ritonavir

Action

Inhibits human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase by binding directly to reverse transcriptase and blocking RNA-dependent and DNA-dependent polymerase activity

Availability

Capsules: 100 mg

Oral solution: 80 mg/ml

Tablets: 100 mg

Indications and dosages

➣ HIV in combination with other antiretrovirals

Adults: Initially, 300 mg P.O. b.i.d.; increase by 100 mg b.i.d. q 2 to 3 days, up to a usual maintenance dosage of 600 mg b.i.d.

Children age 1 month and older: 350 to 400 mg/m² P.O. b.i.d., not to exceed 600 mg b.i.d. Start with 250 mg/m² P.O. b.i.d.; increase by 50 mg/m² P.O. b.i.d. q 2 to 3 days, up to a usual maintenance dosage of 400 mg P.O. b.i.d. If patient doesn't tolerate 400 mg/m² b.i.d. due to adverse reactions, the highest tolerated dose may be used for maintenance therapy, or alternative therapy should be considered.

Children ages 2 and older: 400 mg/m² b.i.d., not to exceed 600 mg b.i.d. Start with 250 mg/m² to minimize nausea.

Dosage adjustment

• Concurrent use of other protease inhibitors

Off-label uses

• Chronic hepatitis B

Contraindications

• Hypersensitivity to drug or its components

• Concurrent use of alfuzosin, amiodarone, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, lovastatin, methylergonovine, oral midazolam, pimozide, propafenone, quinidine, sildenavir (Revatio, when used for pulmonary arterial hypotension), simvastatin, triazolam, voriconazole, or St. John's wort

Precautions

Use cautiously in:

• hepatic disease, diabetes mellitus, hemophilia types A and B

• underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, cardiomyopathies

• concurrent use with drugs that prolong PR interval (including calcium channel blockers, beta-adrenergic blockers, digoxin, atazanavir)

• concurrent use with drugs for erectile dysfunction (such as sildenafil, tadalafil, vardenafil)

• concurrent use with fluticasone, atorvastatin, lovastatin, simvastatin, and St. John's wort (use not recommended)

• pregnant or breastfeeding patients.

Administration

• Give with meals to increase absorption.

• Mix oral solution with chocolate milk or liquid nutritional supplement to mask taste.

• Know that drug is usually given with other antiretrovirals.

☞ Don't give concurrently with amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, methylergonovine, midazolam, pimozide, propafenone, quinidine, terfenadine, or triazolam. Serious interactions may occur.

Adverse reactions

CNS: headache, dizziness, depression, insomnia, drowsiness, asthenia, paresthesia, syncope, malaise

CV: vasodilation, prolonged PR interval

EENT: pharyngitis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, flatulence, abdominal pain, anorexia, pancreatitis

Musculoskeletal: myalgia

Skin: diaphoresis, mild skin eruptions, Stevens-Johnson syndrome (rare)

Respiratory: bronchospasm

Other: abnormal taste, fever, pain, allergic reactions including anaphylaxis (rare), immune reconstitution syndrome

Interactions

Drug-drug. Amiodarone, bepridil, cisapride, flecainide, midazolam, pimozide, propafenone, quinidine, triazolam: inhibited metabolism of these drugs, leading to life-threatening reactions (such as arrhythmias, prolonged sedation, and respiratory depression) Amitriptyline, anticoagulants, atovaquone, carbamazepine, clozapine, cyclosporine, desipramine, diltiazem, disopyramide, divalproex, dofetilide, dronabinol, ethinyl estradiol, lamotrigine, phenytoin, sulfamethoxazole, theophylline, zidovudine: increased risk of toxicity of these drugs

Amprenavir: increased amprenavir blood level

Astemizole, cisapride, encainide: increased risk of arrhythmias

Atorvastatin, cerivastatin, lovastatin, simvastatin, terfenadine: increased blood levels of these drugs, increased risk of rhabdomyolysis

Barbiturates, nevirapine, phenytoin, rifamycins: decreased ritonavir blood level

Bupropion: increased risk of seizures

Clarithromycin, efavirenz: increased blood levels of both drugs

Dihydroergotamine, ergonovine, ergotamine, methylergonovine: ergot toxicity

Fluconazole: increased ritonavir blood level

Fluticasone: increased fluticasone exposure resulting in decreased cortisol concentration

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, cholesterol, creatine kinase, gamma-glutamyltransferase, triglycerides, uric acid: increased levels

Hematocrit, hemoglobin, neutrophils, red blood cells, white blood cells: decreased levels

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

Patient monitoring

• Monitor CBC, liver function tests, electrolyte levels, and lipid panel.

• Assess neurologic status closely. Stay alert for depression.

• Monitor bone mineral density in patients with history of pathologic fractures or who are at risk for osteopenia.

☞ Monitor for signs and symptoms of immune reconstitution syndrome, especially during initial phase of combination antiretroviral treatment when patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalo virus, Pneumocystis jiroveci pneumonia, or tuberculosis), which may necessitate further evaluation and treatment.

• Monitor vital signs and watch for syncope.

• Closely monitor nutritional and hydration status.

Patient teaching

• Advise patient to take with meals to increase absorption.

• Encourage patient or caregiver to mix oral solution with chocolate milk or liquid nutritional supplement to mask taste. Tell caregiver that oral solution is recommended for children older than age 1 month who can't swallow capsules or tablets and, when possible, to administer dose using a calibrated dosing syringe.

• Tell patient to swallow tablets whole and not to chew, break, or crush them.

• Tell patient drug may cause numbness, tingling, weakness, and other CNS effects that increase his injury risk. Urge him to use appropriate safety precautions.

• Instruct patient to report depression.

• Advise patient not to take nonprescription drugs or herbal products, particularly St. John's wort, without consulting prescriber.

• Tell female patient not to breastfeed because of risk of serious adverse reactions and possible HIV transmission to infant.

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