Ciprofloxacin is a fluoroquinolone (flor-o-KWIN-o-lone) antibiotic, it is used to treat different types of bacterial infections. It is also used to treat people who have been exposed to anthrax or certain types of plague. Ciprofloxacin extended-release is only approved for use in adults.

Fluoroquinolone antibiotics can cause serious or disabling side effects that may not be reversible.

Ciprofloxacin should be used only for infections that cannot be treated with a safer antibiotic.

Warnings

Ciprofloxacin can cause serious side effects, including tendon problems, nerve damage, serious mood or behavior changes, or low blood sugar.

Stop using ciprofloxacin and call your doctor at once if you have: headache, hunger, irritability, numbness, tingling, burning pain, confusion, agitation, paranoia, problems with memory or concentration, thoughts of suicide, or sudden pain or movement problems in any of your joints.

In rare cases, ciprofloxacin may cause damage to your aorta, which could lead to dangerous bleeding or death. Get emergency medical help if you have severe and constant pain in your chest, stomach, or back.

You may not be able to use this medicine if you have a muscle disorder. Tell your doctor if you have a history of myasthenia gravis.

Before taking this medicine

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

• you also take tizanidine; or
• you are allergic to other fluoroquinolones (levofloxacin, moxifloxacin, norfloxacin, ofloxacin).

Ciprofloxacin may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles’ tendon of the heel. This can happen during treatment or several months after you stop taking ciprofloxacin. Tendon problems may be more likely in children and older adults, or people who use steroid medicine or have had an organ transplant.

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

• arthritis or problems with your tendons, bones or joints (especially in children);
• diabetes, low blood sugar;
• nerve problems;
• an aneurysm or blood circulation problems;
• heart problems, or a heart attack;
• muscle weakness, myasthenia gravis;
• liver or kidney disease;
• a seizure, head injury, or brain tumor;
• trouble swallowing pills;
• long QT syndrome (in you or a family member); or
• low levels of potassium in your blood (hypokalemia).

Do not give this medicine to a child without medical advice.

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

You should not breastfeed while taking ciprofloxacin and for 2 days after your last dose. Ask your doctor about breastfeeding if you take this medicine for anthrax exposure.

How should I take ciprofloxacin?

Take ciprofloxacin exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

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

Shake the oral suspension (liquid) for 15 seconds before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon). Do not give ciprofloxacin oral suspension through a feeding tube.

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

Drink plenty of liquids while you are taking this medicine.

Use ciprofloxacin for the full prescribed length of time, even if your symptoms quickly improve. Skipping doses can increase your risk of infection that is resistant to medication. Ciprofloxacin will not treat a viral infection such as the flu or a common cold.

Do not share this medicine with another person.

Store at room temperature away from moisture and heat. Do not allow the liquid medicine to freeze. Throw away any unused liquid after 14 days.

What happens if I miss a dose?

If you take regular tablets or oral suspension: Take the medicine as soon as you can, but skip the missed dose if your next dose is due in less than 6 hours.

If you take extended-release tablets: Take the medicine as soon as you can, but skip the missed dose if your next dose is due in less than 8 hours.

Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What to avoid

Do not take ciprofloxacin with dairy products such as milk or yogurt, or with calcium-fortified juice. You may eat or drink these products with your meals, but do not use them alone when taking this medicine.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor before using anti-diarrhea medicine.

Ciprofloxacin could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors. Tell your doctor if you have severe burning, redness, itching, rash, or swelling after being in the sun.

Avoid driving or hazardous activity until you know how ciprofloxacin will affect you. Your reactions could be impaired.

Ciprofloxacin side effects

Get emergency medical help if you have signs of an allergic reaction to ciprofloxacin (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Ciprofloxacin can cause serious side effects, including tendon problems, damage to your nerves (which may be permanent), serious mood or behavior changes (after just one dose), or low blood sugar (which can lead to coma).

Stop taking this medicine and call your doctor at once if you have:

• low blood sugar – headache, hunger, irritability, dizziness, nausea, fast heart rate, or feeling shaky;
• nerve damage symptoms – numbness, tingling, burning pain in your hands, arms, legs, or feet:
• serious mood or behavior changes – nervousness, confusion, agitation, paranoia, hallucinations, memory problems, trouble concentrating, thoughts of suicide; or
• signs of tendon rupture – sudden pain, swelling, bruising, tenderness, stiffness, movement problems, or a snapping or popping sound in any of your joints (rest the joint until you receive medical care or instructions).

In rare cases, ciprofloxacin may cause damage to your aorta, the main blood artery of the body. This could lead to dangerous bleeding or death. Get emergency medical help if you have severe and constant pain in your chest, stomach, or back.

Also, stop using this medicine and call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;
• fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
• any skin rash, no matter how mild;
• muscle weakness, breathing problems;
• little or no urination;
• jaundice (yellowing of the skin or eyes); or
• increased pressure inside the skull – severe headaches, ringing in your ears, dizziness, nausea, vision problems, pain behind your eyes.

Common ciprofloxacin side effects may include:

• nausea, vomiting, diarrhea, stomach pain;
• headache; or
• abnormal liver function tests.

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 ciprofloxacin?

Some medicines can make ciprofloxacin much less effective when taken at the same time. If you take any of the following medicines, take your ciprofloxacin dose 2 hours before or 6 hours after you take the other medicine.

• the ulcer medicine sucralfate, or antacids that contain calcium, magnesium, or aluminum (such as Maalox, Milk of Magnesia, Mylanta, Pepcid Complete, Rolaids, Tums, and others);
• didanosine (Videx) powder or chewable tablets;
• vitamin or mineral supplements that contain calcium, iron, magnesium, or zinc.

Tell your doctor about all your other medicines, especially:

• clozapine, cyclosporine, methotrexate, phenytoin, probenecid, ropinirole, sildenafil, or theophylline;
• a blood thinner (warfarin, Coumadin, Jantoven);
• heart medication or a diuretic or “water pill”;
• oral diabetes medicine;
• products that contain caffeine;
• medicine to treat depression or mental illness;

Cipro is a fluoroquinolone (flor-o-KWIN-o-lone) antibiotic that fights bacteria in the body.

Cipro is used to treat different types of bacterial infections. Cipro is also used to treat people who have been exposed to anthrax or certain types of plague.

Fluoroquinolone antibiotics can cause serious or disabling side effects that may not be reversible.

Cipro should be used only for infections that cannot be treated with a safer antibiotic.

Warnings

Cipro can cause serious side effects, including tendon problems, nerve damage, serious mood or behavior changes, or low blood sugar.

Stop using this medicine and call your doctor at once if you have: headache, hunger, irritability, numbness, tingling, burning pain, confusion, agitation, paranoia, problems with memory or concentration, thoughts of suicide, or sudden pain or movement problems in any of your joints.

In rare cases, ciprofloxacin may cause damage to your aorta, which could lead to dangerous bleeding or death. Get emergency medical help if you have severe and constant pain in your chest, stomach, or back.

You may not be able to use Cipro if you have a muscle disorder. Tell your doctor if you have a history of myasthenia gravis.

Before taking this medicine

You should not use Cipro if you are allergic to ciprofloxacin, or if:

• you also take tizanidine; or
• you are allergic to other fluoroquinolones (levofloxacin, moxifloxacin, norfloxacin, ofloxacin).

Ciprofloxacin may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles’ tendon of the heel. This can happen during treatment or several months after you stop taking Cipro. Tendon problems may be more likely in children and older adults, or people who use steroid medicine or have had an organ transplant.

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

• arthritis or problems with your tendons, bones or joints (especially in children);
• diabetes, low blood sugar;
• nerve problems;
• an aneurysm or blood circulation problems;
• heart problems, or a heart attack;
• muscle weakness, myasthenia gravis;
• liver or kidney disease;
• a seizure, head injury, or brain tumor;
• trouble swallowing pills;
• long QT syndrome (in you or a family member); or
• low levels of potassium in your blood (hypokalemia).

Do not give Cipro to a child without medical advice.

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

You should not breastfeed while taking ciprofloxacin and for 2 days after your last dose. Ask your doctor about breastfeeding if you take ciprofloxacin for anthrax exposure.

How should I take Cipro?

Take Cipro exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

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

Shake the Cipro oral suspension (liquid) for 15 seconds before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon). Do not give Cipro oral suspension through a feeding tube.

Drink plenty of liquids while you are taking this medicine .

Use this medicine for the full prescribed length of time, even if your symptoms quickly improve. Skipping doses can increase your risk of infection that is resistant to medication. Ciprofloxacin will not treat a viral infection such as the flu or a common cold.

Do not share Cipro with another person.

Store at room temperature away from moisture and heat. Do not allow the liquid medicine to freeze. Throw away any unused liquid after 14 days.

What happens if I miss a dose?

If you take regular tablets or oral suspension: Take the medicine as soon as you can, but skip the missed dose if your next dose is due in less than 6 hours.

Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What to avoid

Do not take Cipro with dairy products such as milk or yogurt, or with calcium-fortified juice. You may eat or drink these products with your meals, but do not use them alone when taking Cipro.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor before using anti-diarrhea medicine.

Ciprofloxacin could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors. Tell your doctor if you have severe burning, redness, itching, rash, or swelling after being in the sun.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired.

Ciprofloxacin side effects

Get emergency medical help if you have signs of an allergic reaction to Cipro (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Ciprofloxacin can cause serious side effects, including tendon problems, damage to your nerves (which may be permanent), serious mood or behavior changes (after just one dose), or low blood sugar (which can lead to coma).

Stop taking this medicine and call your doctor at once if you have:

• low blood sugar – headache, hunger, irritability, dizziness, nausea, fast heart rate, or feeling shaky;
• nerve damage symptoms – numbness, tingling, burning pain in your hands, arms, legs, or feet:
• serious mood or behavior changes – nervousness, confusion, agitation, paranoia, hallucinations, memory problems, trouble concentrating, thoughts of suicide; or
• signs of tendon rupture – sudden pain, swelling, bruising, tenderness, stiffness, movement problems, or a snapping or popping sound in any of your joints (rest the joint until you receive medical care or instructions).

In rare cases, ciprofloxacin may cause damage to your aorta, the main blood artery of the body. This could lead to dangerous bleeding or death. Get emergency medical help if you have severe and constant pain in your chest, stomach, or back.

Also, stop using Cipro and call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;
• fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
• any skin rash, no matter how mild;
• muscle weakness, breathing problems;
• little or no urination;
• jaundice (yellowing of the skin or eyes); or
• increased pressure inside the skull – severe headaches, ringing in your ears, dizziness, nausea, vision problems, pain behind your eyes.

Common Cipro side effects may include:

• nausea, vomiting, diarrhea, stomach pain;
• headache; or
• abnormal liver function tests.

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 Cipro?

Some medicines can make Cipro much less effective when taken at the same time. If you take any of the following medicines, take your dose 2 hours before or 6 hours after you take the other medicine.

• the ulcer medicine sucralfate, or antacids that contain calcium, magnesium, or aluminum (such as Maalox, Milk of Magnesia, Mylanta, Pepcid Complete, Rolaids, Tums, and others);
• didanosine (Videx) powder or chewable tablets;
• vitamin or mineral supplements that contain calcium, iron, magnesium, or zinc.

Tell your doctor about all your other medicines, especially:

• clozapine, cyclosporine, methotrexate, phenytoin, probenecid, ropinirole, sildenafil, or theophylline;
• a blood thinner (warfarin, Coumadin, Jantoven);
• heart medication or a diuretic or “water pill”;
• oral diabetes medicine;
• products that contain caffeine;
• medicine to treat depression or mental illness;
• steroid medicine (such as prednisone)

Antibacterial; β-lactam antibiotic; second generation cephalosporin.

Uses for Cefuroxime

Acute Otitis Media (AOM)

Treatment of AOM caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains), or S. pyogenes in adults and pediatric patients ≥13 years of age.

When anti-infectives indicated, AAP recommends high-dose amoxicillin or amoxicillin and clavulanate as drugs of choice for initial treatment of AOM; certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) recommended as alternatives for initial treatment in penicillin-allergic patients without a history of severe penicillin-allergic reactions.

Bone and Joint Infections

Parenteral treatment of bone and joint infections caused by susceptible Staphylococcus aureus (including penicillinase-producing strains).

Gonorrhea and Associated Infections

Has been used orally or parenterally for treatment of uncomplicated urethral, endocervical, or rectal gonorrhea caused by susceptible Neisseria gonorrhoeae.

Has been used parenterally for treatment of disseminated gonococcal infections caused by susceptible N. gonorrhoeae.

Not included in current CDC recommendations for gonococcal infections.

Because of concerns related to reports of N. gonorrhoeae with reduced susceptibility to cephalosporins, CDC states that oral cephalosporins no longer recommended as first-line treatment for uncomplicated gonorrhea. For treatment of uncomplicated urogenital, anorectal, or pharyngeal gonorrhea, CDC recommends a single dose of IM ceftriaxone.

Lyme Disease

Treatment of early Lyme disease manifested as erythema migrans in adults and pediatric patients ≥13 years of age. IDSA, the American Academy of Neurology (AAN), the American College of Rheumatology (ACR), AAP, and other clinicians recommend oral doxycycline, oral amoxicillin, or oral cefuroxime axetil as first-line therapy for treatment of Lyme disease associated with erythema migrans, in the absence of specific neurologic involvement or advanced atrioventricular (AV) heart block.

In patients with acute neurologic Lyme disease^{† [off-label]} including Lyme disease-associated meningitis, cranial neuropathy, radiculoneuropathy, or with other peripheral nervous system manifestations, recommended treatment is parenteral therapy with ceftriaxone, cefotaxime, or penicillin G, or oral therapy with doxycycline. Route of therapy may be changed from IV to oral during treatment in patients who have experienced clinical improvement. Recommended treatment duration is 14–21 days. In patients with acute neurologic Lyme disease with parenchymal involvement of the brain or spinal cord, IV antibiotic treatment recommended for entire 14–21 days.

In outpatients with Lyme carditis^{† [off-label]}, oral antibiotics (doxycycline, amoxicillin, cefuroxime axetil, or azithromycin) recommended by IDSA/AAN/ACR. In patients with or at high risk of severe cardiac complications, including those with a PR interval >0.3 seconds, other arrhythmias, or clinical manifestations of myopericarditis, hospitalization with continuous ECG monitoring and treatment with IV ceftriaxone recommended; upon clinical improvement, may switch to oral antibiotics to complete recommended 14–21 days of treatment. For patients with symptomatic bradycardia that cannot be managed medically, temporary pacing modalities recommended over a permanent pacemaker.

In pediatric patients with Lyme disease associated with atrioventricular heart block or carditis^{† [off-label]}, oral treatment with doxycycline, amoxicillin, or cefuroxime axetil for 14 days (range: 14–21 days) or IV treatment with ceftriaxone for 14 days (range: 14–21 days for a hospitalized patient) recommended by AAP. May substitute oral antibiotics for IV treatment when patient stabilized or discharged from hospital to complete recommended 14–21 days of treatment. According to AAP, azithromycin not sufficiently studied for manifestations of Lyme disease other than erythema migrans.

Treatment of Lyme disease associated arthritis^{† [off-label]} without clinical evidence of neurologic disease. In patients with Lyme disease-associated arthritis^{† [off-label]}, recommended initial treatment is a 28-day course of oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil). In patients who experience a partial response to an initial course of treatment, a second course of oral antibiotics for up to 1 month may be reasonable. In patients with minimal or no response (moderate to severe joint swelling with minimal reduction of the joint effusion) to an initial 28-day course of oral antibiotic, a 2- to 4-week course of IV ceftriaxone is recommended. In patients who have failed one course of oral antibiotics and one course of IV antibiotics, refer to rheumatologist or other trained specialist. Antibiotic therapy for >8 weeks (including one course of IV antibiotic) not expected to provide additional benefit to patients with persistent arthritis.

For patients with persistent or recurring nonspecific symptoms (e.g., fatigue, pain, cognitive impairment) following recommended treatment for Lyme disease, but without objective evidence of reinfection or treatment failure, IDSA/AAN/ACR and AAP recommend against additional antibiotic therapy. However, retreatment in patients who experience subsequent acute infections caused by B. burgdorferi considered appropriate.

Meningitis

Parenteral treatment of meningitis caused by susceptible S. pneumoniae, H. influenzae (including ampicillin-resistant strains), Neisseria meningitidis, or S. aureus (including penicillinase-producing strains).

Not a drug of choice for meningitis; treatment failures have been reported, especially in meningitis caused by H. influenzae. In addition, bacteriologic response to cefuroxime appears to be slower than that reported with ceftriaxone, which may increase the risk for hearing loss and neurologic sequelae. When a cephalosporin is indicated for the treatment of bacterial meningitis, a parenteral third generation cephalosporin (usually ceftriaxone or cefotaxime) generally recommended.

Perioperative Prophylaxis

Perioperative prophylaxis in patients undergoing cardiac surgery; a drug of choice for cardiac procedures (e.g., coronary artery bypass, pacemaker or other cardiac device insertion, ventricular assist devices).

Perioperative prophylaxis in patients undergoing clean head and neck surgery involving placement of prosthesis (excluding tympanostomy); perioperative prophylaxis in conjunction with metronidazole in patients undergoing clean-contaminated cancer surgery of the head and neck or other clean-contaminated head and neck procedures (excluding tonsillectomy and functional endoscopic sinus procedures). A drug of choice.

Has been used for perioperative prophylaxis in patients undergoing noncardiac thoracic surgery, GI or biliary tract surgery, gynecologic or obstetric surgery (e.g., vaginal hysterectomy), orthopedic procedures, or heart transplantation. Other anti-infectives (e.g., cefazolin) usually preferred.

Pharyngitis and Tonsillitis

Treatment of mild to moderate pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci) in adults and pediatric patients ≥13 years of age. Efficacy in prevention of subsequent rheumatic fever not established.

AAP, IDSA, AHA, and others recommend a penicillin regimen (10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as treatments of choice for S. pyogenes pharyngitis and tonsillitis; other anti-infectives (oral cephalosporins, oral macrolides, oral clindamycin) recommended as alternatives in penicillin-allergic patients.

If an oral cephalosporin used treatment for S. pyogenes pharyngitis and tonsillitis, 10 day regimen of first generation cephalosporin (cefadroxil, cephalexin) preferred instead of other cephalosporins with broader spectrums of activity (e.g., cefaclor, cefdinir, cefixime, cefpodoxime, cefuroxime).

Respiratory Tract Infections

Treatment of acute maxillary sinusitis caused by susceptible S. pneumoniae or H. influenzae (non-β-lactamase-producing strains only) in adults and pediatric patients ≥13 years of age. Safety and effectiveness of cefuroxime axetil for pediatric patients 3 months to 12 years of age have been established for acute bacterial maxillary sinusitis based upon its approval in adults. Data insufficient to date to establish efficacy for treatment of acute maxillary sinusitis known or suspected to be caused by β-lactamase-producing strains of H. influenzae or M. catarrhalis. Because of variable activity against S. pneumoniae and H. influenzae, IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of acute bacterial sinusitis. Oral amoxicillin or amoxicillin and clavulanate usually recommended by IDSA and AAP for empiric treatment. If an oral cephalosporin used as an alternative in children (e.g., in penicillin-allergic individuals), combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid) recommended.

Treatment of secondary bacterial infections of acute bronchitis^† caused by susceptible S. pneumoniae, H. influenzae (non-β-lactamase-producing strains only), or H. parainfluenzae (non-β-lactamase-producing strains only).

Treatment of acute exacerbations of chronic bronchitis caused by susceptible S. pneumoniae, H. influenzae (non-β-lactamase-producing strains only), or H. parainfluenzae (non-β-lactamase-producing strains only) in adults and pediatric patients ≥13 years of age.

Parenteral treatment of lower respiratory tract infections (including pneumonia) caused by susceptible S. pneumoniae, S. aureus (including penicillinase-producing strains), S. pyogenes (group A β-hemolytic streptococci), H. influenzae (including ampicillin-resistant strains), Escherichia coli, or Klebsiella.

Treatment of community-acquired pneumonia (CAP)^†. Recommended by ATS and IDSA as an alternative in certain combination regimens used for empiric treatment of CAP. Select regimen for empiric treatment of CAP based on most likely pathogens, local susceptibility patterns, and individual patient characteristics.

For empiric outpatient treatment of CAP in adults with comorbidities (e.g., chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; asplenia), IDSA/ATS recommend either combination therapy with a ß-lactam antibiotic (amoxicillin/clavulanate, cefpodoxime, or cefuroxime) and a macrolide (azithromycin, clarithromycin, or extended-release clarithromycin) or doxycycline; or, monotherapy with a respiratory fluoroquinolone (levofloxacin, moxifloxacin, or gemifloxacin).

Septicemia

Parenteral treatment of septicemia caused by susceptible S. aureus (including penicillinase-producing strains), S. pneumoniae, E. coli, H. influenzae (including ampicillin-resistant strains), or Klebsiella.

In the treatment of known or suspected sepsis or the treatment of other serious infections when the causative organism is unknown, concomitant therapy with an aminoglycoside may be indicated.

Skin and Skin Structure Infections

Oral treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus (including β-lactamase-producing strains) or S. pyogenes in adults and pediatric patients ≥13 years of age.

Parenteral treatment of skin and skin structure infections caused by susceptible S. aureus (including β-lactamase-producing strains), S. pyogenes, E. coli, Klebsiella, or Enterobacter.

Urinary Tract Infections (UTIs)

Oral treatment of uncomplicated UTIs caused by susceptible E. coli or K. pneumoniae in adults and pediatric patients ≥13 years of age.

Parenteral treatment of UTIs caused by susceptible E. coli or K. pneumoniae.

Cefuroxime Dosage and Administration

General

Pretreatment Screening

• Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.

Patient Monitoring

• Monitor prothrombin time (PT) in patients at risk of cephalosporin-associated decreased prothrombin activity, including those with renal or hepatic impairment, poor nutritional state, receiving prolonged cefuroxime therapy, or stabilized on anticoagulant therapy. Administer vitamin K when indicated.
• Carefully monitor patients receiving prolonged cefuroxime therapy for superinfection. Institute appropriate therapy if superinfection occurs.
• Periodically evaluate renal status during therapy, especially in seriously ill patients receiving maximum dosage. Renal function monitoring also may be useful in geriatric patients because of possible age-related decreases in renal function.

Other General Considerations

• To reduce development of drug-resistant bacteria and maintain effectiveness of cefuroxime and other antibacterials, use cefuroxime only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

Administration

Administer cefuroxime axetil orally. Administer cefuroxime sodium by IV injection or infusion or deep IM injection.

IV route may be preferred in patients with septicemia or other severe or life-threatening infections or in patients with lowered resistance, particularly if shock is present or impending.

Oral Administration

Tablets may be given orally without regard to meals, but administration with food maximizes bioavailability. The manufacturer states that the tablets should be swallowed whole.

Oral suspension of cefuroxime axetil is no longer commercially available in the US. Although the tablets have been crushed and mixed with food (e.g., applesauce, ice cream), the crushed tablets have a strong, persistent taste and the manufacturers state that the drug should not be administered in this manner.

IV Injection

Reconstitution

Reconstitute vials of cefuroxime sodium containing 750 mg or 1.5 g of cefuroxime with 8.3 or 16 mL of sterile water for injection, respectively, to provide solutions containing approximately 90 mg/mL. Withdraw entire contents of vial for each dose.

Rate of Administration

Inject appropriate dose of reconstituted solution directly into a vein over a period of 3–5 minutes or slowly into the tubing of a freely flowing compatible IV solution.

IV Infusion

Other IV solutions flowing through a common administration tubing or site should be discontinued while cefuroxime is being infused. If an aminoglycoside is administered concomitantly with cefuroxime, the drugs should be administered at separate sites.

Reconstitution and Dilution

Reconstitute 7.5-g pharmacy bulk vial with 77 mL of sterile water for injection to provide solution containing approximately 750 mg of cefuroxime per 8 mL; then, further dilute in a compatible IV infusion solution.

Rate of Administration

Intermittent IV infusions generally infused over 15–60 minutes.

IM Injection

Administer IM injections deeply into a large muscle mass such as the gluteus or lateral aspect of the thigh. Use aspiration to ensure needle is not in a blood vessel.

Reconstitution

Prepare IM injections by reconstituting vial containing 750 mg of cefuroxime with 3 mL of sterile water for injection to provide a suspension containing approximately 225 mg/mL.

Shake IM suspension gently prior to administration.

Dosage

Available as cefuroxime axetil or cefuroxime sodium ; dosage expressed in terms of cefuroxime.

Pediatric Patients

General Pediatric Dosage

Neonates

IV or IM

Neonates with gestational age (GA) ≤31 weeks and 6 days and postnatal age (PNA) of <7 days of age: 50 mg/kg every 12 hours.

Neonates with GA ≤31 weeks and 6 days and PNA 7–28 days of age: 50 mg/kg every 8 hours.

Neonates with GA ≥32 weeks and PNA ≤7 days: 50 mg/kg every 12 hours.

Neonates with GA ≥32 weeks and PNA 8–28 days: 50 mg/kg every 8 hours.

Mild to Moderate Infections

Oral

Children beyond neonatal period: AAP recommends 20–30 mg/kg daily (maximum 1 g/day) given in 2 divided doses.

Children beyond neonatal period with bone or joint infections: AAP recommends up to 100 mg/kg daily (maximum 3 g/day) given in 3 divided doses.IV or IM

Children beyond neonatal period: AAP recommends 100–150 mg/kg daily (maximum 6 g/day) given in 3 divided doses.

Children ≥3 months of age: Manufacturer states 50–100 mg/kg daily given in 3 or 4 equally divided doses has been effective for most infections in children .

Severe Infections

IV or IM

Children ≥3 months of age: Manufacturer recommends 100 mg/kg daily (not to exceed the maximum adult dosage) given in 3 or 4 equally divided doses.

Acute Otitis Media (AOM)

Children 3 Months to 12 Years of Age

Oral

Tablets (for children able to swallow tablets whole): 250 mg every 12 hours for 10 days.

Has been given in a 5-day regimen^†. AAP does not recommend oral anti-infective regimens of <10 days’ duration in children <2 years of age or in patients with severe symptoms.

Pharyngitis and Tonsillitis

Children 2 to 15 Years of Age

Oral

Oral suspension (no longer commercially available in US) has been given in a dosage of 20 mg/kg daily in 2 divided doses for 10 days.

Adolescents ≥13 Years of Age

Oral

Tablets: 250 mg every 12 hours for 10 days.

Bone and Joint Infections

Children ≥3 Months

IV or IM

150 mg/kg daily (not to exceed the maximum adult dosage) given in equally divided doses every 8 hours.

Meningitis

Children ≥3 Months

IV or IM

200–240 mg/kg daily given in equally divided doses every 6–8 hours.

Respiratory Tract Infections

Acute Sinusitis in Children 3 Months to 12 Years of Age

Oral

Tablets (for children able to swallow tablets whole): 250 mg every 12 hours for 10 days.

Acute Sinusitis in Adolescents ≥13 Years of Age

Oral

Tablets: 250 mg every 12 hours for 10 days.

Acute Exacerbations of Chronic Bronchitis in Adolescents ≥13 Years of Age

Oral

Tablets: 250 or 500 mg every 12 hours for 10 days. Efficacy of regimens <10 days has not been established.

Skin and Skin Structure Infections

Uncomplicated Infections in Adolescents ≥13 Years of Age

Oral

Tablets: 250 or 500 mg every 12 hours for 10 days.

Urinary Tract Infections (UTIs)

Uncomplicated Infections in Adolescents ≥13 Years of Age

Oral

Tablets: 250 mg every 12 hours for 7–10 days.

Gonorrhea and Associated Infections

Uncomplicated Urethral, Cervical, or Rectal Gonorrhea In Adolescents ≥13 Years of Age

Oral

Tablets: 1 g as a single dose recommended by manufacturer.

Not recommended by CDC as treatment for gonorrhea.

Lyme Disease

Lyme Disease Manifested as Erythema Migrans

Oral

Tablets: 500 mg twice daily for 20 days in adolescents ≥13 years of age.

AAP, IDSA, AAN, ACR, and others recommend 30 mg/kg administered in 2 divided doses (up to 500 mg per dose) for 14 days in children without specific neurologic involvement or advanced AV heart block.

Lyme Carditis†

Oral

30 mg/kg daily in 2 equally divided doses (up to 500 mg per dose) for 14–21 days recommended by IDSA, AAN, ACR, AAP, and others.

Lyme Arthritis†

Oral

30 mg/kg daily in 2 equally divided doses (up to 500 mg per dose) for 28 days recommended by IDSA, AAN, ACR, AAP, and others for children with uncomplicated Lyme arthritis without clinical evidence of neurologic disease.

Perioperative Prophylaxis

Cardiac, Cardiothoracic, or Noncardiac Thoracic Surgery

IV

50 mg/kg given within 1 hour prior to incision. If procedure is prolonged (>4 hours) or if major blood loss occurs, additional 50-mg/kg doses may be given. No evidence of benefit if continued beyond 48 hours and no evidence to support continuing prophylaxis until all drains and indwelling catheters are removed.

Adults

General Adult Dosage

IV or IM

750–1.5 g every 8 hours for 5–10 days.

Severe or complicated infections generally require 1.5 g every 8 hours.

Life-threatening Infections or Those Caused by Less Susceptible Organisms

IV or IM

1.5 g every 6 hours.

Pharyngitis and Tonsillitis

Oral

Tablets: 250 mg every 12 hours for 10 days.

Bone and Joint Infections

IV or IM

1.5 g every 8 hours.

Meningitis

IV or IM

Up to 3 g every 8 hours.

Respiratory Tract Infections

Acute Sinusitis

Oral

Tablets: 250 mg every 12 hours for 10 days.

Secondary Bacterial Infections of Acute Bronchitis†

Oral

Tablets: 250 mg twice daily for 5–10 days.

Acute Exacerbations of Chronic Bronchitis

Oral

Tablets: 250 or 500 mg every 12 hours for 10 days. Efficacy of regimens <10 days has not been established.

Pneumonia

Oral

500 mg twice daily recommended by ATS and IDSA for empiric treatment of community-acquired pneumonia^† (CAP). Must be used in conjunction with other anti-infectives for empiric treatment of CAP.IV or IM

750 mg every 8 hours. For severe or complicated infections, 1.5 g every 8 hours.

Skin and Skin Structure Infections

Uncomplicated Infections

Oral

Tablets: 250 or 500 mg every 12 hours for 10 days.IV or IM

750 mg every 8 hours.

Severe or Complicated Infections

IV or IM

1.5 g every 8 hours.

Urinary Tract Infections (UTIs)

Uncomplicated Infections

Oral

Tablets: 250 mg every 12 hours for 7–10 days.IV or IM

750 mg every 8 hours.

Severe or Complicated Infections

IV or IM

1.5 g every 8 hours.

Gonorrhea and Associated Infections

Uncomplicated Urethral, Cervical, or Rectal Gonorrhea

Oral

Tablets: 1 g as a single dose has been used.

Not recommended by CDC as treatment for gonorrhea.IM

1.5 g as a single dose recommended by manufacturer; divide the dose, give at 2 different sites. Given in conjunction with 1 g of oral probenecid.

Not included in CDC recommendations.

Disseminated Gonococcal Infections

IV or IM

750 mg every 8 hours recommended by manufacturer.

Not included in CDC recommendations.

Lyme Disease

Early Localized or Early Disseminated Lyme Disease Manifested as Erythema Migrans

Oral

Tablets: 500 mg every 12 hours for 20 days.

IDSA, AAN, ACR, and others recommend 500 mg twice daily for 14 days in adults without specific neurologic involvement or advanced AV heart block.

Lyme Carditis†

Oral

500 mg twice daily for 14–21 days recommended by IDSA, AAN, ACR, and others.

Lyme Arthritis†

Oral

500 mg twice daily for 28 days recommended by IDSA, AAN, ACR, and others for adults with uncomplicated Lyme arthritis without clinical evidence of neurologic disease.

Perioperative Prophylaxis

Cardiac Surgery

IV

For open-heart surgery, manufacturers recommend 1.5 g given at the time of induction of anesthesia and 1.5 g every 12 hours thereafter for a total dosage of 6 g.

For cardiac procedures, some experts recommend 1.5 g given within 1 hour prior to surgical incision and additional 1.5-g doses every 4 hours during prolonged procedures (>4 hours) or if major blood loss occurs.

Various data support a duration of perioperative prophylaxis ranging from a single preoperative dose to continuation for 24 hours postoperatively; no evidence of benefit beyond 48 hours and no evidence to support continuing prophylaxis until all drains and indwelling catheters are removed.

Other Surgery

IV or IM

Manufacturer recommends 1.5 g given IV just prior to surgery (approximately 0.5–1 hour prior to initial incision) and, in lengthy operations, 750 mg given IV or IM every 8 hours. Postoperative doses usually unnecessary and may increase risk of bacterial resistance.

Some experts recommend 1.5 g given within 1 hour prior to surgical incision and additional 1.5-g doses every 4 hours during prolonged procedures (>4 hours) or if major blood loss occurs.

Special Populations

Hepatic Impairment

Systemic exposure to cefuroxime not expected to be altered in patients with hepatic impairment.

Renal Impairment

Dosage adjustments of parenteral cefuroxime necessary in patients with Cl_cr ≤20 mL/minute.

Adults with impaired renal function: 750 mg IM or IV every 12 hours in those with Cl_cr 10–20 mL/minute or 750 mg IM or IV every 24 hours in those with Cl_cr <10 mL/minute.

Patients undergoing hemodialysis: Give a supplemental dose of parenteral or oral cefuroxime after each dialysis period.

Children with impaired renal function: Make adjustments to dosing frequency for IM or IV cefuroxime similar to those recommended for adults with renal impairment.

Dosage interval adjustments of oral cefuroxime necessary in patients with Cl_cr ≤30 mL/minute.

Adults with impaired renal function: Give standard oral dose once every 24 hours in those with Cl_cr 10 to <30 mL/minute or standard oral dose once every 48 hours in those with Cl_cr <10 mL/minute who are not receiving hemodialysis.

Geriatric Patients

Cautious dosage selection because of age-related decreases in renal function.

Cautions for Cefuroxime

Contraindications

• Known hypersensitivity to cefuroxime or other ß-lactam antibacterial drugs (e.g., penicillins, cephalosporins).

Warnings/Precautions

Clostridioides difficile-associated Diarrhea and Colitis (CDAD)

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including cefuroxime, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B, which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, may need to discontinue anti-infectives not directed against C. difficile. Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

Hypersensitivity Reactions

Possible hypersensitivity reactions, including rash, pruritus, fever, eosinophilia, urticaria, potentially fatal anaphylaxis, erythema multiforme, interstitial nephritis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

If an allergic reaction occurs, discontinue and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen). Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins.

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs. Cautious use recommended in individuals hypersensitive to penicillins or other drugs; manufacturer states cefuroxime axetil contraindicated in patients with known hypersensitivity to β-lactam antibiotics.

Potential for Microbial Overgrowth

Possible emergence and overgrowth of nonsusceptible organisms with prolonged therapy. Careful observation of the patient is essential. Institute appropriate therapy if superinfection occurs.

History of GI Disease

Use with caution in patients with a history of GI disease, particularly colitis.

Prolonged Prothrombin Time (PT)

Prolonged PT reported with some cephalosporins.

Monitor PT in patients at risk, including those with renal or hepatic impairment, poor nutritional state, receiving prolonged therapy, or stabilized on anticoagulant therapy. Administer vitamin K when indicated.

Renal Effects

Periodically evaluate renal status during therapy, especially in seriously ill patients receiving maximum dosage.

Caution if used concomitantly with nephrotoxic drugs (e.g., aminoglycosides, potent diuretics).

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of cefuroxime and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Interference with Glucose Tests

Possible false-positive result for urine glucose with copper reduction tests in patients receiving cefuroxime axetil.

Possible false-negative result for blood/plasma glucose with ferricyanide tests in patients receiving cefuroxime axetil.

Patients with Meningitis

Mild to moderate hearing loss reported rarely in pediatric patients who received cefuroxime for treatment of meningitis.

Persistence of positive CSF cultures at 18–36 hours reported; clinical importance unknown.

Sodium Content

Cefuroxime sodium contains approximately 54.2 mg (2.4 mEq) of sodium per g of cefuroxime.

Specific Populations

Pregnancy

No adequate and controlled studies to date using cefuroxime in pregnant women; use cefuroxime during pregnancy only when clearly needed. Manufacturer of cefuroxime axetil states that while available studies cannot definitively establish absence of risk, published data from epidemiologic studies, case series, and case reports have not identified an association with the use of cephalosporins (including cefuroxime axetil) during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Lactation

Distributed into milk; use cefuroxime sodium with caution.

According to the manufacturer of cefuroxime axetil, no data available on drug’s effects on breastfed infant or milk production. Consider developmental and health benefits of breastfeeding along with mother’s clinical need for cefuroxime and any potential adverse effects on the breastfed infant from cefuroxime or from the underlying maternal condition.

Pediatric Use

Safety and efficacy of oral or parenteral cefuroxime not established in children <3 months of age. Other cephalosporins accumulate in neonates resulting in prolonged serum half-life.

Safety and efficacy of oral cefuroxime for treatment of acute bacterial maxillary sinusitis in pediatric patients 3 months to 12 years of age have been established based on safety and efficacy of the drug in adults. In addition, use of oral cefuroxime in pediatric patients is supported by pharmacokinetic and safety data in adult and pediatric patients, clinical and microbiologic data from adequate and well-controlled studies of the treatment of acute bacterial maxillary sinusitis in adults and acute otitis media with effusion in pediatric patients, and postmarketing surveillance of adverse effects.

Tablets should not be crushed for pediatric administration since the drug has a strong, persistent, bitter taste; vomiting was induced aversively in some children who received crushed tablets.

Geriatric Use

No overall differences in safety and efficacy in those ≥65 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function. Select dosage with caution; renal function monitoring may be useful because of age-related decreases in renal function.

Hepatic Impairment

Cefuroxime pharmacokinetics not expected to be altered in patients with hepatic impairment.

Renal Impairment

Possible decreased clearance and increased serum half-life.

Dosage adjustments of parenteral cefuroxime necessary in patients with Cl_cr ≤20 mL/minute. Dosage interval adjustments of oral cefuroxime necessary in patients with Cl_cr ≤30 mL/minute.

In patients undergoing hemodialysis, give a supplemental dose of oral or parenteral cefuroxime after each dialysis period.

Common Adverse Effects

Cefuroxime axetil (≥3% of patients: diarrhea, nausea/vomiting, and, in patients receiving the drug for early Lyme disease, Jarisch-Herxheimer reaction, vaginitis.

Cefuroxime sodium (approximately 2% of patients): Local reactions at IV injection sites.

Drug Interactions

Specific Drugs and Laboratory Tests

Cefuroxime Pharmacokinetics

Absorption

Bioavailability

Following oral administration of cefuroxime axetil, the drug is absorbed from the GI tract and rapidly hydrolyzed to cefuroxime. Cefuroxime axetil has little, if any, microbiologic activity until hydrolyzed in vivo to cefuroxime.

In adults receiving film-coated tablets, peak serum concentrations attained approximately 2–3 hours after the dose.

Cefuroxime sodium not appreciably absorbed from the GI tract; must be given parenterally. Following IM administration in healthy adults, peak serum concentrations attained within 15–60 minutes.

In women, serum cefuroxime concentrations are lower when IM injections are given into the gluteus maximus rather than into the thigh.

Food

In adults, bioavailability following oral administration of film-coated tablets averages about 37% when given in the fasting state and 52% when given with or shortly after food.

Absorption increased when cefuroxime axetil given with milk or infant formula. The extent (but not rate) of absorption is substantially greater when administered concomitantly with milk compared with applesauce or fasting.

Distribution

Extent

Following IM or IV administration, widely distributed into body tissues and fluids including pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.

Therapeutic concentrations may be attained in CSF following IV administration in patients with inflamed meninges.

Readily crosses the placenta and is distributed into milk.

Plasma Protein Binding

33–50%.

Elimination

Metabolism

Following oral administration, cefuroxime axetil rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood.

Cefuroxime not metabolized.

Elimination Route

Eliminated unchanged principally in urine.

Half-life

Adults: 1.2–1.6 hours following oral administration and 1–2 hours following IV or IM administration.

Neonates and children: Half-life inversely proportional to age.

Special Populations

Patients with renal impairment: Serum half-life prolonged and generally ranges from 1.9–16.1 hours depending on the degree of impairment. Serum half-life of 15–22 hours has been reported in anuric patients.

Stability

Storage

Oral

Tablets

20–25°C; store in tight container.

Parenteral

Powder for Injection or Infusion

20–25°C; protect from light.

Powder for injection and solutions may darken; does not indicate loss of potency.

Reconstituted 750-mg or 1.5-g vials or 7.5-g pharmacy bulk vial are stable for 24 hours at room temperature or 48 hours (750-mg and 1.5-g vials) or 7 days (7.5-g pharmacy bulk vial) at 5°C. More dilute solutions (e.g., 750 mg or 1.5 g in 100 mL of sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection) also stable for 24 hours at room temperature or 7 days when refrigerated.

IM suspensions containing 225 mg/mL prepared using sterile water for injection are stable for 24 hours at room temperature or 48 hours at 5°C.

Injection (Frozen) for Infusion

−20°C or lower. After thawing, stable for up to 24 hours at room temperature (25°C) or up to 28 days under refrigeration (5°C).

Do not refreeze after thawing.

Actions and Spectrum

• Based on spectrum of activity, classified as a second generation cephalosporin. Generally no more active in vitro against susceptible gram-positive cocci than first generation cephalosporins, but has an expanded spectrum of activity against gram-negative bacteria compared with first generation drugs.
• Usually bactericidal.
• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.
• Spectrum of activity includes many gram-positive aerobic bacteria, some gram-negative aerobic bacteria, and some anaerobic bacteria. Susceptibility to cefuroxime will vary with geography and time; consult local susceptibility data if available.
• Cefuroxime has activity in the presence of some β-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.
• Resistance to cefuroxime is primarily through hydrolysis by β-lactamase, alteration of penicillin-binding proteins (PBPs), decreased permeability, and the presence of bacterial efflux pumps.

Advice to Patients

• Advise patients that antibacterials (including cefuroxime) should only be used to treat bacterial infections; they do not treat viral infections (e.g., the common cold).
• Stress importance of completing full course of therapy, even if feeling better after a few days.
• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefuroxime or other antibacterials in the future.
• Instruct patients to swallow cefuroxime axetil tablets whole and not to crush the tablets.
• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. Stress importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.
• Advise patients to inform a clinician if an allergic reaction occurs.
• Advise patients to inform clinicians if they are or plan to become pregnant or plan to breast-feed.
• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.
• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ceftriaxone for injection, USP and other antibacterial drugs, Ceftriaxone for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Ceftriaxone Description

Ceftriaxone for injection, USP is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous or intramuscular administration. Ceftriaxone sodium is (6 R,7 R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo- as-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7 2-( Z)-( O-methyloxime), disodium salt, sesquaterhydrate.

The chemical formula of ceftriaxone sodium is C 18H 16N 8Na 2O 7S 3•3.5H 2O. It has a calculated molecular weight of 661.59 and the following structural formula:

Ceftriaxone for injection, USP is a white to yellowish-orange crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7. The color of Ceftriaxone for injection, USP solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used. Each vial contains ceftriaxone sodium equivalent to 250 mg, 500 mg, 1 g or 2 g of ceftriaxone activity.

Ceftriaxone for injection, USP contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity.

Ceftriaxone – Clinical Pharmacology

Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (IV) infusion of a 0.5, 1 or 2 g dose and intramuscular (IM) administration of a single 0.5 (250 mg/mL or 350 mg/mL concentrations) or 1 g dose in healthy subjects are presented in Table 1.

Ceftriaxone was completely absorbed following IM administration with mean maximum plasma concentrations occurring between 2 and 3 hours post-dose. Multiple IV or IM doses ranging from 0.5 to 2 g at 12- to 24-hour intervals resulted in 15% to 36% accumulation of ceftriaxone above single dose values.

Ceftriaxone concentrations in urine are shown in Table 2.

Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. After a 1 g IV dose, average concentrations of ceftriaxone, determined from 1 to 3 hours after dosing, were 581 mcg/mL in the gallbladder bile, 788 mcg/mL in the common duct bile, 898 mcg/mL in the cystic duct bile, 78.2 mcg/g in the gallbladder wall and 62.1 mcg/mL in the concurrent plasma.

Over a 0.15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of <25 mcg/mL to a value of 85% bound at 300 mcg/mL. Ceftriaxone crosses the blood placenta barrier.

The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg IV dose and after a 75 mg/kg IV dose in pediatric patients suffering from bacterial meningitis are shown in Table 3. Ceftriaxone penetrated the inflamed meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a 75 mg/kg IV dose are also shown in Table 3.

Compared to that in healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction ( Table 4); therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2 g per day. Ceftriaxone was not removed to any significant extent from the plasma by hemodialysis; in six of 26 dialysis patients, the elimination rate of ceftriaxone was markedly reduced.

The elimination of ceftriaxone is not altered when Ceftriaxone for injection is co-administered with probenecid.

Pharmacokinetics in the Middle Ear Fluid:In one study, total ceftriaxone concentrations (bound and unbound) were measured in middle ear fluid obtained during the insertion of tympanostomy tubes in 42 pediatric patients with otitis media. Sampling times were from 1 to 50 hours after a single intramuscular injection of 50 mg/kg of ceftriaxone. Mean (± SD) ceftriaxone levels in the middle ear reached a peak of 35 (± 12) mcg/mL at 24 hours, and remained at 19 (± 7) mcg/mL at 48 hours. Based on middle ear fluid ceftriaxone concentrations in the 23 to 25 hour and the 46 to 50 hour sampling time intervals, a half-life of 25 hours was calculated. Ceftriaxone is highly bound to plasma proteins. The extent of binding to proteins in the middle ear fluid is unknown.

Interaction with Calcium:Two in vitro studies, one using adult plasma and the other neonatal plasma from umbilical cord blood have been carried out to assess interaction of ceftriaxone and calcium. Ceftriaxone concentrations up to 1 mM (in excess of concentrations achieved in vivo following administration of 2 g ceftriaxone infused over 30 minutes) were used in combination with calcium concentrations up to 12 mM (48 mg/dL). Recovery of ceftriaxone from plasma was reduced with calcium concentrations of 6 mM (24 mg/dL) or higher in adult plasma or 4 mM (16 mg/dL) or higher in neonatal plasma. This may be reflective of ceftriaxone-calcium precipitation.

Microbiology:Mechanism of Action

Ceftriaxone is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Mechanism of Resistance

Resistance to ceftriaxone is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.

Interaction with Other Antimicrobials

In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone.

Ceftriaxone has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE (1) section:

• Gram-negative bacteria
  Acinetobactercalcoaceticus
  Enterobacteraerogenes
  Enterobactercloacae
  Escherichia coli
  Haemophilusinfluenzae
  Haemophilusparainfluenzae
  Klebsiellaoxytoca
  Klebsiellapneumoniae
  Moraxellacatarrhalis
  Morganellamorganii
  Neisseriagonorrhoeae
  Neisseriameningitidis
  Proteus mirabilis
  Proteus vulgaris
  Pseudomonas aeruginosa
  Serratiamarcescens
• Gram-positive bacteria
  Staphylococcus aureus
  Staphylococcus epidermidis
  Streptococcuspneumoniae
  Streptococcuspyogenes
  Viridansgroup streptococci
• Anaerobic bacteria
  Bacteroidesfragilis
  Clostridium species
  Peptostreptococcusspecies

The following in vitrodata are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitrominimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftriaxone. However, the efficacy of ceftriaxone in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

• Gram-negative bacteria
  Citrobacterdiversus
  Citrobacterfreundii
  Providenciaspecies (including Providenciarettgeri)
  Salmonellaspecies (including Salmonellatyphi)
  Shigellaspecies
• Gram-positive bacteria
  Streptococcusagalactiae
• Anaerobic bacteria
  Porphyromonas(Bacteroides)melaninogenicus
  Prevotella(Bacteroides)bivius

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Indications and Usage for Ceftriaxone

Before instituting treatment with Ceftriaxone for injection, USP, appropriate specimens should be obtained for isolation of the causative organism and for determination of its susceptibility to the drug. Therapy may be instituted prior to obtaining results of susceptibility testing.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ceftriaxone for injection, USP and other antibacterial drugs, Ceftriaxone for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Ceftriaxone for injection, USP is indicated for the treatment of the following infections when caused by susceptible organisms:

LOWER RESPIRATORY TRACT INFECTIONScaused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilisor Serratia marcescens.

ACUTE BACTERIAL OTITIS MEDIAcaused by Streptococcuspneumoniae,Haemophilus influenzae(including beta-lactamase producing strains) or Moraxella catarrhalis(including beta-lactamase producing strains).

NOTE: In one study lower clinical cure rates were observed with a single dose of Ceftriaxone for injection, USP compared to 10 days of oral therapy. In a second study comparable cure rates were observed between single dose Ceftriaxone for injection, USP and the comparator. The potentially lower clinical cure rate of Ceftriaxone for injection, USP should be balanced against the potential advantages of parenteral therapy.

SKIN AND SKIN STRUCTURE INFECTIONScaused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Viridans group streptococci, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii,*Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis*or Peptostreptococcusspecies.

URINARY TRACT INFECTIONS (complicated and uncomplicated)caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganiior Klebsiella pneumoniae.

UNCOMPLICATED GONORRHEA (cervical/urethral and rectal)caused by Neisseria gonorrhoeae,including both penicillinase- and nonpenicillinase-producing strains, and pharyngeal gonorrhea caused by nonpenicillinase-producing strains of Neisseria gonorrhoeae.

PELVIC INFLAMMATORY DISEASEcaused by Neisseria gonorrhoeae.Ceftriaxone for injection, USP, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of patients with pelvic inflammatory disease and Chlamydia trachomatisis one of the suspected pathogens, appropriate antichlamydial coverage should be added.

BACTERIAL SEPTICEMIAcaused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzaeor Klebsiella pneumoniae.

BONE AND JOINT INFECTIONScaused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniaeor Enterobacterspecies.

INTRA-ABDOMINAL INFECTIONScaused by Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis, Clostridiumspecies (Note: most strains of Clostridium difficileare resistant) or Peptostreptococcusspecies.

MENINGITIScaused by Haemophilus influenzae, Neisseria meningitidisor Streptococcus pneumoniae.Ceftriaxone for injection, USP has also been used successfully in a limited number of cases of meningitis and shunt infection caused by Staphylococcus epidermidis*and Escherichia coli.*

* Efficacy for this organism in this organ system was studied in fewer than ten infections.

SURGICAL PROPHYLAXIS:The preoperative administration of a single 1 g dose of Ceftriaxone for injection, USP may reduce the incidence of postoperative infections in patients undergoing surgical procedures classified as contaminated or potentially contaminated (eg ,vaginal or abdominal hysterectomy or cholecystectomy for chronic calculous cholecystitis in high-risk patients, such as those over 70 years of age, with acute cholecystitis not requiring therapeutic antimicrobials, obstructive jaundice or common duct bile stones) and in surgical patients for whom infection at the operative site would present serious risk (eg ,during coronary artery bypass surgery). Although Ceftriaxone for injection, USP has been shown to have been as effective as cefazolin in the prevention of infection following coronary artery bypass surgery, no placebo-controlled trials have been conducted to evaluate any cephalosporin antibiotic in the prevention of infection following coronary artery bypass surgery.

When administered prior to surgical procedures for which it is indicated, a single 1 g dose of Ceftriaxone for injection, USP provides protection from most infections due to susceptible organisms throughout the course of the procedure.

Contraindications

Hypersensitivity

Ceftriaxone for injection is contraindicated in patients with known hypersensitivity to ceftriaxone, any of its excipients or to any other cephalosporin. Patients with previous hypersensitivity reactions to penicillin and other beta lactam antibacterial agents may be at greater risk of hypersensitivity to ceftriaxone .

Neonates

Premature neonates: Ceftriaxone for injection is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age).

Hyperbilirubinemicneonates: Hyperbilirubinemic neonates should not be treated with Ceftriaxone for injection. Ceftriaxone can displace bilirubin from its binding to serum albumin, leading to a risk of bilirubin encephalopathy in these patients.

Neonates Requiring Calcium Containing IV Solutions

Ceftriaxone for injection is contraindicated in neonates (≤ 28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium

Cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving Ceftriaxone for injection and calcium-containing fluids.

In some of these cases, the same intravenous infusion line was used for both Ceftriaxone for injection and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. There have been no similar reports in patients other than neonates.

Lidocaine

Intravenous administration of ceftriaxone solutions containing lidocaine is contraindicated. When lidocaine solution is used as a solvent with ceftriaxone for intramuscular injection, exclude all contraindications to lidocaine. Refer to the prescribing information of lidocaine.

Warnings

Hypersensitivity Reactions

Before therapy with Ceftriaxone for injection is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins and other beta-lactam agents or other drugs. This product should be given cautiously to penicillin and other beta-lactam agent-sensitive patients. Antibacterial drugs should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs. Serious acute hypersensitivity reactions may require the use of subcutaneous epinephrine and other emergency measures.

As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions (i.e., anaphylaxis) have been reported. In case of severe hypersensitivity reactions, treatment with ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated.

Interaction with Calcium-Containing Products

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, Ceftriaxone for injection and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. Invitrostudies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium.

Neurological Adverse Reactions

Serious neurological adverse reactions have been reported during postmarketing surveillance with ceftriaxone use. These reactions include encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and non-convulsive status epilepticus . Some cases occurred in patients with severe renal impairment who did not receive appropriate dosage adjustment. However, in other cases, neurological adverse reactions occurred in patients receiving an appropriate dosage adjustment. The neurological adverse reactions were reversible and resolved after discontinuation. If neurological adverse reactions associated with Ceftriaxone for Injection therapy occur, discontinue Ceftriaxone for Injection and institute appropriate supportive measures. Make appropriate dosage adjustments in patients with severe renal impairment .

Clostridiumdifficile-Associated Diarrhea

Clostridium difficileassociated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Ceftriaxone for injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficilecause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Hemolytic Anemia

An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including Ceftriaxone for injection. Severe cases of hemolytic anemia, including fatalities, have been reported during treatment in both adults and children. If a patient develops anemia while on ceftriaxone, the diagnosis of a cephalosporin associated anemia should be considered and ceftriaxone stopped until the etiology is determined.

Precautions

Development of Drug-resistant Bacteria

Prescribing Ceftriaxone for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Prolonged use of Ceftriaxone for injection may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Patients with Renal or Hepatic Impairment

Ceftriaxone is excreted via both biliary and renal excretion . Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of Ceftriaxone for injection are administered.

Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the Ceftriaxone for injection dosage should not exceed 2 g daily.

Ceftriaxone is not removed by peritoneal- or hemodialysis. In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. In patients with both severe renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised.

Effect on Prothrombin Time

Alterations in prothrombin times have occurred in patients treated with Ceftriaxone for injection. Monitor prothrombin time during Ceftriaxone for injection treatment in patients with impaired vitamin K synthesis or low vitamin K stores (eg, chronic hepatic disease and malnutrition). Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy.

Concomitant use of ceftriaxone with Vitamin K antagonists may increase the risk of bleeding. Coagulation parameters should be monitored frequently, and the dose of the anticoagulant adjusted accordingly, both during and after treatment with ceftriaxone .

Gallbladder Pseudolithiasis

Ceftriaxone-calcium precipitates in the gallbladder have been observed in patients receiving Ceftriaxone for injection. These precipitates appear on sonography as an echo without acoustical shadowing suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as gallstones. The probability of such precipitates appears to be greatest in pediatric patients. Patients may be asymptomatic or may develop symptoms of gallbladder disease. The condition appears to be reversible upon discontinuation of ceftriaxone sodium and institution of conservative management. Discontinue ceftriaxone sodium in patients who develop signs and symptoms suggestive of gallbladder disease and/or the sonographic findings described above.

Urolithiasisand Post-Renal Acute Renal Failure

Ceftriaxone-calcium precipitates in the urinary tract have been observed in patients receiving Ceftriaxone for injection and may be detected as sonographic abnormalities. The probability of such precipitates appears to be greatest in pediatric patients. Patients may be asymptomatic or may develop symptoms of urolithiasis, and ureteral obstruction and post-renal acute renal failure. The condition appears to be reversible upon discontinuation of ceftriaxone sodium and institution of appropriate management. Ensure adequate hydration in patients receiving Ceftriaxone for injection. Discontinue Ceftriaxone for injection in patients who develop signs and symptoms suggestive of urolithiasis, oliguria or renal failure and/or the sonographic findings described above.

Pancreatitis

Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported in patients treated with Ceftriaxone for injection. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of Ceftriaxone for injection-related biliary precipitation cannot be ruled out.

Information for Patients:

•Advise patients that neurological adverse reactions could occur with Ceftriaxone for Injection use. Instruct patients or their caregivers to inform their healthcare provider at once of any neurological signs and symptoms, including encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and non-convulsive status epilepticus, for immediate treatment, or discontinuation of Ceftriaxone for Injection .

•Patients should be counseled that antibacterial drugs including Ceftriaxone for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., common cold).

•When Ceftriaxone for injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Ceftriaxone for injection or other antibacterial drugs in the future.

•Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenesis:Considering the maximum duration of treatment and the class of the compound, carcinogenicity studies with ceftriaxone in animals have not been performed. The maximum duration of animal toxicity studies was 6 months.

Mutagenesis:Genetic toxicology tests included the Ames test, a micronucleus test and a test for chromosomal aberrations in human lymphocytes cultured invitrowith ceftriaxone. Ceftriaxone showed no potential for mutagenic activity in these studies.

Impairment of Fertility:Ceftriaxone produced no impairment of fertility when given intravenously to rats at daily doses up to 586 mg/kg/day, approximately 20 times the recommended clinical dose of 2 g/day.

Pregnancy: Teratogenic Effects:Pregnancy Category B.

Reproductive studies have been performed in mice and rats at doses up to 20 times the usual human dose and have no evidence of embryotoxicity, fetotoxicity or teratogenicity. In primates, no embryotoxicity or teratogenicity was demonstrated at a dose approximately 3 times the human dose.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nonteratogenic Effects:In rats, in the Segment I (fertility and general reproduction) and Segment III (perinatal and postnatal) studies with intravenously administered ceftriaxone, no adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behavior and reproductive ability of the offspring, at doses of 586 mg/kg/day or less.

Nursing Mothers:Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when ceftriaxone is administered to a nursing woman.

Pediatric Use:Safety and effectiveness of Ceftriaxone for injection in neonates, infants and pediatric patients have been established for the dosages described in the DOSAGE AND ADMINISTRATIONsection. Invitrostudies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Ceftriaxone for injection should not be administered to hyperbilirubinemic neonates, especially prematures .

Geriatric Use:Of the total number of subjects in clinical studies of Ceftriaxone for injection, 32% were 60 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients compared to healthy adult subjects and dosage adjustments are not necessary for geriatric patients with ceftriaxone dosages up to 2 g per day provided there is no severe renal and hepatic impairment .

Influence on Diagnostic Tests:In patients treated with Ceftriaxone for injection the Coombs’ test may become positive. Ceftriaxone for injection, like other antibacterial drugs, may result in positive test results for galactosemia.

Nonenzymatic methods for the glucose determination in urine may give false-positive results. For this reason, urine-glucose determination during therapy with Ceftriaxone for injection should be done enzymatically.

The presence of ceftriaxone may falsely lower estimated blood glucose values obtained with some blood glucose monitoring systems. Please refer to instructions for use for each system. Alternative testing methods should be used if necessary

Adverse Reactions/Side Effects

Ceftriaxone for injection is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to Ceftriaxone for injection therapy or of uncertain etiology, were observed:

LOCAL REACTIONS—pain, induration and tenderness was 1% overall. Phlebitis was reported in <1% after IV administration. The incidence of warmth, tightness or induration was 17% (3/17) after IM administration of 350 mg/mL and 5% (1/20) after IM administration of 250 mg/mL.

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS—injection site pain (0.6%).

HYPERSENSITIVITY—rash (1.7%). Less frequently reported (<1%) were pruritus, fever or chills.

INFECIONS AND INFESTATIONS—genital fungal infection (0.1%).

HEMATOLOGIC—eosinophilia (6%), thrombocytosis (5.1%) and leukopenia (2.1%). Less frequently reported (<1%) were anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia and prolongation of the prothrombin time.

BLOOD AND LYMPHATIC DISORDERS—granulocytopenia (0.9%), coagulopathy (0.4%).

GASTROINTESTINAL—diarrhea/loose stools (2.7%). Less frequently reported (<1%) were nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment.

HEPATIC—elevations of aspartate aminotransferase (AST) (3.1%) or alanine aminotransferase (ALT) (3.3%). Less frequently reported (<1%) were elevations of alkaline phosphatase and bilirubin.

RENAL—elevations of the BUN (1.2%). Less frequently reported (<1%) were elevations of creatinine and the presence of casts in the urine.

CENTRAL NERVOUS SYSTEM—headache or dizziness were reported occasionally (<1%).

GENITOURINARY—moniliasis or vaginitis were reported occasionally (<1%).

MISCELLANEOUS—diaphoresis and flushing were reported occasionally (<1%).

INVESTIGATIONS—blood creatinine increased (0.6%).

Other rarely observed adverse reactions (<0.1%) include abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness.

Postmarketing Experience:In addition to the adverse reactions reported during clinical trials, the following adverse experiences have been reported during clinical practice in patients treated with Ceftriaxone for injection. Data are generally insufficient to allow an estimate of incidence or to establish causation.

A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving Ceftriaxone for injection and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Ceftriaxone for injection and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom Ceftriaxone for injection and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates.

GASTROINTESTINAL– pancreatitis, stomatitis and glossitis.

GENITOURINARY– oliguria, ureteric obstruction, post-renal acute renal failure.

DERMATOLOGIC –exanthema, allergic dermatitis, urticaria, edema; acute generalized exanthematous pustulosis (AGEP) and isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis) have been reported.

HEMATOLOGICAL CHANGES: Isolated cases of agranulocytosis (< 500/mm3) have been reported, most of them after 10 days of treatment and following total doses of 20 g or more.

NEUROLOGIC:Encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus .

OTHER, Adverse Reactions: symptomatic precipitation of ceftriaxone calcium salt in the gallbladder, kernicterus, oliguria, and anaphylactic or anaphylactoid reactions.

Cephalosporin Class Adverse Reactions

In addition to the adverse reactions listed above which have been observed in patients treated with ceftriaxone, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics:

Adverse Reactions:Allergic reactions, drug fever, serum sickness-like reaction, renal dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, and superinfection.

Altered Laboratory Tests:Positive direct Coombs’ test, false-positive test for urinary glucose, and elevated LDH .

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced . If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Overdosage

Ceftriaxone overdosage has been reported in patients with severe renal impairment. Reactions have included neurological outcomes, including encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus. In the event of overdosage, discontinue Ceftriaxone for Injection therapy and provide general supportive treatment .

In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic.

Ceftriaxone Dosage and Administration

Ceftriaxone for injection may be administered intravenously or intramuscularly.

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line.

Ceftriaxone for injection must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, Ceftriaxone for injection and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid.

There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

NEONATES:Hyperbilirubinemic neonates, especially prematures, should not be treated with Ceftriaxone for injection. Ceftriaxone for injection is contraindicated in premature neonates .

Ceftriaxone for injection is contraindicated in neonates (≤ 28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium .

Intravenous doses should be given over 60 minutes in neonates to reduce the risk of bilirubin encephalopathy.

PEDIATRIC PATIENTS:For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 g.

For the treatment of acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 g) is recommended .

For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 g.

In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 g). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 g daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.

ADULTS:The usual adult daily dose is 1 to 2 g given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. The total daily dose should not exceed 4 g.

If Chlamydia trachomatisis a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism.

For the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended.

For preoperative use (surgical prophylaxis), a single dose of 1 g administered intravenously 1/2 to 2 hours before surgery is recommended.

Generally, Ceftriaxone for injection therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.

When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.

No dosage adjustment is necessary for patients with impairment of renal or hepatic function .

The dosages recommended for adults require no modification in elderly patients, up to 2 g per day, provided there is no severe renal and hepatic impairment .

DIRECTIONS FOR USE: Intramuscular Administration:Reconstitute Ceftriaxone for injection powder with the appropriate diluent .

Inject diluent into vial, shake vial thoroughly to form solution. Withdraw entire contents of vial into syringe to equal total labeled dose.

After reconstitution, each 1 mL of solution contains approximately 250 mg or 350 mg equivalent of ceftriaxone according to the amount of diluent indicated below. If required, more dilute solutions could be utilized. A 350 mg/mL concentration is not recommended for the 250 mg vial since it may not be possible to withdraw the entire contents.

As with all intramuscular preparations, Ceftriaxone for injection should be injected well within the body of a relatively large muscle; aspiration helps to avoid unintentional injection into a blood vessel.

Intravenous Administration:Ceftriaxone for injection should be administered intravenously by infusion over a period of 30 minutes, except in neonates where administration over 60 minutes is recommended to reduce the risk of bilirubin encephalopathy. Concentrations between 10 mg/mL and 40 mg/mL are recommended; however, lower concentrations may be used if desired. Reconstitute vials with an appropriate IV diluent .

After reconstitution, each 1 mL of solution contains approximately 100 mg equivalent of ceftriaxone. Withdraw entire contents and dilute to the desired concentration with the appropriate IV diluent.

COMPATIBILITY AND STABILITY:Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration. Particulate formation can result.

Ceftriaxone has been shown to be compatible with Flagyl ®IV (metronidazole hydrochloride). The concentration should not exceed 5 to 7.5 mg/mL metronidazole hydrochloride with ceftriaxone 10 mg/mL as an admixture. The admixture is stable for 24 hours at room temperature only in 0.9% sodium chloride injection or 5% dextrose in water (D5W). No compatibility studies have been conducted with the Flagyl ®IV RTU ®(metronidazole) formulation or using other diluents. Metronidazole at concentrations greater than 8 mg/mL will precipitate. Do not refrigerate the admixture as precipitation will occur.

Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures. When any of these drugs are to be administered concomitantly with ceftriaxone by intermittent intravenous infusion, it is recommended that they be given sequentially, with thorough flushing of the intravenous lines (with one of the compatible fluids) between the administrations.

Ceftriaxone for injection solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed above, due to possible incompatibility .

Ceftriaxone for injection sterile powder should be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.

Ceftriaxone for injection intramuscularsolutions remain stable (loss of potency less than 10%) for the following time periods:

Ceftriaxone for injection intravenoussolutions, at concentrations of 10, 20 and 40 mg/mL, remain stable (loss of potency less than 10%) for the following time periods stored in glass or PVC containers:

The following intravenousCeftriaxone for injection solutions are stable at room temperature (25°C) for 24 hours, at concentrations between 10 mg/mL and 40 mg/mL: Sodium Lactate (PVC container), 10% Invert Sugar (glass container), 5% Sodium Bicarbonate (glass container), Freamine III (glass container), Normosol-M in 5% Dextrose (glass and PVC containers), Ionosol-B in 5% Dextrose (glass container), 5% Mannitol (glass container), 10% Mannitol (glass container).

After the indicated stability time periods, unused portions of solutions should be discarded.

NOTE: Parenteral drug products should be inspected visually for particulate matter before administration.

Ceftriaxone for injection reconstituted with 5% Dextrose or 0.9% Sodium Chloride solution at concentrations between 10 mg/mL and 40 mg/mL, and then stored in frozen state (-20°C) in PVC or polyolefin containers, remains stable for 26 weeks.

Frozen solutions of Ceftriaxone for injection should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.

ANIMAL PHARMACOLOGY

Concretions consisting of the precipitated calcium salt of ceftriaxone have been found in the gallbladder bile of dogs and baboons treated with ceftriaxone.

These appeared as a gritty sediment in dogs that received 100 mg/kg/day for 4 weeks. A similar phenomenon has been observed in baboons but only after a protracted dosing period (6 months) at higher dose levels (335 mg/kg/day or more). The likelihood of this occurrence in humans is considered to be low, since ceftriaxone has a greater plasma half-life in humans, the calcium salt of ceftriaxone is more soluble in human gallbladder bile and the calcium content of human gallbladder bile is relatively low.

How is Ceftriaxone supplied

Ceftriaxone for injection, USP is supplied as a sterile crystalline powder in glass vials. The following packages are available:

Vials containing 250 mg equivalent of ceftriaxone. Package of 10 (NDC 67184-1005-1).

Vials containing 500 mg equivalent of ceftriaxone. Package of 10 (NDC 67184-1006-1).

Vials containing 1 g equivalent of ceftriaxone. Package of 10 (NDC 67184-1007-1).

Vials containing 2 g equivalent of ceftriaxone. Package of 10 (NDC 67184-1008-1).

Vials containing 250 mg equivalent to ceftriaxone. Package of 1 (67184-1005-2).

Vials containing 500 mg equivalent to ceftriaxone. Package of 1 (67184-1006-2).

Storage Prior to Reconstitution

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light.

Clinical Studies

Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media

Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media:In two adequate and well-controlled US clinical trials a single IM dose of ceftriaxone was compared with a 10 day course of oral antibiotic in pediatric patients between the ages of 3 months and 6 years. The clinical cure rates and statistical outcome appear in the table below:

An open-label bacteriologic study of ceftriaxone without a comparator enrolled 108 pediatric patients, 79 of whom had positive baseline cultures for one or more of the common pathogens. The results of this study are tabulated as follows:

Week 2 and 4 Bacteriologic Eradication Rates in the Per Protocol Analysis in the Roche Bacteriologic Study by pathogen:

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Jinan, 250101, China

Manufactured by:

Qilu Antibiotics Pharmaceutical Co., Ltd.

Jinan,250105, China

Revised:

© October 2021

250 mg Label

NDC 67184-1005-1

Ceftriaxone
for Injection, USP

250 mg/vial

For Intramuscular or
Intravenous Use

Single-use Vial

APOTEX CORP. Rx only

500 mg Label

NDC 67184-1006-1

Ceftriaxone
for Injection, USP

500 mg/vial

For Intramuscular or
Intravenous Use

Single-use Vial

APOTEX CORP. Rx only

1 g Label

NDC 67184-1007-1

Ceftriaxone
for Injection, USP

1 g/vial

For Intramuscular
or Intravenous Use

Single-use Vial

APOTEX CORP. Rx only

2 g Label

NDC 67184-1008-1

for Injection, USP

2 g/vial

For Intramuscular
or Intravenous Use

Single-use Vial

APOTEX CORP. Rx only