cisapride (Propulsid)
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Introduction
Tradename: Propulsid. Cisapride withdrawn from US market 7/14/2000. Available only through a limited access program for specific conditions, including:
- gastroparesis
- severe chronic constipation
- 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
- symptomatic treatment of nocturnal heartburn secondary to gastroesophageal reflux disease (GERD)
- diabetic gastroparesis
- GI mobility disorders
- WARNING ** should ONLY be used as a LAST RESORT
Contraindications
- history of QT prolongation & concurrent administration of medications which prolong the QT interval (see drug interactions below)
- renal failure
- history of ventricular arrhythmias
- ischemic heart disease
- congestive heart failure
- uncorrected electrolyte abnormalities
- respiratory failure
- GI hemorrhage, mechanical obstruction or perforation
Dosage
- 10-20 mg PO before meals & QHS
- daily dosage should be halved in patients with hepatic &/or renal impairment.
Tabs: 10 & 20 mg.
Pharmacokinetics
- metabolized in the liver by cyt P450 3A4
- 10% excreted unchanged in the urine & feces
- 98% of drug is bound to plasma proteins
- 1/2life 6-12 hours
- propulsid & its metabolites accumulate in patients with hepatic & renal impairment
elimination via liver
elimination via kidney
1/2life = 6-12 hours
protein binding = 98 %
Adverse effects
- common (> 5%)
- less common (< 5%)
- ** serious (FATAL) cardiac arrthythmias **
Drug interactions
- coadministration associated with prolonged QT interval
- anti-fungal agents
- macrolides:
- erythromycin
- clarithromycin
- troleandromycin (TAO)
- antiviral agents
- nefazodone
- fluvoxamine
- class IA antiarrhythmic agents
- class III antiarrhythmic agents
- tricyclic antidepressants (TCA)
- maprotiline
- psychotropic agents
- sertindole
- antihistamines
- bepridil
- sparfloxacin
- terodiline
- coadministration with warfarin increases PT
- any drug that inhibits cyt P450 3A4 may increase levels of cisapride
- any drug that induces cyt P450 3A4 may diminish levels of cisapride
Mechanism of action
- prokinetic agent
- enhancement of acetylcholine release at the myenteric plexus
- 5-HT3 antagonist
- 5-HT4 agonist
- increases lower esophageal sphincter (LES) pressure
- does not have anti-emetic properties
More general terms
Additional terms
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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Federal Drug Administration http://www.fda.gov/medwatch/safety/2000/propul1.htm (877) 795-4247