ADVERSE REACTIONS
In the U.S. clinical trial population of 1728 patients (comprising 506 with gastroesophageal reflux disorders, and the remainder with other disorders) the following adverse experiences were reported in more than 1% of patients treated with PROPULSID® (cisapride) and at least as often on PROPULSID® as on placebo.
System/Adverse Event | PROPULSID ® N=1042 | Placebo N=686 |
Central & Peripheral Nervous Systems | | |
Headache | 19.3% | 17.1% |
| | |
Gastrointestinal | | |
Diarrhea | 14.2 | 10.3 |
Abdominal pain | 10.2 | 7.7 |
Nausea | 7.6 | 7.6 |
Constipation | 6.7 | 3.4 |
Flatulence | 3.5 | 3.1 |
Dyspepsia | 2.7 | 1.0 |
| | |
Respiratory System | | |
Rhinitis | 7.3 | 5.7 |
Sinusitis | 3.6 | 3.5 |
Coughing | 1.5 | 1.2 |
| | |
Resistance Mechanism | | |
Viral infection | 3.6 | 3.2 |
Upper respiratory tract infection | 3.1 | 2.8 |
| | |
Body as a Whole | | |
Pain | 3.4 | 2.3 |
Fever | 2.2 | 1.5 |
| | |
Urinary System | | |
Urinary tract infection | 2.4 | 1.9 |
Micturition frequency | 1.2 | 0.6 |
| | |
Psychiatric | | |
Insomnia | 1.9 | 1.3 |
Anxiety | 1.4 | 1.0 |
Nervousness | 1.4 | 0.7 |
| | |
Skin & Appendages | | |
Rash | 1.6 | 1.6 |
Pruritus | 1.2 | 1.0 |
| | |
Musculoskeletal System | | |
Arthralgia | 1.4 | 1.2 |
| | |
Vision | | |
Abnormal vision | 1.4 | 0.3 |
| | |
Reproductive, Female | | |
Vaginitis | 1.2 | 0.9 |
The following adverse events also reported in more than 1% of PROPULSID® patients were more frequently reported on placebo: dizziness, vomiting, pharyngitis, chest pain, fatigue, back pain, depression, dehydration and myalgia.
Diarrhea, abdominal pain, constipation, flatulence and rhinitis all occurred more frequently in patients using 20 mg of PROPULSID® than in patients using 10 mg.
Additional adverse experiences reported to occur in 1% or less of patients in the U.S. clinical studies are: dry mouth, somnolence, palpitation, migraine, tremor and edema.
In other U.S. and international trials and in postmarketing experience, there have been rare reports of seizures and extrapyramidal effects. Also reported have been tachycardia, elevated liver enzymes, hepatitis, thrombocytopenia, leukopenia, aplastic anemia, pancytopenia and granulocytopenia. The relationship of PROPULSID® to the event was not clear in these cases.
Cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation, in some cases resulting in death, have been reported. (See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and Drug Interactions.)
Ongoing Postmarketing Surveillance: Serious cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation have been reported in patients taking PROPULSID ® . From July 1993 through May 1999, more than 270 such cases have been spontaneously reported, including 70 fatalities. In approximately 85% of these cases the events occurred when PROPULSID ® was used in patients with known risk factors. These risk factors included the administration of other drugs which caused QT prolongation, inhibited the cytochrome P450 3A4 enzymes that metabolize cisapride, or depleted serum electrolytes; or the presence of disorders that may have predisposed patients to arrhythmias. In approximately 0.7% of these cases, the events occurred in the absence of identified risk factors; in the remaining cases, risk factor status was unknown. Because the cases were reported voluntarily from a population of unknown size, estimates of adverse event frequency cannot be made. (See Boxed Warning, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and Drug Interactions.) PROPULSID®-induced serious ventricular arrhythmias and death may not correlate with the degree of drug-induced prolongation of the QT interval detected by 12-lead ECG.
In addition to the cardiovascular adverse events, the following events have been identified during post-approval use of PROPULSID® in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion in this insert due to a combination of their seriousness, frequency of reporting, or potential causal connection to PROPULSID®: allergic reactions, including bronchospasm, urticaria, and angioedema; possible exacerbation of asthma; psychiatric events, including confusion, depression, suicide attempt, and hallucinations; extrapyramidal effects including akathisia, Parkinson-like symptoms, dyskinetic and dystonic reactions; gynecomastia, female breast enlargement, urinary incontinence, hyperprolactinemia and galactorrhea.
The following events were specifically reported in the pediatric population: antinuclear antibody (ANA) positive, anemia, hemolytic anemia, methemoglobinemia, hyperglycemia, hypoglycemia with acidosis, unexplained apneic episodes, confusion, impaired concentration, depression, apathy, visual changes accompanied by amnesia, and severe photosensitivity reaction.
There have been rare cases of sinus tachycardia reported. Rechallenge precipitated the tachycardia again in some of those patients.
|