delavirdine mesylate
Rescriptor

Available forms
Available by prescription only
Tablets: 100 mg, 200 mg

Indications and dosages
 HIV infection. Adults: 400 mg P.O. t.i.d. with other antiretrovirals as appropriate.

Pharmacodynamics
Antiviral action: Delavirdine is a nonnucleoside reverse transcriptase inhibitor of HIV-1. It binds directly to reverse transcriptase and blocks RNA- and DNA-dependent DNA polymerase activities.

Pharmacokinetics
Absorption: Rapidly absorbed.
Distribution: 98% bound to plasma proteins, primarily albumin. Distribution into CSF, saliva, and semen is about 0.4%, 6%, and 2% of plasma levels, respectively.
Metabolism: Converted to several inactive metabolites; primarily metabolized in liver by cytochrome P-450 3A (CYP3A) enzyme system; however, CYP2D6 may also be involved. Delavirdine can reduce CYP3A activity and can inhibit its own metabolism; this is usually reversed within 1 week after discontinuation of the drug. CYP2C9 and CYP2C19 activity may also be reduced by delavirdine.
Excretion: About 44% of dose is recovered in feces and 51% is excreted in urine. Less than 5% appears unchanged in urine. Mean elimination half-life is 5.8 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components. Use cautiously in patients with impaired hepatic function. Nonnucleoside reverse transcriptase inhibitors, used alone or in combination, may confer cross-resistance to other drugs in that class.

Interactions
Drug-drug. Amphetamines, benzodiazepines, calcium channel blockers, clarithromycin, dapsone, ergot alkaloid preparations, indinavir, nonsedating antihistamines, quinidine, rifabutin, saquinavir, sedative hypnotics, warfarin: Increases or prolongs both therapeutic and adverse effects of these drugs. Avoid use together; however, reduced doses of indinavir and clarithromycin may be used.
Antacids: Reduces delavirdine absorption. Separate doses by at least 1 hour.
Carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin: Decreases plasma delavirdine levels. Use cautiously. Rifabutin levels increase by 100%. Avoid use together.
Clarithromycin, fluoxetine, ketoconazole: Increase delavirdine bioavailability by 50%. Monitor patient. Reduce dose of clarithromycin.
Didanosine: Decreases absorption of both drugs by 20%. Separate doses by at least 1 hour.
H₂-receptor antagonists: Increased gastric pH reduces absorption of delavirdine. Long-term use of these drugs with delavirdine isn’t recommended.
HMG-CoA reductase inhibitors, such as atorvastatin, lovastatin, and simvastatin: Increases levels of these drugs, increasing risk of myopathy, including rhabdomyolysis. Avoid use together.
Indinavir: Increases plasma levels. Consider a lower indinavir dosage when giving with delavirdine.
Saquinavir: Increases bioavailability fivefold. Monitor AST and ALT levels frequently when used together.
Sildenafil: Increases sildenafil plasma levels and may cause increase in sildenafil-associated adverse events, including hypotension, visual changes, and priapism. Don’t exceed 25 mg sildenafil in 48-hour period.
Drug-herb. St. John’s wort: Decreases delavirdine levels. Avoid use together.

Adverse reactions
CNS: asthenia, fatigue, headache, anxiety, depression, insomnia, fever, localized pain.
EENT: pharyngitis, sinusitis.
GI: nausea, vomiting, diarrhea, abdominal pain (generalized or localized).
Respiratory: upper respiratory tract infection, bronchitis, cough.
Skin: rash.
Other: flu syndrome.

Effects on lab test results
• May increase ALT, AST, amylase, bilirubin, and GGT levels. May increase or decrease glucose levels.
• May increase PT and PTT. May decrease hemoglobin, hematocrit, and neutrophil counts.

Overdose and treatment
No information is available. Provide supportive treatment. Remove drug by gastric lavage or emesis, if needed. Dialysis is unlikely to be effective because drug is highly protein-bound.

Special considerations
• Rash is more common in patients with lower CD4+ cell counts and usually occurs within the first 3 weeks of treatment. Severe rash has occurred in 3.6% of patients. In most cases, rash lasted less than 2 weeks and didn’t need dose reduction or drug discontinuation. Most patients resumed therapy after it was interrupted by rash.
• Rash occurs mainly on the upper body and proximal arms, with decreasing intensity on the neck and face and less on the rest of the trunk and limbs. Erythema multiforme and Stevens-Johnson syndrome are rare and have resolved after drug was stopped. Occurrence of drug-related rash after 1 month of therapy is uncommon except in prolonged interruption of drug treatment.
• Symptomatic relief may be obtained by using diphenhydramine, hydroxyzine, or topical corticosteroids.
• Neutropenia (absolute neutrophil count less than 750/mm³), anemia (hemoglobin less than 7 g/dl), thrombocytopenia (platelet count less than 50,000/mm³), increased ALT and AST levels (more than five times upper limit of normal), increased bilirubin levels (more than 21/2 times the upper limit of normal), and increased amylase levels (more than twice upper limit of normal) may occur during delavirdine therapy. Monitor patient carefully.
Breast-feeding patients
• Advise HIV-infected women not to breast-feed.
Pediatric patients
• Safety and effectiveness haven’t been studied in patients younger than age 16.
Geriatric patients
• Safety and effectiveness haven’t been studied in patients older than age 65.

Patient education
• Instruct patient to discontinue drug and report severe rash or such symptoms as fever, blistering, oral lesions, conjunctivitis, swelling, or muscle or joint aches.
• Advise patient that numerous adverse effects may be related to drug therapy and to call if he has any unusual or worrisome symptoms.
• Tell patient that drug doesn’t cure HIV-1 infection and that he may continue to develop HIV-related illnesses, including opportunistic infections. Therapy doesn’t affect such illnesses.
• Advise patient to remain under medical supervision when taking drug because long-term effects aren’t known.
• Inform patient to take drug as prescribed and not to alter doses without medical approval. If he misses a dose, tell him to take the next dose as soon as possible; he shouldn’t double the next dose.
• Inform patient that drug may be dispersed in water before ingestion. Tell patient to add tablets to at least 3 oz (90 ml) of water, let stand for a few minutes, and stir until a uniform dispersion occurs. Tell patient to drink dispersion promptly, rinse glass, and swallow the rinse to make sure entire dose is consumed.
• Advise patient with achlorhydria to take drug with an acidic beverage such as orange or cranberry juice.
• Advise patient to report the use of other prescription or OTC medications.
• Advise patients receiving sildenafil that there’s an increased risk of sildenafil-associated adverse events, including hypotension, visual changes, and priapism, and to promptly report symptoms. Tell them not to exceed 25 mg of sildenafil in a 48-hour period.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use