Schedule H

Intravenous (IV)

• Oritavancin 400 mg powder for injection (lyophilised powder for reconstitution)

• Reconstituted in 5% dextrose for IV infusion over 3 hours

• Available via import channels only — not locally manufactured

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Acute Bacterial Skin and Skin Structure Infections (ABSSSI) — Adults

Parameter Details

Starting dose 1200 mg IV infused over 3 hours as a single dose

Titration Not applicable (single-dose regimen)

Usual maintenance dose Not applicable (single-dose regimen)

Maximum dose 1200 mg as single dose

Clinical Notes:

• Indicated for Gram-positive pathogens including MRSA, Streptococcus pyogenes, Streptococcus agalactiae, and vancomycin-susceptible Enterococcus faecalis

• CrCl ≥30 mL/min: No dose adjustment required

• Preferred role: Outpatient parenteral antimicrobial therapy (OPAT) or single-administration inpatient management where oral step-down or multiple IV doses are impractical

• No Gram-negative coverage — ensure appropriate co-therapy if polymicrobial infection suspected

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

Indication Dose Duration Notes Evidence Basis

Osteomyelitis (OFF-LABEL) 1200 mg IV once weekly 2–4 weeks (typically 2–3 doses) Specialist only — ID or orthopaedic supervision mandatory Limited RCTs; US registry data and case series; not standardised in Indian protocols

Endocarditis due to MRSA (OFF-LABEL) 1200 mg IV once weekly ≥4 weeks Specialist only — cardiology/ID supervision mandatory; emerging salvage option in intolerance/resistance to standard therapy Case reports and small series; regimen not fully established

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT AVAILABLE in India

• No approved paediatric dosing exists

• Not recommended below 18 years of age

• Safety and efficacy not established in paediatric population

Secondary Indications — Paediatric Doses (Off-label, if any)

NOT AVAILABLE in India

• No off-label paediatric data or dosing recommendations available

• Use in patients <18 years not supported by current evidence

• Known hypersensitivity to oritavancin or other glycopeptide antibiotics (e.g., vancomycin, telavancin, dalbavancin)

• Co-administration with intravenous unfractionated heparin within 120 hours (5 days) after oritavancin dose — interferes with aPTT assay leading to falsely elevated results

• Use of unfractionated heparin sodium for 48 hours after oritavancin administration

• Coagulation test interference: PT, aPTT, INR, and activated clotting time (ACT) may be falsely elevated for up to 120 hours post-dose — inform laboratory personnel

• Bacteraemia and infective endocarditis: Not adequately studied — avoid unless under specialist guidance with no alternatives

• QT prolongation: May cause modest QT prolongation — use with caution in patients with pre-existing QT prolongation, uncontrolled electrolyte abnormalities, or concurrent QT-prolonging medications

• Long half-life (~245 hours): Adverse effects may persist for extended periods; no reversal agent available

• Limited spectrum: No Gram-negative coverage — avoid as monotherapy in polymicrobial or mixed infections

• Infusion reactions: Risk of histamine-mediated reactions including flushing, urticaria, pruritus — slow infusion rate if occurs

• Clostridioides difficile infection: Risk of antibiotic-associated colitis — discontinue if significant diarrhoea develops

Parameter Details

Risk category Limited human data; animal studies show no teratogenicity (Category B-equivalent)

Recommendation Use only if potential benefit justifies potential risk to fetus

Trimester considerations Avoid in first trimester unless no alternatives available

Preferred alternatives Vancomycin (established safety profile), linezolid (if glycopeptide not suitable)

Maternal monitoring Hypersensitivity reactions, infusion-related reactions

Fetal monitoring No specific monitoring established

Parameter Details

Compatibility Not recommended unless essential — excretion in human breast milk unknown

Expected drug levels in milk Assumed low due to high molecular weight and protein binding (~85%)

Preferred alternatives Vancomycin, linezolid (better characterised in lactation)

Infant monitoring GI disturbance (diarrhoea, feeding difficulties), rash, thrush

• Starting dose: No age-based dose adjustment required

• Titration: Not applicable (single-dose regimen)

• Special considerations:

• Assess baseline renal function (eGFR) though dose adjustment not required

• Increased risk of infusion-related reactions — use lower threshold for intervention

• Coagulation test interference may persist longer — monitor carefully if anticoagulation required

• Assess volume status before full 1200 mg infusion (500 mL total volume)

• Higher vigilance for adverse effects due to prolonged half-life

Interacting Drug Mechanism Clinical Consequence Management

IV Unfractionated heparin aPTT assay interference Falsely elevated aPTT leading to potential under-anticoagulation or dosing errors Contraindicated within 120 hours post-oritavancin; use LMWH or direct oral anticoagulants if anticoagulation needed

Warfarin PT/INR assay interference Falsely elevated INR readings Use chromogenic factor X assay for INR monitoring; avoid standard PT/INR for 120 hours post-dose

QT-prolonging drugs (amiodarone, sotalol, fluoroquinolones, ondansetron, antipsychotics) Additive QT prolongation Increased risk of torsades de pointes Avoid combination unless essential; ECG monitoring recommended

Interacting Drug Mechanism Clinical Consequence Management

CYP2C9 substrates (phenytoin, warfarin, glimepiride) Weak CYP2C9 inhibition Possible increased exposure of substrate drugs Monitor for toxicity; adjust doses if clinically indicated

CYP2C19 substrates (omeprazole, clopidogrel, voriconazole) Weak CYP2C19 inhibition Possible altered substrate efficacy/toxicity Clinical monitoring recommended

CYP3A4 substrates (simvastatin, atorvastatin, midazolam) Weak CYP3A4 induction Possible decreased efficacy of substrate drugs Monitor therapeutic response

Direct oral anticoagulants (rivaroxaban, apixaban) No direct interaction but coagulation monitoring affected Anti-Xa assays may be affected Interpret coagulation tests with caution

• Infusion site reactions (phlebitis, erythema, pain)

• Nausea

• Headache

• Vomiting

• Diarrhoea

• Pruritus and rash

• Limb pain

• Subcutaneous abscess (in ABSSSI patients — related to underlying condition)

Adverse Effect Clinical Features Management

Anaphylaxis/hypersensitivity Angioedema, bronchospasm, urticaria, hypotension Immediate cessation; adrenaline, supportive care

Infusion reaction (Red man syndrome-like) Flushing, pruritus, hypotension, chest discomfort Slow or stop infusion; antihistamines; may rechallenge at slower rate

Clostridioides difficile-associated diarrhoea Severe watery diarrhoea, abdominal pain, fever Discontinue drug; metronidazole or oral vancomycin

Coagulation test misinterpretation False elevations leading to inappropriate clinical decisions Ensure laboratory awareness; use alternative assays

QT prolongation Palpitations, syncope, arrhythmia ECG monitoring; correct electrolytes; avoid concurrent QT-prolonging drugs

Osteomyelitis (paradoxical, rare) New bone infection in setting of treatment Re-evaluate diagnosis; specialist consultation

During infusion Vital signs every 15–30 minutes; monitor for hypersensitivity and infusion reactions

Post-dose (48–120 hours) No UFH administration; inform laboratory of drug administration for accurate coagulation test interpretation

Long-term/off-label multi-dose use Weekly: LFTs, CBC; clinical assessment for C. difficile infection

• No local Indian manufacturing

• Available via import/specialty pharmacy channels only:

• Orbactiv® (The Medicines Company/Melinta Therapeutics)

• Kimyrsa® (Melinta Therapeutics)

• Must be ordered through hospital pharmacy import or specialty importers

• Not commonly stocked — advance ordering required

• Not included in NLEM — not under NPPA price control

• Usually reserved for hospital-based therapy in complex or refractory cases

• Cost may vary based on import channel and availability

• Single-dose convenience: Allows complete outpatient treatment for ABSSSI, eliminating need for daily IV access or oral step-down — particularly useful for non-compliant patients or those without reliable follow-up

• Laboratory alert mandatory: Always document oritavancin administration in patient records and inform laboratory staff to prevent misinterpretation of falsely elevated coagulation tests for up to 5 days

• Not for Gram-negatives: Zero activity against Gram-negative organisms — never use as monotherapy if polymicrobial infection suspected; add appropriate Gram-negative coverage

• Long half-life implications: Effects (both therapeutic and adverse) persist for 2+ weeks — not reversible once administered; counsel patients about delayed adverse effect possibility

• Avoid if bacteraemia suspected: Not adequately studied for bloodstream infections — if blood cultures pending or bacteraemia likely, prefer vancomycin/daptomycin with proven efficacy

• Cost-effectiveness consideration: Despite high acquisition cost, may be cost-effective when avoiding hospitalisation, daily nursing visits, or IV catheter complications

oritavancin; orita; lipoglycopeptide; MRSA; ABSSSI; skin infection; single-dose antibiotic; IV once-only; coagulation interference; renal-safe; high-cost; specialist-use; imported drug

RxIndia v1.0 — 11 Jan 2025

• CDSCO (for product import approval status)

• IP: NOT LISTED

• NLEM: Not included

• AIIMS formulary: Not listed

• API Textbook of Medicine — ABSSSI and Gram-positive infections chapters

• ICMR Antimicrobial Resistance Surveillance guidelines (contextual reference)

• Indian specialist consensus on complicated skin infections (informal)

• US FDA Label (for pharmacokinetic data and off-label dosing reference ONLY — not primary recommendation)

• Published case series and registry data for off-label osteomyelitis/endocarditis use (supportive evidence only)