delavirdine mesylate

Action

Binds to reverse transcriptase enzyme, blocking RNA-dependent and DNA-dependent DNA polymerase synthesis

Availability

Tablets: 100 mg, 200 mg

Indications and dosages

➣ Human immunodeficiency virus (HIV)-1 infection
Adults: 400 mg P.O. t.i.d.

Contraindications

• Hypersensitivity to drug

• Concurrent use of alprazolam, astemizole, ergot derivatives, midazolam, pimozide, terfenadine, or triazolam

Precautions

Use cautiously in:

• hepatic impairment

• pregnant or breastfeeding patients

• children younger than age 16 (safety and efficacy not established).

Administration

• Know that drug is usually given with at least two other antiretrovirals.

• If patient can't swallow tablets, dissolve 100-mg tablets in water by adding four tablets to at least 3 oz of water; let stand for a few minutes and then stir until completely dissolved. Have patient swallow entire mixture immediately. Then add small amount of water to glass and have him swallow this mixture to ensure that he consumes entire dose.

• Give 200-mg tablets intact; don't dissolve in water.

• If patient has achlorhydria, give drug with acidic beverage, such as orange juice.

Don't give concurrently with alprazolam, astemizole or terfenadine (no longer available in United States), ergot derivatives, midazolam, pimozide, or triazolam.

Adverse reactions

CNS: confusion, disorientation, dizziness, drowsiness, agitation, amnesia, changes in dreams, hallucinations, hyperesthesia, poor concentration, mania, nervousness, restlessness, paranoia, paresthesia, tremor, migraine, neuropathy, paralysis, seizures

CV: abnormal heart rate and rhythm, peripheral vascular disorder, peripheral edema, hypertension, orthostatic hypotension, cardiac insufficiency, cardiomyopathy

EENT: blurred or double vision, nystagmus, conjunctivitis, dry eyes, scleral yellowing, ear pain, otitis media, tinnitus, epistaxis, rhinitis

GI: nausea, diarrhea, constipation, abdominal pain or cramps, dyspepsia, abdominal distention, bloody stools, colitis, diverticulitis, enteritis, gastroenteritis, gastroesophageal reflux, mouth and tongue irritation and ulcers, increased saliva, difficulty swallowing, GI bleeding, pancreatitis

GU: hematuria, polyuria, chromaturia, proteinuria, nocturia, urinary tract infection, renal calculi, kidney pain, gynecomastia, erectile dysfunction, epididymitis, hemospermia, testicular pain, vaginal candidiasis, amenorrhea, irregular uterine bleeding

Hematologic: purpura, spleen disorders, eosinophilia, granulocytosis, disseminated intravascular coagulation, leukopenia, neutropenia, pancytopenia, hemolytic anemia

Hepatic: hepatotoxicity, hepatic failure, hepatomegaly

Metabolic: hypomagnesemia, hyperglycemia, hyperuricemia, hypocalcemia, hyponatremia, hypoglycemia, hyperkalemia, metabolic acidosis

Musculoskeletal: joint pain, arthritis, bone disorders, myalgia, muscle cramps, muscle weakness, bone pain, bone disorders, tendon disorders, tenosynovitis, neck pain and rigidity, limb pain, tetany, rhabdomyolysis

Respiratory: pulmonary congestion, dyspnea, pneumonia

Skin: pallor, bruising, yellowing of skin, dermal leukocytoblastic vasculitis, dermatitis, skin dryness and discoloration, erythema, folliculitis, herpes zoster or herpes simplex infection, petechiae, petechial or pruritic rash, seborrhea, alopecia, skin nodules, urticaria, sebaceous or epidermal cyst, angioedema, erythema multiforme

Other: tooth abscess, toothache, gingivitis, gum hemorrhage, weight gain or loss, fever, lymphadenopathy, adenopathy, increased thirst, hiccups, facial edema, pain, abscess, bacterial infection, Mycobacterium tuberculosis infection, body fat redistribution, hypersensitivity reaction, sepsis, Stevens-Johnson syndrome

Interactions

Drug-drug. Alprazolam, astemizole, cisapride, ergot derivatives, midazolam, pimozide, terfenadine: increased risk of serious or life-threatening adverse reactions

Antacids, histamine₂-receptor antagonists: reduced delavirdine absorption

Bepridil, clarithromycin, estrogen, hormonal contraceptives, indinavir, lopinavir-ritonavir, saquinavir, sildenafil, warfarin: increased blood levels of these drugs

Carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin: loss of virologic response, resistance to delavirdine

Cholesterol-lowering HMG-CoA reductase inhibitors cleared by the CYP3A4 pathway: increased risk of myopathy and rhabdomyolysis

Dexamethasone: decreased delavirdine blood level

Didanosine: decreased blood levels of both drugs

Fluoxetine, ketoconazole: 50% increase in delavirdine blood level

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, lipase, gamma-glutamyl transpeptidase, triglycerides: increased levels Granulocytes, hemoglobin, neutrophils, platelets, red blood cells, white blood cells: decreased values

Partial thromboplastin time, prothrombin time: increased

Drug-herbs. St. John's wort: loss of virologic response or resistance to delavirdine

Patient monitoring

• Monitor liver function test results frequently when giving drug concurrently with saquinavir.

• Check electrolyte and uric acid levels regularly.

See Monitor patient for serious hepatic, cardiovascular, and CNS problems and hypersensitivity reactions.

Patient teaching

• Tell patient he can take drug with or without food.

• If patient can't swallow tablets, teach him how to dissolve 100-mg tablets in water.

See Tell patient to discontinue drug and consult prescriber immediately if he develops severe rash accompanied by fever, blistering, oral lesions, conjunctivitis, swelling, or muscle aches.

See Tell patient to promptly report unusual fatigue, yellowing of skin or eyes, unusual bruising or bleeding, muscle weakness, or signs and symptoms of infection.

See Advise patient that rash is a major adverse effect, usually occurring 1 to 3 weeks after therapy starts and resolving in 3 to 14 days. Instruct him to report rash promptly.

• Inform patient that drug doesn't cure HIV or reduce its transmission.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.