Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Ferring Pharmaceuticals Ltd., Drayton Hall, Church Road, West Drayton, UB7 7PS, United Kingdom
Pharmacotherapeutic group: Contact Laxatives
ATC code: A06AB58
The active components of PICOLAX are sodium picosulfate and magnesium citrate. Sodium picosulfate is a locally acting stimulant cathartic, which after bacterial cleavage in the colon forms the active laxative compound, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), which has a dual-action with stimulation of the mucosa of both the large intestine and of the rectum. Magnesium citrate acts as an osmotic laxative by retaining moisture in the colon. The combined action of the two substances is of a ‘washing out’ effect combined with peristaltic stimulation to clear the bowel.
The product is not intended for use as a routine laxative.
The dosing regimen as described in section 4.2 Posology, and herein further referred to as the tailored dosing regimen, was investigated and evaluated in trial 000121 (OPTIMA). The efficacy, safety and tolerability of PICOLAX administered according to the tailored dosing regimen was compared with the fixed schedule of dosing (i.e. first dose is taken before 8am and second dose is taken 6-8 hours later on the day before procedure), called Day-before dosing regimen (204 patients were randomized, 131 received tailored dosing, 73 received day before dosing).
Superiority of the tailored dosing regimen was demonstrated compared to the day before dosing regimen in overall colon cleansing and responder status for ascending colon cleansing. For overall colon cleansing (primary endpoint), the tailored dosing regimen was compared to the Day-before dosing regimen, based on the treatment difference in mean total Ottawa Scale score (4.26 versus 8.19 in mean total Ottawa scale score for tailored dosing regimen and Day-before dosing regimen respectively, with a corresponding p-value <0.0001, for the Intend to Treat (ITT) analysis set). For the responder status of the ascending colon (key secondary endpoint), the proportion of patients with an Ottawa Scale score of either 0 (excellent) or 1 (good), was compared between the tailored dosing regimen and the Day-before dosing regimen. Patients randomized to the tailored dosing regimen were observed to have a 4.05 times greater chance of being a responder with respect to ascending colon cleansing compared to patients randomized to the Day-before dosing regimen.
| Endpoint | Study Population (n=204) | PICOLAX day before dosing regimen Estimate (n=73) | PICOLAX tailored dosing regimen Estimate (95%CI) (n=131) |
|---|---|---|---|
| Mean Total Ottawa Scale Score (Adjusted estimate) | ITT | 8.19 | 4.26 -3.93(-4.99,-2.87) p-value <0.0001 |
| Proportion of patients with an Ottawa Scale score of either 0 (excellent) or 1 (good) for Ascending Colon Cleansing (Crude estimate) | ITT | 15.1% | 61.1% RD* 0.46 (0.34; 0.58) RR** 4.05 (2.31; 7.11) |
* Absolute Risk Difference (Crude)
** Relative Risk (Crude)
Both active components are locally active in the colon, and neither are absorbed in any detectable amounts.
Prenatal developmental studies in rats and rabbits did not reveal any teratogenic potential after oral dosing of sodium picosulfate, but embryotoxicity has been observed in rats at 1000 and 10000 mg/kg/day and in rabbits at 1000 mg/kg/day. The corresponding safety margins were 3000 to 30000 times the anticipated human dose. In rats, daily doses of 10 mg/kg during late gestation (foetal development) and lactation reduced body weights and survival of the offspring. Male and female rat fertility was not affected by oral doses of sodium picosulfate up to 100 mg/kg.
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