Tipranavir
Mechanism :
Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV.
Indication :
- HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with ritonavir and other antiretroviral agents.
Contraindications :
Hypersensitivity, Moderate-severe hepatic impairment (Child-Pugh class B&C), Coadministration of tipranavir/ritonavir with drugs highly dependent upon CYP3A for clearance or potent CYP3A inducers, including alfuzosin, amiodarone, bepridil, cisapride, ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine), flecainide, lovastatin, lurasidone, midazolam (oral), pimozide, propafenone, quinidine, rifampin, sildenafil.
Dosing :
Children ≥2 years and Adolescents:
Oral: 14 mg/kg or 375 mg/m² (Maximum: 500 mg/dose) twice daily.
Note:Co-administration with
ritonavir (6 mg/kg or 150 mg/m² [maximum: 200 mg/dose] twice daily) is required.
Adverse Effect :
Increased transaminases, diarrhea, hypertriglyceridemia, rash, abdominal pain, fatigue, headache, pyrexia, nausea, vomiting.
Interaction :
Amiodarone: Tipranavir may increase the serum concentration of Amiodarone.
Atorvastatin: Tipranavir may increase the serum concentration of Atorvastatin.
Clarithromycin: Protease Inhibitors may diminish the therapeutic effect of Clarithromycin.
Rifampin: Rifampin will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May result in loss of antiviral efficacy and/or development of viral resistance.
Terfenadine: tipranavir increases levels of terfenadine by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.
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 for GFR<10 mL/min |
| HD | Not dialysed. Dose as for GFR<10 mL/min |
| HDF/High flux | Unknown dialysability. Dose as for GFR<10 mL/min |
| CAV/VVHD | Not dialysed. Dose as for GFR=10–20 mL/min |
Hepatic Dose :
Mild hepatic impairment: No dosage reduction. Monitor liver function tests closely.
Moderate to severe hepatic impairment: Use of this drug is contraindicated.