Prescription only (Rx) — not under specific schedule as per CDSCO

Oral

• Capsule: 72 mcg

• Capsule: 145 mcg

• Capsule: 290 mcg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Chronic Idiopathic Constipation (CIC)

Parameter Details

Starting dose 145 mcg orally once daily

Titration Not applicable — fixed dose regimen

Usual maintenance dose 145 mcg once daily

Maximum dose 145 mcg/day

Clinical Notes:

• Administer on empty stomach, at least 30 minutes before first meal of the day

• Capsule should be swallowed whole; do not crush or chew

• Clinical effect usually observed within 1 week

• Not intended for PRN (as-needed) use

• 72 mcg formulation available for patients who do not tolerate 145 mcg

1. Irritable Bowel Syndrome with Constipation (IBS-C)

Parameter Details

Starting dose 290 mcg orally once daily

Titration Not applicable — fixed dose regimen

Usual maintenance dose 290 mcg once daily

Maximum dose 290 mcg/day

Clinical Notes:

• Administer on empty stomach, at least 30 minutes before first meal

• Improvement in abdominal pain and bowel frequency typically seen within 1–2 weeks

• Discontinue if severe diarrhoea develops

• Reassess if no response after 4 weeks of continuous therapy

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

Indication Dose Duration Notes

Opioid-induced constipation (non-cancer patients) 145–290 mcg once daily As clinically indicated OFF-LABEL — Specialist only. Limited evidence from international studies; not included in Indian guidelines. Efficacy may be variable. Consider methylnaltrexone or naloxegol as alternatives where available.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT RECOMMENDED for use in children below 18 years of age.

Age Group Recommendation

Below 6 years CONTRAINDICATED — Risk of severe, potentially fatal dehydration (international post-marketing reports)

6–17 years NOT RECOMMENDED — Lack of efficacy and safety data in this age group

Minimum Age: 18 years (adults only)

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

NOT RECOMMENDED — No off-label paediatric use should be considered due to safety concerns.

Mild to moderate impairment No dose adjustment required (minimal systemic absorption)

Severe impairment / ESRD Use with caution; monitor closely for dehydration and electrolyte imbalance

Haemodialysis No specific data available; monitor hydration status

• Known or suspected mechanical gastrointestinal obstruction

• Hypersensitivity to linaclotide or any excipient

• Children below 6 years of age (risk of severe dehydration and death)

• Diarrhoea — may be severe; discontinue if persistent or severe dehydration develops

• Elderly patients — higher susceptibility to dehydration

• Patients with renal impairment — increased risk of electrolyte disturbances with diarrhoea

• Inflammatory bowel disease (IBD) — may worsen diarrhoea; avoid use

• Not appropriate for functional abdominal pain without constipation component

• Patients on diuretics — monitor hydration status closely

Parameter Details

Safety statement Limited human data; systemic absorption is minimal, suggesting low fetal exposure

When may be used Only if clearly necessary and no safer alternative available; specialist input advised

Preferred alternatives Lactulose or polyethylene glycol (PEG) for pregnancy-related constipation

Monitoring Monitor mother for persistent diarrhoea, dehydration, and electrolyte imbalance

Parameter Details

Compatibility Likely compatible — minimal systemic absorption expected

Expected levels in milk Likely negligible due to minimal oral bioavailability

Preferred alternatives Lactulose considered safer for chronic use during breastfeeding

Infant monitoring Monitor stool pattern and hydration; unlikely to cause adverse effects

Parameter Recommendation

Starting dose Same as adults (145 mcg for CIC; 290 mcg for IBS-C)

Titration Not applicable

Special risks Higher risk of diarrhoea-induced dehydration and electrolyte disturbance

Monitoring Close monitoring of hydration status; consider dose interruption if loose stools persist

Precautions Ensure adequate fluid intake; avoid concurrent use with high-dose diuretics

Drug/Class Interaction Recommendation

No significant systemic drug interactions Linaclotide acts locally in GI tract with minimal systemic absorption —

High-dose diuretics or volume-depleting agents Additive risk of dehydration and electrolyte imbalance if diarrhoea occurs Avoid concurrent use or monitor hydration closely

Drug/Class Interaction Recommendation

Other laxatives May compound GI effects leading to excessive fluid loss Avoid concurrent use unless clearly indicated

Antidiarrhoeals (loperamide) Opposing mechanism; may reduce efficacy of linaclotide Avoid concurrent use; reassess need if diarrhoea requires antidiarrhoeal

Drugs with narrow therapeutic index (digoxin, warfarin) Increased GI transit may theoretically affect absorption Monitor clinical response; theoretical risk, not well-established

Note: No relevant CYP450 interactions documented.

• Diarrhoea (most common: 16–25%)

• Flatulence

• Abdominal distension

• Abdominal pain or discomfort

• Headache

Adverse Effect Notes

Severe diarrhoea with electrolyte loss May require IV fluid resuscitation and drug discontinuation

Dehydration Particularly in children (contraindicated <6 years), elderly, or renally impaired patients

Anaphylactic reaction Extremely rare; discontinue immediately if suspected

Timing Parameter

Baseline Rule out mechanical bowel obstruction; assess baseline bowel habits

After initiation (1–2 weeks) Assess stool frequency and consistency; monitor for diarrhoea

Ongoing Monitor for dehydration signs, especially in elderly or those on diuretics

Long-term Periodic assessment of GI symptoms; hydration status if diarrhoea persists

• LINZESS® (AbbVie/Allergan)

• LINAVATE® (Zydus Cadila)

• LINACRA® (Alembic Pharmaceuticals)

• CONSTELA® (Lupin)

Note: Linaclotide is NOT listed in NLEM; available in private market only.

• Always administer on an empty stomach, at least 30 minutes before the first meal — food reduces efficacy

• Never prescribe to children below 6 years — risk of fatal dehydration (boxed warning internationally)

• For CIC, 145 mcg is the standard dose; 72 mcg may be considered if 145 mcg is not tolerated

• Diarrhoea is the most common reason for discontinuation — counsel patients and reassess if persistent beyond a few days

• High-cost medication — reserve for patients who have failed non-pharmacological measures and cheaper osmotic laxatives (lactulose, PEG)

• Unlike stimulant laxatives, linaclotide is suitable for long-term use without tolerance development

linaclotide; chronic idiopathic constipation; CIC; IBS-C; irritable bowel syndrome; guanylate cyclase-C agonist; not for children; diarrhoea risk; minimal systemic absorption; gastroenterology

RxIndia v1.0 — 30 Mar 2025

• CDSCO approved product labels

• Indian Pharmacopoeia (formulation listing)

• AIIMS Adult Drug Formulary

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• ICMR Constipation Consensus Statement (2022) — supportive reference

• International RCTs on IBS-C and opioid-induced constipation (marked off-label where applicable)