ritonavir (Rx)

>10%

Increased triglycerides (17-34%)

Diarrhea (15-23%)

Nausea (26-30%)

Taste perversion (7-11%)

Vomiting (14-17%)

Weakness (10-15%)

Increased GGT (5-20%)

Increased creatinine phosphokinase (9-12%)

1-10%

Abdominal pain (6%)

Anorexia (2-8%)

Dizziness (3-4%)

Dyspepsia (6%)

Eosinophilia

Fever (1-2%)

Flatulence (1-2%)

Headache (6-7%)

Insomnia (2-3%)

Increased uric acid (4%)

Increased LFTs (6-10%)

Local throat irritation (2-3%)

Malaise (1-2%)

Myalgia (2%)

Diaphoresis (2-3%)

Paresthesia (3-7)

Pharyngitis (1-3%)

Rash (<4%)

Somnolence (2-3%)

Pharyngitis (1-3%)

<1%

Adrenal suppression

Cerebral ischemia

Dementia

Edema

Leukopenia

Tachycardia

Ulcerative colitis

Postmarketing Reports

Renal and urinary disorders: Nephrolithiasis

Contraindications

Known hypersensitivity to ritonavir (eg, toxic epidermal necrolysis, Stevens- Johnson syndrome)

Coadministration with drugs highly dependent on CYP3A for clearance or that significantly reduce ritonavir

Coadministration of ritonavir with the following drugs is contraindicated: alfuzosin, amiodarone, flecainide, propafenone, quinidine, voriconazole, rifampin, dihydroergotamine, ergotamine, methylergonovine, cisapride, lomitapide, lovastatin, simvastatin, lurasidone, apalutamide, pimozide, sildenafil for pulmonary arterial hypertension, triazolam, oral midazolam, carbamazepine, ranolazine, dronedarone, flecainide, colchicine, phenobarbital, phenytoin, and St. John’s wort

Cautions

Do not administer with antacids; separate from didanosine by 2 hr

Potent inhibitor of CYP3A4 (but also induces CYP450 enzymes)

Monitor: monthly neurologic evaluation

Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs

Risks of hemolytic anemia and hyperbilirubinemia if used in combination with other antiretroviral drugs

Capsules must be kept refrigerated

Allergic reactions have been reported and include anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson Syndrome, bronchospasm and angioedema; discontinue treatment if severe reactions develop

Consider drug-drug interaction potential to reduce risk of serious or life-threatening adverse reactions

Oral solution not for administration in preterm neonates in the immediate postnatal period; may cause toxicity; safety and efficacy not established

Monitor liver function before and during therapy, especially in patients with underlying hepatic disease, including hepatitis B and hepatitis C, or marked transaminase elevations; fatalities resulting from hepatic reactions reported

Fatalities resulting from pancreatitis reported; suspend therapy as clinically appropriate

PR interval prolongation reported in some patients; cases of second and third degree heart block reported; use with caution with patients with preexisting conduction system disease, ischemic heart disease, cardiomyopathy, underlying structural heart disease or when administering with other drugs that may prolong the PR interval

Total cholesterol and triglycerides elevations may occur; monitor prior to therapy and periodically thereafter

Patients may develop new onset or exacerbations of diabetes mellitus, hyperglycemia

Patients may develop redistribution/accumulation of body fat

Spontaneous bleeding may occur; additional factor VIII may be required

Pregnancy

Advise pregnant women not to use oral solution during pregnancy owing to its alcohol content

Inform patients that there is an antiretroviral (ARVs) pregnancy registry that monitors fetal outcomes of pregnant women exposed to ARVs 1–800–258–4263

Follow current CDC/WHO recommendations for HIV treatment during pregnancy

Lactation

Excreted in human milk

The CDC recommends that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection, risk of developing viral resistance (in HIV-positive infants), and risk of serious adverse reactions

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Protease Inhibitor; inhibits cleavage of Gag-Pol polyprotein precursors, which in turn causes the formation of immature, noninfectious viral particles.

Combination use recommended; typically used to boost levels of other protease inhibitors

Pharmacokinetics

Absorption: variable, with or without food

Vd: 0.16-0.66 L/kg (high concentrations in serum & lymph nodes)

Protein Bound: 98-99%

Metabolism: Hepatic; five metabolites, low concentration of an active metabolite achieved in plasma (oxidative)

Half-life: 3-5 hr

Peak plasma time: 2 hr (oral solution)

Excretion: Urine (11%); feces (86%)

Oral Administration

Gradually increase dose to avoid nausea/vomiting

Take with food

Swallow capsules or tablets whole; do not chew or crush

Oral solution

• May mix with chocolate milk, Ensure, or Advera within 1 hr of dosing to improve taste
• Measure dose precisely with calibrated oral syringe

Oral powder

• Should be mixed with soft food (eg, apple sauce, vanilla pudding) or mixed with liquid (eg, water, chocolate milk, infant formula) within 2 hr of preparation
• If not administered within 2 hr of preparation, the mixture should be discarded and a new dose prepared
• Bitter aftertaste may be lessened if administered with food
• May administer via feeding tube if mixed with water

Storage

Tablets

• Store at or below 30°C (86°F)
• Exposure to temperatures up to 50°C (122°F) for 7 days permitted
• Dispense in original container or USP equivalent tight container (≤60 mL)
• Inform patients that exposure of the tablets to high humidity outside the original container for >2 weeks is not recommended

Capsules

• Store soft gelatin capsules refrigerated at 2-8°C (36-46°F) until dispensed
• Refrigeration by the patient is recommended, but not required if used within 30 days and stored at <25°C (77°F)
• Protect from light
• Avoid exposure to excessive heat
• Store and dispensed in the original container
• Keep cap tightly closed

Oral solution

• Store at room temperature 20-25°C (68-77°F)
• Do not refrigerate
• Shake well before each use
• Use by product expiration date
• Store and dispensed in the original container
• Avoid exposure to excessive heat
• Keep cap tightly closed

Oral powder

• Store at or below 30°C (86°F)