Linaclotide (Linzess) Dosing Guidelines
Linaclotide (Linzess) is available in three specific doses: 72 mcg, 145 mcg, and 290 mcg, with dosing determined by indication and patient age, with no dose adjustments required for renal impairment due to minimal systemic absorption. 1
Standard Dosing by Indication
Adult Dosing
- Irritable Bowel Syndrome with Constipation (IBS-C): 290 mcg once daily 1
- Chronic Idiopathic Constipation (CIC): 72 mcg or 145 mcg once daily 1
Pediatric Dosing
- Functional constipation (children 6-17 years): 72 mcg once daily 1
- Not recommended for IBS-C in patients under 18 years 1
- Contraindicated in children less than 2 years due to risk of severe dehydration 1
Administration Guidelines
- Take on an empty stomach at least 30 minutes before the first meal of the day
- Take at approximately the same time each day
- Do not crush or chew capsules
- For patients with difficulty swallowing, capsules may be opened and contents mixed with applesauce or water 1
Special Population Considerations
Elderly Patients
- Efficacy in persons 65 years and older is comparable to the overall study population
- No dose adjustment required based on age 1
Renal/Hepatic Impairment
- No dose adjustment required due to minimal systemic absorption 1, 2
- Linaclotide undergoes minimal systemic absorption, making it safe for use across varying levels of renal function 1
Clinical Efficacy
Linaclotide has demonstrated significant efficacy in clinical trials:
- 33.7% of linaclotide-treated patients were FDA endpoint responders vs. 13.9% of placebo-treated patients (NNT = 5.1) 1, 3
- Significantly increases complete spontaneous bowel movements (CSBMs) per week (mean difference 1.37) 1
- Improves abdominal pain, with 48.9% of patients reporting ≥30% reduction vs. 34.5% with placebo 1, 3
Common Adverse Effects
- Diarrhea: Most common adverse effect (16-20% of patients), with 90.5% being mild/moderate in intensity 1, 4, 3
- Diarrhea led to discontinuation in 4.5% of linaclotide patients vs. 0.2% of placebo patients 3
- Other common adverse effects (≥2%) include abdominal pain, flatulence, and abdominal distension 1
Clinical Pearls
- For CIC patients, consider starting with 72 mcg to potentially minimize diarrhea risk 1
- Particularly effective for patients with prominent abdominal bloating/discomfort in addition to constipation 1, 5
- In patients with severe abdominal symptoms, linaclotide has shown significant improvement in bloating, fullness, discomfort, pain, and cramping compared to placebo 5
Contraindications
- Known or suspected mechanical GI obstruction 1
- Severe dehydration risk (in children less than 2 years) 1
Linaclotide represents an important treatment option for IBS-C and CIC, with a novel mechanism of action that accelerates intestinal transit and improves both bowel and abdominal symptoms.