Professional Information

Clarithromycin

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

Trade Names:
Biaxin
- Tablets 250 mg
- Tablets 500 mg
- Granules for oral suspension 125 mg per 5 mL after reconstitution
- Granules for oral suspension 250 mg per 5 mL after reconstitution

Trade Names:
Biaxin XL
- Tablets, ER 500 mg

Apo-Clarithromycin (Canada)
Biaxin BID (Canada)

Pharmacology

Binds to the 50S ribosomal subunit of susceptible microorganisms, resulting in inhibition of protein synthesis.

Pharmacokinetics

Absorption

Rapidly absorbed. Bioavailability is about 50%. T _max is 2 to 3 h. Steady state achieved within 3 days.

Distribution

Widely distributed into body tissues and fluids.

Metabolism

Metabolized to 14-OH clarithromycin (active).

Elimination

The half-life is about 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.

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; disseminated mycobacterial 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 Mycobacterium avium complex (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 M. avium or M. intercellulare .

Contraindications

Patients receiving astemizole, cisapride, dihydroergotamine, ergotamine, pimozide, or terfenadine; hypersensitivity to clarithromycin, erythromycin, or any macrolide antibiotic.

Dosage and Administration

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

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 then, for patients with ulcer present at time of initiation of therapy, omeprazole 20 mg once daily for additional 18 days; or clarithromycin 500 mg every 8 h and omeprazole 40 mg every day for 14 days then omeprazole 20 mg once daily for additional 14 days; or clarithromycin 500 mg every 12 or every 8 h and ranitidine bismuth citrate 400 mg every 12 h for 14 days, then ranitidine bismuth citrate 400 mg every 12 h for additional 14 days.

Acute Exacerbation of Chronic Bronchitis Caused By Haemophilus influenza , H. parainfluenza , Moraxella catarrhalis , or Streptococcus pneumoniae
Adults Immediate-release tablets/oral suspension H. influenza

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

H. parainfluenza

PO 500 mg every 12 h for 7 days.

M. catarrhalis or S. pneumoniae

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

Adults

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

Acute Maxillary Sinusitis Caused By H. influenza
Adults Immediate-release tablet/oral suspension

PO 500 mg every 12 h or two 500 mg ER tablets every 24 h for 14 days.

Children 6 mo of age and older

PO 7.5 mg/kg (max, 500 mg) every 12 h for 10 days.

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

PO 7.5 mg/kg (max, 500 mg) every 12 h for 10 days.

Community-Acquired Pneumonia Caused By H. influenza , S. pneumoniae , C. pneumoniae , or M. pneumoniae
Adults Immediate-release tablets/oral suspension H. influenza

PO 250 mg every 12 h for 7 days.

S. pneumoniae , C. pneumoniae , or M. pneumoniae

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

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

PO 7.5 mg/kg (max, 500 mg) every 12 h for 10 days.

Community-Acquired Pneumonia Caused By C. pneumoniae , H. influenzae , H. parainfluenzae , M. catarrhalis , M. pneumoniae , or S. pneumoniae
Adults

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

Mycobacterial Infections
Adults Immediate-release tablets/oral suspension

PO 500 mg every 12 h for prevention and treatment.

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

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

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

PO 250 mg every 12 h for 10 days.

Children 6 months of age and older

PO 7.5 mg/kg (max, 500 mg) every 12 h for 10 days.

Uncomplicated Skin and Skin Structure Infections
Adults Immediate-release tablets/oral suspension

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

Children 6 mo of age and older

PO 7.5 mg/kg (max, 500 mg) every 12 h for 10 days.

Renal Function Impairment
Adults

PO Halve the dose or double the dosing interval in patients with severe renal function 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.
Shake suspension well before measuring dose.
Measure and administer oral suspension using dosing spoon, dosing syringe, or dosing cup.

Storage/Stability

Store 250 mg immediate-release tablets and ER tablets at controlled room temperature (59° to 86°F). Protect from light. Store 500 mg immediate-release tablets at controlled room temperature (68° to 77°F). Store granules for oral suspension at 59° to 86°F. Do not refrigerate.

Reconstituted suspension

Store at controlled room temperature (59° to 86°F). Keep tightly closed. Do not refrigerate suspension. Discard any unused suspension after 14 days.

Drug Interactions

Antiarrhythmic agents (eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol), quinolone antibiotics (ie, gatifloxacin, levofloxacin, moxifloxacin)

Risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased.

Astemizole, cisapride, dihydroergotamine, ergotamine, pimozide, terfenadine

Coadministration with clarithromycin is contraindicated. Coadministration of clarithromycin with astemizole, cisapride, pimozide, or terfenadine may increase the risk of life-threatening cardiac arrhythmias, including torsades de pointes. Coadministration of clarithromycin with dihydroergotamine or ergotamine may increase the risk of acute ergotism.

Benzodiazepines (eg, midazolam, triazolam)

Increased and prolonged CNS effects.

Cabergoline

Cabergoline plasma concentrations may be elevated, increasing the risk of toxicity.

Carbamazepine

May increase plasma concentrations of carbamazepine; monitor carbamazepine levels closely.

Colchicine

Risk of colchicine toxicity may be increased, especially in elderly patients.

Conivaptan

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

Darunavir, fluconazole, grapefruit juice, ritonavir

Clarithromycin plasma levels may be elevated, increasing the risk of side effects.

Digoxin

Elevated serum digoxin levels may occur.

Drugs primarily metabolized by CYP3A4 (eg, alfentanil, benzodiazepines [eg, midazolam], bromocriptine, buspirone, carbamazepine, cilostazol, conivaptan, cyclosporine, dihydroergotamine, disopyramide, eplerenone, ergotamine, HMG-CoA reductase inhibitors [eg, lovastatin, simvastatin], lapatinib, methylprednisolone, proton pump inhibitors [eg, esomeprazole, lansoprazole, omeprazole] quinidine, repaglinide, sildenafil, tacrolimus, temsirolimus, terfenadine, triazolobenziodidiazepines [eg, alprazolam, triazolam])

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions or toxicity.

Eplerenone

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

HMG-CoA reductase inhibitors (eg, lovastatin)

Increased risk of myopathy and rhabdomyolysis.

Ranitidine bismuth citrate

Clarithromycin may increase plasma concentrations of ranitidine bismuth citrate.

Rifamycins (eg, rifabutin)

Antimicrobial effects of clarithromycin may be decreased, while adverse effect of rifamycins may be increased.

Serotonin reuptake inhibitors (eg, fluoxetine, sertraline)

Risk of serotonin syndrome may be increased.

Theophylline

May increase theophylline plasma concentration; monitor theophylline levels.

Verapamil

Risk of cardiotoxicity may be increased.

Warfarin

The anticoagulant effect may be increased, increasing the risk of hemorrhage.

Zidovudine

Serum levels may be increased or decreased by clarithromycin.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

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

CNS

Headache (2%); anxiety, behavioral changes, confusional states, convulsions, depersonalization, disorientation, dizziness, hallucinations, insomnia, manic behavior, nightmares, psychosis, tinnitus, tremor, vertigo (postmarketing).

Dermatologic

Rash (3%); Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).

EENT

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

GI

Abnormal taste (7%); diarrhea, vomiting (6%); abdominal pain/discomfort, nausea (3%); dyspepsia, flatulence (2%); anorexia, glossitis, oral moniliasis, pancreatitis, stomatitis, taste perversion or loss, tongue discoloration, tooth discoloration (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

Elevated alkaline phosphatase, ALT, AST, BUN, gamma-glutamyltransferase, LDH, serum creatinine, and total bilirubin; elevated PT and lactate dehydrogenase; decreased WBC (postmarketing).

Metabolic-Nutritional

Hypoglycemia (postmarketing).

Miscellaneous

Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis (postmarketing).

Precautions

Monitor

Monitor patient's response to therapy. Monitor patient for GI, DERM, and general body side effects, and signs of superinfection. Advise patient to immediately report severe diarrhea, diarrhea containing blood or pus, or severe abdominal cramping.

Pregnancy

Category C . Do not use in pregnant women unless there is no appropriate alternative.

Lactation

Undetermined.

Children

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

Elderly

Consider dosage adjustments in elderly patients with severe renal function impairment.

Renal Function

Use with caution and consider reduced dose or prolonged dosing intervals in patients with severe renal function impairment. Clarithromycin in combination with ranitidine bismuth citrate 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.

Pseudomembranous colitis

Consider possibility in patients in whom diarrhea develops.

Overdosage

Symptoms

Abdominal pain, diarrhea, nausea, vomiting.

Patient Information

Advise patient to review the patient information leaflet carefully before starting therapy and to read and check for new information each time the medication is refilled.
Review dosing schedule and prescribed length of therapy with patient.
Reinforce to patient or caregiver the need to take 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 and increase the possibility that the bacteria will become resistant to the antibiotic and may cause infections that will not be treatable in the future.
Advise patient 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 patient 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 patient to take tablets with a full glass of water.
Instruct patient or caregiver 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 patient that if a dose is missed to take as soon as remembered; however, if it is nearing the time for the next dose to skip the dose and take the next dose at the regularly scheduled time.
Advise patient to discontinue therapy and contact health care provider immediately if fainting, hives, itching, shortness of breath, skin rash, or palpitations occur.
Advise patient 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 patient 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.