Adverse Effects of Laxatives From Randomized Controlled Trials
| RCTs | Comparison | Intervention | Duration | Adverse events | Drop out |
|---|---|---|---|---|---|
| Intra-class comparisons | |||||
| Ewerth et al18 (1980), Sweden | Bulk vs Placebo |
A: Psyllium 6 g bid B: Placebo |
8 wk |
Less AEs during bulk laxative treatments Mild abdominal pain and flatulence during placebo |
10% (1/10) |
| Finlay19 (1988), UK | Bulk vs Placebo |
A: Bran 1.5-4.5 g qd B: Regular diet |
6 wk | One patient reported difficulty in swallowing bran | 14.3% (2/14) (one due to swallowing difficulty and the other due to refusal of bran) |
| Rajala et al20 (1988), Finland | Bulk vs Placebo |
A: Yoghurt + bran 150 mL bid B: Yoghurt bid |
2 wk | No significant changes were observed in blood glucose, serum cholesterol or triglyceride, body weights or fecal pH values in either group | Not described |
| Cheskin et al21 (1995), USA | Bulk vs Placebo |
A: Psyllium 6 g qid B: Placebo |
4 wk | No difference between groups | 30.0% (3/10) (cannot tolerate the repeated perfused catheter for anorectal manometry) |
| Chokhavatia et al22 (1988), USA | Bulk vs Bulk |
A: Calcium polycarbophil 2 g qd B: Psyllium 9.5 g qd |
3 wk | Not described | 7.0% (3/42) (all unrelated to the study medication) |
| Wesselius-De Casparis et al23 (1968), Netherland | Osmotic vs Placebo |
A: Lactulose 15 mL qd B: Placebo |
3 wk | The only AEs sometimes observed was transient gas formation and intestinal bloating | Not described |
| Sanders24 (1978), USA | Osmotic vs Placebo |
A: Lactulose 30 mL qd B: Placebo |
12 wk |
No adverse clinical and laboratory effects in both groups Results of blood and urine laboratory tests were within normal limits |
10.6% (5/47) |
| Vanderdonckt et al25 (1990), Belgium | Osmotic vs Placebo |
A: Lactitol 20 g qd B: Placebo |
4 wk | All reported adverse effects were abdominal symptoms, such as bloating and flatulence, compatible with the administration of a non-absorbable sugar | 8.7% (4/46) |
| Dipalma et al26 (2007), USA | Osmotic vs Placebo |
A: PEG 3350 17 g qd B: Placebo |
6 mo | No treatment emergent safety differences betweenPEG and placebo over the course of the 6-mo study except for gastrointestinal complaints (PEG 39.7%, placebo 25%)a Most of these events were mild or moderate. There were no clinically significant laboratory changes | 0.7% (2/306) (randomization error, noncompliance) |
| Lederle et al27 (1990), USA | Osmotic vs Osmotic |
A: Lactulose 30-60 mL qd B: Sorbitol 30-60 mL qd |
4 wk | There were no significant differences between sorbitol and lactulose in any outcome measured except nausea, which increased with lactulosea | 3.2% (1/31 while receiving lactulose) |
| Seinelä et al28 (2009), Finland | Osmotic vs Osmotic |
A: PEG 4000 without electrolyte 12 g qd B: PEG 4000 with electrolyte 12 g qd |
4 wk |
All AEs: 7 (23.3%) patients in the PEG without electrolyte vs 6 (18.8%) in the PEG with electrolyte group (NS) Serious AEs: 0 patients in PEG without electrolyte vs 3 (9.3%) in PEG with electrolyte group (hospitalization due to hypotension, congestive heart failure, and myocardial infarction) Significant difference in plasma sodium level: 138.8 mEq/L → 137.7 mEq/L in PEG without electrolyte vs 138.6 mEq/L → 138.9 mEq/L in PEG with electrolyte.a However, none were considered to be clinically significant and none led to intervention |
3.3% in PEG without electrolyte group (1/30, for personal reason) 6.3% in PEG with electrolyte group (2/32, 1 due to AE, 1 for personal reason) |
| Chassagne et al29 (2017), France | Osmotic vs Osmotic |
A: PEG 4000 10-30 g qd B: Lactulose 10-30 g qd |
6 mo |
No clinically relevant or statistically significant changes in the proportion of patients with abnormal values between PEG 4000 and lactulose at Month 6 At least one AEs: 64 (50.4%) patients in lactulose vs 67 (56.8%) in PEG 4000 (NS) Serious AEs: 16 (12.6%) patients in lactulose vs 24 (20.3%) in PEG 4000 (NS) AEs that led to permanent discontinuation: 8 (6.3%) patients in lactulose vs 3 (2.5%) in PEG 4000 (NS) |
34.6% (44/127) in lactulose group 24.6% (29/118) in PEG 4000 group |
| Stern 1966, USA | Stimulant vs Placebo |
A: Prucara (162 mg prune concentrate and 162 mg cascarin) 2 tablets bid B: Placebo |
3 wk | Watery stool in 1 treated patient (4%, 1/25) | Not described |
| Hyland and Foran30 (1968), UK | Softener vs Placebo |
A: DSS 100 mg tid B: Placebo |
4 wk | Not described | 13.0% (6/46, 5 unrelated deaths, 1 patient could not tolerate placebo tablet) |
| Fain et al31 (1978), USA | Softener vs Softener |
A: DSS 100 mg qd B: DSS 100 mg bid C: DCS 240 mg qd |
3 wk |
No adverse effect was seen in 3 groups No laboratory abnormalities |
2.0% (1/47) |
| Inter-class comparisons | |||||
| Kinnunen and Salokannel32 (1987), Finland | Bulk vs Osmotic |
A: Magnesiumhydroxide 25 mL qd B: Bulk laxative 8.7 g qd |
8 wk | Serum magnesium 2.92 mEq/L in a patient with impaired renal function and 2.74 mEq/L in a patient with normal creatinine but lowered creatinine clearance after the magnesium hydroxide treatment | 5.1% (3/59, 3 unable to swallow bulk laxative) |
| Kinnunen et al33 (1993), Finland | Bulk + Stimulant vs Osmotic |
A: Agiolax 20 mL qd B: Lactulose 30 mL qd |
5 wk | No adverse effects and changed in laboratory parameters in both treatments | 20.0% (6/30) (1 myocardial infarction, 1 fatal pneumonia in Agiolax group, 1 weakening of general condition and 1 ineffectiveness of medication in lactulose group, 2 referrals to other hospitals) |
| Passmore et al34 (1993), UK | Bulk+Stimulant vs Osmotic |
A: Agiolax 10 mL qd B: Lactulose 15 mL bid |
2 wk | 24 (31.2%) with Agiolax group and 21 (27.3%) with lactulose group (NS). Flatulence, urgency, and cramps were the most common AEs | 9.4% (8/85) (3 withdrawn after first treatment period, 3 unacceptable compliance, 1 deteriorating health, and 1 incomplete data) |
| Pers and Pers35 (1983), Sweden | Bulk + Stimulant vs Bulk + Stimulant |
A: Agiolax 1 sachet qd (15 mg senna) B: Lunelax 1 sachet qd (25 mg senna) |
2 wk | No AEs were seen with either of the preparations | 5.0% (1/20) (severe diarrhea not related with the medication) |
| Novel medications | |||||
| Camilleri et al36 (2009), USA and Belgium | Prucalopride vs Placebo |
A: Placebo B: Prucalopride 0.5 mg qd C: Prucalopride 1 mg qd D: Prucalopride 2 mg qd |
4 wk |
Serious AEs: A: 0 B: 2 (moderate diarrhea and urinary tract infection) C: 0 D: 0 Discontinuation due to AEs: A 0 B 3 (nonsustained ventricular tachycardia, 2 cases as above) C 1 (death d/t lobar pneumonia) D 0 QTc prolongation: A 1 B 1 C 1 D 0 |
A 22.2% (4/18, 2 other reason, 2 withdrawal of consent) B 14.3% (3/21, 3 due to AEs) C 12.5% (3/24, 1 due to AEs, 1 withdrawal of consent, 1 noncompliance) D 7.7% (2/26, 1 other reason, 1 withdrawal of consent) |
| Müller-Lissner et al37 (2010), Germany and Belgium | Prucalopride vs Placebo |
A: Placebo B: Prucalopride 1 mg qd C: Prucalopride 2 mg qd D: Prucalopride 4 mg qd |
4 wk |
Total AEs: A 44.4% B 48.7% C 38.7% D 47.5% Severe AEs: A 1 (“arrythmia” and “myocardial infarction” considered not related to the medication) B 1 (“mild drug abuse”) C 0 D 1 (fracture of the left forearm) Discontinuation due to AEs: A 2.9% (2/70) B 2.6% (2/76) C 5.3% (4/75) D 8.8% (7/79) |
A 10.0% (7/70) B 9.2% (7/76) C 10.7% (8/75) D 13.9% (11/79) |
| Ueno et al38 (2006), USA | Lubiprostone vs Placebo |
A: Lubiprostone 24 mcg bid B: Placebo |
4 wk |
AE incidence rates A 12 (46.2%) B 19 (61.3%) (NS) |
Not identified |
| Nakajima et al39 (2019), Japan | Elobixibat vs Placebo |
A: Elobixibat 10 mg qd B: Placebo |
52 wk |
Abdominal pain Patients < 65 yr: 81 (26%) Patients ≥ 65 yr: 1 (4%) Diarrhea Patients < 65 yr: 47 (15%) Patients ≥ 65 yr: 3 (12%) (NS) |
Not identified |
| Menees et al40 (2020), USA | Plecanatide vs Placebo |
A: Placebo B: Plecanatide 3 mg qd C: Plecanatide 6 mg qd |
12 wk |
Proportions of AEs: A 24.7%, B 35.3%, C 31.9% Proportions of Serious AEs: A 1.9%, B 2.0%, C 1.4% |
A 4.3%, B 6.7%, C 7.3% |
a
bid, 2 times a day; qd, once a day; AEs, adverse effects; RCTs, randomized controlled trials; PEG, polyethylene glycol; mEq/L, milliequivalent per liter; QTc, corrected QT interval.