Saquinavir Disease Interactions

QT and PR interval dose-dependent prolongation and torsades de pointes have been reported with the use of saquinavir (saquinavir should always be used in combination with ritonavir). Saquinavir should not be used in patients with congenital long QT syndrome, patients with refractory hypokalemia or hypomagnesemia, or in combination with other drugs that can both prolong the QT interval and increase the plasma concentration of saquinavir. Saquinavir is also contraindicated in patients with a complete atrioventricular (AV) block without an implanted pacemaker or patients at risk of a complete AV block.
Caution and close EKG and electrolyte monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias, structural heart disease, cardiomyopathies, ischemic heart disease, hepatic impairment, and electrolyte abnormalities.

There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors; however, a causal relationship has not been established. In some patients, additional factor VIII was given. In more than half of the reported cases, protease inhibitor therapy was continued or reintroduced. Patients with hemophilia or other coagulation defects should be monitored closely for bleeding during protease inhibitor therapy.

New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, and some cases of diabetic ketoacidosis have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitors. Some patients required either initiation or dosage adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, hyperglycemia persisted despite discontinuation of protease inhibitor therapy. A causal relationship has not been established between protease inhibitor therapy and these events. Monitoring patients for hyperglycemia, new onset diabetes mellitus, or exacerbation of diabetes mellitus should be considered during protease inhibitor therapy.

Treatment with ritonavir alone or in combination with other protease inhibitors (e.g., lopinavir, saquinavir, tipranavir, fosamprenavir) has resulted in substantial increases in the concentration of total cholesterol and triglycerides. These effects have also been reported with other protease inhibitors but may be the most dramatic with ritonavir. The clinical significance of these elevations is unclear. Marked elevation in triglyceride levels is a risk factor for development of pancreatitis. Triglyceride and cholesterol testing is recommended before starting ritonavir (with or without other protease inhibitors) and periodically during therapy. Lipid disorders should be managed as clinically appropriate.

Saquinavir is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from saquinavir due to decreased drug clearance, so therapy should be administered cautiously in these patients. Additionally, there have been reports of worsening liver disease in patients with underlying hepatitis B or C, cirrhosis, chronic alcoholism, and other liver abnormalities. Close monitoring is recommended. The use of saquinavir when administered with ritonavir is contraindicated in patients with severe hepatic impairment.

The principal route of excretion for saquinavir is by hepatic metabolism, therefore no initial dose adjustment is necessary in patients with renal impairment. However, saquinavir has not been studied in patients with severe renal impairment and end-stage renal disease, and caution should be exercised when prescribing this drug to these patients.