Dosage

In combination therapy for HIV positive treatment-experienced patients

APTIVUS/ritonavir dosing

• APTIVUS may be administered as either capsules or oral solution to either pediatric or adult patients.
• APTIVUS must be co-administered with ritonavir to exert its therapeutic effect. This is known as APTIVUS/r

APTIVUS Capsules or Oral Solution + ritonavir

In Adult Patients
The recommended dose of APTIVUS capsules is 500 mg (two 250 mg capsules or 5 mL of oral solution), co-administered with ritonavir 200 mg (two 100 mg capsules or 2.5 mL oral solution), twice daily.

APTIVUS/r can be co-administered with new classes of agents
In adult patients APTIVUS/r may be co-administered with the 2 recently approved agents according to 24-week data from their package inserts: the CCR5 inhibitor, maraviroc, and the integrase inhibitor, raltegravir.

• Dose maraviroc at 300 mg BID when combining with APTIVUS/r
  • APTIVUS/r induces CYP3A enzymes that are responsible for maraviroc metabolism
  • No dosage adjustments necessary
• Dose raltegravir at 400 mg BID when combining with APTIVUS/r
  •  APTIVUS/r reduces plasma concentrations of raltegravir
  • In clinical studies, because there was no efficacy difference between the subgroup who received APTIVUS/r and those who did not, no dosage adjustment of raltegravir is needed when combining with APTIVUS/r
  • Approximately 100 subjects received raltegravir with APTIVUS/r in clinical trials resulting in comparable efficacy to patients not receiving APTIVUS/r
• APTIVUS should not be coadministered with etravirine
• The studies supporting these dosage recommendations were conducted by Tibotec Pharmaceuticals Limited, Pfizer Inc. and Merck and Co. Inc.

In Pediatric Patients
Healthcare professionals should pay special attention to accurate calculation of the dose of APTIVUS, transcription of the medication order, dispensing information and dosing instruction to minimize risk for medication errors, overdose, and under dose. Prescribers should calculate the appropriate dose of APTIVUS for each individual child based on body weight (kg) or body surface area (BSA, m²) and should not exceed the recommended adult dose. Before prescribing APTIVUS 250 mg capsules, children should be assessed for the ability to swallow capsules. If a child is unable to reliably swallow an APTIVUS capsule, the APTIVUS oral solution formulation should be prescribed. The recommended pediatric dose of APTIVUS is 14 mg/kg with 6 mg/kg ritonavir (or 375 mg/m² co-administered with ritonavir 150 mg/m2) taken twice daily not to exceed a maximum dose of APTIVUS 500 mg co-administered with ritonavir 200 mg twice daily. For children who develop intolerance or toxicity and cannot continue with APTIVUS 14 mg/kg with 6 mg/kg ritonavir, physicians may consider decreasing the dose to APTIVUS 12 mg/kg with 5 mg/kg ritonavir (or APTIVUS 290 mg/m² co-administered with 115 mg/m² ritonavir) taken twice daily provided their virus is not resistant to multiple protease inhibitors. Body surface area can be calculated as follows:

Important Safety Information for APTIVUS
APTIVUS/r has been associated with reports of clinical hepatitis and hepatic decompensation, including some fatalities. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of hepatotoxicity.

Patients with signs or symptoms of clinical hepatitis should discontinue APTIVUS/r treatment and seek medical evaluation. APTIVUS/r has been associated with reports of both fatal and non-fatal intracranial hemorrhage (ICH).

Adverse Events

• In adults the most frequent adverse reactions (incidence > 4%) were diarrhea, nausea, pyrexia, vomiting, fatigue, headache, and abdominal pain
• In pediatric patients (age 2 to 18 years) the most frequent adverse reactions were generally similar to those seen in adults.  However, rash was more frequent in pediatric patients than in adults