequate, in view of its rapid onset and short duration of action, a second or third dose may be given at 4- to 5-hour intervals up to a maximum daily dose of 10 mg. An intermittent dose schedule, whereby Bumex tablets are given on alternate days or for 3 to 4 days with rest periods of 1 to 2 days in between, is recommended as the safest and most effective method for the continued control of edema. In patients with hepatic failure, keep the dosage to a minimum.

Because cross-sensitivity with furosemide has rarely been observed, bumetanide can be substituted at approximately a 1:40 ratio of bumetanide in proportion to furosemide in patients allergic to furosemide.

Parenteral Administration

Bumetanide injection may be administered parenterally (intravenously and intramuscularly) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.

Terminate parenteral treatment and institute oral treatment as soon as possible.

How is Bumex supplied

Bumex Tablets for oral administration are elliptical, flat-faced, and bevel-edged, available as:

Store at 68° to 77°F (20° to 25°C); excursions permitted between 59° to 86°F (15° to 30°C) [See USP Controlled Room Temperature].

Dispense contents in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.

Manufactured for andDistributed by:
Validus Pharmaceuticals LLC
Parsippany, NJ 07054
info@validuspharma.com
www.validuspharma.com
1-866-982-5438

Product of Italy

© 2023 Validus Pharmaceuticals LLC

60018-05 November 2023

PRINCIPAL DISPLAY PANEL

NDC 30698-630-01
Bumex ®
(bumetanide) Tablets
0.5 mg
100 Tablets
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 30698-631-01
Bumex ®
(bumetanide) Tablets
1 mg
100 Tablets
Rx Only

NDC 30698-631-05
Bumex ®
(bumetanide) Tablets
1 mg
500 Tablets
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 30698-632-01
Bumex ®
(bumetanide) Tablets
2 mg
100 Tablets
Rx Only

NDC 30698-632-05
Bumex ®
(bumetanide) Tablets
2 mg
500 Tablets
Rx Only

Bumetanide is a loop diuretic, available as 4 mL vials and 10 mL vials (0.25 mg/mL) for intravenous or intramuscular injection as a sterile solution.

Each mL contains 0.25 mg bumetanide compounded with 0.85% sodium chloride and 0.4% ammonium acetate as buffers; 0.01% edetate disodium; 1% benzyl alcohol as preservative in water for injection and pH adjusted to 6.8 to 7.8 with sodium hydroxide.

Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white or almost white, crystalline powder having a calculated molecular weight of 364.42, and the following structural formula:

Bumetanide – Clinical Pharmacology

Bumetanide is a loop diuretic with a rapid onset and short duration of action. Pharmacological and clinical studies have shown that 1 mg bumetanide has a diuretic potency equivalent to approximately 40 mg furosemide. The major site of bumetanide action is the ascending limb of the loop of Henle.

The mode of action has been determined through various clearance studies in both humans and experimental animals. Bumetanide inhibits sodium reabsorption in the ascending limb of the loop of Henle, as shown by marked reduction of free-water clearance (CH2O) during hydration and tubular free-water reabsorption (TcH2O) during hydropenia. Reabsorption of chloride in the ascending limb is also blocked by bumetanide, and bumetanide is somewhat more chloruretic than natriuretic.

Potassium excretion is also increased by bumetanide, in a dose-related fashion.

Bumetanide may have an additional action in the proximal tubule. Since phosphate reabsorption takes place largely in the proximal tubule, phosphaturia during bumetanide induced diuresis is indicative of this additional action. This is further supported by the reduction in the renal clearance of bumetanide by probenecid, associated with diminution in the natriuretic response. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase. Bumetanide does not appear to have a noticeable action on the distal tubule.

Bumetanide decreases uric acid excretion and increases serum uric acid. Diuresis starts within minutes following an intravenous injection and reaches maximum levels within 15 to 30 minutes.

Several pharmacokinetic studies have shown that bumetanide, administered orally or parenterally, is eliminated rapidly in humans, with a half-life of between 1 and 1½ hours. Plasma protein-binding is in the range of 94% to 96%.

Oral administration of carbon-14 labeled bumetanide to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Urinary and biliary metabolites identified in this study were formed by oxidation of the N-butyl side chain. Biliary excretion of bumetanide amounted to only 2% of the administered dose.

Pediatric Pharmacology

Elimination of bumetanide appears to be considerably slower in neonatal patients compared with adults, possibly because of immature renal and hepatobiliary function in this population. Small pharmacokinetic studies of intravenous bumetanide in preterm and full-term neonates with respiratory disorders have reported an apparent half-life of approximately 6 hours, with a range up to 15 hours and a serum clearance ranging from 0.2 to 1.1 mL/min/kg. In a population of neonates receiving bumetanide for volume overload, mean serum clearance rates were 2.17 mL/min/kg in patients less than 2 months of age and 3.8 mL/min/kg in patients aged 2 to 6 months. Mean serum half-life of bumetanide was 2.5 hours and 1.5 hours in patients aged less than 2 months and those aged 2 to 6 months, respectively. Elimination half-life decreased considerably during the first month of life, from a mean of approximately 6 hours at birth to approximately 2.4 hours at 1 month of age.

In preterm neonates, mean serum concentrations following a single 0.05 mg/kg dose ranged from 126 mcg/L at 1 hour to 57 mcg/L at 8 hours. In another study, mean serum concentrations following a single 0.05 mg/kg dose were 338 ng/mL at 30 minutes and 176 ng/mL after 4 hours. A single dose of 0.1 mg/kg produced mean serum levels of 314 ng/mL at 1 hour, and 195 ng/mL at 6 hours. Mean volume of distribution in neonates and infants has been reported to range from 0.26 L/kg to 0.39 L/kg.

The degree of protein binding of bumetanide in cord sera from healthy neonates was approximately 97%, suggesting the potential for bilirubin displacement. A study using pooled sera from critically ill neonates found that bumetanide at concentrations of 0.5 to 50 mcg/mL, but not 0.25 mcg/mL, caused a linear increase in unbound bilirubin concentrations.

In 56 infants aged 4 days to 6 months, bumetanide doses ranging from 0.005 mg/kg to 0.1 mg/kg were studied for pharmacodynamic effect. Peak bumetanide excretion rates increased linearly with increasing doses of drug. Maximal diuretic effect was observed at a bumetanide excretion rate of about 7 mcg/kg/hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a higher bumetanide excretion rate but no increase in diuretic effect. Urine flow rate peaked during the first hour after drug administration in 80% of patients and by 3 hours in all patients.

Geriatric Pharmacology

In a group of ten geriatric subjects between the ages of 65 and 73 years, total bumetanide clearance was significantly lower (1.8 ± 0.3 mL/min/kg) compared with younger subjects

(2.9 ± 0.2 mL/min/kg) after a single oral bumetanide 0.5 mg dose. Maximum plasma concentrations were higher in geriatric subjects (16.9 ± 1.8 ng/mL) compared with younger subjects (10.3 ± 1.5 ng/mL). Urine flow rate and total excretion of sodium and potassium were increased less in the geriatric subjects compared with younger subjects, although potassium excretion and fractional sodium excretion were similar between the two age groups. Nonrenal clearance, bioavailability, and volume of distribution were not significantly different between the two groups.

Indications and Usage for Bumetanide

Bumetanide injection, USP is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome.

Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route.

Successful treatment with bumetanide injection, USP following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.

Contraindications

Bumetanide is contraindicated in anuria. Although bumetanide can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with bumetanide. Bumetanide is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the condition is improved or corrected. Bumetanide is contraindicated in patients hypersensitive to this drug.

Warnings

Volume and Electrolyte Depletion

The dose of bumetanide should be adjusted to the patient’s need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients.

Hypokalemia

Hypokalemia can occur as a consequence of bumetanide administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, i.e., history of ventricular arrhythmias.

In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient’s clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients.

Ototoxicity

In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals, bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk.

Allergy to Sulfonamides

Patients allergic to sulfonamides may show hypersensitivity to bumetanide.

Thrombocytopenia

Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.

Precautions

General

Serum potassium should be measured periodically and potassium supplements or potassium-sparing diuretics added if necessary. Periodic determinations of other electrolytes are advised in patients treated with high doses or for prolonged periods, particularly in those on low-salt diets.

Hyperuricemia may occur; it has been asymptomatic in cases reported to date. Reversible elevations of the BUN and creatinine may also occur, especially in association with dehydration and particularly in patients with renal insufficiency. Bumetanide may increase urinary calcium excretion with resultant hypocalcemia.

Diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Laboratory Tests

Studies in normal subjects receiving bumetanide revealed no adverse effects on glucose tolerance, plasma insulin, glucagon and growth hormone levels, but the possibility of an effect on glucose metabolism exists. Periodic determinations of blood sugar should be done, particularly in patients with diabetes or suspected latent diabetes.

Patients under treatment should be observed regularly for possible occurrence of blood dyscrasias, liver damage or idiosyncratic reactions, which have been reported occasionally in foreign marketing experience. The relationship of these occurrences to bumetanide use is not certain.

Drug Interactions

Drugs with Ototoxic Potential

Especially in the presence of impaired renal function, the use of parenterally administered bumetanide in patients to whom aminoglycoside antibiotics are also being given should be avoided, except in life-threatening conditions.

Drugs with Nephrotoxic Potential

There has been no experience with the concurrent use of bumetanide with drugs known to have a nephrotoxic potential. Therefore, the simultaneous administration of these drugs should be avoided.

Lithium

Lithium should generally not be given with diuretics (such as bumetanide) because they reduce its renal clearance and add a high risk of lithium toxicity.

Probenecid

Pretreatment with probenecid reduces both the natriuresis and hyperreninemia produced by bumetanide. This antagonistic effect of probenecid on bumetanide natriuresis is not due to a direct action on sodium excretion but is probably secondary to its inhibitory effect on renal tubular secretion of bumetanide. Thus, probenecid should not be administered concurrently with bumetanide.

Indomethacin

Indomethacin blunts the increases in urine volume and sodium excretion seen during bumetanide treatment and inhibits the bumetanide-induced increase in plasma renin activity. Concurrent therapy with bumetanide is thus not recommended.

Antihypertensives

Bumetanide may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.

Digoxin

Interaction studies in humans have shown no effect on digoxin blood levels.

Anticoagulants

Interaction studies in humans have shown bumetanide to have no effect on warfarin metabolism or on plasma prothrombin activity.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Bumetanide was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system. An 18-month study showed an increase in mammary adenomas of questionable significance in female rats receiving oral doses of 60 mg/kg/day (2000 times a 2-mg human dose). A repeat study at the same doses failed to duplicate this finding.

Reproduction studies were performed to evaluate general reproductive performance and fertility in rats at oral dose levels of 10, 30, 60 or 100 mg/kg/day. The pregnancy rate was slightly decreased in the treated animals; however, the differences were small and not statistically significant.

Pregnancy

Teratogenic Effects

Bumetanide is neither teratogenic nor embryocidal in mice when given in doses up to 3400 times the maximum human therapeutic dose.

Bumetanide has been shown to be nonteratogenic, but it has a slight embryocidal effect in rats when given in doses of 3400 times the maximum human therapeutic dose and in rabbits at doses of 3.4 times the maximum human therapeutic dose. In one study, moderate growth retardation and increased incidence of delayed ossification of sternebrae were observed in rats at oral doses of 100 mg/kg/day, 3400 times the maximum human therapeutic dose. These effects were associated with maternal weight reductions noted during dosing. No such adverse effects were observed at 30 mg/kg/day (1000 times the maximum human therapeutic dose). No fetotoxicity was observed at 1000 to 2000 times the human therapeutic dose.

In rabbits, a dose-related decrease in litter size and an increase in resorption rate were noted at oral doses of 0.1 and 0.3 mg/kg/day (3.4 and 10 times the maximum human therapeutic dose). A slightly increased incidence of delayed ossification of sternebrae occurred at 0.3 mg/kg/day; however, no such adverse effects were observed at the dose of 0.03 mg/kg/day. The sensitivity of the rabbit to bumetanide parallels the marked pharmacologic and toxicologic effects of the drug in this species.

Bumetanide was not teratogenic in the hamster at an oral dose of 0.5 mg/kg/day (17 times the maximum human therapeutic dose). Bumetanide was not teratogenic when given intravenously to mice and rats at doses up to 140 times the maximum human therapeutic dose.

There are no adequate and well-controlled studies in pregnant women. A small investigational experience in the United States and marketing experience in other countries to date have not indicated any evidence of adverse effects on the fetus, but these data do not rule out the possibility of harmful effects. Bumetanide should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while the patient is on bumetanide since it may be excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 have not been established.

In vitro studies using pooled sera from critically ill neonates have shown bumetanide to be a potent displacer of bilirubin [see Clinical Pharmacology: Pediatric Pharmacology]. The administration of bumetanide could present a particular concern if given to critically ill or jaundiced neonates at risk for kernicterus.

Geriatric Use

Clinical studies of bumetanide did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Adverse Reactions/Side Effects

The most frequent clinical adverse reactions considered probably or possibly related to bumetanide are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with preexisting liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with bumetanide.

Less frequent clinical adverse reactions to bumetanide are impaired hearing (0.5%), pruritus (0.4%), electrocardiogram changes (0.4%), weakness (0.2%), hives (0.2%), abdominal pain (0.2%), arthritic pain (0.2%), musculoskeletal pain (0.2%), rash (0.2%) and vomiting (0.2%). One or more of these adverse reactions have been reported in approximately 2.9% of patients treated with bumetanide.

Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are vertigo, chest pain, ear discomfort, fatigue, dehydration, sweating, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, diarrhea, premature ejaculation and difficulty maintaining an erection.

Laboratory abnormalities reported have included hyperuricemia (in 18.4% of patients tested), hypochloremia (14.9%), hypokalemia (14.7%), azotemia (10.6%), hyponatremia (9.2%), increased serum creatinine (7.4%), hyperglycemia (6.6%), and variations in phosphorus (4.5%), CO2 content (4.3%), bicarbonate (3.1%) and calcium (2.4%). Although manifestations of the pharmacologic action of bumetanide, these conditions may become more pronounced by intensive therapy.

Also reported have been thrombocytopenia (0.2%) and deviations in hemoglobin (0.8%), prothrombin time (0.8%), hematocrit (0.6%), WBC (0.3%) and differential counts (0.1%). There have been rare spontaneous reports of thrombocytopenia from postmarketing experience.

Diuresis induced by bumetanide may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), SGOT (0.6%), SGPT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.

Overdosage

Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.

Bumetanide Dosage and Administration

Dosage should be individualized with careful monitoring of patient response.

Parenteral Administration

Bumetanide Injection may be administered parenterally (IV or IM) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.

Parenteral treatment should be terminated and oral treatment instituted as soon as possible.

The usual initial dose is 0.5 mg to 1 mg intravenously or intramuscularly. Intravenous administration should be given over a period of 1 to 2 minutes. If the response to an initial dose is deemed insufficient, a second or third dose may be given at intervals of 2 to 3 hours, but should not exceed a daily dosage of 10 mg.

Miscibility and Parenteral Solutions

The compatibility tests of bumetanide injection with 5% dextrose in water, 0.9% sodium chloride and lactated Ringer’s solution in both glass and plasticized PVC (Viaflex) containers have shown no significant absorption effect with either containers, nor a measurable loss of potency due to degradation of the drug. However, solutions should be freshly prepared and used within 24 hours.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

How is Bumetanide supplied

Bumetanide Injection USP, 0.25 mg/mL is a sterile, clear, colorless to slightly yellow solution free from visible particulate matter supplied in amber vials as follows:

4 mL Single Dose Vial packaged in 10s (NDC 70748-323-10)

Discard unused portion.

10 mL Multiple Dose Vial packaged in 10s (NDC 70748-323-11)

This container closure is not made with natural rubber latex.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30° C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from light.

To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Naples, FL 34108

United States

Manufactured by:

Lupin Limited

Nagpur – 441108

India

Revised: November 2024 #ID: 278600

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Bumetanide Injection, USP

1 mg/4 mL (0.25 mg/mL)

4 mL Single Dose Vial

NDC 70748-323-01

Bumetanide Injection, USP

1 mg/4 mL (0.25 mg/mL)

10 x 4 mL Single Dose Vials

NDC 70748-323-10

Bumetanide Injection, USP

2.5 mg/10 mL (0.25 mg/mL)

10 mL Multiple Dose Vial

NDC 70748-323-02

Bumetanide Injection, USP

2.5 mg/10 mL (0.25 mg/mL)

10 x 10 mL Multiple Dose Vials

NDC 70748-323-11

Bisoprolol is a beta-blocker that affects the heart and circulation (blood flow through arteries and veins).

Bisoprolol is used to treat hypertension (high blood pressure).

Bisoprolol may also be used for purposes not listed in this medication guide.

Warnings

Do not skip doses or stop taking bisoprolol without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems.

If you need to have any type of surgery, tell the surgeon ahead of time that you are using this medicine.

You should not use bisoprolol if you have a serious heart condition such as “AV block,” severe heart failure, or slow heartbeats that have caused you to faint.

Keep using bisoprolol as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Before taking this medicine

You should not use bisoprolol if you you are allergic to it, or if you have a serious heart condition such as:

• “AV block”;
• severe heart failure; or
• slow heartbeats that have caused you to faint.

To make sure bisoprolol is safe for you, tell your doctor if you have:

• congestive heart failure or other heart problems;
• coronary artery disease;
• circulation problems (such as Peripheral Vascular Disease or Raynaud’s syndrome);
• asthma, chronic obstructive pulmonary disease (COPD), or other breathing disorder;
• diabetes (taking bisoprolol can make it harder for you to tell when you have low blood sugar);
• liver or kidney disease;
• a thyroid disorder; or
• a history of allergies.

It is not known whether bisoprolol is harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether bisoprolol passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Bisoprolol is not approved for use by anyone younger than 18 years old.

How should I take bisoprolol?

Take bisoprolol exactly as it was prescribed for you. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Do not skip doses or stop taking bisoprolol without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems.

If you need surgery, tell the surgeon ahead of time that you are using bisoprolol.

Your blood pressure will need to be checked often.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.

Store bisoprolol at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What to avoid

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Minimize drinking alcohol. It can increase some of the side effects of bisoprolol.

Bisoprolol side effects

Get emergency medical help if you have signs of an allergic reaction to bisoprolol: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• shortness of breath (even with mild exertion), swelling, rapid weight gain;
• slow heart rate;
• pounding heartbeats or fluttering in your chest;
• numbness, tingling, or cold feeling in your hands or feet;
• a light-headed feeling, like you might pass out;
• eye pain, vision problems; or
• bronchospasm (wheezing, chest tightness, trouble breathing).

Common bisoprolol side effects may include:

• headache;
• feeling tired;
• sleep problems (insomnia);
• joint pain;
• swelling; or
• cold symptoms such as stuffy nose, runny nose, cough, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect bisoprolol?

Tell your doctor about all your current medicines and any you start or stop using, especially:

• insulin or oral diabetes medicine;
• rifampin; or
• heart or blood pressure medicine–clonidine, digitalis, digoxin, diltiazem, reserpine, or verapamil.

Benicar is an angiotensin II receptor blocker (sometimes called an ARB). Olmesartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.

Benicar is used to treat high blood pressure (hypertension) in adults and children at least 6 years old.

Benicar is sometimes given together with other blood pressure medications.

Warnings

Do not use if you are pregnant. Stop using Benicar and tell your doctor right away if you become pregnant. Olmesartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

If you have diabetes, do not take Benicar with any medication that contains aliskiren (a blood pressure medicine – brand names include Amturnide, Tekturna, and Tekamlo).

Before taking this medicine

You should not take Benicar if you are allergic to olmesartan.

If you have diabetes, do not use Benicar together with any medication that contains aliskiren (a blood pressure medicine).

You may also need to avoid taking Benicar with aliskiren if you have kidney disease.

To make sure Benicar is safe for you, tell your doctor if you have:

• a heart condition other than one being treated with Benicar;
• kidney disease; or
• if you are on a low salt diet.

Do not use if you are pregnant. Stop using the medicine and tell your doctor right away if you become pregnant. Olmesartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

If you plan to get pregnant, ask your doctor for a safer medicine to use before and during pregnancy. Having high blood pressure during pregnancy may cause complications in the mother and the baby.

You should not breastfeed while using this medicine.

How should I take Benicar?

Take Benicar exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

You may take Benicar with or without food.

For a child who cannot swallow a tablet whole, a pharmacist can mix the medicine into a liquid.

Shake the liquid before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Olmesartan doses are based on weight in children and/or teenagers. Your child’s dose needs may change if the child gains or loses weight.

Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking Benicar.

It may take up to 2 weeks before your blood pressure is under control. Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms.

You may need to use blood pressure medicine for the rest of your life. Treatment may also include diet, exercise, lowering cholesterol, not smoking, and controlling diabetes.

Your blood pressure will need to be checked often. Your kidney function may also need to be checked.

Store tablets at room temperature away from moisture and heat.

Store the liquid in a refrigerator. Throw away any liquid leftover after 4 weeks.

Dosing information

Usual Adult Dose for Hypertension:

20 mg orally once a day; may increase dose to 40 mg in two weeks if further blood pressure reduction is needed.

Maximum dose: 40 mg orally once a day

Comments:
-For patients with possible intravascular volume depletion (e.g., patients treated with diuretics, especially those with impaired renal function), initiate this drug under close supervision and give consideration to a lower starting dose.
-Twice daily dosing offers no additional benefit over the same total dose give once daily.

Usual Pediatric Dose for Hypertension:

6 to 16 years:
-20 to less than 35 kg: 10 mg orally once a day; may increase dose to 20 mg in two weeks if further blood pressure reduction is needed
-35 kg or more: 20 mg orally once a day; may increase dose to 40 mg in two weeks if further blood pressure reduction is needed

Comments:
-For children who cannot swallow tablets, the same dose can be given using an extemporaneously compounded oral suspension.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include fast heartbeats or fainting.

What should I avoid while taking Benicar?

Do not use potassium supplements or salt substitutes, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Benicar side effects

Get emergency medical help if you have signs of an allergic reaction to Benicar: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• little or no urination;
• severe diarrhea and weight loss; or
• high potassium level – nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement.

Benazepril is used alone or in combination with other medications to treat high blood pressure in adults and children at least 6 years old.

Lowering blood pressure may lower your risk of a stroke or heart attack.

Benazepril may also be used for purposes not listed in this medication guide.

Benazepril side effects

Get emergency medical help if you have signs of an allergic reaction: hives, severe stomach pain, difficulty breathing, swelling of your face, lips, tongue, or throat.

Benazepril may cause serious side effects. Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• kidney problems–swelling, urinating less, feeling tired or short of breath;
• high blood potassium–nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement; or
• liver problems–loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects of benazepril may include:

• headache; or
• cough.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Warnings

Do not use if you are pregnant. Stop using benazepril and tell your doctor right away if you become pregnant.

Tell your doctor about all your other medicines. Some drugs should not be used with benazepril.

Before taking this medicine

You should not use benazepril if you are allergic to it or to any other ACE (angiotensin converting enzyme) inhibitor such as captopril, fosinopril, enalapril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.

Do not take benazepril within 36 hours before or after taking medicine that contains sacubitril (such as Entresto).

If you have diabetes, do not use benazepril together with any medication that contains aliskiren (a blood pressure medicine).

Do not take benazepril if you have a history of angioedema (severe allergic reaction).

Tell your doctor if you have ever had:

• heart disease, heart problems such as a recent heart attack;
• stomach pain;
• low blood pressure;
• if you are on a low-salt diet;
• diabetes;
• liver disease; or
• kidney disease (or if you are on dialysis).

You may also need to avoid taking benazepril with aliskiren if you have kidney disease.

Stop using this medicine and tell your doctor right away if you become pregnant. Benazepril can cause injury or death to the unborn baby if you use the medicine during your second or third trimester.

Do not breastfeed.

How should I take benazepril?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

You may take benazepril with or without food.

Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking benazepril. This can lead to very low blood pressure, an electrolyte imbalance, or kidney failure.

Your blood pressure will need to be checked often and you may need frequent blood tests. Your treatment may also include diet, exercise, lifestyle changes, and other medications. Follow your doctor’s instructions very carefully.

Tell your doctor if you have a planned surgery.

Keep using benazepril even if you feel well. High blood pressure often has no symptoms.

Store tightly closed at room temperature, away from moisture and heat.

Benazepril dosing information

Usual Adult Dose for Hypertension:

Initial dose: With a diuretic: 5 mg orally once a day; without a diuretic: 10 mg orally once a day
Maintenance dose: 20 to 40 mg/day orally as a single dose or in two equally divided doses
Maximum dose: 80 mg/day

Comments:
-The divided dose regimen was more effective in controlling pre-dosing blood pressure.
-If discontinuing a diuretic prior to initiating this drug to reduce the likelihood of hypotension, conclude diuretic therapy 2 to 3 days prior to starting this drug.

Usual Pediatric Dose for Hypertension:

6 YEARS OR OLDER:
Initial dose: 0.2 mg/kg orally once a day as monotherapy
Maximum dose: 0.6 mg/kg; 40 mg/day

Comments:
-Doses between 0.1 and 0.6 mg/kg once a day have been studied; doses greater than 0.1 mg/kg were shown to reduce blood pressure; doses above 0.6 mg/kg or 40 mg/day have not been studied in pediatric patients.
-Prepare a suspension for pediatric patients who cannot swallow tablets or for whom the calculated dosage does not correspond to available tablet strengths.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid while taking benazepril?

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Do not take potassium supplements or use salt substitutes, unless your doctor has told you to.

Avoid becoming overheated or dehydrated during exercise, in hot weather, or by not drinking enough fluids. Follow your doctor’s instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

What other drugs will affect benazepril?

Benazepril can harm your kidneys, especially if you also use certain medicines for infections, cancer, or osteoporosis.

Tell your doctor about all your other medicines, especially:

• a diuretic or “water pill” that may increase blood potassium such as spironolactone, triamterene, or amiloride;
• NSAIDs (nonsteroidal anti-inflammatory drugs)–aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others;
• insulin or diabetes medications;
• medicine to prevent organ transplant rejection such as temsirolimus, sirolimus, or everolimus; or
• heart or blood pressure medication.

What is atenolol?

Atenolol is a beta-blocker that affects the heart and circulation (blood flow through arteries and veins).

Atenolol is used to treat angina (chest pain) and hypertension (high blood pressure).

Atenolol is also used to lower the risk of death after a heart attack.

Warnings

You should not use this atenolol if you have a serious heart condition such as “AV block,” very slow heartbeats, or heart failure.

Do not stop taking atenolol without first talking to your doctor. Stopping suddenly may make your condition worse.

If you are having any type of surgery, be sure the surgeon knows ahead of time that you are using this medicine.

Atenolol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking this medicine.

Atenolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

If you are being treated for high blood pressure, keep using this medication even if you feel fine. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Before taking this medicine

You should not use atenolol if you are allergic to it, or if you have:

• a serious heart condition such as “AV block” (second or third degree);
• slow heartbeats;
• heart failure; or
• if your heart cannot pump blood properly.

To make sure atenolol is safe for you, tell your doctor if you have:

• congestive heart failure;
• coronary artery disease (hardened arteries);
• asthma, bronchitis, emphysema;
• diabetes;
• overactive thyroid;
• liver or kidney disease;
• pheochromocytoma (tumor of the adrenal gland);
• peripheral vascular disease such as Raynaud’s syndrome; or
• allergies (or if you are undergoing allergy treatments or skin-testing).

Atenolol may harm an unborn baby. Tell your doctor if you are pregnant or if you become pregnant while using this medicine.

Atenolol can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breastfeeding a baby.

Atenolol is not approved for use by anyone younger than 18 years old.

How should I take atenolol?

Take atenolol exactly as it was prescribed for you. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Your blood pressure will need to be checked often.

If you need surgery, tell the surgeon ahead of time that you are using atenolol. You may need to stop using the medicine for a short time.

Keep using the medication as directed and tell your doctor if your symptoms do not improve.

You should not stop taking atenolol suddenly. Stopping suddenly may make your condition worse.

If you are being treated for high blood pressure: Keep using this medicine even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.

Your condition may need to be treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor’s advice.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Atenolol dosing information

Usual Adult Dose of Atenolol for Hypertension:

Initial dose: 50 mg orally once a day
Maintenance dose: 50 to 100 mg orally once a day
Maximum dose: 100 mg per day

Comments:
-If desired response not achieved after 1 to 2 weeks, increase to 100 mg may be beneficial.
-Doses greater than 100 mg once a day did not result in significant additional antihypertensive effects.

Use: For the treatment of hypertension alone or in combination with other antihypertensive agents.

Usual Adult Dose of Atenolol for Angina Pectoris Prophylaxis:

Initial dose: 50 mg orally once a day
-Increase to 100 mg orally once a day after 1 week if optimal response not achieved
Maintenance dose: 50 to 200 mg orally once a day
Maximum dose: 200 mg per day

Comments:
-Some patients may require 200 mg per day to attain optimal effect.

Use: For the long-term management of angina pectoris due to coronary atherosclerosis.

Usual Adult Dose of Atenolol for Angina Pectoris:

Initial dose: 50 mg orally once a day
-Increase to 100 mg orally once a day after 1 week if optimal response not achieved
Maintenance dose: 50 to 200 mg orally once a day
Maximum dose: 200 mg per day

Comments:
-Some patients may require 200 mg per day to attain optimal effect.

Use: For the long-term management of angina pectoris due to coronary atherosclerosis.

Usual Adult Dose of Atenolol for Myocardial Infarction:

50 mg orally twice a day or 100 mg orally once a day

Comments:
-If IV beta blockers are contraindicated or inappropriate, oral therapy should continue for at least 7 days post-myocardial infarction (MI).
-Treatment with beta blockers post MI should generally continue for 1 to 3 years if there are no contraindications.

Use: For the management of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality.

Usual Geriatric Dose of Atenolol for Hypertension:

Initial dose: Consider reducing the starting dose to 25 mg orally once a day

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include extreme weakness or lack of energy, very slow heart rate, shortness of breath, or fainting.

What should I avoid while taking atenolol?

Follow your doctor’s instructions about any restrictions on food, beverages, or activity.

Atenolol side effects

Get emergency medical help if you have signs of an allergic reaction to atenolol: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• new or worsening chest pain;
• slow or uneven heartbeats;
• a light-headed feeling, like you might pass out;
• shortness of breath (even with mild exertion), swelling, rapid weight gain; or
• a cold feeling in your hands and feet.

Common atenolol side effects may include include:

• cold hands or feet;
• dizziness;
• tiredness; or
• depressed mood.

What is Aldactone?

Aldactone is a potassium-sparing diuretic (water pill) that prevents your body from absorbing too much salt and keeps your potassium levels from getting too low.

Aldactone is used to treat heart failure, high blood pressure (hypertension), or hypokalemia (low potassium levels in the blood).

Aldactone also treats fluid retention (edema) in people with congestive heart failure, cirrhosis of the liver, or a kidney disorder called nephrotic syndrome.

Aldactone is also used to diagnose or treat a condition in which you have too much aldosterone in your body. Aldosterone is a hormone produced by your adrenal glands to help regulate the salt and water balance in your body.

Warnings

You should use Aldactone with caution if you have kidney problems, high levels of potassium in your blood, Addison’s disease, if you are unable to urinate, or if you are also taking eplerenone.

Aldactone has caused tumors in animals but it is not known whether this could occur in people. Do not use this medicine for any condition that has not been checked by your doctor.

Before taking this medicine

You should not use Aldactone if you are allergic to spironolactone, or if you have:

• Addison’s disease (an adrenal gland disorder);
• high levels of potassium in your blood (hyperkalemia);
• if you are unable to urinate; or
• if you are also taking eplerenone.

To make sure Aldactone is safe for you, tell your doctor if you have:

• an electrolyte imbalance (such as low levels of calcium, magnesium, or sodium in your blood);
• kidney disease;
• liver disease; or
• heart disease.

Tell your doctor if you are pregnant or plan to become pregnant. Having congestive heart failure, cirrhosis, or uncontrolled high blood pressure during pregnancy may lead to medical problems in the mother or the baby. Your doctor should decide whether you take Aldactone if you are pregnant.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

How should I take Aldactone?

Take Aldactone exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Do not share this medicine with another person, even if they have the same symptoms you have.

You may take Aldactone with or without food, but take it the same way each time.

You will need frequent medical tests.

This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using Aldactone.

If you need surgery, tell your surgeon you currently use this medicine. You may need to stop for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from heat, light, and moisture.

Dosing information

Usual Adult Dose of Aldactone for Edema:

25 to 200 mg orally per day in single or divided doses

Duration of therapy: When given as the sole diuretic, continue the initial dose for at least 5 days, after which the initial dose may be adjusted to an optimal maintenance dose.

Comments:

-A second diuretic that acts more proximally at the renal tubule may be added if adequate diuresis has not been achieved after 5 days. The dose of this drug should remain unchanged if a second diuretic is added.

Uses:

-Treatment of edematous conditions in patients with congestive heart failure who are only partially responsive to or intolerant of other therapeutic measures or who are taking digitalis when other therapies are considered inappropriate.

-Treatment of edematous conditions in patients with liver cirrhosis accompanied by edema and/or ascites.

-Treatment of edematous conditions in patients with nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics do not provide an adequate response.

Usual Adult Dose of Aldactone for Hypertension:

Initial dose: 50 to 100 mg orally per day in single or divided doses

Duration of therapy: Treatment should be continued for at least 2 weeks to achieve a maximum response. Subsequently, the dose may be adjusted according to patient response.

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 25 mg orally once a day assuming serum potassium is less than or equal to 5 mEq/L and serum creatinine is less than or equal to 2.5 mg/dL

Maintenance dose:

-Patients tolerant of initial dose: May increase to 50 mg orally once a day as clinically indicated

-Patients intolerant of initial dose: May decrease to 25 mg orally every other day

Use: To increase survival and reduce the need for hospitalization of severe heart failure patients (New York Heart Association [NYHA] class III to IV) when used in addition to standard therapy.

Usual Adult Dose for Primary Hyperaldosteronism:

Diagnostic dose:

-Long test: 400 mg orally per day for 3 to 4 weeks

-Short test: 400 mg orally per day for 4 days

Maintenance dose: 100 to 400 mg orally per day until surgery; may be used long-term at the lowest effective dose in patients deemed unsuitable for surgery.

Comments:

-For the long test, correction of hypokalemia and hypertension provides presumptive evidence of primary hyperaldosteronism.

-For the short test, increased serum potassium with this drug and a decrease upon discontinuation provide presumptive evidence of primary hyperaldosteronism.

Uses:

-Initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

-Short-term preoperative treatment of patients with primary hyperaldosteronism.

-Long-term maintenance therapy for patients deemed unsuitable for surgery or those with idiopathic hyperaldosteronism.

Usual Adult Dose for Hypokalemia:

25 to 100 mg orally per day

Uses:

-Treatment of patients with hypokalemia when other measures are considered inappropriate or inadequate.

-Prophylaxis of hypokalemia in patients taking digitalis when other measures are considered inadequate or inappropriate.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line.

What to avoid

Drinking alcohol can increase certain side effects.

Do not use potassium supplements or salt substitutes, unless your doctor has told you to.

Avoid a diet high in salt. Too much salt will cause your body to retain water and can make this medication less effective.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Aldactone side effects

Get emergency medical help if you have signs of an allergic reaction to Aldactone: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• little or no urination;
• high potassium level – nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement; o
• signs of other electrolyte imbalances – increased thirst or urination, confusion, vomiting, muscle pain, slurred speech, severe weakness, numbness, loss of coordination, feeling unsteady.

Common Aldactone side effects may include:

• breast swelling or tenderness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect Aldactone?

Using Aldactone with other drugs that make you dizzy can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your other medicines, especially:

• colchicine;
• digoxin;
• lithium;
• loperamide;
• trimethoprim;
• heart or blood pressure medicine (especially another diuretic);
• medicine to prevent a blood clot; or