Schedule H

Oral

• Granules for oral suspension: 4 g sachets

• Tablets: NOT AVAILABLE in India

• Injectable formulations: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

◾ Multidrug-Resistant Tuberculosis (MDR-TB)

As part of longer MDR-TB regimens under NTEP/PMDT supervision when Group A and B agents insufficient

Parameter Recommendation

Starting dose 8 g/day in 2–3 divided doses (approximately 150 mg/kg/day)

Titration Start at lower dose (4–6 g/day) and increase over 1–2 weeks to improve GI tolerability

Usual maintenance dose 8–12 g/day in 2–3 divided doses

Maximum dose 12 g/day

Weight-Based Dosing Reference (Adults):

Body Weight Daily Dose Dosing Schedule

33–50 kg 8 g/day 4 g BD

51–70 kg 8–10 g/day 4 g BD to TDS

70 kg 10–12 g/day 4 g TDS

Clinical Notes:

• Never use as monotherapy — always as part of DST-guided MDR-TB regimen per ICMR/NTEP guidelines

• Administer with food or acidic beverages (orange juice) to reduce GI upset and mask bitter taste

• Duration: As per MDR-TB regimen protocol (typically 18–20 months in longer regimens)

• Reserve use when effective Group A/B agents are unavailable or contraindicated

• Granules must be dissolved in water or juice before administration; do not crush or chew

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

Not applicable

PAEDIATRIC DOSING (Specialist Only)

Primary Indications – Paediatric Drug-Resistant Tuberculosis

Only under DR-TB specialist or NTEP centre supervision

Parameter Recommendation

Starting dose 150 mg/kg/day in 2–3 divided doses

Titration Start at lower dose; increase gradually over 1–2 weeks based on GI tolerability

Usual maintenance dose 200–300 mg/kg/day in 2–3 divided doses

Maximum dose 12 g/day

Weight-Based Paediatric Dosing:

Body Weight Daily Dose Schedule

<10 kg 200–300 mg/kg/day Divided into 2–3 doses

10–20 kg 150–200 mg/kg/day Divided into 2–3 doses

20–30 kg 150 mg/kg/day Divided into 2–3 doses

30 kg Adult dosing applies —

Clinical Notes:

• Granule formulation preferred for accurate dosing

• Round doses to nearest 4 g sachet increments

• Minimum age: Not well-defined; use under specialist supervision for all paediatric patients

• Mix granules with acidic juice or yogurt to improve palatability

Safety Monitoring:

• Baseline and monthly: LFTs, TFTs (especially with concurrent ethionamide)

• Monitor for GI intolerance, hypothyroidism, hepatotoxicity

• Weight and nutritional status monitoring essential

• CBC at baseline and periodically

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

Not applicable

50 mL/min No adjustment required

30–50 mL/min 8 g/day maximum; monitor for toxicity

10–30 mL/min 4–6 g/day in divided doses; close monitoring required

<10 mL/min 4 g/day; use only if essential with close monitoring

Haemodialysis Avoid if possible due to poor clearance and increased toxicity risk; if unavoidable, 4 g/day post-dialysis

Peritoneal dialysis Avoid; consult specialist

Note: Sodium load from PAS sodium granules may be problematic in patients with fluid retention or renal impairment

Note: PAS is hepatotoxic — baseline and periodic LFT monitoring mandatory in all patients

• Known hypersensitivity to para-aminosalicylic acid or related compounds

• Severe hepatic impairment or active hepatitis

• History of hepatotoxicity from prior PAS use

• Active peptic ulcer disease or severe GI ulceration

• Severe renal impairment (CrCl <10 mL/min) unless no alternatives available

• Pre-existing hypothyroidism or concurrent use of goitrogens (ethionamide, prothionamide)

• History of peptic ulcer disease (may exacerbate)

• Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency

• Cardiac patients — high sodium content of granules may worsen fluid retention

• Concurrent use of other hepatotoxic drugs

• Folate deficiency states — may worsen; consider supplementation

• Elderly patients — increased risk of GI intolerance and toxicity

• Alcohol use — additive hepatotoxic risk

Parameter Details

Risk category Limited human data; animal studies inconclusive; use only if clearly needed

Preferred alternatives Fluoroquinolones (levofloxacin/moxifloxacin), linezolid, bedaquiline may be considered based on DST and risk-benefit under specialist guidance

When may be used Only when benefit clearly outweighs risk in MDR-TB; under NTEP/specialist supervision

Monitoring Maternal LFTs and TFTs; fetal growth monitoring via ultrasound

Parameter Details

Breastfeeding compatibility Limited data; compatibility not well established

Expected drug levels in milk Low to moderate (secreted in breast milk)

Preferred alternatives Consider other MDR-TB agents with better safety profile if possible

Infant monitoring GI disturbances (diarrhoea, poor feeding), irritability, growth

Additional notes If PAS essential, breastfeeding may continue with close infant monitoring

Parameter Recommendation

Starting dose 4–6 g/day in 2–3 divided doses

Titration Slower titration over 2–3 weeks; increase by 2 g/week as tolerated

Maximum dose 8–10 g/day (lower than younger adults)

Special risks Increased GI intolerance, hepatotoxicity, hypothyroidism, sodium-fluid overload

Additional monitoring Baseline and periodic renal function, LFTs, TFTs; nutritional status

Interacting Drug Effect Management

Rifampicin Antagonistic interaction; reduced PAS absorption and efficacy Avoid concurrent use in same regimen when possible

Ethionamide/Prothionamide Additive goitrogenic effect; significant hypothyroidism risk Monitor TFTs monthly; may require thyroxine supplementation

Digoxin PAS reduces GI absorption of digoxin Monitor digoxin levels; may need dose adjustment

Vitamin B12 PAS impairs intestinal B12 absorption Monitor for B12 deficiency; supplement if needed

Interacting Drug Effect Management

Antacids/PPIs May alter PAS absorption Stagger administration by at least 2 hours

Warfarin Possible INR fluctuations Monitor INR more frequently

Oral hypoglycaemics GI symptoms may complicate diabetes control Monitor blood glucose closely

Methotrexate/Folate antagonists May aggravate folate deficiency Consider folate supplementation

Isoniazid May increase PAS levels; additive hepatotoxicity Monitor LFTs; use with caution

Ammonium chloride Increases PAS crystalluria risk Ensure adequate hydration

• Nausea and vomiting (10–30%)

• Diarrhoea and abdominal discomfort

• Anorexia

• Metallic or bitter taste

• Hypothyroidism (especially with ethionamide co-administration)

• Malabsorption syndrome (with prolonged use)

• Sodium and fluid retention (due to sodium salt formulation)

Adverse Effect Clinical Action

Hepatotoxicity (elevated LFTs, drug-induced hepatitis) Discontinue immediately; hepatology input if severe

Hypersensitivity reactions (fever, rash, eosinophilia) Discontinue; may require corticosteroids

Agranulocytosis (rare) Discontinue; supportive care

Crystalluria/Acute interstitial nephritis (rare) Discontinue; ensure hydration; nephrology review

Severe hypothyroidism May require thyroid hormone replacement

Löffler syndrome (pulmonary eosinophilia — rare) Discontinue; evaluate for alternative causes

Phase Parameters

Baseline LFTs (ALT, AST, bilirubin), TFTs (TSH, fT4), renal function (creatinine, eGFR), CBC, vitamin B12 levels

After initiation (first 2 months) LFTs every 2–4 weeks; TFTs monthly (especially with ethionamide); GI tolerability assessment

Long-term Monthly LFTs and TFTs; CBC every 2–3 months; B12 levels every 6 months; weight and nutritional monitoring

Additional Adherence monitoring (critical due to poor GI tolerance); symptoms of hypothyroidism

• PASER® (Jacobus Pharmaceutical/Cipla) — Granules for suspension 4 g sachets

• Generic PAS sodium granules — available under NTEP supply

Note: Tablet formulations NOT AVAILABLE in India

Source Price

Private market ₹140–200 per 4 g sachet

Government/NTEP supply Free for enrolled DR-TB patients

Note: Not listed under NLEM; not under NPPA price control

1. GI tolerability is the major limiting factor — Start low, titrate slowly; administer with food and acidic beverages to reduce nausea and mask taste

1. Never use as monotherapy — Always part of DST-guided MDR-TB regimen; monotherapy rapidly selects resistant strains

1. Thyroid monitoring is essential — Hypothyroidism risk is significant, especially when combined with ethionamide; check TFTs monthly

1. Consider folate and B12 supplementation — PAS impairs folate and B12 absorption with prolonged use

1. High sodium content — Each 4 g sachet contains significant sodium; use cautiously in patients with heart failure, hypertension, or renal impairment

1. Poor adherence is common — GI side effects lead to high dropout rates; proactive management with antiemetics and dietary advice improves compliance

Para-aminosalicylic acid; PAS; MDR-TB; XDR-TB; second-line antitubercular; antimycobacterial; NTEP India; hepatotoxic; hypothyroidism; GI intolerance; Group C TB drug

RxIndia v1.0 — 01 Jul 2025

• CDSCO (Central Drugs Standard Control Organisation)

• IP/NFI (Indian Pharmacopoeia / National Formulary of India)

• NTEP PMDT Guidelines (2021)

• ICMR Expert Committee for Drug-Resistant TB

• API Textbook of Medicine, 11th Edition

• AIIMS Adult TB Treatment Protocols

• WHO Consolidated Guidelines on Drug-Resistant Tuberculosis Treatment (supportive reference)

• PASER India product insert (Cipla)