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Delavirdine Mesylate

Pronunciation: DEL-a-VIR-deen MES-i-late
Class: Antiretroviral, NNRTI

Trade Names

Rescriptor
- Tablets, oral 100 mg
- Tablets, oral 200 mg

Pharmacology

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

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Rapidly absorbed. T max is approximately 1 h. C max is approximately 35 mcM. AUC is approximately 180 mcM•h. When multiple doses were administered with food, mean C max was reduced by 25% but AUC and C min were not altered.

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). Half-life is approximately 5.8 h.

Indications and Usage

Treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted.

Contraindications

Hypersensitivity to delavirdine or any of its ingredients; coadministration with alprazolam, astemizole, cisapride, dihydroergotamine, ergonovine, ergotamine, methylergonovine, midazolam, pimozide, terfenadine, triazolam.

Dosage and Administration

Adults and Children older than 16 y 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 100 mg tablets in water prior to administration. Add four 100 mg tablets to at least 3 oz of water. Allow to stand for a few minutes and then stir until uniformly dispersed and administer promptly. Rinse glass and have patient swallow the rinse to ensure the entire dose is consumed.
  • The 200 mg tablets should be taken as intact tablets; they are not readily dispersible in water.
  • If patient also takes antacids, separate doses by at least 1 h.

Storage/Stability

Store between 68° and 77°F. Store at controlled room temperature in a tightly closed container. Protect from high humidity.

Drug Interactions

Amphetamines, calcium channel blockers (eg, amlodipine, diltiazem, nifedipine, verapamil), trazodone

Plasma concentrations of these agents may be elevated. Use with caution. Monitor the patient response and adjust the dose of these agents as needed.

Antacids

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

Antiarrhythmic agents (eg, amiodarone, flecainide, lidocaine systemic, quinidine, propafenone)

Use with caution. Drug concentration monitoring is recommended when available.

Anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), St. John's wort

Coadministration is not recommended because anticonvulsants may decrease plasma delavirdine concentrations, which may lead to loss of virologic response and possible resistance to delavirdine or to the class of NNRTIs.

Benzodiazepines (eg, alprazolam, midazolam, triazolam), cisapride, ergot derivatives (eg, ergonovine, ergotamine), pimozide

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

Clarithromycin

Coadministration may increase blood levels of clarithromycin. Adjust the clarithromycin dose in patients with impaired renal function. In patients with CrCl 30 to 60 mL/min, reduce the dose of clarithromycin by 50%. In patients with CrCl less than 30 mL/min, reduce the dose of clarithromycin by 75%.

Dexamethasone

Use with caution. Delavirdine plasma concentrations may be reduced, decreasing the efficacy.

Didanosine

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

Everolimus, nilotinib

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid coadministration.

Fluoxetine, ketoconazole

Increased delavirdine plasma concentrations. Monitor the patient response and adjust treatment as needed.

Fosamprenavir

Plasma concentrations of amprenavir may be increased. Monitor the patient response.

H 2 antagonists (eg, cimetidine)

Concurrent use may reduce absorption of delavirdine. Long-term use of these drugs with delavirdine is not recommended.

HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin)

Risk for serious reactions, such as myopathy including rhabdomyolysis, may be increased. Coadministration of delavirdine with lovastatin or simvastatin is not recommended. Use the lowest possible dose of atorvastatin or fluvastatin. Pravastatin is less likely to interact with delavirdine.

Hormonal contraceptives

Ethinyl estradiol concentrations may be increased. However, the clinical importance is unknown.

Immunosuppressants (eg. cyclosporine, tacrolimus)

Immunosuppressant concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Therapeutic concentration monitoring is warranted. Adjust the immunosuppressant dose as needed.

Indinavir

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

Inhaled steroids (eg, fluticasone)

Fluticasone plasma concentrations may be elevated, increasing the risk of adverse reactions. Use with caution and consider alternatives to fluticasone, especially for long-term use.

Ixabepilone

Ixabepilone plasma concentration may be elevated, increasing the risk of toxicity. If coadministration cannot be avoided, consider reducing the dosage of ixabepilone to 20 mg/m 2 every 3 weeks. If delavirdine is discontinued, allow a washout period of approximately 1 week before adjusting the ixabepilone dose upward to the indicated dose.

Lopinavir/Ritonavir

Lopinavir and ritonavir plasma concentrations may be elevated. Appropriate doses with respect to safety and efficacy have not been established.

Maraviroc

Maraviroc plasma concentrations may be elevated, increasing the risk of adverse reactions. A maraviroc dose decrease may be needed during concomitant use with delavirdine. Coadministration is contraindicated in patients with severe renal impairment (CrCl 30 mL/min).

Methadone

Methadone plasma concentrations may be increased. Methadone dose reduction may be needed with concomitant use of delavirdine.

Nelfinavir

Delavirdine plasma concentrations may be decreased while nelfinavir concentrations are increased. Appropriate doses with respect to safety and efficacy have not been established.

Proton pump inhibitors (eg, lansoprazole, omeprazole)

Proton pump inhibitors increase gastric pH and may decrease absorption of delavirdine. Although the effect on delavirdine absorption is unknown, long-term use is not recommended.

Rifabutin, rifampin

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

Saquinavir

Saquinavir C max , C min , and AUC may be increased. A dose reduction in saquinavir soft-gelatin capsules may be considered when coadministered with delavirdine. Appropriate doses with respect to safety and efficacy have not been established.

Sildenafil

Delavirdine may increase sildenafil plasma concentrations, increasing the risk of adverse reactions (eg, hypotension). Do not exceed a single 25 mg dose of sildenafil in a 48-hour period.

Warfarin

Plasma concentrations of warfarin may be increased. Monitor the INR and adjust the warfarin dose as needed.

Adverse Reactions

The following adverse reactions have been reported with use of delavirdine in combination with 1 or more antiretroviral agent.

CNS

Headache (17%); asthenia/fatigue (16%); depressive symptoms (13%); anxiety (7%); insomnia (5%).

Dermatologic

Rash (35%).

EENT

Sinusitis (7%); pharyngitis (5%).

GI

Nausea (20%); vomiting (7%); diarrhea (6%); generalized abdominal pain (5%).

Genitourinary

Acute renal failure (postmarketing).

Hematologic

Hemolytic anemia (postmarketing).

Hepatic

Hepatic failure (postmarketing).

Lab Tests

Decreased neutrophils (8%); increased ALT (5%); decreased hemoglobin, increased amylase, increased AST, increased bilirubin (3%); increased GGT, increased or decreased glucose, increased PT or APTT (2%)

Musculoskeletal

Rhabdomyolysis (postmarketing).

Respiratory

Upper respiratory tract infection (8%); bronchitis (7%); cough (5%).

Miscellaneous

Fever, flu syndrome (7%); localized pain (6%).

Precautions

Pregnancy

Category C .

Lactation

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

Children

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

Hepatic Function

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

Fat redistribution

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, have been observed in patients receiving antiretroviral therapy.

Immune reconstitution syndrome

During initial phase of treatment, patients may develop an inflammatory response to indolent or residual opportunistic infections.

Rash

Rash is the most common adverse reaction and may range from minor to severe, including rare cases of erythema multiforme and Stevens-Johnson syndrome.

Resistance

Resistant virus emerges rapidly when delavirdine is administered as monotherapy. Always use in combination with appropriate antiretroviral therapy. NNRTIs, when used alone or in combination, may confer cross-resistance to other NNRTIs.

Overdosage

Symptoms

Experience with acute overdosage is limited.

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 it as soon as possible and return to normal dosing. However, if a dose is skipped, advise patient not to double the next dose.
  • Instruct patient not to take any other medications (including OTC) without checking with health care provider. This medication interacts with a wide range of medications.
  • Advise 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 health care provider should rash occur.
  • Advise patient to discontinue therapy and contact health care provider immediately should any of the following occur: severe rash or rash accompanied by fever, blistering, oral lesions, conjunctivitis, swelling, and 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.

Copyright © 2009 Wolters Kluwer Health.

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