ritonavir

ritonavir /ri·to·na·vir/ (rĭ-to´nah-vir) an HIV protease inhibitor used in treatment of HIV infection and AIDS.

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ri·ton·a·vir (r-tn-vîr)

n.

A protease-inhibiting drug usually used in combination with other drugs to suppress the replication of HIV.

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ritonavir,

a protease inhibitor.

indications It is prescribed in the treatment of acquired immunodeficiency syndrome, as part of a multidrug regimen including at least three antiretroviral drugs.

contraindications Hypersensitivity to ritonavir precludes its use. Concurrent use of any of several other drugs is either contraindicated or warrants caution, including ergot derivatives, benzodiazepine sedative-hypnotics, some antiarrhythmic medications, some HMG-CoA reductase inhibitors (statins), some erectile dysfunction medicines, and some analgesics.

adverse effects Protease inhibitors cause problems with lipid metabolism and lead to hyperlipidemia, hyperglycemia and redistribution of body fat (e.g., buffalo hump), central obesity, breast enlargement, and facial atrophy. Additional side effects often reported include nausea, vomiting, diarrhea, and numbness about the lips.

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ritonavir

Norvir

Pharmacologic class: Protease inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category B

FDA Boxed Warning

• Coadministration with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot alkaloids may cause potentially serious or life-threatening adverse events.

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

⊘Indications and dosages

➣ HIV

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 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.

Off-label uses

• Chronic hepatitis B

Contraindications

• Hypersensitivity to drug or its components
• Concurrent use of astemizole and terfenadine (not available in U.S.), amiodarone, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, methylergonovine, midazolam, pimozide, propafenone, quinidine, or triazolam

Precautions

Use cautiously in:
• hepatic disease, diabetes mellitus, hemophilia types A and B
• 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.

Route	Onset	Peak	Duration
P.O.	Rapid	2-4 hr	Unknown

Adverse reactions

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

CV: vasodilation

EENT: pharyngitis

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

Musculoskeletal: myalgia

Skin: diaphoresis

Other: abnormal taste, fever, pain

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

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

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ritonavir

Norvir^® AIDS A potent HIV protease inhibitor which is combined with reverse transcriptase inhibitors, nucleoside analogues to manage AIDS Adverse effects GI tract complaints–nausea, diarrhea, perioral paresthesiae, ↑ liver function tests, lipodystrophy–↑ glucose, ↑ fat, ↑ abdominal girth, ↓ fatty tissue from face, arms, legs, ↑ TGs, paresthesias. See AIDS, Antiretroviral, Protease inhibitor; Cf Reverse transcriptase inhibitor.