Saquinavir drug interactions

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. 

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. 

Saquinavir is subject to extensive first-pass metabolism by CYP3A4 and functions as a CYP3A4 inhibitor as well as a substrate thus, there are many potential drug-drug interactions (Table 49-4). A decreased dose of saquinavir is recommended when -administered with nelfinavir. Increased saquinavir levels when -administered with omeprazole necessitate close monitoring for toxicities. Digoxin levels may increase if co administered with saquinavir and should therefore be monitored. Liver function tests should be monitored if saquinavir is -administered with delavirdine or rifampin. There is no evidence of human teratogenicity from saquinavir there is short-term safety data for both mother and infant. 

As with other HIV-1 protease inhibitors, saquinavir may be associated with drug interactions as a result of the effect of saquinavir on the hepatic cytochrome P450 oxidase system. Although compared with other HIV protease inhibitors, saquinavir has less of an inhibitory effect on cytochrome P450 isozymes clinically relevant interactions can nevertheless occur. Drug interactions with saquinavir have been reviewed (3). 

Ritonavir (RTV) is also an inhibitor of HIV proteases, approved for use in combination with nucleoside analog, for the treatment of HIV-l infected adults, adolescents, and children. It is a potent CYP 3A4 inhibitor and is used at low doses to elevate plasma concentrations of other protease inhibitors being primarily metabolized by CYP 3A4. In combination with saquinavir, this type of interaction has proved favourable (28). The combination with nelfinavir showed much smaller effects on nelfinavir levels, but it appears to change in normal metabolizers the M8/nelfinavir concentration ratio from 0.3 to 0.6. In poor CYP 2C19 metaboliz-ers (-3-5% of Caucasians and African-Americans, -12-20% of Asians), ritonavir addition is not expected to have such an effect on the nelfinavir/M8 ratio (29). In addition, ritonavir induces CYP isoenzymes, so that the full effect of the nelfina-vir-ritonavir drug-drug interaction is considered stable after a treatment duration of 10-14 days (30). 

PI Protease inhibitors amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir Also note additional drug interactions above. 

Sahai J, Cameron W, Salgo M, Stewart F, Myers M, Lamson M, Gagnier P. Drug interaction study between saquinavir (SQV) and nevirapine (NVP). 4th Conference on Retroviruses and Opportunistic Infections, Washington, 1997. Abstract 613. 

Khaliq Y, Gallicano K, Leger R, Foster B, Badley A. A drug interaction between fusidic acid and a combination of ritonavir and saquinavir. BrJ CUn Pharmacol (2000) 50, 82-3. 

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. 

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. 

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... 

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