Schedule H

Oral, Intravenous (limited availability)

• Immediate-release tablets: 250 mg, 500 mg

• Modified-release (MR/XL) tablets: 500 mg

• Oral suspension (powder for reconstitution): 125 mg/5 mL, 250 mg/5 mL

• Injection (lyophilised powder for reconstitution): 500 mg/vial (limited availability in tertiary care settings)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Helicobacter pylori Eradication (Triple Therapy)

Used as part of combination regimen with a proton pump inhibitor and amoxicillin or metronidazole.

Standard Triple Therapy Regimen:

Component Dose Frequency

Clarithromycin 500 mg Twice daily

Amoxicillin 1 g Twice daily

PPI (omeprazole/pantoprazole/esomeprazole) Standard dose Twice daily

OR (in penicillin allergy):

Component Dose Frequency

Clarithromycin 500 mg Twice daily

Metronidazole 400–500 mg Twice daily

PPI Standard dose Twice daily

Parameter Recommendation

Starting dose 500 mg twice daily

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily (1 g/day total)

Duration: 14 days (preferred); 10 days minimum

Clinical Notes:

• Avoid clarithromycin-based regimen if prior treatment failure with clarithromycin

• Bismuth quadruple therapy or levofloxacin-based regimen preferred for rescue therapy

• Take with meals to improve tolerability

1. Community-Acquired Pneumonia (CAP)

Used for mild-moderate CAP, especially when atypical pathogens (Mycoplasma, Chlamydophila, Legionella) suspected, or in beta-lactam allergy.

Parameter Recommendation

Starting dose 500 mg twice daily orally

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily (1 g/day)

Duration: 7–10 days (may extend to 14 days for Legionella)

IV Dosing (severe CAP, unable to take oral):

• 500 mg IV twice daily; switch to oral when stable

Clinical Notes:

• Covers atypical pathogens effectively

• Not first-line for typical bacterial pneumonia; consider beta-lactam combinations

• Modified-release formulation (500 mg once daily) may be used for mild CAP

1. Acute Exacerbation of Chronic Bronchitis (AECB)

Parameter Recommendation

Starting dose 250–500 mg twice daily orally

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily

Duration: 7–10 days

Clinical Notes:

• Reserve for patients with purulent sputum and increased dyspnoea

• Consider local resistance patterns

1. Acute Bacterial Sinusitis

Parameter Recommendation

Starting dose 500 mg twice daily orally

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily

Duration: 10–14 days

Clinical Notes:

• Second-line option; amoxicillin-clavulanate preferred first-line

• Use in beta-lactam allergy or treatment failure

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Respiratory Tract Infections (Pharyngitis, Otitis Media, Sinusitis, Pneumonia)

Weight-based Dosing (using oral suspension):

Parameter Recommendation

Starting dose 7.5 mg/kg twice daily

Titration Not applicable

Usual maintenance dose 7.5 mg/kg twice daily

Maximum dose 500 mg twice daily (1 g/day total)

Fixed Dose by Weight (practical dosing):

Body Weight Dose per Administration Frequency Formulation

8–11 kg 62.5 mg (2.5 mL of 125 mg/5 mL) Twice daily Suspension

12–19 kg 125 mg (5 mL of 125 mg/5 mL OR 2.5 mL of 250 mg/5 mL) Twice daily Suspension

20–29 kg 187.5 mg (3.75 mL of 250 mg/5 mL) Twice daily Suspension

30–40 kg 250 mg (5 mL of 250 mg/5 mL) Twice daily Suspension or tablet

40 kg 250–500 mg Twice daily Tablet

Duration: 5–10 days depending on indication

1. Helicobacter pylori Eradication (Triple Therapy)

Age ≥6 years:

Parameter Recommendation

Starting dose 7.5 mg/kg twice daily (max 500 mg per dose)

Titration Not applicable

Usual maintenance dose 7.5 mg/kg twice daily

Maximum dose 500 mg twice daily

Duration: 14 days

Combination: With amoxicillin 25 mg/kg twice daily (max 1 g) + PPI

Clinical Notes:

• Paediatric gastroenterologist supervision recommended

• Ensure adequate compliance for full 14-day course

1. Mycobacterium avium Complex (MAC) — in Paediatric HIV

Age ≥6 months:

Parameter Recommendation

Starting dose 7.5 mg/kg twice daily

Titration May increase to 15 mg/kg twice daily (max 500 mg per dose) if tolerated

Usual maintenance dose 7.5–15 mg/kg twice daily

Maximum dose 500 mg twice daily

Duration: Long-term; per paediatric HIV specialist guidance

Clinical Notes:

• Always use in combination with ethambutol ± rifabutin

• Specialist use only

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Pertussis ≥1 month 7.5 mg/kg twice daily (max 500 mg per dose); Duration: 7 days OFF-LABEL — Azithromycin preferred in young infants. Based on IAP/ICMR guidelines.

Atypical Mycobacterial Skin Infections ≥6 months 7.5 mg/kg twice daily (max 500 mg per dose) OFF-LABEL — Specialist only. Long-term combination therapy required.

Minimum Age Statement: Not recommended in infants below 6 months of age except under specialist supervision for specific indications (e.g., pertussis). Oral suspension required for accurate dosing in young children.

Safety Monitoring:

• GI tolerability (nausea, diarrhoea, abdominal pain)

• Taste disturbance (metallic taste — common)

• Monitor for signs of hepatotoxicity in prolonged use

• ECG if risk factors for QT prolongation

30 No dose adjustment required

≤30 Reduce dose by 50% (e.g., 250 mg twice daily instead of 500 mg twice daily) OR give standard dose once daily; limit duration to 14 days if possible

Haemodialysis Administer dose after dialysis session; use reduced dose regimen

Peritoneal dialysis Use reduced dose; limited data

Note: Clarithromycin is extensively hepatically metabolised. History of cholestatic jaundice or hepatitis with prior clarithromycin use is a contraindication to rechallenge.

• Known hypersensitivity to clarithromycin, erythromycin, or any macrolide antibiotic

• History of cholestatic jaundice or hepatic dysfunction associated with prior clarithromycin use

• Concurrent use with drugs highly dependent on CYP3A4 for metabolism and associated with serious toxicity:

• Cisapride, pimozide, terfenadine, astemizole (risk of QT prolongation, torsades de pointes)

• Ergot alkaloids (ergotamine, dihydroergotamine) — risk of ergotism

• Oral midazolam (risk of prolonged sedation)

• Simvastatin, lovastatin (risk of rhabdomyolysis)

• Colchicine in patients with renal or hepatic impairment

• Lomitapide

• Concurrent use with ticagrelor (major interaction)

• Patients with known QT prolongation or ventricular arrhythmias including torsades de pointes

• Concurrent use with drugs known to cause QT prolongation and metabolised by CYP3A4

• Pre-existing cardiac disease — QT prolongation risk; obtain baseline ECG in high-risk patients

• Electrolyte disturbances (hypokalaemia, hypomagnesaemia) — correct before initiating; increases arrhythmia risk

• Renal impairment — dose reduction required; increased toxicity risk

• Hepatic impairment — use with caution; monitor LFTs

• Myasthenia gravis — may exacerbate weakness; use with caution

• Elderly patients — increased susceptibility to QT prolongation and drug interactions

• Concurrent use with other CYP3A4 substrates/inhibitors — multiple significant interactions

• Concurrent statin therapy (atorvastatin, rosuvastatin) — reduce statin dose and monitor for myopathy; simvastatin/lovastatin contraindicated

• History of ventricular arrhythmia — avoid or use with ECG monitoring

• Concurrent warfarin therapy — enhanced anticoagulation; INR monitoring required

• Diabetes mellitus on oral hypoglycaemics — risk of hypoglycaemia

• Long-term use (>14 days) — monitor for superinfection and hepatotoxicity

Parameter Recommendation

Safety Category Limited human data; animal studies show some developmental toxicity; generally avoided especially in first trimester

Preferred Alternatives Azithromycin (preferred macrolide in pregnancy); erythromycin (except estolate form); amoxicillin for susceptible infections

When to Use Only if clearly needed and no safer alternative available; requires risk-benefit discussion; specialist input recommended

Monitoring Standard fetal monitoring; no specific teratogenic monitoring established

Parameter Recommendation

Breastfeeding Compatibility Compatible with breastfeeding; low levels excreted in breast milk

Drug Levels in Milk Low (relative infant dose <2%)

Preferred Alternatives Azithromycin if short course needed; erythromycin

Infant Monitoring Monitor for GI disturbance (diarrhoea, vomiting), feeding intolerance, oral candidiasis

Parameter Recommendation

Starting dose 250 mg twice daily (consider lower starting dose due to age-related renal decline)

Titration Increase to 500 mg twice daily if needed and tolerated

Maximum dose 500 mg twice daily; duration ≤14 days preferred

Additional Risks Increased QT prolongation risk; higher risk of drug interactions due to polypharmacy; age-related renal impairment requiring dose adjustment; increased falls risk if on multiple sedating medications; greater susceptibility to hepatotoxicity and C. difficile colitis

Monitoring Baseline and periodic ECG if cardiac risk factors; renal function assessment; monitor for confusion or delirium

Interacting Drug Mechanism/Effect Management

Simvastatin, lovastatin Strong CYP3A4 inhibition by clarithromycin; massively increased statin levels; high risk of rhabdomyolysis Contraindicated — avoid concurrent use; withhold statin during clarithromycin course

Atorvastatin, rosuvastatin CYP3A4 inhibition (atorvastatin); increased statin levels Reduce statin dose to lowest available; monitor for myopathy; maximum atorvastatin 20 mg/day

Colchicine CYP3A4 and P-gp inhibition; markedly increased colchicine levels; risk of fatal colchicine toxicity Avoid in renal/hepatic impairment (contraindicated); in normal organ function, reduce colchicine dose significantly and limit duration

Ergot alkaloids (ergotamine, dihydroergotamine) CYP3A4 inhibition; increased ergot levels; risk of acute ergotism (vasospasm, gangrene) Contraindicated — avoid concurrent use

Cisapride, pimozide, terfenadine, astemizole CYP3A4 inhibition + additive QT prolongation; risk of torsades de pointes Contraindicated — avoid concurrent use

Warfarin Enhanced anticoagulant effect via CYP inhibition and possible antibiotic effect on gut flora producing vitamin K Monitor INR closely (every 2–3 days initially); adjust warfarin dose as needed

Digoxin P-glycoprotein inhibition; increased digoxin absorption and reduced clearance; risk of digoxin toxicity Monitor digoxin levels and clinical signs of toxicity (bradycardia, nausea, visual disturbances); reduce digoxin dose if needed

Carbamazepine CYP3A4 inhibition; increased carbamazepine levels; risk of toxicity (ataxia, nystagmus, drowsiness) Monitor carbamazepine levels; reduce carbamazepine dose if toxicity signs appear

Ticagrelor CYP3A4 inhibition; significantly increased ticagrelor levels; bleeding risk Avoid concurrent use if possible

Oral midazolam CYP3A4 inhibition; prolonged sedation Contraindicated with oral midazolam; use with caution with IV midazolam (reduce dose)

Cyclosporine, tacrolimus CYP3A4 inhibition; increased immunosuppressant levels; nephrotoxicity risk Monitor drug levels closely; reduce immunosuppressant dose; monitor renal function

Interacting Drug Effect Management

Rifampicin, rifabutin Strong CYP3A4 induction; significantly reduced clarithromycin levels; treatment failure risk Avoid rifampicin with clarithromycin if possible; rifabutin reduces levels less; monitor efficacy; consider alternative macrolide or different antibiotic class

Theophylline CYP3A4 inhibition; increased theophylline levels; toxicity risk Monitor theophylline levels; reduce dose if needed

Oral hypoglycaemics (sulfonylureas, repaglinide) Enhanced hypoglycaemic effect Monitor blood glucose closely; adjust hypoglycaemic dose if needed

Calcium channel blockers (verapamil, diltiazem, amlodipine) CYP3A4 inhibition; increased CCB levels; hypotension and bradycardia risk Monitor blood pressure and heart rate; reduce CCB dose if needed

Phenytoin, valproate Altered antiepileptic levels (variable; may increase or decrease) Monitor antiepileptic levels and clinical response

Sildenafil, tadalafil CYP3A4 inhibition; increased PDE5 inhibitor levels Reduce sildenafil dose (max 25 mg/48 hours); avoid high tadalafil doses

Omeprazole, other PPIs Mutual increase in plasma levels (both CYP2C19/3A4 substrates); generally beneficial for H. pylori eradication Usually not clinically significant; combination used therapeutically

Benzodiazepines (alprazolam, triazolam) CYP3A4 inhibition; increased sedation Reduce benzodiazepine dose; avoid triazolam if possible

Quetiapine CYP3A4 inhibition; increased quetiapine levels Reduce quetiapine dose; monitor for sedation and other adverse effects

• Diarrhoea

• Nausea

• Vomiting

• Abdominal pain, dyspepsia

• Taste disturbance (metallic or bitter taste — very common)

• Headache

• Insomnia

• Rash

• Abnormal liver function tests (transient elevations)

Adverse Effect Clinical Significance

QT prolongation and torsades de pointes Risk increased with concurrent QT-prolonging drugs, electrolyte abnormalities, cardiac disease; obtain ECG if risk factors present

Hepatotoxicity Cholestatic hepatitis, hepatocellular injury, mixed pattern; may occur during or weeks after treatment; discontinue if jaundice or significant LFT elevation

Clostridioides difficile-associated diarrhoea (CDAD) May range from mild diarrhoea to fatal colitis; can occur during or weeks after treatment; discontinue if significant diarrhoea

Severe hypersensitivity reactions Anaphylaxis, angioedema, Stevens-Johnson syndrome/TEN, DRESS syndrome; discontinue immediately

Rhabdomyolysis Especially with concurrent statin use (simvastatin, lovastatin); presents with muscle pain, weakness, dark urine

Acute kidney injury May occur with concurrent nephrotoxic drugs or in renal impairment

Ototoxicity Hearing loss (usually reversible); reported with high doses or prolonged therapy

Exacerbation of myasthenia gravis May worsen muscle weakness

Hypoglycaemia Especially with concurrent oral hypoglycaemic agents

Baseline:

• Liver function tests (ALT, AST, bilirubin) — especially if hepatic impairment or prolonged therapy planned

• Renal function (serum creatinine, eGFR) — for dose adjustment

• ECG — if cardiac risk factors, concurrent QT-prolonging drugs, or electrolyte abnormalities

• Electrolytes (potassium, magnesium) — if arrhythmia risk

After Initiation/During Therapy:

• INR monitoring (every 2–3 days) if on warfarin

• Blood glucose in diabetics

• Clinical assessment for GI adverse effects

• LFTs at day 7–10 if therapy extended beyond 7 days

• Monitor for signs of hepatotoxicity (jaundice, fatigue, abdominal pain)

Long-term (MAC therapy):

• Monthly LFTs initially, then every 3 months

• Periodic hearing assessment

• Monitor for drug interactions with ART medications

• Claribid® (Abbott)

• Klaricid® (Abbott)

• Clariwin® (Alkem)

• Clarithro® (Cipla)

• Synclar® (Alkem)

• Klarimac® (Macleods)

• Clarimac® (Macleods)

• Biomycin® (Biochem)

• Claritop® (Torrent)

Fixed-Dose Combinations (H. pylori triple therapy kits):

• HP Kit® (clarithromycin + amoxicillin + PPI)

• Pylori Kit® (various manufacturers)

• Helicure® Kit

Note: Many brands available. FDC kits improve compliance for H. pylori eradication.

• Not included as single agent in NLEM 2022; included in some state essential drug lists

• FDC kits may be under NPPA control

• Significant price variation between brands

• H. pylori first-line use: Clarithromycin-based triple therapy is first-line for H. pylori eradication; ensure 14-day duration for optimal efficacy; avoid if prior clarithromycin exposure due to resistance concerns

• Statin interaction critical: Simvastatin and lovastatin are contraindicated; for patients on atorvastatin, either hold statin during antibiotic course or reduce to lowest dose with myopathy monitoring

• Taste disturbance counselling: Metallic taste is very common and may affect compliance; counsel patients that it is temporary and resolves after treatment completion

• QT prolongation awareness: Obtain baseline ECG in elderly, cardiac patients, or those on multiple medications; avoid concurrent QT-prolonging drugs when possible

• Modified-release formulation: 500 mg MR once daily may be used for respiratory infections to improve compliance; not appropriate for H. pylori eradication (requires twice-daily dosing)

• Macrolide choice in pregnancy/lactation: Azithromycin is preferred over clarithromycin during pregnancy; both are compatible with breastfeeding

clarithromycin; macrolide; antibiotic; H. pylori; CAP; respiratory infection; QT-prolongation; statin-interaction; CYP3A4-inhibitor; paediatric-use; breastfeeding-compatible

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• NLEM 2022 (for FDC reference)

• API Textbook of Medicine

• ICMR Guidelines for H. pylori Management

• AIIMS Antibiotic Policy

• IAP Guidelines for Antibiotic Use in Children

• Indian Association of Gastroenterology Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine