darunavir ethanolate

Action

Inhibits human immunodeficiency virus-1 (HIV-1) protease, preventing formation of mature virus particles

Availability

Oral suspension: 100 mg/ml

Tablets: 75 mg, 150 mg, 400 mg, 600 mg

Indications and dosages

➣ HIV infection in treatment-naïve and treatment-experienced patients with no darunavir resistanceassociated substitutions

Adults: 800 mg (two 400-mg tablets) or 8 ml (two 4-ml doses) oral suspension P.O. with ritonavir 100 mg P.O. daily

➣ HIV infection in treatment-experienced patients with at least one darunavir resistance-associated substitution

Adults: 600 mg (one 600-mg tablet) or 6 ml oral suspension P.O. b.i.d. with ritonavir 100 mg P.O. b.i.d.

➣ HIV infection (with ritonavir and other retrovirals)

Children age 3 to younger than 18 weighing 40 kg (88 lb) or more: 600 mg (tablets) or 6 ml (oral suspension) P.O. b.i.d. with ritonavir 100 mg (capsules or tablets) or 1.25 ml (oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 30 kg (66 lb) to less than 40 kg: 450 mg (tablets) or 4.6 ml (oral suspension) P.O. b.i.d. with ritonavir 60 mg (0.75 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 15 kg (33 lb) to less than 30 kg: 375 mg (tablets) or 3.8 ml (oral suspension) P.O. b.i.d. with ritonavir 50 mg (0.6 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 14 kg (31 lb) to less than 15 kg: 280 mg (2.8 ml oral suspension) P.O. b.i.d. with ritonavir 48 mg (0.6 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 13 kg (29 lb) to less than 14 kg: 260 mg (2.6 ml oral suspension) P.O. b.i.d. with ritonavir 40 mg (0.5 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 12 kg (26 lb) to less than 13 kg: 240 mg (2.4 ml oral suspension) P.O. b.i.d. with ritonavir 40 mg (0.5 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 11 kg (24 lb) to less than 12 kg: 220 mg (2.2 ml oral suspension) P.O. b.i.d. with ritonavir 32 mg (0.4 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 10 kg (22 lb) to less than 11 kg: 200 mg (2 ml oral suspension) P.O. b.i.d. with ritonavir 32 mg (0.4 ml oral solution) P.O. b.i.d.

Children's dosage shouldn't exceed treatment-experienced adult dosage.

Contraindications

• Concurrent administration with drugs (including alfuzosin, cisapride, dihydroergotamine, ergonovine, ergotamine, lovastatin, methylergonovine, midazolam, pimozide, rifampin, sildenafil, simvastatin, terfenadine, triazolam, and St. John's wort)

Precautions

Use cautiously in:

• hypersensitivity to drug or its components (including sulfa)

• severe hepatic impairment (use not recommended)

• diabetes mellitus, hemophilia, hepatic dysfunction or disease

• concurrent use of carbamazepine, phenobarbital, phenytoin (use not recommended)

• elderly patients

• pregnant or breastfeeding patients

• children younger than age 3 (safety and efficacy not established; don't use).

Administration

• Give with ritonavir and food.

• Before administering, assess children weighing 15 kg (33 lb) or more for the ability to swallow tablets. If a child is unable to reliably swallow a tablet, consider using oral suspension. Give 8ml dose as two 4-ml administrations using the oral dosing syringe included.

Don't give concurrently with alfuzosin, cisapride, dihydroergotamine, ergonovine, ergotamine, methylergonovine, midazolam, pimozide, rifampin, sildenafil, simvastatin, terfenadine, terfenadine, or St. John's wort.

• Don't use once-daily dosing in children.

Adverse reactions

CNS: asthenia, fatigue, headache, transient ischemic attack, confusion, disorientation, anxiety, irritability, altered mood, memory impairment, vertigo, rigors, peripheral neuropathy, paresthesia, hypoesthesia, somnolence, nightmares

CV: tachycardia, hypertension, myocardial infarction

EENT: nasopharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, abdominal distention, flatulence, dry mouth, anorexia

GU: renal insufficiency, nephrolithiasis, polyuria, gynecomastia, acute renal failure

Metabolic: diabetes mellitus, polydipsia, obesity

Musculoskeletal: arthralgia, myalgia, extremity pain, osteopenia, osteoporosis

Respiratory: dyspnea, cough

Skin: allergic dermatitis, eczema, inflammation, toxic skin eruption, dermatitis medicamentosa, hyperhidrosis, folliculitis, maculopapular rash, alopecia, erythema multiforme, Stevens-Johnson syndrome

Other: body fat redistribution, lipoatrophy, decreased appetite, hiccups, pyrexia, night sweats, hyperthermia, peripheral edema, immune reconstitution syndrome (inflammatory response to indolent or residual opportunistic infections)

Interactions

Drug-drug. Amiodarone, atorvastatin, bepridil, clarithromycin, cyclosporine, felodipine, fluticasone propionate (inhalation), lidocaine (systemic), nicardipine, nifedipine, pravastatin, quinidine, sildenafil, sirolimus, tacrolimus, tadalafil, trazodone, vardenafil: increased blood levels of these drugs

Astemizole, cisapride, terfenadine: increased risk of serious or lifethreatening reactions (such as arrhythmias)

Carbamazepine, dexamethasone (systemic), phenobarbital, phenytoin, rifampin: decreased darunavir blood level

Efavirenz: decreased blood levels of both drugs

Ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine): increased risk of acute ergot toxicity

Hormonal contraceptives: decreased ethinyl estradiol blood level; may decrease contraceptive efficacy

Itraconazole, ketoconazole: increased blood levels of these drugs and darunavir

Lopinavir/ritonavir, saquinavir: decreased effects of these drugs

Lovastatin, pimozide, simvastatin: increased risk of myopathy

Methadone, voriconazole, warfarin: decreased blood levels of these drugs

Midazolam, triazolam: increased risk of respiratory depression or increased sedation

Paroxetine, sertraline: decreased effects of these drugs

Rifabutin: increased rifabutin blood level, decreased darunavir blood level (when given with ritonavir)

Voriconazole: decreased voriconazole and increased darunavir blood levels

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, gamma-glutamyltransferase, lipase, lipids, partial thromboplastin time, plasma prothrombin time, total cholesterol, triglycerides, uric acid: increased levels

Bicarbonate, calcium, lymphocytes, platelets, total absolute neutrophils, white blood cells: decreased levels

Bilirubin, serum glucose, sodium: increased or decreased levels

Drug-food. Any food: increased drug absorption

Drug-herbs. St. John's wort: decreased darunavir blood level

Patient monitoring

• During initial treatment phase, stay alert for immune reconstitution syndrome.

• Monitor liver function studies frequently in patients with preexisting hepatic dysfunction or disease.

• Monitor blood glucose levels frequently in patients with diabetes mellitus.

• Carefully monitor patient receiving antiarrhythmics and HMG-CoA reductase inhibitors while taking this drug.

• Monitor International Normalized Ratio when giving drug with warfarin.

Patient teaching

• Instruct patient to take drug with ritonavir and food, as prescribed.

• Advise patient to inform prescriber of other drugs and supplements he's taking (including vitamins and herbs) before starting drug or taking new medication.

Urge patient to immediately report side effects (especially rash).

• Emphasize that drug doesn't cure HIV infection.

• Advise patient using hormonal contraceptives to use alternative contraceptive method while taking this drug.

• Advise patients who are pregnant or recently gave birth not to breastfeed because of risk of passing HIV infection to infant and potentially serious adverse drug reactions.

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