Dosing and uses of Propulsid (cisapride)
Adult dosage forms and strengths
Available through investigational limited access program
GERD or Gastrointestinal Dysmotility
5-10 mg PO q6hr at least 15 minutes PC and Hs
May need to increase to 20 mg in some patients
Pediatric dosage forms and strengths
Available through investigational limited access program
Gastrointestinal Dysmotility
0.15-0.3 mg/kg/dose PO q6-8hr; not to exceed 10 mg/dose
Propulsid (cisapride) adverse (side) effects
>10%
Headache
Diarrhea
1-10%
Abdominal pain
Constipation
Tachycardia
Rash
Somnolence
Fatigue
Anxiety
Insomnia
Extrapyramidal effects
Nausea
Sinusitis
Rhinitis
Upper respiratory tract infection
Increased incidence of viral infection
<1%
Bronchospasm
Gynecomastia
Hyperprolactenemia
Methemoglobinemia
Seizure
Psychiatric disturbances
Apnea
Posmarketing Surveillance
Serious cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation reported primarily in patients with known risk factors
Warnings
Black box warnings
Cardiovascular: Serious cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation; risk factors include concurrent therapy with drugs known to cause QT prolongation or depletion of serum electrolytes
Drug Interactions: Contraindicated with numerous drugs including those known to cause QT prolongation (eg, tricyclics, certain antipsychotics) or CYP450 3A4 inhibitors (eg, fluconazole, ketoconazole, itraconazole); see list of disallowed medications at www.propulsid-lap.com
Do not exceed recommended doses
MONITORINg
- Perform baseline 12-lead ECG
- Do not initiate therapy if QTc >450 msec
- Assess serum electrolyte and creatinine levels before initiating and whenever condition develops affecting electrolyte balance or renal function
- Discontinue drug if syncope, tachycardia, or arrhythmia develops
- Drug withdrawn from market in 2000 and is available only via limited access program, see www.propulsid-lap.com
Contraindications
Hypersensitivity
Serious cardiac arrhythmias (V. tach, V. fib, torsades de pointes, and QT prolongation) have been reported in pts taking cisapride with other drugs that inhibit cytochrome CYP3A4**. Some of these events have been fataL
Drugs that increase cisapride levels
- Antibiotics: Oral or iv ERYTHROMYCIN**, CLARITHROMYCIN** (Biaxin), TROLEANDOMYCIN** (TAO)
- Antidepressants: NEFAZODONE** (Serzone)
- Antifungals: Oral or iv FLUCONAZOLE** (Diflucan), ITRACONAZOLE** (Sporanox), ORAL KETOCONAZOLE** (Nizoral), MICONAZOLE**
- Protease Inhibitors: INDINAVIR** (Crixivan), RITONAVIR** (Norvir)
Cisapride also contraindicated for pts w/Hx of, or family Hx of, prolonged QT**; renal failure, ventricular arrhythmias, ischemic heart disease, CHF, clinically significant bradycardia, uncorrected electrolyte disorders (decr K+, decr Mg+), respiratory failure, and concomitant meds known to prolong QT and incr risk of arrhythmia, such as certain antidysrhythmics, certain antipsychotics, certain antidepressants, ASTEMIZOLE**, BEPRIDIL**, SPARFLOXACIN** and TERODILINE**. The preceding lists of drugs are not comprehensive
Cautions
Decrease dose by 50% with liver impairment
Potential benefits should be weighed against risks prior to initiating therapy in patients that may develop prolongation of cardiac conduction intervals, especially QTc
Serious cardiac arrhythmias, tachycardia, ventricular fibrillation, torsade de pointes, and QT prolongation reported in patients taking CYP3A4 inhibitors
Not for use in patients that might experience rapid reduction of plasma potassium as those resulting from potassium wasting diuretics and/or insulin in acute settings
Pregnancy and lactation
Pregnancy category: C
Lactation: enters breast milk; use with caution (AAP Committee states compatible with nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Propulsid (cisapride)
Metabolism: hepatic P450 enzyme CYP3A4
Mechanism of action
Promotes gastric emptying, increases lower esophageal sphincter tone and esophageal peristalsis
Increases gastric motility and cardiac rate possibly by releasing acethylcholine at the myenteric plexus; may act at the serotonin-4 receptor
Pharmacokinetics
Onset of action: 0.5-1 hr
Bioavailability: 35-40%
Half-life: 6-12 hr
Protein binding: 97.5-98%
Metabolism: Liver
Excretion: Urine and feces
