Drug reference

Clarithromycin

Macrolide · Antibacterials

START

500 mg PO BID × 7-14 days

TYPICAL MAX

1,000 mg/day

STOP IF

QT prolongation · history of cholestatic jaundice · pregnancy

WATCH

QTc · LFTs · CYP3A4 drug interactions

CDSCO approvedSchedule H

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · tissue distribution
PEAK: 2h · Cmax
t½: 5h · plasma t½ (parent)
DURATION: 12h · BID dosing window

EXCRETION

CYP3A4 hepatic + 30% renal

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Category C — avoid first trimester; azithromycin preferred

FDA category + note

Top interactionssee all 12 →

AstemizoleContraindicatedTextbook-citedKDT 7e · p948
CisaprideContraindicatedTextbook-citedKDT 7e · p948
TerfenadineContraindicatedTextbook-citedKDT 7e · p948
CilostazoleContraindicatedTextbookKDT 7e · p555

Mechanism

Clarithromycin binds reversibly to the 23S rRNA component of the bacterial 50S ribosomal subunit, blocking the translocation step of protein synthesis where the elongated peptide is moved from the aminoacyl (A) site to the peptidyl (P) site. This produces primarily bacteriostatic activity against gram-positive cocci, atypical organisms, and H. pylori. Clarithromycin is also a potent inhibitor of cytochrome P450 3A4 (CYP3A4), producing clinically significant drug interactions with substrates such as statins, calcineurin inhibitors, and HIV protease inhibitors.

Indications

Bacterial oral infectionsmycobacterium avium complex infectiondisseminated mycobacterium avium complex prophylaxis in hivdisseminated mycobacterium avium complex treatmentmycobacterium abscessus (in combination)mycobacterium haemophilum (in combination)mycobacterium marinummycobacterium malmoenseH. pylori eradication therapyProphylaxis against Mycobacterium avium complex (MAC) in HIV/AIDS patients with low CD4 countSurgical prophylaxis (for penicillin allergic patients)upper respiratory tract infectionslower respiratory tract infectionssinusitisotitis mediawhooping coughatypical pneumoniaskin infections (due to Strep. pyogenes and some Staph. aureus)skin structure infections (due to Strep. pyogenes and some Staph. aureus)H. pylori eradication (as a component of triple drug regimen)MAC infection in AIDS patients (first line in combination regimens)atypical mycobacterial diseases (second line)leprosy (second line)Treatment of MAC infection in immunocompromized (HIV-AIDS) patientsProphylaxis of MAC infection in HIV-AIDS patientsM. fortuitum infectionM. kansasii infectionM. marinum infectionLeprosy (being included in alternative MDT regimens)

Dosing

Adult: Oral: 250-500 mg BD for 7-14 days. MR: 500 mg OD. IV: 500 mg BD (max 5 days). H. pylori: 500 mg BD for 7 days (triple therapy).
Pediatric: Body weight based: 8-11 kg: 62.5 mg BD. 12-19 kg: 125 mg BD. 20-29 kg: 187.5 mg BD. 30-40 kg: 250 mg BD.
Renal adjustment: Max 1 g daily if CrCl <30 mL/min; halve dose if severe impairment
Hepatic adjustment: Caution in hepatic impairment with renal impairment
Max dose: 500 mg BD oral; 500 mg BD IV

Pharmacokinetics

Half-life

3–6 hours at lower doses to 6–9 hours at higher doses

Bioavailability

55 ± 8%

Protein binding

42–50%

Metabolism

Clarithromycin is an inhibitor of CYP3A4/5.

Excretion

36 ± 7%

Contraindications

QT prolongation
History of ventricular arrhythmias including torsades de pointes
Concurrent use with ergot alkaloids

Side effects

Common

Taste disturbanceNauseaVomitingAbdominal painDiarrhoeaHeadachegastric intoleranceDiarrhea

Serious

QT prolongation
Torsades de pointes
Hepatotoxicity
Stevens-Johnson syndrome
C. difficile colitis
reversible hearing loss (high doses)
pseudomembranous enterocolitis
hepatic dysfunction
rhabdomyolysis
QTc interval prolongation
Exacerbation of myasthenia gravis
Tinnitus and reversible deafness (especially in elderly)

Pregnancy & lactation

Pregnancy

Category C — avoid first trimester; azithromycin preferred

Drug interactions

Astemizole

Contraindicated

Textbook-cited

Dangerous ventricular arrhythmia (QT prolongation, torsades de pointes)

Concurrent use is contraindicated

Source: KDT 7e · p948

Cisapride

Contraindicated

Textbook-cited

QT prolongation and ventricular arrhythmia

Concurrent use is contraindicated

Source: KDT 7e · p948

Terfenadine

Contraindicated

Textbook-cited

Dangerous ventricular arrhythmia (QT prolongation, torsades de pointes)

Concurrent use is contraindicated

Source: KDT 7e · p948

Cilostazole

Contraindicated

Textbook

Increased plasma levels and toxicity of cilostazole.

Should not be administered along with inhibitors of CYP3A4.

Source: KDT 7e · p555

Colchicine

Contraindicated

Database

Life-threatening toxicities of colchicine.

The drug is contraindicated in patients with hepatic or renal impairment requiring concomitant therapy with CYP3A4 inhibitors.

Source: DDInter

Domperidone

Contraindicated

Database

Increased domperidone plasma levels, leading to increased risk of QT prolongation and Torsades de Pointes (TdP)

Concomitant use is contraindicated. Avoid co-administration.

Ergotamine

Contraindicated

Database

Ergotism: severe peripheral vasospasm, ischemia of extremities, gangrene

Absolutely contraindicated. Use alternative antibiotic or alternative migraine therapy

Source: DDInter

Pimozide

Contraindicated

Database

Cardiac arrhythmias may occur.

Never combine.

Source: DDInter

Silodosin

Contraindicated

Database

Significantly increased plasma concentrations of silodosin, leading to an increased risk of orthostatic hypotension and other dose-dependent adverse effects.

Concomitant use is contraindicated. An alternative alpha-blocker or antibiotic should be considered.

Source: DDInter

Atorvastatin

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Carbamazepine

Severe

Textbook-cited

Carbamazepine toxicity (diplopia, ataxia, drowsiness).