Schedule H

Subcutaneous (SC), Intramuscular (IM)

• Interferon beta-1a injection (IM): 30 mcg per prefilled syringe

• Interferon beta-1a injection (SC): 22 mcg / 44 mcg per prefilled syringe

• Interferon beta-1b injection (SC): 250 mcg per vial (requires reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Relapsing Forms of Multiple Sclerosis (RRMS) — Including Clinically Isolated Syndrome (CIS)

Option A: Interferon beta-1a (Intramuscular)

Parameter Details

Starting dose 30 mcg IM once weekly

Titration Not required

Usual maintenance dose 30 mcg IM once weekly

Maximum dose 30 mcg once weekly

Key notes Often first-line choice; lower injection site reactions compared to SC forms; monitor LFTs and CBC baseline and periodically

Option B: Interferon beta-1a (Subcutaneous)

Parameter Details

Starting dose 22 mcg SC three times per week

Titration May increase to 44 mcg SC three times per week after 2 weeks if tolerated

Usual maintenance dose 22–44 mcg SC three times per week

Maximum dose 44 mcg SC three times per week

Key notes Higher incidence of injection site reactions; rotate injection sites; administer on same 3 days each week with at least 48 hours between doses

Option C: Interferon beta-1b (Subcutaneous)

Parameter Details

Starting dose 62.5 mcg (0.25 mL) SC every other day

Titration Week 1: 62.5 mcg → Week 2: 125 mcg → Week 3: 187.5 mcg → Week 4 onwards: 250 mcg

Usual maintenance dose 250 mcg SC every other day

Maximum dose 250 mcg every other day

Key notes Requires reconstitution with supplied diluent; administer at same time each dosing day; gradual titration reduces flu-like symptoms

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

• NOT ROUTINELY USED OFF-LABEL IN INDIA

• No established off-label adult indications documented in current Indian clinical practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Relapsing Multiple Sclerosis in Adolescents (≥12 years)

Limited data available; use only under paediatric neurologist supervision experienced in MS management.

Interferon beta-1a (SC) — Age ≥12 years:

Parameter Details

Starting dose 5–10 mcg SC three times weekly

Titration Gradual increase over 4–6 weeks based on tolerability

Usual maintenance dose 22 mcg SC three times weekly

Maximum dose 22 mcg SC three times weekly (lower than adult dose)

Key notes Monitor growth parameters, thyroid function, mood/psychiatric symptoms; baseline and periodic LFTs and CBC mandatory

Interferon beta-1a (IM) — Age ≥12 years:

• Starting dose: 15 mcg IM once weekly

• Titration: Increase to 30 mcg after 4 weeks if tolerated

• Maintenance: 30 mcg IM once weekly

• Initiated only by specialist

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

• Not recommended in children below 12 years except in exceptional research settings

• Safety and efficacy not established in children <12 years

• Any use below age 12: Specialist only, case-by-case basis with informed consent

Severe impairment (eGFR <30) Use with caution; no specific dose reduction but enhanced monitoring for toxicity advised

Haemodialysis Limited data; use with caution under specialist supervision

• Hypersensitivity or anaphylaxis to natural or recombinant interferon beta or any formulation excipient

• Severe active depression with suicidal ideation

• Decompensated liver disease or severe hepatic impairment

• Current treatment with drugs known to cause severe hepatotoxicity (combination contraindicated)

• History of depression or other psychiatric disorders — close psychiatric monitoring essential

• Pre-existing seizure disorder — may lower seizure threshold; ensure adequate anticonvulsant control

• Bone marrow suppression or cytopenias — monitor CBC

• Pre-existing cardiac disease — flu-like symptoms may exacerbate

• Thyroid dysfunction — periodic thyroid function monitoring required

• History of injection site necrosis with previous interferon use

• Patients with limited compliance capacity (complex dosing regimen)

Aspect Details

Overall safety Not routinely recommended; theoretical risk of spontaneous abortion reported in some studies

When may be used Only if benefit clearly outweighs risk; requires neurologist and obstetrician joint decision

Preferred alternative Glatiramer acetate (considered safer profile in pregnancy)

What to monitor Maternal LFTs, CBC; fetal growth via ultrasound; discontinue if pregnancy confirmed unless benefits strongly favour continuation

Aspect Details

Compatibility Generally compatible with breastfeeding

Drug levels in milk Trace amounts; not orally bioavailable to infant

Preferred alternative Glatiramer acetate if maternal preference to avoid

Infant monitoring Routine monitoring of feeding patterns and growth; no specific drug monitoring required

• Starting dose: Use lower end of dose range; consider starting with prolonged titration period

• Titration: Slower titration recommended; assess tolerability at each step

• Special risks: Limited clinical trial data in elderly; increased susceptibility to infections, bone marrow suppression, and hepatotoxicity; higher baseline risk of depression

• Monitoring: More frequent CBC, LFTs, renal function; assess cognition and mood at each visit

Drug Interaction Recommendation

Clozapine Additive risk of bone marrow suppression and agranulocytosis Avoid combination; if essential, intensive haematological monitoring

Zidovudine Additive myelosuppression Avoid combination if possible; monitor CBC closely if co-administered

Methotrexate Increased hepatotoxicity risk Avoid combination; if unavoidable, frequent LFT monitoring essential

Live vaccines Reduced vaccine efficacy; potential for vaccine-strain infection Contraindicated during therapy; complete vaccinations before initiating interferon

Drug/Class Interaction Recommendation

Antiepileptics (phenytoin, carbamazepine) Interferon may lower seizure threshold Monitor seizure control; may need antiepileptic dose adjustment

SSRIs/SNRIs Additive risk of depression, mood disturbances Close psychiatric monitoring; educate patient on warning signs

Paracetamol (chronic use) Additive hepatotoxic potential Monitor LFTs; limit chronic paracetamol use

Hepatotoxic agents (isoniazid, rifampicin) Increased LFT derangement risk More frequent LFT monitoring; consider alternative TB regimens if feasible

Alcohol (chronic use) Additive hepatotoxicity Counsel on alcohol cessation

• Flu-like syndrome (fever, chills, myalgia, arthralgia) — most common early in therapy, typically diminishes over 2–3 months

• Injection site reactions (erythema, pain, induration) — more frequent with SC administration

• Headache

• Fatigue and asthenia

• Transient elevation of liver transaminases

• Leucopenia (usually mild)

• Menstrual irregularities

• Severe depression / suicidal ideation — discontinue immediately if mood deteriorates significantly

• Hepatotoxicity — including rare cases of fulminant hepatic failure; discontinue if ALT >5× ULN

• Severe bone marrow suppression — neutropenia, thrombocytopenia, anaemia requiring dose reduction or discontinuation

• Injection site necrosis — discontinue if necrosis develops

• New onset or worsening seizures

• Anaphylaxis / severe hypersensitivity reactions

• Autoimmune disorders (thyroid dysfunction, rare)

Baseline (Before Initiation):

• Complete blood count with differential

• Liver function tests (ALT, AST, bilirubin)

• Thyroid function (TSH)

• Renal function (serum creatinine, eGFR)

• Psychiatric screening for depression and suicidal ideation

• Seizure history documentation

During Therapy:

Timeframe Parameters

Months 1–3 CBC and LFTs monthly

Months 4–12 CBC and LFTs every 3 months

Long-term (>1 year) CBC and LFTs every 6 months

Ongoing Psychiatric monitoring at each visit; TSH every 6–12 months

• Avonex (Interferon beta-1a, IM) — Biogen

• Rebif (Interferon beta-1a, SC) — Merck Serono

• Betaferon (Interferon beta-1b, SC) — Bayer

• Extavia (Interferon beta-1b, SC) — Novartis

Brand Strength/Form Approximate Price

• NLEM status: Not included in NLEM 2022

• Note: Prices may vary; government schemes (CGHS, ESIC) and insurance may provide coverage

1. Managing flu-like symptoms: Pre-medicate with paracetamol 500–650 mg 30 minutes before injection and at bedtime; evening dosing may help patients sleep through symptoms

1. Injection site management: Rotate sites systematically (thighs, abdomen, upper arms for SC); allow medication to reach room temperature before injection

1. Depression screening: Mandatory before initiation; use validated tools (e.g., PHQ-9); contraindicated in active suicidal ideation

1. IM vs SC choice: IM beta-1a (Avonex) offers once-weekly convenience with fewer injection reactions but may have modestly lower efficacy than SC forms

1. Adherence support: Complex regimens and flu-like symptoms lead to poor adherence; patient education and support programmes are essential

1. Neutralizing antibodies: May develop over time, potentially reducing efficacy; consider testing if relapses recur despite adherence

Interferon beta; multiple sclerosis; RRMS; immunomodulator; CNS; hepatotoxicity-monitoring; depression-risk; SC injection; IM injection; specialist-only; biologics

RxIndia v1.0 — 24 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI) 2021

• AIIMS Neurology MS Management Protocols

• API Textbook of Medicine

• Indian MS Society Consensus Document

• WHO Drug Information — Interferon Safety in Lactation

• Select international RCTs (supportive evidence for paediatric use — clearly marked)