Pronunciation: kla-RITH-roe-MYE-sin
Class: Macrolide antibiotic

Trade Names

Biaxin
- Tablets, oral 250 mg
- Tablets, oral 500 mg
- Granules for oral suspension 250 mg per 5 mL after reconstitution

Biaxin XL
- Tablets, ER, oral 500 mg

Clarithromycin
- Granules for oral suspension 125 mg per 5 mL after reconstitution

Apo-Clarithromycin (Canada)
Biaxin BID (Canada)

Pharmacology

Binds to the 50S ribosomal subunit of susceptible microorganisms, resulting in inhibition of protein synthesis. Active in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative microorganisms, as well as most Mycobacterium avium complex (MAC) microorganisms.

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Pharmacokinetics

Absorption

Bioavailability is approximately 50% (tablets). T _max is 2 to 3 h (tablets), approximately 3 h (oral suspension), and 5 to 8 h (ER tablets). Steady-state C _max is achieved within 2 to 3 days (tablets, oral suspension).

Distribution

Widely distributed into body tissues and fluids; low protein binding.

Metabolism

Metabolized to 14-OH clarithromycin (active).

Elimination

The half-life is approximately 3 to 4 h (250 mg) and 5 to 7 h (500 mg). 20% to 40% is excreted in urine as unchanged drug; 10% to 15% is excreted as 14-OH clarithromycin.

Special Populations

Renal Function Impairment

The pharmacokinetics of clarithromycin were altered in subjects with impaired renal function. Dosage adjustment is required for CrCl less than 30 mL/min.

Hepatic Function Impairment

The 14-OH clarithromycin concentrations were lower in subjects with hepatic impairment but may be partially offset by an increase in renal Cl of clarithromycin.

Elderly

The C _max and AUC of clarithromycin and 14-OH clarithromycin were increased in elderly patients because of age-related decreases in renal function.

Children

Dosages of 7.5 mg/kg every 12 h produced steady-state C _max of 3 to 7 mcg/mL for clarithromycin and 1 to 2 mcg/mL for 14-OH clarithromycin. In HIV-infected children taking 15 mg/kg every 12 h, steady-state clarithromycin C _max generally ranged from 6 to 15 mcg/mL. Clarithromycin penetrates into the middle ear fluid of children with secretory otitis media.

Indications and Usage

Adults Immediate-release tablets and oral suspension

Treatment of pharyngitis/tonsillitis; acute maxillary sinusitis; acute bacterial exacerbation of chronic bronchitis; community-acquired pneumonia; uncomplicated skin and skin structure infections; Helicobacter pylori and duodenal ulcer disease when used in combination with amoxicillin and lansoprazole or omeprazole; H. pylori and active duodenal ulcer when used in combination with omeprazole or ranitidine bismuth citrate; prevention of disseminated MAC disease in patients with advanced HIV infection; treatment of disseminated mycobacterial infections caused by M. avium or Mycobacterium intracellulare .

ER tablets

Treatment of acute maxillary sinusitis; acute bacterial exacerbation of chronic bronchitis; community-acquired pneumonia.

Children Immediate-release tablets and oral suspension

Pharyngitis/tonsillitis; community-acquired pneumonia; acute maxillary sinusitis; acute otitis media; uncomplicated skin and skin structure infections; prevention of disseminated MAC disease in children with advanced HIV infection; treatment of disseminated mycobacterial infections caused by M. avium or M. intercellulare .

Contraindications

Hypersensitivity to clarithromycin, erythromycin, or any macrolide antibiotic; history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin; coadministration with astemizole, cisapride, dihydroergotamine, ergotamine, pimozide, or terfenadine; coadministration with colchicine in patients with renal or hepatic impairment.

Dosage and Administration

Active Duodenal Ulcer Associated With H. pylori Infection
Adults Immediate-release tablets/oral suspension Triple therapy

PO Clarithromycin 500 mg, lansoprazole 30 mg, and amoxicillin 1 g every 12 h for 10 or 14 days; or clarithromycin 500 mg, omeprazole 20 mg, and amoxicillin 1 g every 12 h for 10 days, and, for patients with ulcer present at time of initiation of therapy, omeprazole 20 mg once daily for an additional 18 days.

Dual therapy

PO Clarithromycin 500 mg every 8 h and omeprazole 40 mg every morning for 14 days, then omeprazole 20 mg once daily for an additional 14 days; or clarithromycin 500 mg every 8 or 12 h and ranitidine bismuth citrate 400 mg every 12 h for 14 days, then ranitidine bismuth citrate 400 mg every 12 h for an additional 14 days.

Acute Exacerbation of Chronic Bronchitis
Adults Immediate-release tablets/oral suspension Haemophilus influenzae

PO 500 mg every 12 h for 7 to 14 days.

Haemophilus parainfluenzae

PO 500 mg every 12 h for 7 days.

Moraxella catarrhalis or Streptococcus pneumoniae

PO 250 mg every 12 h for 7 to 14 days.

ER tablets H. influenzae , H. parainfluenzae , M. catarrhalis , or S. pneumoniae

PO Two 500 mg ER tablets every 24 h for 7 days.

Acute Maxillary Sinusitis Caused By H. influenza , M. catarrhalis , or S. pneumoniae
Adults

PO 500 mg (immediate-release tablets/oral suspension) every 12 h or two 500 mg ER tablets every 24 h for 14 days.

Children 6 mo and older Immediate-release tablets/oral suspension

PO 7.5 mg/kg every 12 h for 10 days.

Acute Otitis Media
Children 6 mo and older Immediate-release tablets/oral suspension

PO 7.5 mg/kg every 12 h for 10 days.

Community-Acquired Pneumonia
Adults Immediate-release tablets/oral suspension H. influenzae

PO 250 mg every 12 h for 7 days.

S. pneumoniae , Chlamydophila pneumoniae , or Mycoplasma pneumoniae

PO 250 mg every 12 h for 7 to 14 days.

ER tablets C. pneumoniae , H. influenzae , H. parainfluenzae , M. catarrhalis , M. pneumoniae , or S. pneumoniae

Two 500 mg ER tablets every 24 h for 7 days.

Children 6 mo and older Immediate-release tablets/oral suspension S. pneumoniae , C. pneumoniae , or M. pneumoniae

PO 7.5 mg/kg every 12 h for 10 days.

Mycobacterial Infections

Clarithromycin should be used in combination with other antimycobacterials. Continue therapy for life if clinical and mycobacterial improvements are observed.

Adults Immediate-release tablets/oral suspension

PO 500 mg every 12 h for prevention and treatment.

Children 20 mo and older Immediate-release tablets/oral suspension

PO 7.5 mg/kg (max, 500 mg twice daily) every 12 h for prevention and treatment.

Pharyngitis/Tonsillitis Caused By Streptococcus pyogenes
Adults Immediate-release tablet/oral suspension

PO 250 mg every 12 h for 10 days.

Children 6 months and older Immediate-release tablets/oral suspension

PO 7.5 mg/kg every 12 h for 10 days.

Uncomplicated Skin and Skin Structure Infections Caused By Staphylococcus aureus , S. pyogenes
Adults Immediate-release tablets/oral suspension

PO 250 mg every 12 h for 7 to 14 days.

Children 6 mo and older Immediate-release tablets/oral suspension

PO 7.5 mg/kg every 12 h for 10 days.

Renal Function Impairment
Adults

PO Reduce dose by 50% in patients with severe renal impairment (CrCl less than 30 mL/min).

General Advice

• Administer immediate-release tablets and oral suspension without regard to meals. Administer with food if GI upset occurs.
• Administer ER tablets with food.
• Administer tablets with a full glass of water. The ER tablets should be swallowed whole and not chewed, broken, or crushed.
• Shake suspension well before measuring dose.
• Measure and administer oral suspension using dosing spoon, dosing syringe, or dosing cup.
• Bioavailability of 10 mL of the 125 mg per 5 mL suspension or 10 mL of the 250 mg per 5 mL suspension is similar to a 250 or 500 mg tablet, respectively.

Storage/Stability

Store 250 mg immediate-release tablets, granules for oral suspension, and ER tablets between 59° and 86°F. Protect immediate-release tablets from light. Store 500 mg immediate-release tablets between 68° and 77°F.

Reconstituted suspension

Store between 59° and 86°F. Store tightly closed. Do not refrigerate suspension. Discard any unused suspension after 14 days.

Drug Interactions

Amlodipine

The risk of hypotension may be increased. Monitor BP and adjust the amlodipine dose as needed.

Atazanavir

Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A4. When coadministered, the clarithromycin dose should be decreased by 50%. Do not administer clarithromycin dosages greater than 1,000 mg daily with protease inhibitors. Consider alternative antibacterial therapy for treatment of infections other than MAC.

Benzodiazepines (eg, alprazolam, diazepam, midazolam, triazolam)

Increased and prolonged CNS effects. Use with caution. Monitor for increased CNS effects. Consider benzodiazepine dosage adjustments.

Cabergoline

Cabergoline plasma concentrations may be elevated, increasing the risk of toxicity. If coadministration cannot be avoided, carefully monitor the clinical response of the patient, especially patients with Parkinson disease who have shown levodopa-induced psychosis or dyskinesia.

Carbamazepine

Coadministration may increase plasma concentrations of carbamazepine; monitor carbamazepine levels closely. If coadministration cannot be avoided, closely monitor carbamazepine concentrations. Azithromycin is unlikely to interact.

Cimetidine

The antimicrobial effects of clarithromycin may be decreased. Closely monitor the response to clarithromycin and adjust the clarithromycin dose as needed.

Clopidogrel

The antiplatelet effect of clopidogrel may be inhibited by clarithromycin. Closely monitor platelet function and adjust the clopidogrel dose as needed. Azithromycin may be a safer alternative.

Colchicine

Risk of colchicine toxicity may be increased, especially in elderly patients. Deaths have been reported. If coadministration cannot be avoided, reduce the colchicine dose. Coadministration is contraindicated in patients with renal or hepatic impairment.

Conivaptan, tolvaptan

Because of the increased risk of adverse reactions, clarithromycin is contraindicated in patients receiving conivaptan or tolvaptan.

Darunavir, diltiazem, fluconazole, grapefruit juice

Clarithromycin plasma levels may be elevated, increasing the risk of adverse effects. If coadministration cannot be avoided, use with caution and closely monitor the patient.

Digoxin

Elevated serum digoxin levels may occur, increasing the risk of toxicity. Monitor digoxin concentrations and adjust dose as needed.

Drugs primarily metabolized by CYP3A4 (eg, alfuzosin, benzodiazepines [eg, alprazolam, midazolam, triazolam], bromocriptine, buspirone, carbamazepine, cilostazol, cinacalcet, conivaptan, cyclosporine, dihydroergotamine, disopyramide, docetaxel, dronedarone, efavirenz, eplerenone, ergotamine, erlotinib, eszopiclone, etravirine, everolimus, felodipine, HMG-CoA reductase inhibitors [eg, lovastatin, simvastatin], iloperidone, imatinib, ixabepilone, lapatinib, lurasidone, methylprednisolone, nifedipine, nilotinib, opioid analgesics [eg, alfentanil, fentanyl, oxycodone], pazopanib, phosphodiesterase type 5 inhibitors [eg, sildenafil, tadalafil, vardenafil], proton pump inhibitors [PPIs] [eg, esomeprazole, lansoprazole], quinidine, romidepsin, salmeterol, silodosin, sirolimus, tacrolimus, tamsulosin, temsirolimus, ticagrelor, toremifene, trazodone, verapamil)

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions or toxicity. If concurrent use is not contraindicated in the respective product information, use with caution and monitor patients for adverse reactions. Consider dose reduction or alternative antibacterial treatment.

Drugs that prolong the QT interval (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol], arsenic trioxide, chloroquine, chlorpromazine, cisapride, dolasetron, droperidol, gatifloxacin, halofantrine, haloperidol, lapatinib, levomethadyl, maprotiline, mefloquine, mesoridazine, methadone, moxifloxacin, paliperidone, pazopanib, pentamidine, pimozide, probucol, quinupristin/dalfopristin, sparfloxacin, tacrolimus, tetrabenazine, thioridazine, tricyclic antidepressants [eg, desipramine], vandetanib, ziprasidone)

Prolongation of the QT interval with possible development of cardiac arrhythmias, including torsades de pointes, may occur when clarithromycin is administered with these agents. Caution is advised when 2 agents that are suspected to prolong the QT interval are used concomitantly. If concurrent use is not contraindicated in the respective product information, monitor patients for QT prolongation, especially when adding clarithromycin to a stable regimen of another QT prolonging agent or vice versa.

Eletriptan

Eletriptan plasma concentrations may be elevated, increasing the pharmacologic and toxic effects. Eletriptan should not be taken within 72 h of potent CYP3A4 inhibitors (eg, clarithromycin).

Eplerenone

Plasma concentrations of eplerenone may be elevated, increasing the risk of hyperkalemia and associated serious arrhythmias. Eplerenone is contraindicated in patients receiving clarithromycin.

Ergot derivatives (dihydroergotamine, ergotamine)

Coadministration with clarithromycin is contraindicated. Coadministration of clarithromycin with dihydroergotamine or ergotamine may increase the risk of acute ergotism.

HMG-CoA reductase inhibitors (eg, lovastatin)

Increased risk of myopathy and rhabdomyolysis. Consider use of alternative therapy. Fluvastatin, pravastatin, and rosuvastatin are not metabolized by CYP3A4 and may be less likely to interact.

Itraconazole

Because both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, a bidirectional interaction may occur. Plasma concentrations of clarithromycin and itraconazole may be increased. Closely monitor for signs or symptoms of increased and prolonged adverse reactions.

Maraviroc

Maraviroc concentrations and pharmacologic effects may be increased. Maraviroc dosage adjustment is recommended during coadministration. Concurrent use is contraindicated in patients with severe renal impairment (CrCl less than 30 mL/min).

Muscarinic receptor antagonists. (eg, darifenacin, fesoterodine, solifenacin, tolterodine)

Muscarinic receptor antagonist serum concentrations may be elevated, increasing the pharmacologic effect and risk of adverse reactions. When administered with clarithromycin, the dosage of darifenacin should not exceed 7.5 mg daily; the dosage of fesoterodine should not exceed 4 mg daily; and the dosage of solifenacin should not exceed 5 mg daily. A dosage of tolterodine 1 mg twice daily is recommended in patients deficient in CYP2D6 activity (ie, poor metabolizers).

Nevirapine

Because nevirapine is a CYP3A inducer, clarithromycin plasma concentrations may be reduced, while 14-OH clarithromycin concentrations may be increased. Consider alternative antibacterial treatment.

Omeprazole

Coadministration of clarithromycin and omeprazole may increase the serum concentrations of both drugs. Monitor for signs of an increase in adverse reactions due to PPIs. Adjust treatment as needed.

Quetiapine

Quetiapine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Closely monitor patients when clarithromycin is started or stopped. The quetiapine dose may need to be adjusted.

Ranolazine

Increased ranolazine plasma concentrations with cardiotoxicity may occur. Coadministration is contraindicated.

Repaglinide

Coadministration may increase repaglinide plasma levels, increasing the pharmacologic and adverse effects. Monitor blood glucose levels carefully and adjust the repaglinide dose as needed.

Rifamycins (eg, rifabutin, rifampin, rifapentine)

Antimicrobial effects of clarithromycin may be decreased, while the adverse effect of rifamycins may be increased. Azithromycin may be a safer alternative.

Ritonavir

Concurrent use may increase the clarithromycin AUC and decrease the AUC of the clarithromycin active metabolite. For patients with CrCl of 30 to 60 mL/min, decrease the clarithromycin dose by 50%. For patients with CrCl of less than 30 mL/min, decrease the clarithromycin dose by 75%. Dosages greater than clarithromycin 100 mg daily should not be administered with protease inhibitors.

Saquinavir

Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A. No clarithromycin dosage adjustment is needed when saquinavir is coadministered to patients with normal renal function.

Saxagliptin

Saxagliptin concentrations and pharmacologic effects may be increased. Limit the dosage of saxagliptin to 2.5 mg daily in patients receiving clarithromycin.

Sulfonylureas (eg, glipizide, glyburide)

Hypoglycemic action of sulfonylureas may be increased. Monitor blood glucose and observe patients for signs of hypoglycemia when starting clarithromycin.

Theophylline

May increase theophylline plasma concentrations; monitor theophylline levels.

Vilazodone

Vilazodone concentrations and pharmacologic effects may be increased. The vilazodone dose should be reduced to 20 mg in patients receiving clarithromycin.

Warfarin

The anticoagulant effect may be increased, increasing the risk of hemorrhage. Monitor anticoagulant parameters and adjust the warfarin dose as needed.

Zidovudine

Serum levels may be increased or decreased by clarithromycin. Separate the administration times by at least 2 h.

Adverse Reactions

Cardiovascular

QT prolongation, ventricular arrhythmias including ventricular tachycardia and torsades de pointes (postmarketing).

CNS

Headache (3%); anxiety, behavioral changes, confusional states, convulsions, depersonalization, depression, disorientation, dizziness, hallucinations, insomnia, manic behavior, nightmares, psychosis, tinnitus, tremor, vertigo (postmarketing).

Dermatologic

Diaper rash, rash (3%); Stevens-Johnson syndrome, TEN (postmarketing).

EENT

Alterations in sense of smell, reversible hearing loss (postmarketing).

GI

Diarrhea (15%); nausea (12%); taste perversion, vomiting (8%); abnormal taste (7%); abdominal pain/discomfort (5%); dyspepsia (4%); flatulence (2%); anorexia, glossitis, oral moniliasis, pancreatitis, stomatitis, taste loss, tongue discoloration, tooth discoloration (usually reversible with professional dental cleaning) (postmarketing).

Genitourinary

Interstitial nephritis (postmarketing).

Hematologic-Lymphatic

Leukopenia, neutropenia, thrombocytopenia (postmarketing).

Hepatic

Hepatic dysfunction including increased liver enzymes, hepatocellular and/or cholestatic hepatitis with or without jaundice (postmarketing).

Lab Tests

Decreased WBC, elevated BUN and AST (4%); elevated ALT (3%); elevated PT (1%).

Metabolic-Nutritional

Hypoglycemia (postmarketing).

Miscellaneous

Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis, ER tablets in the stool (many of which have occurred in patients with anatomic or functional GI disorders with shortened GI transit times) (postmarketing).

Precautions

Pregnancy

Category C . Do not use in pregnant women unless there is no appropriate alternative. However, the available human pregnancy experience suggests that the risk (if it exists) is low. Clarithromycin does cross the placenta.

Lactation

Undetermined. However, the risk to a breast-fed infant is probably low based on experience with other antibiotics.

Children

Safety and efficacy in children younger than 6 mo are not established. Safety in treatment of MAC in children younger than 20 mo is not established.

Elderly

Consider dosage adjustments in elderly patients with severe renal impairment.

Renal Function

Use with caution and consider reduced dose or prolonged dosing intervals in patients with severe renal impairment (CrCl less than 30 mL/min). Clarithromycin in combination with ranitidine bismuth citrate (not available in the United States) therapy is not recommended in patients with CrCl less than 25 mL/min.

Hepatic Function

Dosage adjustments are not needed in patients with hepatic function impairment.

Special Risk Patients

Do not use clarithromycin in combination with ranitidine bismuth citrate in patients with a history of acute porphyria. Note: Ranitidine bismuth citrate is no longer marketed in the United States.

Clostridium difficile –associated diarrhea

Consider the possibility in patients in whom diarrhea develops.

Hepatotoxicity

Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis with or without jaundice, has been reported with clarithromycin. This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur.

Myasthenia gravis

Exacerbation of myasthenia gravis symptoms and new onset of symptoms of myasthenic syndrome have been reported.

Overdosage

Symptoms

Abdominal pain, diarrhea, nausea, vomiting.

Patient Information

• Counsel patients or caregivers about the need to take clarithromycin exactly as prescribed and complete the entire course of therapy, even if symptoms of infection have disappeared. Caution patient or caregiver that skipping doses or not completing the full course of therapy may allow the infection to worsen, increase the possibility that the bacteria will become resistant to the antibiotic, and possibly cause infections that will not be treatable in the future.
• Advise patients taking immediate-release tablets or oral suspension that medication can be taken without regard to meals, but to take with food if GI upset occurs.
• Advise patients taking ER tablets to take each dose with food. Caution patient to swallow whole and not to chew, crush, split, or break the tablet.
• Instruct patients to take tablets with a full glass of water.
• Instruct patients or caregivers using oral suspension to shake well before measuring dose and to use dosing spoon, dosing syringe, or dosing cup to measure and administer dose.
• Advise patients that if a dose is missed to take it as soon as remembered; however, if it is nearing the time for the next dose, the dose should be skipped and the next dose taken at the regularly scheduled time.
• Remind patients that clarithromycin is an antibiotic that should only be used to treat bacterial infections and not to treat viral infections.
• Advise patients to discontinue therapy and contact their health care provider immediately if fainting, hives, itching, shortness of breath, skin rash, or palpitations occur.
• Advise patients to report the following signs of superinfection to health care provider: black, “furry” tongue; foul-smelling stools; vaginal itching or discharge; white patches in mouth.
• Warn patients that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and not to treat at home.

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