Ritonavir
Mechanism :
Ritonavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in non-infectious, immature viral particles.
Indication :
- Treatment of HIV infection as part of combination boosted protease inhibitor (PI).
Contraindications :
Hypersensitivity; Caution if hepatic impairment, HBV or HCV co-infection, structural heart disease, cardiac conduction disturbance, ischemic heart disease, cardiomyopathy, diabetes mellitus, hemophilia.
Dosing :
>1 month:
Use in children along with other PIs.
Initial dose:
250 mg/m² orally twice a day. Maintenance dose: Increase by 50 mg/m² twice daily every 2 to 3 days to the full dose of 350 to 400 mg/m² orally twice a day. Maximum dose: 600 mg/dose. Use of ritonavir as the sole protease inhibitor is not recommended.
Adults:
Amprenavir 600 mg twice daily with ritonavir 100 mg twice daily PO.
Atazanavir 300 mg OD with ritonavir 100 mg once daily PO.
Fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily PO.
Lopinavir co-formulated with ritonavir (lopinavir/ritonavir) 400 mg/100 mg or 800 mg/200 mg PO.
Saquinavir 1000 mg twice daily with ritonavir 100 mg twice daily in ART experienced patients PO.
Tipranavir 500 mg twice daily with ritonavir 200 mg twice daily PO.
Darunavir 600 mg twice daily with ritonavir 100 mg twice daily in ART experienced patients PO.
Darunavir 800 mg once daily with ritonavir 100 mg once daily in ART-naive patients PO.
Adverse Effect :
PR prolongation, AV block, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, pancreatitis, hepatotoxicity, hypersensitivity reactions, anaphylaxis, toxic epidermal necrolysis, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, thrombocytopenia, neutropenia, immune reconstitution syndrome, autoimmune disorders, nausea/vomiting, diarrhea, asthenia, taste changes, paraesthesia, dizziness, vasodilation, anorexia, abdominal pain, headache, dyspepsia, myalgia, rash, insomnia, lipodystrophy,
elevated ALT/AST/amylase/CPK/uric acid.
Interaction :
Interaction Characteristics:
CYP1A2 inducer, major
CYP2B6 inducer, major
CYP2C9 inducer, major
CYP2D6 inhibitor, weak
CYP3A4 inhibitor, strong
CYP3A4 substrate
GI absorption enhanced by GLP-2 receptor agonist
OATP1B3 inhibitor, strong
P-gp (MDR1) inhibitor, weak
UGT1A1 inhibitor
UGT2B4 inducer
Hyperglycemia
Prolongs PR interval
Contraindicated:
Alfuzosin, Alprazolam, Amiodarone, Cabazitaxel, Chlorpropamide, Cisapride, Cobicistat, Conivaptan, Dihydroergotamine, Disopyramide, Disulfiram, Dronedarone, Eletriptan, Enzalutamide, Eplerenone, Ergotamine, Etravirine, Flecainide, Ifosfamide, Lomitapide, Lovastatin, Lurasidone, Mefloquine, Methylergonovine, Metronidazole, Midazolam, Pimozide, Quinidine (Antiarrhythmic), Ranolazine, Rifampin, Sildenafil, Silodosin, Simvastatin, St. John's Wort, Tamsulosin, Thioridazine, Tinidazole, Tolvaptan, Triazolam, Voriconazole.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Not dialysed. Dose as in normal renal function |
| CAV/VVHD | Unlikely to be dialysed. Dose as in normal renal function |
Hepatic Dose :
Mild to moderate hepatic impairment: Dose adjustment recommendations not given, however monitor carefully and use with caution.
Severe hepatic impairment: Avoid using the drug.
In patients with marked rise in hepatic transaminase levels or suffering from hepatitis B or C be very careful and monitor closely as hepatic reactions can be fatal.