Schedule H

Oral, Intravenous, Intramuscular

• Capsules: 250 mg, 500 mg

• Oral Syrup: 125 mg/5 mL

• Injection (powder for reconstitution): 250 mg, 500 mg, 1 g per vial

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

⮞ Skin and Soft Tissue Infections (MSSA)

(Cellulitis, abscess, wound infections, furuncles, impetigo)

Oral Route (Mild to Moderate Infections):

Parameter Recommendation

Starting dose 250–500 mg orally every 6 hours

Titration Increase to 500 mg every 6 hours for moderate infections

Usual maintenance dose 500 mg every 6 hours

Maximum dose 4 g/day (oral)

Parenteral Route (Severe Infections):

Parameter Recommendation

Starting dose 500 mg–1 g IV/IM every 6 hours

Titration Not applicable

Usual maintenance dose 1 g IV every 6 hours

Maximum dose 8 g/day (IV)

Key Clinical Notes:

• Administer oral dose 30–60 minutes before meals for optimal absorption

• Duration: 7–14 days depending on severity

• Switch from IV to oral when clinically improving and afebrile for 48 hours

⮞ Osteomyelitis (MSSA)

Specialist supervision required

Parameter Recommendation

Starting dose 1–2 g IV every 6 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 6 hours

Maximum dose 8 g/day

Key Clinical Notes:

• Minimum total treatment duration: 4–6 weeks (IV phase followed by oral step-down)

• Oral switch: 500 mg–1 g every 6 hours after 2–4 weeks IV therapy if clinically stable

• Monitor inflammatory markers (ESR, CRP) for response assessment

• Orthopaedic and infectious disease specialist input recommended

⮞ Staphylococcal Pneumonia

Parameter Recommendation

Starting dose 1 g IV every 6 hours

Titration Increase to 2 g every 6 hours for severe cases

Usual maintenance dose 1–2 g IV every 6 hours

Maximum dose 8 g/day

Key Clinical Notes:

• Duration: 7–14 days based on clinical and radiological response

• Switch to oral (500 mg every 6 hours) when afebrile and clinically stable

• Confirm staphylococcal aetiology with culture whenever possible

⮞ Septicaemia (Due to Susceptible Gram-positive Cocci)

Specialist supervision and antimicrobial stewardship recommended

Parameter Recommendation

Starting dose 1–2 g IV every 6 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 6 hours

Maximum dose 8 g/day

Key Clinical Notes:

• Adjust therapy based on blood culture and sensitivity results

• Duration determined by source control and clinical response

• Minimum 10–14 days for uncomplicated bacteraemia

⮞ Infective Endocarditis (MSSA — Combination Regimen)

Specialist-only; requires prolonged IV therapy

Parameter Recommendation

Starting dose 2 g IV every 4–6 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 4 hours

Maximum dose 12 g/day

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

⮞ Skin and Soft Tissue Infections (MSSA)

Oral Route (Age-based dosing):

<2 years 62.5–125 mg Every 6 hours 500 mg/day

2–10 years 125–250 mg Every 6 hours 1 g/day

10 years Adult dosing (250–500 mg) Every 6 hours 2 g/day

Parenteral Route (Weight-based dosing):

Parameter Recommendation

Starting dose 25 mg/kg/day IV divided every 6 hours

Titration Increase to 50 mg/kg/day for severe infections

Usual maintenance dose 25–50 mg/kg/day divided every 6 hours

Maximum single dose 1 g

Key Clinical Notes:

• Administer oral doses on empty stomach

• Duration: 7–14 days depending on severity

• IV-to-oral switch when clinically stable and afebrile

⮞ Staphylococcal Pneumonia (Paediatric)

Parameter Recommendation

Starting dose 50 mg/kg/day IV in 4 divided doses

Titration Not applicable

Usual maintenance dose 50 mg/kg/day divided every 6 hours

Maximum dose 100 mg/kg/day or adult dose (whichever is lower)

Key Clinical Notes:

• Oral switch after 3–5 days if clinically stable

• Total duration: 7–10 days

Safety Monitoring:

• Baseline and weekly LFTs if therapy exceeds 7 days

• Monitor for GI tolerance and hypersensitivity reactions

• Watch for signs of C. difficile-associated diarrhoea

Secondary Indications — Paediatrics (Off-label, if any)

Indication Dose Duration Notes

Neonatal sepsis (Suspected Staphylococcal) 25–50 mg/kg/dose IV every 12 hours (<7 days old); every 8 hours (7–28 days old) Culture-directed; typically 10–14 days OFF-LABEL; Specialist only; Based on tertiary NICU protocols (AIIMS, PGI); Requires culture guidance and toxicity monitoring

Age Restriction Statement:

Not recommended in neonates (<1 month) without specialist supervision due to risk of bilirubin displacement and immature renal clearance. Premature neonates require individual dose calculation by neonatologist.

• History of immediate hypersensitivity (anaphylaxis, angioedema) to penicillins or any beta-lactam antibiotic

• Prior cholestatic jaundice or hepatic dysfunction associated with flucloxacillin use

• Known allergy to flucloxacillin or any excipient in the formulation

• History of penicillin allergy (non-anaphylactic) — assess risk before use

• Cephalosporin allergy (cross-reactivity risk approximately 5–10%)

• Pre-existing hepatic disorders — increased risk of cholestatic hepatitis, especially with prolonged use

• Renal impairment — adjust dosing interval accordingly

• High-dose IV use — monitor for sodium overload (formulation contains sodium)

• Prolonged therapy — increased risk of superinfection and C. difficile-associated diarrhoea

• Not effective against MRSA — confirm susceptibility before use

• Infectious mononucleosis — higher risk of maculopapular rash

Parameter Information

Risk category Generally considered safe (Category B equivalent)

Safety statement No evidence of teratogenicity; penicillins cross placenta but extensive clinical experience supports safety

Preferred use Flucloxacillin is preferred for MSSA infections requiring treatment during pregnancy

Preferred alternative Cefazolin (in penicillin intolerance without anaphylaxis history)

Monitoring Monitor maternal liver function with prolonged use

Parameter Information

Compatibility Compatible with breastfeeding

Drug level in milk Low (small amounts excreted)

Preferred alternatives None required; flucloxacillin is acceptable

Infant monitoring Watch for diarrhoea, oral thrush, or skin rash in nursing infant

• Starting dose: Lower end of adult dose range recommended (e.g., 250–500 mg every 6 hours orally)

• Titration: Gradual increase based on clinical response and tolerance

• Additional considerations:

• Assess baseline renal function and adjust dosing interval accordingly

• Increased susceptibility to hepatotoxicity with age and prolonged therapy

• IV formulation contains sodium — caution in heart failure and fluid-restricted patients

• Monitor hydration status and renal function during therapy

• Higher vigilance for drug-induced cholestatic hepatitis

Interacting Drug Effect Management

Methotrexate Increased risk of methotrexate toxicity due to reduced renal tubular secretion; may cause myelosuppression and mucositis Avoid concurrent use if possible; if unavoidable, monitor methotrexate levels and toxicity closely

Probenecid Increases and prolongs serum levels of flucloxacillin by inhibiting renal tubular secretion Avoid unless intentional for dose enhancement; reduce flucloxacillin dose if combination used

Interacting Drug Effect Management

Warfarin Possible alteration in INR with prolonged therapy (>7 days) Monitor INR closely; adjust warfarin dose as needed

Oral contraceptives Possible reduced efficacy via gut flora disturbance Advise additional barrier contraception during therapy and for 7 days after completion

Oral typhoid vaccine (Ty21a) Reduced vaccine immunogenicity Avoid live oral vaccines during or shortly after antibiotic therapy

Aminoglycosides Potential in vitro inactivation if mixed in same infusion Administer via separate IV lines; do not mix in same bag

• Nausea and vomiting

• Diarrhoea

• Abdominal discomfort

• Maculopapular rash (especially in infectious mononucleosis)

• Mild transient elevation of liver enzymes (ALT, AST)

• Injection site pain and phlebitis (IV administration)

• Oral candidiasis (with prolonged use)

Adverse Effect Clinical Notes

Cholestatic hepatitis Usually delayed onset (1–4 weeks after starting or post-therapy); presents with jaundice, pruritus, elevated bilirubin and ALP; requires immediate discontinuation

Anaphylaxis Immediate hypersensitivity; medical emergency requiring adrenaline and supportive care

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Rare; discontinue immediately and refer urgently

Pseudomembranous colitis (C. difficile) Suspect with severe or persistent diarrhoea; discontinue and treat appropriately

Neutropenia / Agranulocytosis Rare; associated with prolonged high-dose therapy; monitor CBC

Interstitial nephritis Rare; presents with fever, rash, eosinophilia, renal impairment

Phase Parameters

Baseline LFTs; renal function (if IV or prolonged course planned); allergy history documentation

During therapy (<7 days) Clinical response; signs of hypersensitivity; GI tolerance

During prolonged therapy (>7 days) LFTs weekly; CBC if high-dose IV; renal function monitoring

Post-therapy Monitor for delayed-onset cholestatic hepatitis (can occur 1–4 weeks after stopping); counsel patient about jaundice warning signs

• FLOXIPEN (Cipla)

• PHLOXIN (Abbott)

• FLUCLOX (Knoll)

• STAPHYCLIN (Alkem)

• FLOXAPEN

• Multiple generic preparations available

Capsule 250 mg ₹6–15 per capsule Brand-dependent

Capsule 500 mg ₹10–25 per capsule Brand-dependent

Syrup 125 mg/5 mL (60 mL) ₹30–45 per bottle —

Injection 500 mg vial ₹40–70 per vial —

Injection 1 g vial ₹60–120 per vial —

Note: Not included in NLEM (as of 2022); not NPPA price-controlled; variable pricing in private sector.

1. Optimal oral absorption: Administer oral dose 30–60 minutes before meals — food significantly reduces bioavailability.

1. Preferred antistaphylococcal penicillin: Flucloxacillin is the preferred narrow-spectrum agent for confirmed MSSA infections in India when IV therapy is required.

1. Hepatotoxicity vigilance: Cholestatic hepatitis may have delayed onset (up to 4 weeks after stopping therapy) — counsel patients about jaundice warning signs and monitor LFTs with prolonged use.

1. No MRSA activity: Completely ineffective against methicillin-resistant Staphylococcus aureus — always confirm susceptibility before prolonged use.

1. Sodium content caution: IV formulation contains significant sodium; exercise caution in heart failure, hypertension, or fluid-restricted patients.

1. IV-to-oral switch strategy: For deep-seated infections, oral flucloxacillin (500 mg–1 g every 6 hours on empty stomach) can replace IV therapy once patient is afebrile and clinically stable.

Flucloxacillin; antibiotic; beta-lactam; penicillinase-resistant penicillin; MSSA; staphylococcal infection; skin infection; osteomyelitis; endocarditis; hepatic monitoring; renal adjustment; Schedule H; pregnancy-safe

RxIndia v1.0 — 10 Jan 2025

• CDSCO Drug Formulations List

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Antimicrobial Stewardship Guidelines

• ICMR-AMR Treatment Guidelines

• NLEM 2022

• IAP Paediatric Drug Formulary

• Harrison's Principles of Internal Medicine

• Indian neonatal & paediatric infectious disease protocols (tertiary centres)

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics