Schedule H

Oral

• Tablets: Amoxicillin 250 mg + Metronidazole 200 mg

• Tablets: Amoxicillin 500 mg + Metronidazole 400 mg

• Fixed-dose injectable combination: NOT AVAILABLE in India (IV forms available separately)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Acute Dental Infections (Periapical Abscess, Acute Periodontitis, Dentoalveolar Abscess) — Adults

Parameter Recommendation

Starting dose Amoxicillin 500 mg + Metronidazole 400 mg orally every 8 hours

Titration Not applicable

Usual maintenance dose Same as starting dose

Maximum dose Amoxicillin 500 mg + Metronidazole 400 mg every 8 hours

Duration 5–7 days

Clinical note Synergistic coverage against oral aerobes (Streptococci) and anaerobes (Bacteroides, Fusobacterium); adjunct to dental drainage procedures

1. Periodontal Infections (Chronic Periodontitis, Aggressive Periodontitis, Necrotizing Ulcerative Gingivitis) — Adults

Parameter Recommendation

Starting dose Amoxicillin 500 mg + Metronidazole 400 mg orally every 8 hours

Titration Not applicable

Usual maintenance dose Same as starting dose

Maximum dose Amoxicillin 500 mg + Metronidazole 400 mg every 8 hours

Duration 7–10 days

Clinical note Must be used as adjunct to mechanical debridement/scaling; dental referral essential; not for prophylaxis

1. Mixed Aerobic-Anaerobic Infections (Oral Step-down Therapy) — Adults

Post-surgical wounds, intra-abdominal infections, gynaecological infections — when transitioning from IV antibiotics

Parameter Recommendation

Starting dose Amoxicillin 500 mg + Metronidazole 400 mg orally every 8 hours

Titration Not applicable

Usual maintenance dose Same as starting dose

Maximum dose Amoxicillin 500 mg + Metronidazole 400 mg every 8 hours

Duration 7–10 days total (including IV phase); guided by clinical response and culture sensitivity

Clinical note Suitable for step-down after IV amoxicillin/ampicillin + metronidazole; confirm organism sensitivity before switch

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Helicobacter pylori eradication (Triple therapy component) Amoxicillin 1000 mg + Metronidazole 500 mg BD (with PPI) 14 days OFF-LABEL; Specialist only. Used in metronidazole-based regimens where clarithromycin resistance is prevalent. Evidence: Indian gastroenterology specialist practice; ICMR guidelines acknowledge metronidazole-based alternatives

PAEDIATRIC DOSING (Specialist Only)

Primary Indications: Dental and Orofacial Infections

⚠️ Fixed-dose tablets NOT recommended for children <6 years or <20 kg — use individual components in suspension form

Weight/Age Dose (Amoxicillin + Metronidazole) Frequency Duration

<20 kg (typically <6 years) Use separate components only: Amoxicillin 25–50 mg/kg/day + Metronidazole 20–30 mg/kg/day in divided doses Every 8 hours 5–7 days

20–30 kg (6–10 years approx.) 250 mg + 200 mg tablet Every 8 hours 5–7 days

30 kg (>10 years approx.) 500 mg + 400 mg tablet Every 8 hours 5–7 days

Safety Monitoring:

• GI tolerance (nausea, vomiting, diarrhoea)

• Signs of allergic reaction (rash, urticaria)

• Oral thrush with prolonged use

Minimum age for FDC tablets: 6 years (or weight ≥20 kg)

Secondary Indications — Paediatrics (Off-label)

Not routinely indicated in paediatric population. For any off-label use (e.g., H. pylori in children), individual agents with weight-based dosing must be used separately under paediatric gastroenterologist supervision.

30 No dose adjustment required

10–30 Extend dosing interval to every 12 hours; monitor for accumulation

<10 Extend interval to every 24 hours; avoid fixed-combination; use individual agents with careful adjustment

Haemodialysis Administer after dialysis session; supplemental dose may be required (both components are partially dialysable)

Peritoneal dialysis No specific data; use with caution at reduced frequency

• Known hypersensitivity to penicillins, cephalosporins (cross-reactivity), or nitroimidazoles

• History of immediate/severe allergic reaction (anaphylaxis, angioedema) to β-lactams

• Concurrent disulfiram therapy

• Active alcohol consumption (during therapy and 48 hours post-completion)

• Severe hepatic impairment (for fixed-dose combination)

• History of blood dyscrasias with metronidazole

• History of seizures or CNS disorders (metronidazole lowers seizure threshold)

• Mild-moderate renal impairment (dose adjustment required)

• Mild-moderate hepatic dysfunction

• Chronic alcohol use disorder (high interaction risk)

• History of antibiotic-associated colitis or C. difficile infection

• Infectious mononucleosis (amoxicillin may cause maculopapular rash)

• Prolonged therapy beyond 10 days (increased peripheral neuropathy risk with metronidazole)

• Patients on oral anticoagulants

Aspect Recommendation

Overall safety Generally considered safe; both components have favourable safety profiles in pregnancy

Amoxicillin Safe throughout pregnancy; extensive use data

Metronidazole Avoid high doses in first trimester if possible; short courses acceptable when clinically indicated

Preferred alternatives Amoxicillin alone (if anaerobic coverage not essential); Penicillin V for streptococcal infections

When to use May be used when mixed aerobic-anaerobic infection confirmed or strongly suspected; benefit must outweigh theoretical risk

Monitoring Standard antenatal monitoring; no specific fetal surveillance required for short courses

Aspect Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Both agents excreted in low concentrations

Preferred alternatives Amoxicillin alone if anaerobic coverage not essential; Clindamycin if metronidazole not tolerated

Infant monitoring GI disturbance (loose stools, diarrhoea), oral thrush, feeding intolerance

Additional advice Avoid breastfeeding for 12–24 hours after completing therapy if concerned (optional, not mandatory)

• Starting dose: Standard adult dose unless renal/hepatic impairment present

• Titration: Not applicable; short-course therapy preferred

• Special considerations:

• Assess renal function before initiating; adjust dose if eGFR <30

• Higher risk of CNS effects (dizziness, confusion, ataxia) from metronidazole

• Increased fall risk due to vestibular effects

• Monitor for C. difficile colitis, especially in frail elderly

• Ensure adequate hydration

Drug Interaction Management

Warfarin/Acenocoumarol Both agents increase INR significantly → bleeding risk Monitor INR within 3–5 days of starting; may need anticoagulant dose reduction

Disulfiram Risk of acute psychosis with metronidazole Contraindicated — do not co-administer

Alcohol Disulfiram-like reaction (flushing, nausea, vomiting, hypotension) Avoid alcohol during and 48 hours after therapy

Methotrexate Amoxicillin reduces renal clearance → methotrexate toxicity Avoid combination; if essential, monitor methotrexate levels and toxicity signs

Lithium Metronidazole may increase serum lithium levels Monitor lithium levels; adjust dose as needed

Busulfan Metronidazole increases busulfan toxicity Avoid combination

Drug Interaction Management

Oral contraceptives Theoretical reduced efficacy with amoxicillin (gut flora disruption) Counsel for backup barrier method during therapy

Phenytoin Metronidazole inhibits phenytoin metabolism; phenytoin induces metronidazole metabolism Monitor phenytoin levels; clinical response

Phenobarbital Increases hepatic metabolism of metronidazole → reduced efficacy Consider dose increase or alternative

Carbamazepine Induces metronidazole metabolism Monitor clinical response

Rifampicin Reduces amoxicillin levels via enzyme induction Use alternative antibiotic in TB patients if possible

Cyclosporine Metronidazole may increase cyclosporine levels Monitor cyclosporine levels

5-Fluorouracil Metronidazole reduces clearance → increased toxicity Avoid if possible; oncologist input required

• Nausea and vomiting

• Metallic or bitter taste (metronidazole)

• Diarrhoea or loose stools

• Abdominal discomfort or cramping

• Headache

• Dizziness

• Skin rash (amoxicillin)

• Glossitis or oral thrush (with prolonged use)

• Dark-coloured urine (harmless; metronidazole metabolite)

• Anorexia

• Anaphylaxis/Angioedema (amoxicillin) — requires immediate discontinuation and emergency treatment

• Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis — rare; discontinue immediately

• Seizures (metronidazole, especially at high doses or in patients with CNS disorders) — discontinue

• Peripheral neuropathy (metronidazole, with prolonged use >10 days) — discontinue; may be irreversible

• Optic neuropathy (rare; metronidazole) — discontinue immediately

• Cholestatic hepatitis — discontinue and investigate

• Clostridioides difficile colitis — discontinue; initiate specific therapy

• Leukopenia/Neutropenia (rare) — monitor CBC if prolonged use

During therapy (day 3–5) Clinical response; GI tolerance; signs of allergic reaction; INR if on anticoagulants

Prolonged therapy (>7–10 days) LFTs; CBC; neurological examination (peripheral neuropathy, ataxia signs)

If on warfarin INR at baseline, day 3–5, and weekly during therapy

• Metrogyl-A (J.B. Chemicals)

• Flagyl-A

• Aldezol-AM

• Metron-A

• Amomet

• Metgyl Plus

• Multiple regional branded generics available

Strength Price Range

• NPPA status: Fixed combination not under price control; individual components (Amoxicillin, Metronidazole) are in NLEM and price-controlled

• Availability: Widely available in private sector; government facilities typically stock individual agents

1. Alcohol counselling is essential — clearly warn patients to avoid alcohol during therapy and for 48 hours after last dose; disulfiram-like reaction with metronidazole can be severe

1. Adjunct, not replacement for drainage — in dental abscesses, antibiotics are adjunctive; definitive treatment requires incision and drainage or root canal therapy

1. In children <6 years, always use separate components — suspensions of amoxicillin and metronidazole allow accurate weight-based dosing

1. Metallic taste is dose-related and reversible — reassure patients; taking with food may help tolerance

1. Limit duration to <10 days when possible — prolonged metronidazole use increases peripheral neuropathy risk

1. Always confirm penicillin allergy history — many reported "allergies" are non-immune adverse effects; true IgE-mediated reactions require alternative antibiotics

amoxicillin; metronidazole; FDC; dental infections; periodontitis; anaerobic infection; nitroimidazole; Schedule H; alcohol-warning; pregnancy-compatible

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations List

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine (2022)

• AIIMS Antimicrobial Stewardship Guidelines (2023)

• Indian Dental Association Clinical Protocols

• ICMR Treatment Guidelines for H. pylori (for off-label reference)

• Harrison's Principles of Internal Medicine (supportive)

• Goodman & Gilman's Pharmacological Basis of Therapeutics (supportive)