Pharm

Ritonavir

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Ritonavir, Norvir

  • See Also
  1. Anti-Retroviral Therapy
  2. Protease Inhibitor
  • Indications
  1. Used at low dose to "boost" most of the Protease Inhibitors
  • Mechanism
  1. See Protease Inhibitor
  • Medications
  1. Most Protease Inhibitors are "boosted" with either Ritonavir or Cobicistat (Tybost)
  2. Ritonavir (Norvir) used at low dose in combination with other Protease Inhibitors
    1. Ritonavir at high standard dose is limited by adverse gastrointestinal effects
    2. Suffix '/r' added when a protease inhibutor is combined with Ritonavir
  3. Examples of Combinations with Ritonavir
    1. Atazanavir/r
    2. Darunavir/r
    3. Fosamprenavir/r
    4. Lopinavir/r (Kaletra, LPV/r)
  4. Formulations
    1. Tablets or Capsules: 100 mg
    2. Oral Powder: 100 mg/packet
    3. Oral Solution: 80 mg/ml
      1. Ritonavir solution contains Alcohol and propylene glycol
      2. Risk of propylene glycol and Alcohol Toxicity in infants age <6 months (esp <4 weeks)
      3. With Feeding Tube administration, use only silicone or PVC
        1. Avoid polyurethane tubing due to Alcohols in solution
  • Dosing
  • Adult
  1. Take with food
  2. Anticipate bad taste (Mix with Chocolate milk)
  3. Boosting dose (added to other Protease Inhibitors)
    1. Typical boosting dose: 100 mg daily
    2. Boosting Doses as high as 400 mg twice daily have been used in some protocols
  4. Full dose (non-boosting)
    1. Take 600 mg orally twice daily
    2. Full dose is not typically used due to adverse effects (esp. gastrointestinal)
  • Dosing
  • Child
  1. See specific dosing protocols in which Ritonavir is used as the boosting agent
  • Adverse Effects
  1. Adverse effects reflect Ritonavir used at full dose
    1. Adverse effects are less common with the lower, "boosting dose"
  2. Gastrointestinal (adverse effects may limit medication use)
    1. Nausea or Vomiting
    2. Diarrhea
  3. Asthenia
  4. Paresthesias (Circumoral or peripheral)
  5. Pancreatitis
  6. Triglycerides elevated
  7. Liver Function Tests
    1. Cholestatic enzymes elevated
    2. Hepatic transaminases elevated
  8. Electrocardiogram changes
    1. First degree AV Block
    2. Second or third degree AV Block (rare)
  • Safety
  1. Avoid in Lactation
  2. Pregnancy
    1. Pregnancy registry exists
    2. Frequently used in pregnancy added in low dose to other Protease Inhibitors
  • Drug Interactions
  1. Multiple Drug Interactions
    1. See Protease Inhibitor
    2. Ritonavir, even at its lower boosting dose, has numerous Drug Interactions
    3. As with other Protease Inhibitors, check a formal Drug Interaction application before prescribing
  2. Many contraindicated drugs (do not coadminister)
    1. Check a formal Drug Interaction application before prescribing
    2. Examples include Amiodarone, Flecainide, Propafenone, Quinidine, rivaroxiban
  3. Oral Contraceptives (OCP)
    1. Decreased OCP effectiveness
    2. Use backup or alternative Contraception
  4. Voriconazole
    1. Ritonavir (esp. at 400 mg twice daily) decreases Voriconazole levels and efficacy
    2. Avoid concurrent use if possible
  5. Opioids
    1. Methadone dose may need to be increased
    2. Fentanyl serum levels may be increased
  6. Clarithromycin
    1. Decrease Clarithromycin dose if Creatinine Clearance <60 ml/min
  7. Didanosine
    1. Didanosine is buffered with decreased Ritonavir oral absorption
    2. Take Ritonavir at least 2.5 hours before or after Didanosine
  8. Digoxin
    1. Ritonavir may increase Digoxin levels
  • Efficacy
  1. Very effective when "boosting" other Protease Inhibitors
  • Resources
  1. Ritonavir (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2849298e-de6e-47bb-8194-56e075b33fc3
  • References
  1. (1998) Med Lett Drugs Ther 40(1041):115 [PubMed]
  2. (2009) Treat Guidel Med Lett 7(78): 11-22 [PubMed]
  3. Reust (2011) Am Fam Physician 83(12): 1443-51 [PubMed]