Schedule H

Oral

• Tablets (film-coated): 400 mg, 600 mg

• Chewable tablets: 25 mg, 100 mg

• Granules for oral suspension: 100 mg per packet

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ HIV-1 Infection — Combination Antiretroviral Therapy (Adults)

Regimen A: Standard Twice-Daily Dosing (400 mg tablet)

Parameter Details

Starting dose 400 mg orally twice daily

Titration Not applicable

Usual maintenance dose 400 mg twice daily

Maximum dose 400 mg twice daily

Regimen B: Once-Daily Dosing (600 mg tablet)

Parameter Details

Starting dose 1,200 mg orally once daily (2 × 600 mg tablets taken together)

Titration Not applicable

Usual maintenance dose 1,200 mg once daily

Maximum dose 1,200 mg once daily

Eligibility for once-daily regimen:

• ART-naïve adults initiating treatment, OR

• Virologically suppressed patients switching from another stable regimen

• ❌ NOT for patients with prior INSTI exposure or documented resistance

Regimen C: With Rifampicin Co-administration (Specialist Only)

Parameter Details

Starting dose 800 mg orally twice daily

Titration Not applicable

Usual maintenance dose 800 mg twice daily

Maximum dose 800 mg twice daily

Key Clinical Notes:

• Must always be used as part of combination antiretroviral therapy with 2 NRTIs or per NACO guidelines

• Once-daily regimen suitable when adherence support is needed and no resistance expected

• Duration: Lifelong as part of cART

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

None well-established in Indian specialist practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indication: HIV-1 Infection in Children

Approved age: ≥4 weeks of age AND ≥3 kg body weight

⚠️ NOT recommended in neonates <4 weeks or infants <3 kg except under specialist supervision at tertiary HIV care centres

▶ Oral Suspension (Granules for Suspension: 100 mg/packet)

For infants 4 weeks to <2 years (or weight-appropriate younger children)

Parameter Details

Starting dose 6 mg/kg per dose orally, twice daily

Titration Not applicable

Usual maintenance dose 6 mg/kg twice daily

Maximum dose 100 mg twice daily

▶ Chewable Tablets (Weight-Based Dosing)

Weight (kg) Dose (twice daily)

3 to <4 25 mg

4 to <6 50 mg

6 to <8 75 mg

8 to <11 100 mg

11 to <14 150 mg

14 to <20 200 mg

20 to <28 300 mg

28 to <40 400 mg

≥40 Adult dosing

▶ Film-Coated Tablets (400 mg/600 mg)

For adolescents ≥40 kg: Use adult dosing regimens as above

Critical Formulation Notes:

• Chewable tablets and oral suspension are NOT bioequivalent to film-coated tablets — do NOT interchange doses directly

• Avoid chewable tablets in children with phenylketonuria (contains phenylalanine)

Safety Monitoring:

• Baseline: CBC, LFTs, weight, HIV viral load, CD4 count

• Ongoing: Weight monitoring, LFTs, viral load every 3 months initially

Secondary Indications – Paediatric (Off-label, if any)

None established. Use restricted to specialist paediatric HIV care centres only.

Raltegravir is not significantly cleared renally; primary elimination via glucuronidation.

• Known hypersensitivity to raltegravir or any excipient in the formulation

• Previous history of severe cutaneous reaction to raltegravir (Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Drug Reaction with Eosinophilia and Systemic Symptoms)

• History of rhabdomyolysis or myopathy (increased risk)

• Coexisting hepatitis B or C infection (closer LFT monitoring required)

• Concurrent use of aluminium- or magnesium-containing antacids (significantly reduces absorption)

• Phenylketonuria — chewable tablets contain phenylalanine

• Known or suspected integrase inhibitor resistance mutations

• History of psychiatric illness including depression (monitor for mood changes)

• Immune reconstitution inflammatory syndrome (IRIS) may occur after ART initiation

Parameter Details

Risk category Not formally classified; human data limited but reassuring

Safety statement Considered safe in pregnancy per ICMR/NACO guidelines

Preferred alternatives May be used as preferred agent; alternative to efavirenz when contraindicated

When it may be used Throughout pregnancy as part of combination ART; can be initiated in any trimester

What to monitor Maternal: LFTs, viral load every trimester; Fetal: growth by ultrasonography

Parameter Details

Compatible with breastfeeding Breastfeeding NOT routinely recommended for HIV-positive mothers in India per NACO guidelines (risk of vertical transmission)

Drug levels in milk Low (based on limited data)

Preferred alternatives Not applicable — breastfeeding generally avoided

What to monitor in infant If inadvertent exposure: GI symptoms, rash, feeding pattern, growth

Parameter Recommendation

Starting dose Standard adult dose (400 mg twice daily or 1,200 mg once daily if eligible)

Need for slower titration Not routinely required

Extra risks Increased susceptibility to myopathy; hepatic dysfunction; polypharmacy increases drug interaction risk

Monitoring LFTs baseline and periodically; CK if muscle symptoms develop; review concurrent medications

Interacting Drug Effect & Mechanism Recommendation

Rifampicin ↓↓ Raltegravir levels (~40-60%) via UGT1A1 induction Increase raltegravir to 800 mg twice daily; avoid once-daily regimen; specialist supervision mandatory

Aluminium/Magnesium antacids Significant ↓ raltegravir absorption via chelation Avoid concurrent administration; if essential, separate by ≥6 hours

Carbamazepine May substantially ↓ raltegravir levels (enzyme induction) Avoid combination; consider alternative anticonvulsant; ART specialist consultation required

Phenytoin May substantially ↓ raltegravir levels Avoid unless under specialist supervision; consider valproate or levetiracetam

Phenobarbital May substantially ↓ raltegravir levels Avoid; seek alternative anticonvulsant

Interacting Drug Effect Recommendation

Atazanavir ↑ Raltegravir levels (UGT1A1 inhibition) Can be used together; monitor for increased adverse effects

Omeprazole / PPIs ↑ Raltegravir absorption (pH alteration) No dose adjustment needed; clinically manageable

Tipranavir/ritonavir ↓ Raltegravir levels Monitor viral response; may need specialist input

Calcium supplements May reduce absorption Consider separating doses by 2 hours

Tenofovir, Lamivudine, Emtricitabine No significant interaction Compatible; standard cART combinations

Efavirenz No significant interaction Compatible

Metformin No CYP-mediated interaction Monitor glucose control as standard

• Headache

• Nausea

• Diarrhoea

• Fatigue

• Elevated hepatic transaminases (ALT/AST)

• Insomnia

• Myalgia

• Dizziness

• Abdominal discomfort

• Flatulence

Adverse Effect Action Required

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Immediate discontinuation; dermatology referral; supportive care

Severe hypersensitivity reaction (rash with fever, organ involvement) Discontinue permanently; supportive management

Rhabdomyolysis / severe myopathy Discontinue; check CK urgently; hydration; nephrology input if needed

Hepatotoxicity (especially with HBV/HCV co-infection) Discontinue or reduce dose; hepatology consultation

Depression / suicidal ideation Psychiatric evaluation; consider ART regimen modification

4–6 weeks post-initiation LFTs, CK (if symptomatic), clinical review for tolerability

Every 3 months (initial year) HIV viral load, CD4 count

Every 6 months (stable patients) LFTs, renal function, HIV viral load

As clinically indicated CK levels if myalgia, fatigue, or muscle weakness reported

• Isentress® (MSD/Merck)

• Ralsonix® (Macleods)

• Raltegravir (Hetero) — generic

• Raltegravir (Emcure) — generic

• Available through National AIDS Control Programme (NACO) supply

Note: Fixed-dose combinations with raltegravir are not commonly available in India; mostly prescribed as individual agent.

Chewable tablets Variable; primarily through specialist programmes

Oral suspension granules Variable; primarily through specialist programmes

Note: Available at no cost to eligible patients through National AIDS Control Programme (NACO). Not included in NLEM 2022.

• Adherence consideration: Twice-daily dosing may reduce long-term adherence; switch to once-daily 1,200 mg regimen in eligible virologically suppressed patients

• Antacid warning: Counsel patients to never take raltegravir simultaneously with aluminium/magnesium antacids — separate by at least 6 hours

• Renal safety: Preferred agent in patients with renal impairment as no dose adjustment needed, unlike tenofovir disoproxil

• Pregnancy utility: Good option when efavirenz is contraindicated or not tolerated; safe profile throughout pregnancy

• Polypharmacy advantage: Minimal CYP450-mediated interactions; suitable choice in patients on multiple medications

• Myopathy vigilance: Promptly check CK if patient reports unexplained muscle pain or weakness — early discontinuation prevents progression

• Resistance prevention: Never use as monotherapy; rapid resistance development occurs with suboptimal viral suppression — always ensure full combination therapy

Raltegravir; HIV; antiretroviral therapy; integrase inhibitor; INSTI; pregnancy-safe; renal-safe; NACO; second-line ART; paediatric HIV; Schedule H

RxIndia v1.0 — 02 Apr 2025

• CDSCO Drug Formulations List

• Indian Pharmacopoeia (IP)

• NACO (National AIDS Control Organisation) ART Guidelines 2021–2022

• AIIMS HIV Clinic Treatment Protocols

• WHO Consolidated Guidelines on HIV Treatment (supportive for paediatric dosing)

• Indian Journal of Medical Research — ART resistance patterns

• NLEM 2022 India (for scheduling reference)