Schedule H

Oral

• Capsules: 30 mg, 45 mg, 75 mg

• Powder for oral suspension: 12 mg/mL (after reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Treatment of Influenza A and B (confirmed or clinically suspected)

Used for treatment of acute uncomplicated influenza in patients symptomatic for ≤48 hours. May be considered beyond 48 hours in severe/hospitalised cases per MoHFW guidelines.

Adult Dosing:

Parameter Recommendation

Starting dose 75 mg twice daily

Titration Not applicable

Usual maintenance dose 75 mg twice daily

Maximum dose 75 mg twice daily (150 mg/day)

Duration: 5 days for uncomplicated influenza; may extend to 10 days in hospitalised/severe cases

Clinical Notes:

• Initiate treatment as early as possible, ideally within 48 hours of symptom onset

• May be initiated beyond 48 hours in hospitalised patients, immunocompromised individuals, or those with progressive illness

• Administer with food to reduce GI adverse effects

• Clinical benefit is reduction in symptom duration by approximately 1–2 days when started early

1. Post-Exposure Prophylaxis of Influenza

Used for prevention of influenza following close contact with a confirmed or suspected case.

Parameter Recommendation

Starting dose 75 mg once daily

Titration Not applicable

Usual maintenance dose 75 mg once daily

Maximum dose 75 mg once daily

Duration:

• Post-exposure prophylaxis: 10 days (or 7 days after last known exposure)

• Seasonal/institutional prophylaxis: Up to 6 weeks during community outbreak

Clinical Notes:

• Begin within 48 hours of exposure for optimal efficacy

• Consider for household contacts, healthcare workers with unprotected exposure, high-risk individuals

• Vaccination remains preferred prevention strategy; prophylaxis does not replace vaccination

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Severe/Critical Influenza (ICU patients) 75–150 mg twice daily 5–10 days (or until clinical improvement) OFF-LABEL for higher dose — Specialist only (Critical Care/ID). Standard dose (75 mg BD) is approved; higher dose (150 mg BD) based on pharmacokinetic considerations in severely ill patients with altered absorption. No proven survival benefit for higher doses in RCTs. AIIMS ICU protocols may include higher dosing.

Avian Influenza (H5N1, H7N9) 75–150 mg twice daily 5–10 days OFF-LABEL — Specialist only. Public health emergency context. Based on WHO recommendations and Indian outbreak response protocols (NCDC). Higher doses considered due to higher viral loads.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Treatment of Influenza A and B

Weight-based Dosing (≥1 year of age):

Body Weight Dose per Administration Frequency Duration

≤15 kg 30 mg Twice daily 5 days

15–23 kg 45 mg Twice daily 5 days

23–40 kg 60 mg Twice daily 5 days

40 kg 75 mg Twice daily 5 days

Infants 2 weeks to <1 year (during influenza outbreak/pandemic):

Age Dose Frequency Duration

2 weeks to <3 months 2 mg/kg Twice daily 5 days

3 months to <12 months 2.5–3 mg/kg Twice daily 5 days

Parameter Recommendation

Starting dose Weight-based as per table above

Titration Not applicable

Usual maintenance dose Same as starting dose

Maximum dose 75 mg twice daily

Clinical Notes:

• Use oral suspension for accurate dosing in young children

• Shake suspension well before each dose

• May administer with food to improve tolerability

• Reconstituted suspension stable for 17 days at room temperature or 10 weeks refrigerated

1. Post-Exposure Prophylaxis

Weight-based Once Daily Dosing (≥1 year of age):

Body Weight Dose Duration

≤15 kg 30 mg once daily 10 days

15–23 kg 45 mg once daily 10 days

23–40 kg 60 mg once daily 10 days

40 kg 75 mg once daily 10 days

Minimum Age Statement: Use in infants <2 weeks of age is not recommended except under paediatric infectious disease specialist supervision in outbreak/pandemic settings.

Safety Monitoring:

• GI tolerance (nausea, vomiting — common)

• Neuropsychiatric symptoms (delirium, abnormal behaviour, hallucinations — rare but more common in children/adolescents)

• Hydration status if vomiting occurs

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Avian Influenza (H5N1, H7N9) All ages Weight-based dosing as for treatment (may use higher end of dosing range); Duration: 5–10 days OFF-LABEL — Specialist only. Public health emergency context. Based on WHO/NCDC guidance.

Severe Influenza (hospitalised) All ages Standard weight-based twice daily dosing; Duration: Up to 10 days OFF-LABEL for extended duration — Specialist only. Based on clinical practice for severe illness.

Treatment Dosing:

60 75 mg twice daily (no adjustment)

30–60 30 mg twice daily OR 75 mg once daily

10–30 30 mg once daily

<10 (not on dialysis) Not recommended; if essential, 30 mg single dose (specialist input)

Haemodialysis 30 mg after each dialysis session (typically 3 times weekly)

CAPD 30 mg once weekly

Prophylaxis Dosing:

60 75 mg once daily

30–60 30 mg once daily OR 75 mg every other day

10–30 30 mg every other day

<10 (not on dialysis) Not recommended

Haemodialysis 30 mg after alternate dialysis sessions

CAPD 30 mg once weekly

• Known hypersensitivity to oseltamivir phosphate or any excipient

• Previous severe hypersensitivity reaction (anaphylaxis, angioedema, SJS/TEN) to oseltamivir

• Hereditary fructose intolerance (oral suspension contains sorbitol — applicable to suspension formulation only)

• Renal impairment — dose adjustment required; accumulation may increase adverse effects

• History of psychiatric disorders — monitor for neuropsychiatric events (delirium, hallucinations, abnormal behaviour)

• Children and adolescents — increased risk of neuropsychiatric events; close monitoring advised

• Immunocompromised patients — may have prolonged viral shedding; consider extended treatment; monitor for resistance

• Late presentation (>48 hours after symptom onset) — reduced benefit expected; consider treatment in severe/hospitalised cases regardless of timing

• Influenza vaccination within 2 weeks — oseltamivir may reduce vaccine efficacy if live attenuated intranasal vaccine used

• Underlying cardiac or respiratory disease — close monitoring for influenza complications despite treatment

Parameter Recommendation

Safety Category Generally considered safe; extensive post-marketing and pandemic experience (H1N1 2009); no documented increase in adverse fetal outcomes

Preferred Alternatives Oseltamivir is the preferred antiviral for influenza treatment and prophylaxis during pregnancy per MoHFW and ICMR guidelines; zanamivir (inhaled) is alternative but requires intact respiratory function

When to Use Should be used when clinically indicated; pregnant women are at higher risk of severe influenza complications; benefits outweigh theoretical risks

Monitoring Monitor maternal renal function (physiological changes in pregnancy); standard obstetric monitoring

Note: MoHFW specifically recommends oseltamivir for pregnant women with suspected or confirmed influenza during H1N1/seasonal influenza outbreaks.

Parameter Recommendation

Breastfeeding Compatibility Compatible with breastfeeding

Drug Levels in Milk Very low (oseltamivir and carboxylate metabolite detected at very low concentrations)

Preferred Alternatives Not required; oseltamivir is preferred antiviral during lactation

Infant Monitoring Routine monitoring only; no specific concerns

Note: Continue breastfeeding during maternal influenza treatment; breast milk provides protective antibodies to infant.

Parameter Recommendation

Starting dose 75 mg twice daily (standard adult dose)

Titration Not applicable

Additional Risks Age-related renal decline may require dose adjustment (calculate CrCl/eGFR); increased susceptibility to neuropsychiatric adverse effects (confusion, delirium); influenza itself carries higher morbidity/mortality in elderly

Monitoring Assess renal function before prescribing; monitor for confusion, delirium, behavioural changes

Interacting Drug Mechanism/Effect Management

Live attenuated influenza vaccine (LAIV — intranasal) Oseltamivir may inactivate live vaccine virus; reduced vaccine efficacy Do not administer LAIV within 2 weeks before or 48 hours after oseltamivir; inactivated influenza vaccine not affected

Probenecid Inhibits renal tubular secretion of oseltamivir carboxylate; doubles plasma levels of active metabolite Not contraindicated; consider dose reduction in patients with renal impairment receiving both drugs

Interacting Drug Effect Management

Warfarin Theoretical interaction; INR changes reported rarely (mechanism unclear — possibly effect on vitamin K metabolism during illness) Monitor INR during and shortly after oseltamivir treatment; adjust warfarin if needed

Methotrexate No direct interaction documented; both renally excreted Monitor for methotrexate toxicity if concurrent use in patients with impaired renal function

Amantadine/Rimantadine No pharmacokinetic interaction; different mechanisms of action Combination generally not required; current influenza strains largely resistant to adamantanes

Other nephrotoxic drugs May compound renal impairment affecting oseltamivir clearance Monitor renal function; adjust oseltamivir dose as needed

• Nausea (most common — 10–15%)

• Vomiting (more common in children — 8–15%)

• Abdominal pain

• Headache

• Fatigue

• Diarrhoea

• Dizziness

Note: GI adverse effects typically occur in first 1–2 days of treatment; administering with food may reduce GI symptoms.

Adverse Effect Clinical Significance

Neuropsychiatric events Delirium, hallucinations, abnormal behaviour, self-injury, confusion; more common in children and adolescents; onset typically within first 2 days; may occur without preceding psychiatric history; discontinue if significant neuropsychiatric symptoms occur; hospitalisation may be required

Anaphylaxis/Severe hypersensitivity Rare; presents with bronchospasm, angioedema, hypotension, rash; discontinue immediately

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Very rare; discontinue immediately if mucocutaneous reaction occurs

Hepatitis Elevated transaminases reported rarely; discontinue if hepatotoxicity suspected

Haemorrhage GI bleeding reported rarely, particularly in children

Baseline:

• Renal function (serum creatinine, eGFR) — for dose adjustment

• Clinical assessment of symptom duration (efficacy greatest when started within 48 hours)

• Mental status baseline (especially in elderly, children, adolescents)

After Initiation:

• GI tolerability (nausea, vomiting) — usually most prominent in first 1–2 days

• Neuropsychiatric assessment (especially in children and adolescents) — daily during treatment

• Clinical response (fever defervescence, symptom improvement by day 3–5)

Long-term:

• Not applicable — oseltamivir is used for short-term treatment (5 days) or prophylaxis (7–10 days)

• Extended monitoring only if prolonged courses used in immunocompromised patients

• Tamiflu® (Roche) — reference brand

• Fluvir® (Hetero)

• Antiflu® (Cipla)

• Fluhalt® (Glenmark)

• Starflu® (Strides)

• Oseflu® (Sun Pharma)

• Oscarvir® (Lupin)

• Flubex® (Dr. Reddy's)

Paediatric Formulations:

• Fluvir Oral Suspension® (Hetero)

• Antiflu Oral Suspension® (Cipla)

• Fluhalt DT® (dispersible tablets — Glenmark)

• Oseltamivir 75 mg capsule included in NLEM 2022

• NPPA price ceiling applicable for 75 mg capsule

• Available through government supply channels during influenza outbreaks (H1N1 pandemic preparedness)

• Significant price variation between brands in private market

• Timing is critical: Most effective when started within 48 hours of symptom onset; however, hospitalised patients and high-risk individuals may benefit even with later initiation

• Take with food: Administering with food significantly reduces nausea and vomiting (most common adverse effects)

• Pregnancy is not a contraindication: Pregnant women are at HIGH risk for severe influenza complications; oseltamivir should NOT be withheld — it is the recommended antiviral per Indian guidelines

• Watch for neuropsychiatric symptoms in children: Abnormal behaviour, hallucinations, and delirium are rare but serious; more common in children/adolescents; counsel parents to monitor

• Reconstituted suspension storage: Store at 2–8°C and use within 10 days (17 days at room temperature per some products — check specific brand)

• Does not replace vaccination: Oseltamivir prophylaxis is adjunct to vaccination, not substitute; encourage influenza vaccination for at-risk groups

oseltamivir; influenza; antiviral; neuraminidase inhibitor; H1N1; pandemic flu; seasonal influenza; pregnancy-safe; breastfeeding-compatible; NLEM; renal-adjustment; paediatric-use

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• National List of Essential Medicines (NLEM 2022)

• MoHFW National Guidelines for H1N1 Influenza Management

• ICMR Guidelines on Seasonal Influenza

• NCDC Guidelines for Influenza Surveillance and Response

• AIIMS Antimicrobial Policy — Influenza Treatment Protocols

• API Textbook of Medicine

• IAP Guidelines on Influenza in Children

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO Guidelines on Influenza Antivirals (supportive)