Table 22Summary of trials assessing the general safety and harms of tegaserod for the treatment of chronic constipation and IBS-C in adults

Author, yearStudy designN; Study durationComparisonsPopulation, % female, settingResultsQuality rating
CHRONIC CONSTIPATION
Johanson et al., 200437RCT1348; 12 weeksTegaserod (2 mg and 6 mg BID) vs. placeboAdults with chronic constipation, 90% femaleNo significant differences in AEs or discontinuation due to AEs; Diarrhea (4.5% vs. 7.3% vs. 3.8%); Most frequent AEs were headache (9.2% vs. 9.8% vs. 12.8%) and nasopharyngitis (7.6% vs. 8.4% vs. 10.8%)N/A*
Kamm et al., 200538RCT1264; 12 weeksTegaserod (2 mg and 6 mg BID) vs. placeboAdults with chronic constipation, 86% femaleNo significant differences in AEs or discontinuation due to AEs between groups; Diarrhea was more common in 6mg than placebo (P = 0.007) but not in 2mg (P = 0.1516 vs. placebo); most common AEs were headache and abdominal pain; both were more common among placebo.N/A*
Lin et al., 200739RCT607; 4 weeksTegaserod 6 mg BID vs. placeboChina; adults with chronic constipation, 78% femaleDiarrhea was the most common AE and was more common with tegaserod (3.6% vs. 1.7%). Frequency and severity of AEs and withdrawal due to AEs was otherwise comparable.N/A*
Quigley et al., 2006402 RCTs – pooled for safety analysis2612; 12 weeksTegaserod (2 mg and 6 mg BID) vs. placeboAdults with chronic constipation, 88% femaleAE incidence was similar for all groups (56.3% vs. 57.1% vs. 59.6% for 2mg, 6mg, and placebo); most common AE was headache which was more common with placebo (10.1% vs. 11% vs. 13.2%); only diarrhea was significantly different between groups (6.6% for 6mg vs. 3.0% for placebo; P = 0.0005)N/A*
Fried et al., 200759RCT322; 12 weeksTegaserod (6mg BID) vs. placeboAdults with chronic constipation, 0% femaleSimilar frequency of total AEs (37.3% vs. 32.3%); GI disturbances were more common with tegaserod (17.1% vs. 8.5%); diarrhea (8.2% vs. 0.6%); Among 4 non-fatal serious AEs in the tegaserod group (vs. 2 with placebo), all were cardiac disorders (2 CAD, 1angina, 1 atrial fibrillation)N/A*
Muller-Lissner et al., 200664Uncontroll ed extension of a 12 week RCT842 entered, 451 completed ; 13 monthsTegaserod (2mg BID or 6mg BID)Adults with chronic constipation, 87% femaleNo notable differences in AEs compared to short- term treatment; only half of patients completed the extension study; discontinuation reasons: 19.3% lack of efficacy, 11% withdrawal of consent; 6.3% AEs; headache and abdominal pain were the most common AEs; diarrhea in 2.0–8.5%N/A*
IRRITABLE BOWEL SYNDROME
Evans et al., 200460Systematic review4040; 8 to 12 weeksTegaserod (2 mg and 6 mg BID) vs. placebo12 years or older with IBS-C, primarily female (overall % NR)Diarrhea was significantly higher in the tegaserod 6mg BID than placebo (RR 2.75; 95% CI 1.90, 3.97); NNH 20; trend toward higher frequency of headache (RR 1.18; 95% CI 0.97–1.44) abdominal pain (RR 1.11; 95% CI 0.86, 1.43) and nausea (RR 1.20; 95% CI 0.88, 1.63) with tegaserod (6mg BID) than placebo.N/A*
Fried et al., 200562Open- label PCS843; 8 weeksTegaserod 6mg BIDAdults with IBS-C, 72% femaleAEs in 38%; diarrhea in 13% during first week and 7% thereafter; headache 12%; about 25% left the study early, mainly due to AEs; 0.9% serious AEs, 1 was cardiovascular (chest pain); no deathsN/A*
Kellow et al., 200348RCT520 12 weeksTegaserod 6 mg BID vs. placeboAdults with constipation predominant IBS-C, 88% female, Asia-Pacific regionDiarrhea (10% vs. 3.1%) and abdominal pain (5.8% vs. 3.1%) were more frequent with tegaserod; other AE frequencies were similar; headache was most common AE (12% tegaserod vs. 11.1% placebo); discontinuation due to diarrhea in 2.3% of tegaserod; serious AEs (1.5% vs. 3.4%); more SAEs in the placebo group; no deathsN/A*
Morganroth et al., 2002613 RCTs – pooled for safety analysis2516; 12 weeksTegaserod (2 mg and 6 mg BID) vs. placeboAdults with IBS-C, 84% femaleNo difference in new or worsening EKG abnormalities (tegaserod groups 11% vs. placebo 10%), QTc interval changing from normal to prolonged (0.4% vs. 0.6%), or frequency of cardiac arrhythmias (1.5% vs. 1.5%); no VT or SVT; diarrhea 11.7% vs. 5.4%N/A*
Muller-Lissner et al., 200149RCT881 12 weeksTegaserod (2 mg and 6 mg BID) vs. placeboAdults with 3- month history of IBS-C, 83% femaleAEs were similar in all groups; only diarrhea was more frequent with tegaserod than placebo (7.1%, 9.6%, 2.5%); headache (27.3%– 30.6%) and abdominal pain (16.5%–17.1%) were the most common AEsN/A*
Novick et al., 200250RCT1519; 12 weeksTegaserod 6 mg BID vs. placeboAdult females with IBS-C, 100% femaleOverall AEs (58.3% vs. 55.7%); headache (9.0 vs. 5.7%), nausea (6.8% vs. 4.7%), and diarrhea (6.4% vs. 2.9%) were more frequent in the tegaserod groupN/A*
Nyhlin et al., 200447RCT647; 12 weeksTegaserod 6 mg BID vs. placeboAdults with constipation predominant IBS-C, 86% femaleMore overall AEs with tegaserod (55% vs. 50%); headache was the most frequently reported AE overall (8.0% vs. 4.7%); diarrhea more frequent with tegaserod (9.2% vs. 1.3%) and led to discontinuation in 2.8% of tegaserod group; 1 death in the tegaserod group due to acute myocardial infarctionN/A*
Tack et al., 200551RCT2660; 1 monthTegaserod 6 mg BID vs. placeboAdult females with IBS-C, 100% femaleOnly diarrhea was reported significantly more frequently with tegaserod (3.8% vs. 0.6%; P < 0.0001); headache was the most common AE reported (5.5% vs. 5.0%; P NS); discontinuations due to AEs were similar; no deathsN/A*
Tougas et al., 200263Open- label PCS579 (53% completed trial); 12 monthsTegaserod 2 or 6 mg BID, flexible dose titrationAdults with constipation predominant IBS-C, 90% femaleDiarrhea 10.1%; headache 8.3%; abdominal pain 7.4%; flatulence 5.5%; SAEs in 4.4% including chest pain in 2 patients; 11.2% of all subjects discontinued due to AEsN/A*

AE: adverse events; BID: twice a day; CAD: coronary artery disease; EKG: electrocardiogram; GI: gastrointestinal; IBS-C: Irritable Bowel Syndrome; NNH: number needed to harm; NR: not reported; NS: not significant; QTC: Q; PCS: prospective cohort study; PEG: polyethylene glycol; RCT: randomized controlled trial; RR: risk ratio; SAEs: serious adverse events; SVT: supraventricular tachycardia; VT: ventricular tachycardia

*Because tegaserod has been taken off the market in the US, we did not rate the internal validity of individual studies

From: Results

Cover of Drug Class Review: Constipation Drugs
Drug Class Review: Constipation Drugs: Final Report [Internet].
Gartlehner G, Jonas DE, Morgan LC, et al.
Portland (OR): Oregon Health & Science University; 2007 Sep.
Copyright © 2007, Oregon Health & Science University, Portland, Oregon.

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