No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Non-Nucleoside)

Treatment of HIV-1 infection in combination with at least two additional antiretroviral agents

C

Clinical effects on the fetus: Administer during pregnancy only if benefits to mother outweigh risks to the fetus

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV

Known hypersensitivity to delavirdine or any components

Avoid use with terfenadine, astemizole, benzodiazepines, clarithromycin, dapsone, cisapride, rifabutin, rifampin; use with caution in patients with hepatic or renal dysfunction; due to rapid emergence of resistance, delavirdine should not be used as monotherapy; cross-resistance may be conferred to other non-nucleoside reverse transcriptase inhibitors, although potential for cross-resistance with protease inhibitors is low. Long-term effects of delavirdine are not known. Safety and efficacy have not been established in children. Rash, which occurs frequently, may require discontinuation of therapy; usually occurs within 1-3 weeks and lasts <2 weeks. Most patients may resume therapy following a treatment interruption.

>2%:

Dermatologic: Rash, pruritus

Gastrointestinal: Nausea, diarrhea, vomiting

Metabolic: Increased ALT/AST

Human reports of overdose with delavirdine are not available

GI decontamination and supportive measures are recommended, dialysis unlikely to be of benefit in removing drug since it is extensively metabolized by the liver and is highly protein bound

CYP2D6 and 3A3/4 enzyme substrate; CYP2D6 and 3A3/4 enzyme inhibitor

Decreased plasma concentrations of delavirdine: Carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, didanosine, saquinavir

Decreased absorption of delavirdine: Antacids, histamine-2 receptor antagonists, didanosine

Delavirdine increases plasma concentrations of: Indinavir, saquinavir, terfenadine, astemizole, clarithromycin, dapsone, rifabutin, ergot derivatives, alprazolam, midazolam, triazolam, dihydropyridines, cisapride, quinidine, warfarin, antiarrhythmics, nonsedating antihistamines, sedative-hypnotics, calcium channel blockers, amprenavir

Delavirdine decreases plasma concentrations of: Didanosine

Delavirdine binds directly to reverse transcriptase, blocking RNA-dependent and DNA-dependent DNA polymerase activities

Absorption: Rapid; peak plasma concentrations at 1 hour

Distribution: Not reported

Metabolism: Hepatic; extensively metabolized by the cytochrome P-450 3A or possibly 2D6

Bioavailability: 85%; AUC may be higher in female patients

Protein binding: ~98%, primarily albumin

Half-life: 2-11 hours

Elimination: 44% in feces, 51% in urine, and <5% unchanged in urine; nonlinear kinetics exhibited. (Note: May reduce CYP3A activity and inhibit its own metabolism.)

Adults: Oral: 400 mg 3 times/day

Delavirdine may be taken without regard to food

Liver function tests if administered with saquinavir

May cause sedation

Fluoxetine may increase plasma concentrations of delavirdine; carbamazepine and phenobarbital may decrease plasma concentrations of delavirdine; delavirdine may increase concentrations of alprazolam, midazolam, and triazolam

No information available to require special precautions

No effects or complications reported

Delavirdine is not a cure for HIV nor has it been found to reduce transmission of HIV. Take as directed, with food. Do not take antacids within 1 hour of delavirdine. Mix 4 tablets in 3-5 ounces of water, allow to stand a few minutes, and stir; drink immediately. You may experience nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help - consult prescriber if nausea or vomiting persists). Report mouth sores; skin rash or irritation; muscle weakness or tremors; easy bruising or bleeding, fever or chills; CNS changes (eg, hallucinations, confusion, dizziness, altered coordination); swelling of face, lips, or tongue; yellowing of eyes or skin; or dark urine or pale stools. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Capsule: 200 mg

Tablet: 100 mg

A dispersion of delavirdine may be prepared by adding 4 tablets to at least 3 oz of water; allow to stand for a few minutes and stir until uniform dispersion; drink immediately; rinse glass and mouth following ingestion to ensure total dose administered

Havlir DV and Lange JM, "New Antiretrovirals and New Combinations," AIDS, 1998, 12(Suppl A):S165-74.

Hilts AE and Fish DN, "Dosage Adjustment of Antiretroviral Agents in Patients With Organ Dysfunction," Am J Health Syst Pharm, 1998, 55:2528-33.