Saquinavir interactions

Merry C, Mulcahy F, Barry M, Gibbons S, Back D. Saquinavir interaction with midazolam pharmacokinetic considerations when prescribing protease inhibitors for patients with HIV disease (letter). AIDS 1997 11 268-9. 

In the following example the authors studied the thermodynamics of several HIV-protease inhibitors (Amperavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir) interacting with the immobiUzed protein [Ilj. In Fig. 5... 

Viral protease cleaves precursor proteins into proteins required for viral replication. The inhibitors of this protease (saquinavir, ritonavir, indinavir, and nelfinavir) represent abnormal proteins that possess high antiviral efficacy and are generally well tolerated in the short term. However, prolonged administration is associated with occasionally severe disturbances of lipid and carbohydrate metaboUsm Biotransformation of these drugs involves cytochrome P450 (CYP 3A4) and is therefore subject to interaction with various other drugs inactivated via this route. 

HIV protease inhibitors (eg, indinavir, ritonavir, nelfinavir, saquinavir [see Rifapentine-indinavir interaction above]). 

Dose adjustment for combination therapy with saquinavir For serious toxicities that may be associated with saquinavir mesylate, the drug should be interrupted. Saquinavir mesylate at doses less than 1,000 mg with ritonavir 100 mg twice daily are not recommended since lower doses have not shown antiviral activity. For recipients of combination therapy with saquinavir mesylate and ritonavir, dose adjustments may be necessary. These adjustments should be based on the known toxicity profile of the individual agent and the pharmacokinetic interaction between saquinavir and the coadministered drug. Health care providers should refer the complete monographs for these drugs for comprehensive dose adjustment recommendations and drug-associated adverse reactions of nucleoside analogues. 

Do not administer saquinavir mesylate concurrently with drugs listed in the Drug Interactions section. Inhibition of CYP3A4 by saquinavir could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions such as cardiac arrhythmias or prolonged sedation. 

NA /D, abd pain, bleeding, fevCT, T QT Interactions t Effects W7 atazanavir, clarithromycin, CT5rthromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi-navir, ritonavir, saquinavir, telithromycin X effects W7 antacids, carbamazqjine, dexamethasone, phenobarbital, phenytoin, rifampicin, St. John s wort EMS Drug contains lactose, may cause D/abd discomfort in pts w/ lactose intolerance OD Sxs unknown symptomatic and supportive... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

Ten healthy volunteers participated in a three-period, single-sequence interaction study. In period 1, they received 1200 mg of saquinavir three... 

Interactions with drugs have also been demonstrated for flavonoids from citrus. Naringin and naringenin were shown to interact with simvastatin and saquinavir in in vitro experiments (41,42) and caused alterations in the pharmacokinetics of quinine in rats (44). Moreover, naringenin and naringin were found to inhibit the OATP-B-mediated uptake of estrone-3-sulfate into human embryonic kidney cells (23). 

Amprenavir (151) and indinavir (27,152) showed no changes in pharmacokinetic parameters when administered concomitantly with GFJ. Even 180mL double-strength GFJ had no effect on indinavir pharmacokinetics. The AUC of saquinavir was increased after predosing with GFJ. The mean increase was 1.5-fold (8). In a study performed with one subject, a 5-fold (153) increase was reported. The reported interactions can be considered weak and are unlikely to be clinically relevant. 

The most common adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea often responds to antidiarrheal medications but can be dose-limiting. Nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur (Tables 49-3 and 49-4). An increased dosage of nelfinavir is recommended when co-administered with rifabutin (with a decreased dose of rifabutin), whereas a decrease in saquinavir dose is suggested with concurrent nelfinavir. Co-administration with efavirenz should be avoided due to decreased indinavir levels. Nelfinavir has a favorable safety and pharmacokinetic profile for pregnant women compared with that of other Pis (Table 49-5) there is no evidence of human teratogenicity. 

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