Schedule H

Intravenous (IV) only

Powder for Injection (Lyophilised):

• Daptomycin 350 mg per vial

• Daptomycin 500 mg per vial

Note: Daptomycin requires reconstitution with 0.9% sodium chloride before IV administration. Administer as IV infusion over 30 minutes or slow IV injection over 2 minutes.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

⚠️ CRITICAL: Daptomycin is CONTRAINDICATED for pneumonia — it is inactivated by pulmonary surfactant and shows no efficacy in lung infections.

1. Complicated Skin and Skin Structure Infections (cSSSI)

Including deep soft tissue infections, surgical site infections, diabetic foot infections (without osteomyelitis)

Parameter Dosing Details

Starting dose 4 mg/kg IV once daily

Titration Not applicable

Usual maintenance dose 4 mg/kg IV once daily

Maximum dose 6 mg/kg/day (for MRSA or severe infections)

Key Clinical Notes:

• Administer as IV infusion over 30 minutes

• Duration: 7–14 days based on clinical response

• Active against MRSA, MSSA, Streptococci, and Enterococci (including VRE)

• Bactericidal activity — rapid killing of Gram-positive organisms

• Weight-based dosing — use actual body weight

1. Staphylococcus aureus Bacteraemia (SAB)

Including right-sided infective endocarditis

Parameter Dosing Details

Starting dose 6 mg/kg IV once daily

Titration May increase to 8–10 mg/kg for complicated/persistent bacteraemia

Usual maintenance dose 6 mg/kg IV once daily

Maximum dose 10 mg/kg/day (off-label high-dose for refractory cases)

Key Clinical Notes:

• Duration: Minimum 2–6 weeks depending on source, complications, and clinical response

• For uncomplicated SAB (negative follow-up cultures at 48–72 hours, no metastatic foci): minimum 2 weeks

• For complicated SAB (persistent bacteraemia, metastatic infection, endocarditis): 4–6 weeks

• Repeat blood cultures every 48–72 hours until clearance documented

• Specialist infectious diseases input recommended

1. Right-Sided Infective Endocarditis (RIE)

Due to Staphylococcus aureus (MSSA or MRSA)

Parameter Dosing Details

Starting dose 6 mg/kg IV once daily

Titration May increase to 8–10 mg/kg if clinical response inadequate

Usual maintenance dose 6–8 mg/kg IV once daily

Maximum dose 10 mg/kg/day

Key Clinical Notes:

• Duration: 2–6 weeks

• NOT approved/recommended for left-sided endocarditis (limited penetration)

• Echocardiography and repeat cultures essential for monitoring

• Consider combination therapy with rifampicin for prosthetic valve involvement

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes

Vancomycin-Resistant Enterococcus (VRE) Bacteraemia (OFF-LABEL) 8–10 mg/kg IV once daily Minimum 14 days; longer for endocarditis Specialist/ID consultation mandatory. High-dose required for VRE. Evidence: International RCTs; commonly used in Indian tertiary ICUs.

Left-Sided Infective Endocarditis (MRSA/VRE) (OFF-LABEL) 8–12 mg/kg IV once daily 4–6 weeks Specialist only. Limited efficacy data; use when no alternative. Often combined with another agent. Evidence: Case series, expert consensus.

Prosthetic Joint Infection (PJI) (OFF-LABEL) 6–8 mg/kg IV once daily Several weeks (part of staged therapy) Orthopaedic ID specialist required. Often combined with rifampicin. Evidence: International guidelines, Indian specialist practice.

Bone and Joint Infections (Osteomyelitis) (OFF-LABEL) 6–8 mg/kg IV once daily 4–6 weeks Specialist only. Consider for MRSA osteomyelitis when vancomycin not suitable.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Complicated skin and skin structure infections, Staphylococcus aureus bacteraemia

⚠️ Minimum age: 1 year (limited safety data below 1 year)

Age-Based Dosing:

1–<2 years 10 mg/kg IV once daily 12 mg/kg IV once daily 12 mg/kg/day Higher doses needed due to faster clearance

2–<6 years 9 mg/kg IV once daily 12 mg/kg IV once daily 12 mg/kg/day

6–<12 years 7 mg/kg IV once daily 9 mg/kg IV once daily 9 mg/kg/day

12–17 years 5 mg/kg IV once daily 7 mg/kg IV once daily 7 mg/kg/day

≥18 years Adult dosing Adult dosing As per adult

Key Clinical Notes:

• Administer as IV infusion over 30 minutes

• Duration: 7–14 days for cSSSI; up to 6 weeks for bacteraemia

• Children have higher daptomycin clearance — require higher mg/kg doses than adults

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

VRE Bacteraemia (OFF-LABEL) 10–12 mg/kg IV once daily Minimum 14 days Paediatric ID specialist only. Limited data.

Osteomyelitis/Bone Infections (OFF-LABEL) 8–10 mg/kg IV once daily 4–6 weeks Specialist only. MRSA bone infections.

Clear Statement: NOT recommended below 1 year of age except under paediatric infectious disease specialist supervision with careful risk-benefit assessment. Limited safety and efficacy data in neonates and infants.

Safety Monitoring in Children:

• CPK levels at baseline and weekly

• Renal function at baseline and weekly

• Monitor for muscle pain, weakness, or tenderness

• Watch for signs of eosinophilic pneumonia (dyspnoea, fever, hypoxia)

Creatinine Clearance (CrCl) Recommendation

≥30 mL/min No dose adjustment required

<30 mL/min (not on dialysis) Standard dose (4–6 mg/kg) every 48 hours

Haemodialysis Standard dose (4–6 mg/kg) every 48 hours; administer AFTER dialysis on dialysis days

CAPD Standard dose every 48 hours

CRRT (CVVH/CVVHDF) 4–6 mg/kg every 24–48 hours; adjust based on effluent rate; consider TDM

Note: Monitor CPK more frequently in renal impairment due to increased drug accumulation and myopathy risk.

• Known hypersensitivity to daptomycin or any formulation component

• History of daptomycin-induced eosinophilic pneumonia

• Pneumonia — daptomycin is inactivated by pulmonary surfactant and MUST NOT be used for any pulmonary infection (including CAP, HAP, VAP)

• Pre-existing myopathy or muscle disorders — increased risk of daptomycin-associated myopathy

• Concurrent or recent statin therapy — additive myopathy risk; consider temporary discontinuation

• Renal impairment — dose adjustment required; increased risk of adverse effects

• Peripheral neuropathy — monitor for new/worsening symptoms during prolonged therapy

• Eosinophilic pneumonia risk — typically occurs 2–4 weeks after initiation; monitor for new respiratory symptoms

• Prolonged therapy (>14 days) — increased risk of musculoskeletal adverse effects

• Obesity — use actual body weight for dosing; limited data in morbidly obese patients

• Concurrent nephrotoxic drugs — monitor renal function closely

Parameter Details

Risk Category Limited human data; animal studies show no teratogenicity at therapeutic doses

Preferred alternatives Vancomycin (for MRSA if susceptible); linezolid (with caution)

When may be used Reserved for serious MRSA/VRE infections when safer alternatives not suitable; benefit must clearly outweigh risk; specialist input required

Monitoring Maternal CPK, renal function; fetal growth surveillance

Parameter Details

Compatibility Probably compatible; low levels expected in breast milk based on molecular weight and protein binding

Preferred alternatives Vancomycin (if susceptible); consider individual case assessment

Drug levels in milk Low (minimal excretion expected due to high protein binding ~92%)

Infant monitoring Monitor for diarrhoea, oral thrush, feeding difficulties; no significant absorption expected in infant

Parameter Recommendation

Starting dose Standard weight-based dosing if renal function preserved

Titration Not applicable; single daily dosing

Special risks Higher prevalence of renal impairment — always calculate CrCl and adjust accordingly; increased myopathy risk; often on statins (consider discontinuation); more frequent CPK monitoring recommended

Monitoring Baseline and weekly CrCl, CPK; clinical assessment for muscle symptoms

Interacting Drug Mechanism & Effect Management

HMG-CoA Reductase Inhibitors (Statins) — atorvastatin, rosuvastatin, simvastatin Additive risk of myopathy and rhabdomyolysis Consider temporary discontinuation of statin during daptomycin therapy. If continuation essential, monitor CPK at least twice weekly and for muscle symptoms.

Warfarin / Acenocoumarol Possible modest INR elevation (mechanism unclear) Monitor INR at baseline, day 3–5, then weekly; adjust anticoagulant dose as needed

Tobramycin / Aminoglycosides Additive nephrotoxicity; potential for daptomycin accumulation Monitor renal function closely; avoid combination if possible

Interacting Drug Effect Management

Fibrates (Fenofibrate, Gemfibrozil) Additive myopathy risk Avoid if possible; if used, monitor CPK twice weekly

Ciclosporin / Tacrolimus Potential additive nephrotoxicity Monitor renal function closely

Loop Diuretics (Furosemide) May affect renal function and daptomycin clearance Monitor renal function

NSAIDs Additive nephrotoxicity potential Monitor renal function; avoid prolonged concurrent use

Vancomycin Both active against Gram-positives; no antagonism but additive nephrotoxicity Monitor renal function if combination used

Note: Daptomycin is NOT significantly metabolised by CYP450 enzymes — minimal pharmacokinetic drug interactions.

• Elevated CPK (usually asymptomatic)

• Diarrhoea

• Headache

• Nausea, vomiting

• Injection site reactions

• Rash

• Constipation

• Limb pain

• Insomnia

Adverse Effect Clinical Notes

Myopathy / Rhabdomyolysis CPK elevation with muscle pain, weakness, tenderness. More common with higher doses, prolonged therapy, renal impairment, concurrent statins. Discontinue if CPK >5× ULN with symptoms OR >10× ULN regardless of symptoms.

Eosinophilic Pneumonia Typically develops 2–4 weeks after initiation. Presents with fever, dyspnoea, hypoxia, new pulmonary infiltrates, peripheral eosinophilia. Discontinue immediately; usually resolves after stopping; may require corticosteroids.

Peripheral Neuropathy Sensory and/or motor neuropathy with prolonged use. Monitor and discontinue if significant.

Anaphylaxis / Severe Hypersensitivity Rare; immediate discontinuation required

Clostridioides difficile-Associated Diarrhoea (CDAD) Can occur during or after therapy; treat appropriately

Acute Renal Failure Rare; monitor renal function, especially with concurrent nephrotoxins

During treatment CPK weekly (twice weekly if on statins, renal impairment, or higher doses); renal function twice weekly in hospitalised patients; monitor for myopathy symptoms (muscle pain, weakness); monitor for respiratory symptoms (eosinophilic pneumonia)

Prolonged therapy (>14 days) CPK weekly minimum; consider more frequent monitoring; repeat blood cultures to document microbiologic clearance; monitor for peripheral neuropathy

Clinical monitoring Signs of myopathy; new respiratory symptoms (dyspnoea, cough, fever); neurological symptoms

Originator:

• Cubicin® (Merck/MSD) — limited availability; may require import

Generic/Other Brands:

• Dapmicin® (Cipla)

• Daptocid® (Glenmark)

• Dapytin® (Zydus)

• Daptogen® (Sun Pharma)

• Daptosyn® (Hetero)

• Daptokern® (Lupin)

• Various other generics

1. NEVER use for pneumonia — Daptomycin is rapidly inactivated by pulmonary surfactant. It is ineffective for any pulmonary infection including CAP, HAP, and VAP. This is a common prescribing error.

1. Bactericidal Gram-positive coverage — Daptomycin is rapidly bactericidal against MRSA, MSSA, VRE, and other Gram-positive organisms. It is an excellent alternative when vancomycin fails, is contraindicated, or when vancomycin MIC is elevated (≥2 mg/L).

1. Temporary statin discontinuation recommended — Concurrent statin therapy significantly increases myopathy/rhabdomyolysis risk. Consider holding statins during daptomycin therapy and resuming after completion.

1. Weekly CPK monitoring is mandatory — Myopathy is dose- and duration-related. Monitor CPK weekly (more frequently in high-risk patients). Discontinue if CPK >5× ULN with symptoms or >10× ULN regardless of symptoms.

1. Higher doses for serious infections — Standard 4 mg/kg for cSSSI is often inadequate for bacteraemia or endocarditis. Use 6–10 mg/kg for SAB, endocarditis, and VRE infections. Higher doses are increasingly used in Indian ICUs.

1. Once-daily dosing is convenient — Unlike vancomycin, daptomycin's concentration-dependent killing and long half-life allow once-daily administration, simplifying therapy.

1. Watch for eosinophilic pneumonia — Rare but serious adverse effect occurring 2–4 weeks after initiation. New respiratory symptoms in a patient on daptomycin should prompt evaluation; discontinue if suspected.

lipopeptide; MRSA; VRE; bacteraemia; infective-endocarditis; skin-infection; NOT-for-pneumonia; CPK-monitoring; renal-dose-adjust; Gram-positive; Daptomycin; Schedule-H

RxIndia v1.0 — 06 Jun 2025

RxIndia v1.0 — 06 Jun 2025