Delavirdine Mesylate

Pronunciation: (Dell-ah-ver-deen MEH-sih-late)Class: Antiretroviral, Non-nucleoside reverse transcriptase inhibitor

Trade Names:Rescriptor- Tablets 100 mg

Pharmacology

Inhibits replication of HIV-1 infection by interfering with DNA synthesis.

Pharmacokinetics

Absorption

Rapidly absorbed. T _max approximately 1 h. C _max approximately 35 mcM. AUC approximately 180 mcM•h.

Distribution

Approximately 98% protein bound, primarily albumin.

Metabolism

Primarily metabolized by CYP3A and possibly CYP2D6 to several inactive metabolites.

Elimination

Approximately 44% excreted in feces and approximately 51% in urine (less than 5% as unchanged drug). t _½ is approximately 5.8 h.

Indications and Usage

Treatment of HIV-1 infection in combination with appropriate antiretroviral agents when therapy is warranted.

Contraindications

Standard considerations.

Dosage and Administration

Adults and Children older than 16 yr of age

PO 400 mg 3 times daily in combination with appropriate antiretroviral therapy.

General Advice

• Administer with an acidic beverage (eg, orange or cranberry juice) if patient has achlorhydria.
• May disperse tablets in water prior to administration. Add tablets to at least 3 oz of water. Stir until uniformly dispersed and administer promptly. Rinse glass and have patient swallow the rinse to ensure the entire dose is consumed.
• If patient also takes antacids, separate doses by at least 1 h.

Storage/Stability

Store at controlled room temperature in tightly closed container. Protect from high humidity.

Drug Interactions

Antacids

Antacids reduce absorption of delavirdine. Separate doses by at least 1 h.

Anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin)

Induce hepatic metabolism of delavirdine resulting in decreased plasma concentrations.

Benzodiazepines (eg, alprazolam, midazolam, triazolam)

Delavirdine may increase blood levels of these drugs, which may produce extreme sedation and respiratory depression.

Cisapride, dapsone, ergot derivatives, quinidine, rifabutin, warfarin

Delavirdine may elevate blood levels of these drugs, which may increase the risk of arrhythmias or other potentially serious adverse reactions.

Clarithromycin

Coadministration may increase blood levels of delavirdine or clarithromycin.

Didanosine

Separate administration of didanosine and delavirdine by at least 1 h; coadministration results in a 20% reduction in systemic exposure of both drugs.

Dihydropyridine calcium channel blockers (eg, nifedipine)

Delavirdine may elevate blood levels, which may increase toxicity.

Fluoxetine, ketoconazole

Increased delavirdine plasma concentrations.

H ₂ antagonists (eg, cimetidine)

Concurrent use may reduce absorption of delavirdine. Chronic use of these drugs with delavirdine is not recommended.

Indinavir

Delavirdine inhibits metabolism of indinavir. Consider indinavir dosage reduction if coadministered with delavirdine.

Rifabutin, rifampin

Induce hepatic metabolism of delavirdine resulting in decreased plasma concentrations. These agents should not be coadministered with delavirdine.

Saquinavir

Delavirdine inhibits metabolism of saquinavir. Monitor hepatocellular enzymes frequently if coadministered.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Fatigue; tachycardia; bradycardia; pallor; palpitation; postural hypotension; syncope; vasodilation.

CNS

Lethargy; headache; migraine; abnormal coordination; agitation; amnesia; anxiety; change in dreams; cognitive impairment; confusion; depression; disorientation; dizziness; emotional lability; hallucination; hyperesthesia; impaired concentration; insomnia; manic symptoms; nervousness; neuropathy; nightmares; paranoid symptoms; paresthesia; restlessness; somnolence; tingling; tremor; vertigo.

Dermatologic

Rash; pruritus; angioedema; dermal leukocytoblastic vasculitis; dermatitis; desquamation; sweating; dry skin; erythema; erythema multiforme; folliculitis; fungal dermatitis; alopecia; nail disorder; petechial rash; seborrhea; skin nodule; Stevens-Johnson syndrome; urticaria; vesiculobullous rash; bruise; ecchymosis; petechia; purpura.

EENT

Nystagmus; blepharitis; conjunctivitis; diplopia; dry eyes; photophobia; tinnitus; ear pain; esophagitis; laryngismus; pharyngitis; sinusitis; rhinitis; epistaxis.

GI

Nausea; diarrhea; vomiting; abdominal cramps; distention; pain; lip edema; anorexia; aphthous stomatitis; bloody stool; colitis; constipation; decreased appetite; diverticulitis; duodenitis; dry mouth; dyspepsia; dysphagia; enteritis; fecal incontinence; flatulence; gagging; gastritis; gastroesophageal reflux; GI bleeding; gingivitis; gum hemorrhage; increased appetite; increased saliva; thirst; mouth ulcer; pancreatitis; rectal disorder; sialadenitis; stomatitis; tongue edema; ulceration; taste perversion.

Genitourinary

Decreased libido; breast enlargement; kidney calculi; epididymitis; hematuria; hemospermia; impotence; kidney pain; metrorrhagia; nocturia; polyuria; proteinuria; vaginal moniliasis.

Hematologic

Anemia; eosinophilia; granulocytosis; neutropenia; pancytopenia; prolonged partial thromboplastin; spleen disorder; thrombocytopenia.

Hepatic

Increased ALT; increased AST; hepatitis.

Metabolic

Bilirubinemia; hyperkalemia; hyperuricemia; hypocalcemia; hyponatremia; hypophosphatemia; increased gamma glutamyl transpeptidase, lipase, serum alkaline phosphatase, serum amylase, serum creatinine phosphokinase, or serum creatinine; peripheral edema.

Respiratory

Upper respiratory infection; bronchitis; chest congestion; cough; dyspnea.

Miscellaneous

Asthenia; back pain; chest pain; flank pain; chills; edema; fever; flu-like syndrome; lethargy; weakness; malaise; neck rigidity; sebaceous and epidermal cysts; muscle cramps; paralysis; weight increase or decrease; arthralgia; arthritis; bone disorder; bone pain; myalgia; tendon disorder; tenosynovitis; tetany.

Precautions

Pregnancy

Category C .

Lactation

Undetermined. HIV infected mothers should not breast-feed their infants.

Children

Safety and efficacy in children younger than 16 yr of age not established.

Hepatic Function

Delavirdine is metabolized primarily by the liver. Use with caution in patients with hepatic function impairment.

Rash

Rash is the most common adverse reaction and may range from minor to severe.

Resistance

Resistant virus emerges rapidly when delavirdine is administered as monotherapy. Always use in combination with appropriate antiretroviral therapy.

Patient Information

• Advise patient to take medication with or without food exactly as prescribed.
• If patient has difficulty swallowing tablets, instruct patient in proper method for dispersing tablets in water.
• Advise patients with achlorhydria to take each dose with an acidic beverage (eg, orange or cranberry juice).
• Advise patients who are also taking antacids or didanosine to separate doses by at least 1 h.
• Warn patient not to alter dose or discontinue the medication without consulting health care provider.
• Advise patient that if dose is missed, take as soon as possible and return to normal dose. However, if a dose is skipped, do not double the next dose.
• Instruct patient not to take any other medications (including OTC), without checking with the health care provider. This medication interacts with a wide range of medications.
• Explain to the patient to have frequent follow-up blood and urine tests during the course of treatment and to keep appointments.
• Inform patients that this medication is not a cure for HIV infection and they may continue to acquire secondary illnesses associated with the disease.
• Emphasize to patient, family, and significant others that this medication does not reduce the risk of transmitting HIV to others through sexual contact or blood contamination.
• Inform patient that rash is the most common adverse reaction and advise patient to promptly notify the health care provider should rash occur.
• Advise patient to discontinue therapy and contact the health care provider immediately should any of the following occur: severe rash; rash accompanied by fever, blistering, oral lesions, conjunctivitis, swelling, muscle or joint aches.
• Instruct patient to report serious or bothersome adverse reactions to health care provider.
• Explain that the long-term effects of this medication are not known at this time.

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