Drug General Information (ID: DDI30MJUSB)
Drug Name			Loperamide		Drug Info		Saquinavir		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antidiarrheals				Anti-Hiv Agents
Structure

Mechanism of Loperamide-Saquinavir Interaction (Severity Level: Moderate)
Altered gastrointestinal dynamics Click to Show/Hide Mechanism Graph
Drug Name		Loperamide				Saquinavir
Mechanism 1		Decrease gastrointestinal motility				Absorption is influenced by gastrointestinal motility
Key Mechanism Factor 1
		Factor Name		Gastrointestinal Motility
		Factor Description		Gastrointestinal motility is an important factor in determining the absorption of orally administered drugs, and it controls the residence time of the drug in the digestive tract.
Mechanism Description		Altered absorption of Saquinavir due to GI dynamics variation caused by Loperamide
Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Drug Name		Loperamide				Saquinavir
Mechanism 2		Prolong QT interval				Prolong QT interval
Key Mechanism Factor 2
		Factor Name		QT interval
		Factor Description		Long QT syndrome is a heart signaling disorder that can cause a fast, chaotic heartbeat (arrhythmia). Many people may not exhibit symptoms, and usually the condition is detected during routine medical tests. In others, the most common symptoms include: sudden fainting, palpitations, dizziness, seizures, sudden death.
Mechanism Description		Increased risk of prolong QT interval by the combination of Loperamide and Saquinavir

Recommended Action
Management		Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, prolonged use of loperamide should preferably be avoided in patients treated with saquinavir. However, the effect of loperamide on the pharmacokinetics of ritonavir-boosted saquinavir is unknown. Caution is recommended if coadministration is required. Patients should be counseled to not exceed the recommended dosage and frequency or duration of use of loperamide, and to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. If loperamide-induced cardiotoxicity is suspected, promptly discontinue loperamide and initiate therapy to manage and prevent cardiac arrhythmias and adverse outcomes. Electrical pacing or cardioversion may be necessary if torsade de pointes persists despite pharmacotherapy. In many of the reported cases of loperamide-induced cardiotoxicity, standard antiarrhythmic drugs were ineffective, and electrical pacing or cardioversion was necessary.

References
1	John L, Marra F, Ensom MH "Role of therapeutic drug monitoring for protease inhibitors." Ann Pharmacother 35 (2001): 745-54. [PMID: 11408994]
2	Mikus G, Schmidt L, Burhenne J, et al. "Reduction of saquinavir exposure by coadministration of loperamide : a two-way pharmacokinetic interaction." Clin Pharmacokinet 43 (2004): 1015-24. [PMID: 15530130]
3	Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, DelGiudice P, Montagne N, Schapiro JM, Dellamonica P "Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study." Aids 14 (2000): 1333-9. [PMID: 10930147]
4	US Food and Drug Administration "FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse.".