Cisapride and patient information leaflets
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* Sana R. Sukkari
* Larry D. Sasich

To measure the quality and usefulness of patient information leaflets distributed in Canadian pharmacies, we compared the information contained in 3 leaflets distributed in Canada for cisapride monohydrate (Prepulsid in Canada, Propulsid in the United States) with that in the leaflet approved by the US Food and Drug Administration (FDA). Cisapride has been withdrawn from the US and Canadian markets. 

We obtained 3 patient information leaflets from southern Ontario pharmacies. One was produced by Janssen- Ortho Inc. and another was produced by First DataBank (a US company); the publisher of the third one is unknown. We looked for 5 types of information: a statement of the most serious risk associated with use of cisapride; drugs with which cisapride use is contraindicated; medical conditions with which cisapride use is contraindicated; the safety and effectiveness of the drug in children; and explicit instructions on contacting the prescriber if specific adverse effects are experienced. We found substantial variability in the quality of the leaflets. 

The first paragraph in the FDA- approved patient information leaflet for cisapride begins as follows: “Propulsid may cause serious irregular heartbeats that may cause death.” None of the 3 patient information leaflets distributed in Canada that we looked at contain a statement on potentially fatal cardiac arrhythmia, the most serious risk associated with cisapride. 

The FDA-approved patient information leaflet for cisapride lists 21 generic names and 25 brand names for drugs whose use is contraindicated with cisapride, followed by a caution that “This is not a complete list of medications that you should not take. Therefore, tell your doctor about all other prescription and nonprescription drugs you are taking, including herbal supplements.” The First DataBank patient information leaflet lists 8 drugs and provides brand names for 7 of them. The Janssen-Ortho patient information leaflet lists 24 drugs, but brand names are given for only 9 of them. The patient information leaflet from the unknown publisher lists no drugs whose use is contraindicated with cisapride.

The FDA-approved leaflet lists 12 medical conditions for which cisapride use is contraindicated. The patient information leaflets from the unknown publisher and from First DataBank do not list any of these. The Janssen- Ortho leaflet lists 11 of these 12 contraindications. 

The FDA-approved patient information states that “the safety and effectiveness of Propulsid in children younger than 16 years have not been demonstrated for any use.” The Janssen-Ortho patient information leaflet does indicate that cisapride should not be used in children, but no age range is given. The other 2 patient information leaflets distributed to Canadian patients make no reference to the use of cisapride in children.

The FDA-approved leaflet places the risks of the drug in a useful context for patients, in stating that it may cause serious irregular heartbeats that may cause death. It also gives explicit instructions on the steps a patient should take if the symptoms of cardiac toxicity develop, including stopping use of the drug immediately. None of the leaflets being distributed to Canadian patients that we assessed contained both information on the most serious risk associated with the use of the drug and explicit instructions on the actions that should be taken if the symptoms of toxicity occur. The Janssen-Ortho leaflet instructs patients to stop taking the drug and get medical help if they experience dizziness or irregular heartbeats. The only advice the First DataBank leaflet provides to patients is to “contact your doctor immediately” if any of a long list of adverse effects are experienced, including irregular heartbeats. This leaflet does not instruct patients to stop taking the drug if these symptoms occur. The leaflet from the unknown publisher contains no information of this type. 

Patients or their caregivers may think that the drug information leaflet is all they need in order to understand how to use a drug safely and effectively. If the leaflet omits important information it is thus potentially dangerous. We suggest that the federal government regulate the patient information leaflets distributed by pharmacists for all drugs marketed in Canada. The contents of patient information leaflets should meet regulated standards and should be derived from or consistent with a drug's approved labelling.