Dosing and uses of Norvir (ritonavir)
Adult dosage forms and strengths
capsule
- 100mg
tablet
- 100mg
oral solution
- 80mg/mL
HIV Infection
Not typically used as sole protease inhibitor (PI), but as pharmacokinetic enhancer of other PIs
Indicated in combination with other antiretroviral agents for the treatment of HIV-infection
300 mg PO q12hr intially; increase by 100 mg q12hr to 600 mg PO q12hr over 5 days as tolerated
Use as booster with another protease inhibitor: 100-400 mg PO qDay or divided q12hr
Hepatic Impairment
Monitor therapy carefully with moderate and severe hepatic impairment
Pediatric dosage forms and strengths
capsule
- 100mg
tablet
- 100mg
oral solution
- 80mg/mL
HIV Infection
Not typically used as sole protease inhibitor (PI), but as pharmacokinetic enhancer of other PIs
Age <1 month: Safety and efficacy not established
Age ≥1 month: 250 mg/m² PO q12hr initially; increase by 50 mg/m² q2-3days to 350-450 mg/m² q12hr; not to exceed 600 mg q12hr
Adolescents: 300 mg PO q12hr intially; increase by 100 mg q12hr to 600 mg PO q12hr over 5 days as tolerated
Norvir (ritonavir) adverse (side) effects
>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
Warnings
Black box warnings
Coadministration with sedative-hypnotics, antiarrhythmics, or ergot alkaloids may result in serious and/or life-threatening adverse events due to ritonavir’s effect on hepatic metabolism
Ritonavir inhibits CYP450 3A; drugs that are extensively metabolized by CYP3A and have high first pass metabolism are most susceptible to increased serum levels when coadministered
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, lovastatin, simvastatin, lurasidone, pimozide, sildenafil for pulmonary arterial hypertension, triazolam, oral midazolam, carbamazepine, 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 and lactation
Pregnancy category: B
Lactation: HIV+ women shouldn't breastfeed
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.
Pharmacology of Norvir (ritonavir)
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%)
Administration
Oral Administration
Gradually increase to dose to avoid nausea/vomiting
Tablet: Take with food
Capsule and oral solution: Take with food if possible (may improve tolerability)
May mix capsules/oral solution with chocolate milk, Ensure
Storage
Tablets: May be stored at room temperature
Capsules: Must be refrigerated; may be left at room temperature for up to 30 days
