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.

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.

Camzyos (mavacamten) is a prescription medicine used to treat symptomatic obstructive hypertrophic cardiomyopathy (HCM), helping improve shortness of breath and the ability to be active.  Camzyos is a cardiac myosin inhibitor that relaxes heart muscles so the heart can fill with more blood and pump blood around your body more effectively.

In obstructive hypertrophic cardiomyopathy (HCM), the walls of the heart become excessively thickened and stiff. This reduces blood flow from the heart to your body, which causes symptoms of shortness of breath, rapid heartbeat, feeling light-headed, chest pain, fainting, and tiredness. Camzyos relaxes the heart muscles and reduces heart obstruction, which improves your ability to be active and other symptoms.

How does Camzyos work?

The heart pumps blood around the body as heart muscles contract and release. Heart muscles contract when two proteins called myosin and actin join together, and then muscles relax when myosin and actin are not joined. In obstructive HCM, too many myosin and actin connect, making the heart contract too much, thickening the heart walls, reducing blood flow from the heart, and causing symptoms.

Camzyos’s mechanism of action is a cardiac myosin inhibitor that works by binding to the myosin protein, which stops the actin proteins from binding to it. As a result, the heart muscle relaxes, the heart fills with more blood, and it can pump more effectively. Camzyos is an allosteric and reversible inhibitor selective for cardiac myosin.

Camzyos Indications

Camzyos is indicated for adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM) to help improve functional capacity and symptoms. It can be used in patients with New York Heart Association (NYHA) class II-III obstructive HCM. Camzyos became an FDA-approved medicine on April 28, 2022.

Camzyos side effects

Common Camzyos side effects

Common Camzyos side effects include dizziness (27%) or fainting (6%).

Serious Camzyos side effects

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

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

• heart failure symptoms, such as shortness of breath, chest pain, tiredness, swelling in your legs, rapid weight gain, or racing or pounding heartbeats.

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

Camzyos REMS program

Camzyos is only available through the Camzyos REMS program, which is required by the FDA to monitor the safe use of this medication. The REMS  (Risk Evaluation and Mitigation Strategy) program is required as this medicine can cause the heart muscles to become too relaxed, which increases the risk of heart failure.  Your doctor will review and discuss the REMS Patient Brochure with you and talk to you about how to enroll in the program.

Warnings

Camzyos may cause serious side effects, and carries a Boxed Warning for a risk of heart failure.

Heart failure:

Heart failure is a condition where the heart cannot pump with enough force. Heart failure is a serious condition that can lead to death. You must have echocardiograms before you take the first dose and also during your treatment with this medicine. This is important to help your healthcare provider understand how your heart is responding to this medicine. People who develop a serious infection or irregular heartbeat have a greater risk of heart failure during treatment.

Call your doctor at once if you have shortness of breath, chest pain, tiredness, swelling in your legs, rapid weight gain, or racing or pounding heartbeats.

The risk of heart failure is also increased when Camzyos is taken with certain other medicines. Tell your healthcare provider about the medicines you take, both prescribed and obtained over-the-counter, before and during treatment.

Because of the serious risk of heart failure, this medicine is only available through a restricted program called the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program.

See Camzyos side effects for information about side effects.

It is not known if Camzyos is safe and effective in children.

Before taking this medicine

Your treatment plan may change if you also use certain other medications such as:

• nefazodone;
• St. John’s wort;
• an antibiotic eg.clarithromycin, rifabutin, rifampin, rifapentine, telithromycin;
• antifungal medicine eg. itraconazole, ketoconazole;
• antiviral medicine for HIV or hepatitis C eg. boceprevir, cobicistat, dasabuvir, elvitegravir, indinavir, lopinavir/ritonavir, nelfinavir, ombitasvir, paritaprevir saquinavir, telaprevir, tipranavir;
• cancer medicine eg. apalutamide, enzalutamide, mitotane;
• seizure medicine eg. carbamazepine, oxcarbazepine, phenytoin, primidone;
• steroid medicine eg. dexamethasone, prednisone;

Tell your doctor if you have ever had:

• an irregular heartbeat;
• heart failure; or
• if you have an infection.

Pregnancy

Camzyos may harm an unborn baby. You may need a pregnancy test to make sure you are not pregnant before using this medicine. Use effective birth control while using this medicine and for at least 4 months after your last dose. Tell your doctor if you become pregnant.

Hormonal contraceptives containing a combination of ethinyl estradiol and norethindrone may be used with this medicine, but it can make other birth control pills less effective. Ask your doctor about all birth control options, such as an injection, implant, skin patch, vaginal ring, condom, diaphragm, cervical cap, or contraceptive sponge.

Breastfeeding

Ask a doctor if it is safe to breastfeed while using this medicine.

How should I take Camzyos?

Take Camzyos once a day.

Swallow the capsule whole. Do not break, open, or chew the capsule.

You will start with an initial dose, and over weeks, your Doctor will increase your dose depending on how you respond to the medicine.

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

Take Camzyos capsules exactly as your healthcare provider tells you to take them.

Do not change your dose without talking to your healthcare provider first.

What happens if I miss a dose?

If you miss a dose, take it as soon as possible and take your next dose at your regularly scheduled time the next day. Do not take 2 doses on the same day to make up for a missed dose.

What happens if I overdose?

If you take too much or overdose, call your healthcare provider or go to the nearest hospital emergency room right away.

Dosing information

Usual Adult Dosage for Hypertrophic Cardiomyopathy

Starting dose: 5 mg orally once a day

• Reduce starting dosage to 2.5 mg/day in those taking moderate CYP2C19 inhibitors or a strong CYP3A4 inhibitor.
• See the Camzyos Prescribing Information for complete dosing information and instructions for regular left ventricular ejection fraction (LVEF) and Valsalva left ventricular outflow tract (LVOT) gradient assessment.

Allowable subsequent doses with titration: 2.5, 5, 10, or 15 mg orally once a day.

Available Strengths 

• 2.5mg, 5mg, 10mg, 15mg capsules.

What other drugs will affect Camzyos?

Tell your doctor about all your other medicines, especially:

• moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
• moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers
• heart medications such as disopyramide, ranolazine, or verapamil that are taken with a beta blocker, or diltiazem with a beta blocker, as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms
• other medicines to treat obstructive hypertrophic cardiomyopathy; or
• omeprazole, esomeprazole, or cimetidine.

Camzyos is an inducer of CYP3A4, CYP2C9, and CYP2C19. Concomitant use with CYP3A4, CYP2C9, or CYP2C19 substrates may reduce the plasma concentration of these drugs. Ask your healthcare provider if you are taking one of these medications. 

Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of Camzyos may decrease blood levels of certain progestins, which may lead to contraceptive failure. Combined hormonal contraceptives (CHCs) containing a combination of ethinyl estradiol and norethindrone may be used, but if other CHCs are used, patients should add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of Camzyos.

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

Brilinta prevents platelets in your blood from sticking together to form an unwanted blood clot that could block an artery.

Brilinta is used to lower your risk of heart attack, stroke, or death due to a blocked artery or a prior heart attack.

Brilinta is also used to lower your risk of blood clots if you have coronary artery disease (decreased blood flow to the heart) and have been treated with stents to open clogged arteries.

Brilinta is also used to lower your risk of a first heart attack or stroke if you have decreased blood flow to the heart.

Brilinta is also used to lower the risk of stroke and death in adults with a blockage or decreased blood flow in an artery that supplies blood to the brain.

This medicine is usually given together with low-dose aspirin. Carefully follow your doctor’s dosing instructions. Using too much aspirin can make ticagrelor less effective.

Warnings

You should not use Brilinta if you have any active bleeding (including a bleeding stomach ulcer), or a history of bleeding in the brain. Do not use this medicine just before heart bypass surgery (coronary artery bypass graft, or CABG).

You may need to stop using this medicine for a short time before having surgery or dental work, to prevent excessive bleeding. Do not stop taking Brilinta without first talking to your doctor, even if you have signs of bleeding. Stopping this medicine may increase your risk of a heart attack or stroke.

Brilinta may cause you to bleed more easily, which can be severe or life-threatening. Avoid activities that may increase your risk of bleeding or injury.

Call your doctor or seek emergency medical attention if you have bleeding that will not stop. You may also have bleeding on the inside of your body, such as in your stomach or intestines. Call your doctor at once if you have black or bloody stools, red or pink urine, or if you cough up blood or vomit that looks like coffee grounds. These could be signs of internal bleeding.

Many drugs (including some over-the-counter medicines and herbal products) can cause serious medical problems if you take them with Brilinta. It is very important to tell your doctor about all medicines you have recently used.

Before taking this medicine

You should not use Brilinta if you are allergic to ticagrelor, or if you have:

• any active bleeding; or
• a history of bleeding in the brain (such as from a head injury).

Tell your doctor if you have ever had:

• a stroke;
• heart problems;
• high cholesterol;
• bleeding problems;
• a stomach ulcer or colon polyps;
• liver disease; or
• kidney disease;
• asthma, COPD (chronic obstructive pulmonary disorder) or other breathing problems;
• recent surgery or serious injuries; or
• if you are planning to have surgery or a dental procedure; or

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

It is not known whether Brilinta passes into breastmilk. Talk to your doctor before using Brilinta if you are breastfeeding.

How should I take Brilinta?

Take Brilinta exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Brilinta is taken together with aspirin. Use these medicines exactly as directed.

Do not take more aspirin than your doctor has prescribed. Taking too much aspirin can make Brilinta less effective.

Take this medicine at the same time each day, with or without food.

If you cannot swallow a tablet whole, crush the pill and mix it with water. Stir and drink this mixture right away. Add more water to the glass, stir, and drink right away.

Brilinta keeps your blood from coagulating (clotting) and can make it easier for you to bleed, even from a minor injury. Contact your doctor or seek emergency medical attention if you have any bleeding that will not stop.

To prevent excessive bleeding, you may need to stop using Brilinta for a short time before a surgery, medical procedure, or dental work. Any healthcare provider who treats you should know that you are taking ticagrelor.

Do not stop taking Brilinta without first talking to your doctor, even if you have signs of bleeding. Stopping the medicine could increase your risk of a heart attack or stroke.

Ticagrelor may affect medical testing for platelets in your blood and you may have false results. Tell the laboratory staff that you use Brilinta.

Store at room temperature away from moisture and heat.

Dosing information

Usual Adult Dose for Acute Coronary Syndrome:

Following an acute coronary syndrome (ACS) event:

Loading dose: 180 mg orally once
Maintenance dose: 90 mg orally twice a day for 1 year
Maintenance dose after 1 year: 60 mg orally twice a day

Comments:
-This drug should be taken in conjunction with a daily maintenance dose of aspirin 75 to 100 mg orally once a day.
-For at least the first 12 months following ACS, this drug is superior to clopidogrel.

Uses:
-To reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction.
-To reduce the rate of stent thrombosis in patients who have been stented for treatment of ACS.

Usual Adult Dose for Prevention of Atherothrombotic Events:

Following an acute coronary syndrome (ACS) event:

Loading dose: 180 mg orally once
Maintenance dose: 90 mg orally twice a day for 1 year
Maintenance dose after 1 year: 60 mg orally twice a day

Comments:
-This drug should be taken in conjunction with a daily maintenance dose of aspirin 75 to 100 mg orally once a day.
-For at least the first 12 months following ACS, this drug is superior to clopidogrel.

Uses:
-To reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction.
-To reduce the rate of stent thrombosis in patients who have been stented for treatment of ACS.

Usual Adult Dose for Thromboembolic Stroke Prophylaxis:

60 mg orally twice a day

Use: To reduce the risk of a first myocardial infarction (MI) or stroke in patients with coronary artery disease (CAD) at high risk for such events; while use is not limited to this setting, efficacy of this drug was established in a population with type 2 diabetes mellitus (T2DM).

Usual Adult Dose for Coronary Artery Disease:

60 mg orally twice a day

Use: To reduce the risk of a first myocardial infarction (MI) or stroke in patients with coronary artery disease (CAD) at high risk for such events; while use is not limited to this setting, efficacy of this drug was established in a population with type 2 diabetes mellitus (T2DM).

Usual Adult Dose for Myocardial Infarction — Prophylaxis:

60 mg orally twice a day

Use: To reduce the risk of a first myocardial infarction (MI) or stroke in patients with coronary artery disease (CAD) at high risk for such events; while use is not limited to this setting, efficacy of this drug was established in a population with type 2 diabetes mellitus (T2DM).

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 can cause excessive bleeding.

What to avoid

Drinking alcohol while taking aspirin can increase your risk of stomach bleeding.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

While taking Brilinta with aspirin, avoid using medicines for pain, fever, swelling, or cold/flu symptoms. They may contain ingredients similar to aspirin (such as salicylates, ibuprofen, ketoprofen, or naproxen). Taking certain products together can cause you to get too much aspirin which can increase your risk of bleeding.

Brilinta side effects

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

Call your doctor at once if you have:

• chest pain;
• fainting or dizzy spells;
• nosebleeds, or any bleeding that will not stop;
• shortness of breath even with mild exertion or while lying down;
• easy bruising, unusual bleeding, purple or red spots under your skin;
• red, pink, or brown urine;
• black, bloody, or tarry stools; or
• coughing up blood or vomit that looks like coffee grounds.

Common Brilinta side effects may include:

• bleeding; or
• shortness of breath.

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 Brilinta?

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.

Tell your doctor about all your current medicines. Many drugs can interact with Brilinta, especially:

• antifungal medicine (including ketoconazole, itraconozole, voriconazole, and others);
• antibiotic medication (including clarithromycin);
• antiviral medicine to treat HIV or AIDS;
• other blood thinners;
• cholesterol medication (including simvastatin or lovastatin);
• heart or blood pressure medication;
• opioid medication;
• seizure medicine; or
• tuberculosis medicine (especially rifampin).

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.

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.