Norvir

NORVIR — ritonavir tablet, film coated
DOH CENTRAL PHARMACY

1 INDICATIONS AND USAGE

NORVIR tablets and oral solution are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

NORVIR oral powder is indicated in combination with other antiretroviral agents for the treatment of pediatric patients with HIV-1 infection.

2.1 General Administration Recommendations

• NORVIR must be used in combination with other antiretroviral agents.
• NORVIR is administered orally. NORVIR tablets should be swallowed whole, and not chewed, broken or crushed. Take NORVIR with meals.
• Patients may improve the taste of NORVIR oral solution by mixing with chocolate milk, Ensure^® , or Advera^® within one hour of dosing.
• NORVIR oral powder should be mixed with soft food such as apple sauce or vanilla pudding, or mixed with liquid such as water, chocolate milk, or infant formula [see Dosage and Administration (2.5) and Instructions for Use]. The bitter aftertaste of NORVIR oral powder may be lessened if administered with food.

General Dosing Guidelines

Patients who take the 600 mg twice daily soft gel capsule NORVIR dose may experience more gastrointestinal side effects such as nausea, vomiting, abdominal pain or diarrhea when switching from the soft gel capsule to the tablet formulation because of greater maximum plasma concentration (C_max ) achieved with the tablet formulation relative to the soft gel capsule [see Clinical Pharmacology (12.3)]. Patients should also be aware that these adverse events (gastrointestinal or paresthesias) may diminish as therapy is continued.

2.2 Administering Oral Solution by Feeding Tube

Because NORVIR oral solution contains ethanol and propylene glycol, it is not recommended for use with polyurethane feeding tubes due to potential incompatibility. Feeding tubes that are compatible with ethanol and propylene glycol, such as silicone and polyvinyl chloride (PVC) feeding tubes, can be used for administration of NORVIR oral solution. Follow instructions for use of the feeding tube to administer the medicine.

2.3 Dosage Recommendations in Adults

Recommended Dosage for Treatment of HIV-1:

The recommended dosage of NORVIR is 600 mg twice daily by mouth to be taken with meals. Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels. NORVIR should be started at no less than 300 mg twice daily and increased at 2 to 3 day intervals by 100 mg twice daily. The maximum dose of 600 mg twice daily should not be exceeded upon completion of the titration [see Dosage and Administration (2.6)].

Pregnant Women

NORVIR oral solution is not recommended during pregnancy due to its ethanol content. NORVIR oral solution contains the excipients ethanol (approx. 43% v/v) and propylene glycol (approx. 27% w/v) [see Use in Specific Populations (8.1)].

2.4 Dosage Recommendations in Pediatric Patients

NORVIR must be used in combination with other antiretroviral agents [see Dosage and Administration (2)]. The recommended dosage of NORVIR in pediatric patients older than 1 month is 350 to 400 mg per m² twice daily by mouth to be taken with meals and should not exceed 600 mg twice daily. NORVIR should be started at 250 mg per m² twice daily and increased at 2 to 3 day intervals by 50 mg per m² twice daily. If patients do not tolerate 400 mg per m² twice daily due to adverse events, the highest tolerated dose may be used for maintenance therapy in combination with other antiretroviral agents, however, alternative therapy should be considered [see Dosage and Administration (2.6)].

Pediatric Dosage Guidelines for Oral Solution

NORVIR oral solution should not be administered to neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 44 weeks has been attained [see Warnings and Precautions (5.2)].

NORVIR oral solution contains the excipients ethanol (approx. 43% v/v) and propylene glycol (approx. 27% w/v). Special attention should be given to accurate calculation of the dose of NORVIR, transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors, and overdose. This is especially important for young children. Total amounts of ethanol and propylene glycol from all medicines that are to be given to pediatric patients 1 to 6 months of age should be taken into account in order to avoid toxicity from these excipients [see Warnings and Precautions (5.2) and Overdosage (10)]. When possible, dose should be administered using a calibrated dosing syringe.

Table 1. Pediatric Dosage Guidelines for Oral Solution*

Body Surface Area (m2)	Twice Daily Dose 250 mg per m2	Twice Daily Dose 300 mg per m2	Twice Daily Dose 350 mg per m2	Twice Daily Dose 400 mg per m2
0.20	0.6 mL (50 mg)	0.75 mL (60 mg)	0.9 mL (70 mg)	1.0 mL (80 mg)
0.25	0.8 mL (62.5 mg)	0.9 mL (75 mg)	1.1 mL (87.5 mg)	1.25 mL (100 mg)
0.50	1.6 mL (125 mg)	1.9 mL (150 mg)	2.2 mL (175 mg)	2.5 mL (200 mg)
0.75	2.3 mL (187.5 mg)	2.8 mL (225 mg)	3.3 mL (262.5 mg)	3.75 mL (300 mg)
1.00	3.1 mL (250 mg)	3.75 mL (300 mg)	4.4 mL (350 mg)	5 mL (400 mg)
1.25	3.9 mL (312.5 mg)	4.7 mL (375 mg)	5.5 mL (437.5 mg)	6.25 mL (500 mg)
1.50	4.7 mL (375 mg)	5.6 mL (450 mg)	6.6 mL (525 mg)	7.5 mL (600 mg)
*The concentration of the oral solution is 80 mg per mL.

Body surface area (BSA) can be calculated as follows¹:

Pediatric Dosage Guidelines for Oral Powder

NORVIR oral powder should be used only for dosing increments of 100 mg. NORVIR powder should not be used for doses less than 100 mg or for incremental doses between 100 mg intervals. NORVIR oral solution is the preferred formulation for patients requiring doses less than 100 mg or incremental doses between 100 mg intervals.