Linzess (Linaclotide) Titration
Linzess is not titrated—it is prescribed at a fixed dose based on the indication, with 290 μg once daily for IBS-C and either 72 μg or 145 μg once daily for chronic constipation. 1
Fixed Dosing by Indication
For IBS with Constipation (IBS-C)
- Standard dose: 290 μg once daily 1
- This dose has been extensively studied in over 3,193 patients and demonstrates significant improvements in both abdominal pain and bowel movements 1, 2
- The 290 μg dose is the only FDA-approved strength for IBS-C and should not be adjusted up or down 2, 3
For Chronic Idiopathic Constipation (CIC)
- Two approved doses: 72 μg or 145 μg once daily 4
- The 72 μg dose was specifically developed as a lower-dose option with reduced diarrhea risk (2.4% discontinuation rate vs 3.2% with 145 μg) 4
- Both doses are effective, but the choice between them is made at initiation, not through titration 4
For Pediatric Functional Constipation (Ages 6-17)
- Fixed dose: 72 μg once daily 5
- No dose adjustment based on age or weight within the 6-17 year range 5
Managing Diarrhea (The Primary Side Effect)
If diarrhea occurs, the only adjustment is dose reduction or temporary discontinuation—not gradual titration. 6
- Diarrhea is the most common adverse event, occurring in approximately 16.3% of patients on 290 μg vs 2.3% on placebo 2
- For IBS-C patients experiencing diarrhea on 290 μg: reduce to 145 μg or temporarily stop the medication 6
- For CIC patients on 145 μg with diarrhea: reduce to 72 μg 6, 4
- Diarrhea is generally mild and controllable with dose reduction 6
Key Clinical Pitfalls
Do not attempt to "start low and go slow" with linaclotide—this approach, common with neuromodulators like tricyclic antidepressants (which are titrated from 10 mg by 10 mg increments weekly) 1, does not apply to secretagogues like linaclotide. The drug works through a mechanism-based effect on intestinal fluid secretion, not through dose-dependent receptor modulation requiring gradual adjustment 1.
The evidence base supports fixed dosing from day one, with over 5 RCTs involving 3,193 patients demonstrating efficacy at 290 μg for IBS-C without any titration period 1, 2. Similarly, the 72 μg dose for CIC was studied at that fixed dose in 1,223 patients 4.