Darunavir

Treatment of HIV-1 infections in combination with ritonavir and other antiretroviral agents.

Coadministration with medications highly dependent upon CYP3A4 for clearance and for which increased levels are associated with serious and/or life-threatening events e.g. alfuzosin, cisapride, ergot alkaloids [eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine], lovastatin, midazolam [oral], pimozide, rifampin, sildenafil (when used for pulmonary artery hypertension ) , simvastatin, St John's wort, triazolam.

Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

Hepatotoxicity: Infrequent cases of drug-induced hepatitis (including acute and cytolytic) have been reported. May exacerbate pre-existing hepatic dysfunction.

Hypersensitivity reactions:

Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required.

Increased cholesterol: Increases in total cholesterol and triglycerides have been reported;

Pancreatitis: use caution in patients at risk for pancreatitis including those with elevated triglycerides, advanced HIV disease, or history of pancreatitis.

Sulfonamide allergy: contains sulfa moiety

Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of diabetes, DKA, and new-onset diabetes mellitus have been reported in patients receiving protease inhibitors.

Hemophilia A or B: increased bleeding during protease inhibitor therapy

Colchicine: Do not coadminister in patients with renal or hepatic impairment.

High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates ;

Salmeterol: Concomitant use not recommended due to increased risk of cardiovascular adverse events, including QT_c prolongation.

As a class, protease inhibitors potentially cause dyslipidemias which includes elevated cholesterol and triglycerides and a redistribution of body fat centrally to cause increased abdominal girth, buffalo hump, facial atrophy, and breast enlargement. These agents also cause hyperglycemia.

Endocrine & metabolic: Hypercholesterolemia, LDL increased, Hyperglycemia, triglycerides increased, diabetes mellitus

Gastrointestinal: Vomiting, diarrhea, Abdominal pain, nausea, amylase increased, lipase increased, abdominal distention, anorexia, dyspepsia

Central nervous system: Headache, fatigue

Dermatologic: Rash

Hepatic: ALT increased, AST increased, alkaline phosphatase

Neuromuscular & skeletal: Weakness

Food: Bioavailability is increased when administered with food.

Herb/nutraceutical: St John’s wort may decrease the plasma levels of darunavir; concomitant use is contraindicated

Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. This results in the formation of immature, noninfectious viral particles.

C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Excretion in breast milk unknown/not recommended