Search
cisapride (Propulsid)
Tradename: Propulsid. Cisapride withdrawn from US market 7/14/2000. Available only through a limited access program for specific conditions, including:
1) gastroparesis
2) severe chronic constipation
3) feeding intolerance in neonates. Patients must meet strict criteria for enrollment. Institutional review board approval, completion of Form FDA 1572, & signed informed consent are required. call (877) 795-4247
Indications:
1) symptomatic treatment of nocturnal heartburn secondary to gastroesophageal reflux disease (GERD)
2) diabetic gastroparesis
3) GI mobility disorders
4) ** WARNING ** should ONLY be used as a LAST RESORT
Contraindications:
1) history of QT prolongation & concurrent administration of medications which prolong the QT interval (see drug interactions below)
2) renal failure
3) history of ventricular arrhythmias
4) ischemic heart disease
5) congestive heart failure
6) uncorrected electrolyte abnormalities
7) respiratory failure
8) GI hemorrhage, mechanical obstruction or perforation
Dosage:
1) 10-20 mg PO before meals & QHS
2) daily dosage should be halved in patients with hepatic &/or renal impairment.
Tabs: 10 & 20 mg.
Pharmacokinetics:
1) metabolized in the liver by cyt P450 3A4
2) 10% excreted unchanged in the urine & feces
3) 98% of drug is bound to plasma proteins
4) 1/2life 6-12 hours
5) propulsid & its metabolites accumulate in patients with hepatic & renal impairment
Adverse effects:
1) common (> 5%)
- diarrhea, GI cramping, headache, dyspepsia, flatulence, nausea, dry mouth, rhinitis, rash
2) less common (< 5%)
- tachycardia, extrapyramidal effects, somnolence, fatigue, seizures, insomnia, anxiety
3) ** serious (FATAL) cardiac arrthythmias **
- ventricular tachycardia
- ventricular fibrillation
- torsades de pointes
Drug interactions:
1) coadministration associated with prolonged QT interval
a) anti-fungal agents
- ketoconazole - CONTRAINDICATED
- itraconazole (Sporanox) - CONTRAINDICATED
- miconazole (Monistat) - CONTRAINDICATED
- fluconazole - CONTRAINDICATED
b) macrolides:
- erythromycin
- clarithromycin
- troleandromycin (TAO)
c) antiviral agents
- saquinavir
- ritonavir
- indinavir
d) nefazodone
e) fluvoxamine
f) class IA antiarrhythmic agents
g) class III antiarrhythmic agents
h) tricyclic antidepressants (TCA)
i) maprotiline
j) psychotropic agents
- phenothiazines
- haloperidol
k) sertindole
l) antihistamines
- astemizole
- terfenadine
m) bepridil
n) sparfloxacin
o) terodiline
2) coadministration with warfarin increases PT
3) any drug that inhibits cyt P450 3A4 may increase levels of cisapride
4) any drug that induces cyt P450 3A4 may diminish levels of cisapride
Mechanism of action:
1) prokinetic agent
2) enhancement of acetylcholine release at the myenteric plexus
3) 5-HT3 antagonist
4) 5-HT4 agonist
5) increases lower esophageal sphincter (LES) pressure
6) does not have anti-emetic properties
Related
cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
General
antiulcer agent
benzamide
Properties
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 6-12 HOURS
protein-binding 98%
pregnancy-category C
safety in lactation ?
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Physician's Desk Reference (PDR) 51st edition, Medical
Economics, 1997
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998 - not on National VA formulary
- Kaiser Permanente Northern California Regional
Drug Formulary, 1998 (withdrawn 3/2000)
- Prescriber's Letter 7(2):12, Feb. 2000
- Formulary Update, Kaiser Permanente Northern California,
summer, 2000
- Prescriber's Letter 13(3): 2006
Cytochrome P450 drug interactions
Detail-Document#: 220233
(subscription needed) http://www.prescribersletter.com
- Federal Drug Administration
http://www.fda.gov/medwatch/safety/2000/propul1.htm
(877) 795-4247