Schedule H

Oral, Intravenous, Intramuscular

• Capsules: 250 mg, 500 mg

• Dry syrup (oral suspension): 125 mg/5 mL

• Injection: 250 mg, 500 mg, 1 g vials (as sodium salt)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

⮞ Susceptible Staphylococcal Infections

(Skin & soft tissue infections, osteomyelitis, septic arthritis, pneumonia)

Oral Route:

Parameter Recommendation

Starting dose 500 mg every 6 hours

Titration Increase to 1 g every 6 hours for severe infections

Usual maintenance dose 500 mg–1 g every 6 hours

Maximum dose 4 g/day

IV/IM Route (Moderate to Severe Infections):

Parameter Recommendation

Starting dose 500 mg–1 g every 6 hours

Titration Adjust based on clinical response and infection severity

Usual maintenance dose 1 g every 6 hours

Maximum dose 8 g/day

Key Clinical Notes:

• Administer oral doses 1 hour before or 2 hours after meals

• Duration: 7–14 days for uncomplicated infections; longer for osteomyelitis/deep infections

• IV-to-oral switch when clinically stable and afebrile for 48–72 hours

⮞ Infective Endocarditis (Methicillin-sensitive Staphylococcus aureus)

Specialist use only — part of combination 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

Key Clinical Notes:

• Duration: 4–6 weeks (native valve); 6 weeks or longer (prosthetic valve)

• Combine with gentamicin during first 3–5 days per protocol

• Monitor renal function and drug levels when combined with aminoglycosides

• Cardiology/ID specialist supervision mandatory

⮞ Surgical Prophylaxis (Procedures with MSSA Risk)

Orthopaedic, cardiac surgery

Parameter Recommendation

Starting dose 1–2 g IV at anaesthesia induction

Titration Not applicable

Usual maintenance dose Repeat 1–2 g every 4–6 hours if surgery prolonged (>4 hours)

Maximum dose Single-day prophylaxis only

Key Clinical Notes:

• Do not extend beyond 24 hours post-operatively

• Ensure administration 30–60 minutes before incision

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

Indication Dose Duration Notes

Diabetic foot infection (MSSA-dominated) 500 mg–1 g PO/IV every 6 hours 7–14 days depending on extent OFF-LABEL; Specialist use only; Part of combination regimens; Based on Indian specialist practice (AIIMS protocols)

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

⮞ Staphylococcal Infections

(Skin/soft tissue infections, pneumonia, osteomyelitis, septic arthritis)

Age/Weight Route Dose Frequency Max Single Dose

Neonates (<28 days) IV only 25–50 mg/kg/day (divided) Every 12 hours (first week); Every 8 hours (2–4 weeks) 50 mg/kg/day

1–12 months PO/IV 50–100 mg/kg/day (divided) Every 6 hours 250 mg (PO); 500 mg (IV)

1–12 years PO/IV 50–100 mg/kg/day (divided) Every 6 hours 500 mg (PO); 1 g (IV)

≥12 years PO/IV Adult dosing applies Every 6 hours As per adult limits

Safety Monitoring:

• Baseline LFTs if prolonged therapy anticipated

• Weekly LFTs if treatment exceeds 14 days

• CBC monitoring for prolonged IV courses

• Watch for rash, GI disturbance, signs of hypersensitivity

Key Clinical Notes:

• Oral absorption reduced with food; give on empty stomach

• Duration: Minimum 10 days for skin/soft tissue; 4–6 weeks for osteomyelitis

• IV-to-oral transition when afebrile and clinically improving

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

Indication Dose Duration Notes

Empiric therapy for bone/joint infections (MSSA suspected) 100 mg/kg/day IV divided every 6 hours 4–6 weeks total; IV initially, then oral step-down OFF-LABEL; Based on AIIMS practice guidelines; Specialist supervision required

Age Restriction Statement:

Not recommended in neonates <7 days of life except under specialist guidance with appropriate monitoring. Premature neonates require individual dose calculation by neonatologist.

CrCl >30 mL/min No adjustment required

CrCl 10–30 mL/min No adjustment usually needed; monitor for accumulation with high-dose IV

CrCl <10 mL/min Extend dosing interval to every 8–12 hours

Haemodialysis Not significantly dialysed; no supplemental dose required post-dialysis

Peritoneal dialysis No supplemental dosing needed

• Hypersensitivity to cloxacillin, any penicillin, or beta-lactam antibiotics

• History of penicillin-induced anaphylaxis or severe immediate hypersensitivity reaction

• Prior cholestatic jaundice or hepatic dysfunction associated with cloxacillin use

• Concurrent use with intravenous methotrexate (high-dose regimens)

• History of allergy to cephalosporins (cross-reactivity risk approximately 5–10%)

• Pre-existing hepatic impairment or concurrent hepatotoxic drug use

• Prolonged therapy (>14 days) — increased risk of hepatotoxicity and neutropenia

• History of gastrointestinal disease, particularly antibiotic-associated colitis

• Sodium-restricted patients (IV formulation contains significant sodium load)

• Patients with renal impairment receiving high-dose IV therapy

• History of seizures (very high doses may lower seizure threshold)

Parameter Information

Risk category Generally considered safe; no evidence of teratogenicity

Safety statement Penicillins cross placenta but extensive clinical experience supports safety

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

When to use When benefit clearly outweighs risk; appropriate for indicated infections

Monitoring Monitor maternal liver enzymes if prolonged use; routine obstetric monitoring

Parameter Information

Compatibility Compatible with breastfeeding

Drug level in milk Low (small amounts excreted)

Preferred alternatives None required — cloxacillin is acceptable

Infant monitoring Watch for rash, diarrhoea, oral thrush, or feeding difficulties

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

• Titration: Slower dose escalation for IV therapy in patients with comorbidities

• Additional risks:

• Increased susceptibility to hepatotoxicity with prolonged use

• Reduced renal reserve — assess baseline renal function before initiating high-dose IV therapy

• Higher sodium load from IV formulation may worsen heart failure

• Monitor hydration status and renal function during therapy

Interacting Drug Effect Management

Methotrexate Cloxacillin may reduce renal clearance of methotrexate, leading to increased toxicity (myelosuppression, mucositis) Avoid combination with high-dose methotrexate; if unavoidable, monitor methotrexate levels and toxicity closely

Warfarin Reduced anticoagulant effect reported; possible increased thrombotic risk Monitor INR closely during and after cloxacillin course; adjust warfarin dose as needed

Interacting Drug Effect Management

Oral contraceptives Possible reduced efficacy of hormonal contraception Advise additional barrier contraception during antibiotic course and for 7 days after

Probenecid Increases and prolongs serum levels of cloxacillin by reducing renal tubular secretion Avoid unless intentional for dose-sparing effect; reduce cloxacillin dose if combination necessary

Loop diuretics (furosemide) Potential increased nephrotoxicity risk, especially with high-dose IV cloxacillin Monitor renal function; ensure adequate hydration

Aminoglycosides Potential in vitro inactivation if mixed in same infusion; additive nephrotoxicity risk Administer via separate IV lines; do not mix in same bag; monitor renal function

• Nausea and vomiting

• Diarrhoea

• Maculopapular rash

• Injection site pain and phlebitis (IV administration)

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

• Abdominal discomfort

• Oral candidiasis (with prolonged use)

Adverse Effect Clinical Notes

Cholestatic hepatitis May occur during or weeks after stopping therapy; presents with jaundice, pruritus, elevated bilirubin/ALP; discontinue immediately

Anaphylaxis Immediate hypersensitivity; requires emergency management; absolute contraindication to future penicillin use

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

Neutropenia / Agranulocytosis Associated with prolonged high-dose therapy (>2 weeks); monitor CBC

Eosinophilia Usually resolves on discontinuation

Pseudomembranous colitis (C. difficile) Suspect if severe diarrhoea develops; discontinue and treat appropriately

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

Phase Parameters

Baseline Complete blood count; LFTs (especially if prolonged therapy planned); renal function; allergy history documentation

During therapy (short course <14 days) Clinical response; signs of hypersensitivity; GI tolerance

During prolonged therapy (>14 days) LFTs weekly; CBC weekly; renal function if high-dose IV

Post-therapy Monitor for delayed cholestatic hepatitis (can occur up to 8 weeks after stopping)

• CLOXACIP

• KLOX-DT

• CICLOX

• STAPHYLIN

• OSSOCLOX

• BIOCLOX

• ORCLOX

• Multiple generic preparations available

Capsule 500 mg ₹6–12 per capsule Generic pricing

Capsule 250 mg ₹4–8 per capsule Generic pricing

Dry syrup 125 mg/5 mL (60 mL) ₹30–50 per bottle —

Injection 500 mg vial ₹15–30 per vial —

Injection 1 g vial ₹20–40 per vial —

Note: Not included in NLEM; variable pricing in private sector; government supply pricing may differ.

1. Oral absorption timing: Administer 1 hour before or 2 hours after meals — food significantly reduces bioavailability.

1. Spectrum limitation: Effective only against MSSA; completely ineffective against MRSA — always confirm susceptibility before prolonged use.

1. Hepatotoxicity vigilance: Cholestatic hepatitis can present with delayed onset (even weeks after stopping) — counsel patients about jaundice warning signs.

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

1. Narrow-spectrum preference: When culture confirms MSSA, prefer cloxacillin over broader-spectrum agents to minimise resistance selection.

1. IV-to-oral switch: For deep-seated infections like osteomyelitis, high-dose oral cloxacillin (1 g QID) can replace IV therapy once patient is afebrile and clinically stable — ensures prolonged therapy completion.

Cloxacillin; antibiotic; beta-lactam; penicillinase-resistant penicillin; MSSA; staphylococcal infection; skin infection; osteomyelitis; hepatotoxicity risk; IV-to-oral switch; paediatric-appropriate; NLEM-excluded

RxIndia v1.1 — 10 Jan 2025

• CDSCO Approved Formulations List

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Antimicrobial Policy

• NCDC Hospital Infection Control Guidelines

• IAP Paediatric Drug Formulary

• Harrison's Principles of Internal Medicine

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

• ICMR Antimicrobial Resistance Guidelines