Raltegravirdosage

ISENTRESS and ISENTRESS HD can be administered with or without food. Do not substitute ISENTRESS chewable tablets or ISENTRESS for oral suspension for the ISENTRESS 400 mg or 600 mg film-coated tablet. See specific dosing guidance for chewable tablets and the formulation for oral suspension. Adults Treatment-naïve patients or patients who are virologically suppressed on an initial regimen of ISENTRESS 400 mg twice daily: 1200 mg (2 × 600 mg) film-coated tablet orally, once daily or 400 mg film-coated tablet orally, twice daily.

Treatment-experienced patients: 400 mg film-coated tablet orally, twice daily. During coadministration with rifampin in adults, 800 mg (2 × 400 mg) twice daily. Pediatrics If weighing at least 40 kg, and either treatment-naïve patients or patients who are virologically suppressed on an initial regimen of ISENTRESS 400 mg twice daily: 1200 mg (2 × 600 mg) film-coated tablet orally, once daily or 400 mg film-coated tablet orally, twice daily or 300 mg (3 × 100 mg) chewable tablets, twice daily. If weighing at least 25 kg: One 400 mg film-coated tablet orally, twice daily. If unable to swallow a tablet, consider the chewable tablet, as specified in Table 2. If weighing at least 3 kg to less than 25 kg: Weight-based dosing using the chewable tablet or oral suspension, as specified in Table 4. For neonates (birth to 4 weeks [28 days] of age): Weight-based dosing of the oral suspension as specified in Table 5.

2.1 General

Dosing Recommendations Because the formulations have different pharmacokinetic profiles, do not substitute ISENTRESS chewable tablets or ISENTRESS for oral suspension for the ISENTRESS 400 mg film-coated tablet or the ISENTRESS HD 600 mg film-coated tablet. See specific dosing guidance for chewable tablets and the formulation for oral suspension. Because the extent to which ISENTRESS may be dialyzable is unknown, dosing before a dialysis session should be avoided. ISENTRESS film-coated tablets must be swallowed whole. ISENTRESS chewable tablets may be chewed or swallowed whole. Maximum daily dose is 300 mg taken by mouth twice daily. For children who have difficulty chewing the 25 mg chewable tablet, the tablet may be crushed. Preparation of the crushed 25 mg chewable tablet: Place the tablet(s) in a small, clean cup. For each tablet, add a teaspoonful (~5 mL) of liquid (for example, water, juice, or breast milk). Within 2 minutes, the tablet(s) will absorb the liquid and fall apart. Using a spoon, crush any remaining pieces of the tablet(s). Immediately administer the entire dose orally. If any portion of the dose is left in the cup, add another teaspoonful (~5 mL) of liquid, swirl and administer immediately.

ISENTRESS for oral suspension: See Instructions for Use for details on preparation and administration of ISENTRESS for oral suspension. Using the provided mixing cup, combine 10 mL of water and the entire contents of one packet of ISENTRESS for oral suspension and mix. Each single-use packet for oral suspension contains 100 mg of raltegravir which is suspended in 10 mL of water giving a final concentration of 10 mg per mL. Maximum daily dose is 100 mg taken by mouth twice daily. Gently swirl the mixing cup for 45 seconds in a circular motion to mix the powder into a uniform suspension. Do not shake. Once mixed, measure the prescribed dose volume of suspension with a syringe and administer the dose orally. The dose should be administered orally within 30 minutes of mixing. Discard any remaining suspension into the trash.

2.2 Adults The recommended adult dosage of ISENTRESS film-coated tablets is displayed in

Table 1. ISENTRESS and ISENTRESS HD should be taken by mouth and may be taken with or without food.

Table 1: Dosing Recommendations for ISENTRESS and ISENTRESS HD in Adult Patients Population Recommended Dose Treatment-naïve patients or patients who are virologically suppressed on an initial regimen of ISENTRESS 400 mg twice daily 1200 mg (2 × 600 mg) once daily or 400 mg twice daily Treatment-experienced 400 mg twice daily Treatment-naïve or treatment-experienced when coadministered with rifampin 800 mg (2 × 400 mg) twice daily

2.3 Pediatrics

The recommended pediatric dosage of ISENTRESS is displayed in Table 2. ISENTRESS film-coated tablets, chewable tablets and for oral suspension should be taken by mouth and may be taken with or without food.

Table 2: Dosing Recommendations for ISENTRESS and ISENTRESS HD in Pediatric Patients Recommended Pediatric Dosage and Formulation Population/Weight Film-Coated Tablets 400 mg Film-Coated Tablets 600 mg Chewable Tablets 100 mg and 25 mg For Oral Suspension 100 mg If at least 40 kg and either: treatment-naïve or virologically suppressed on an initial regimen of ISENTRESS 400 mg twice daily 400 mg twice daily 1200 mg (2 × 600 mg) once daily 300 mg twice daily (see Table 3 ) NA If at least 25 kg 400 mg twice daily If able to swallow a tablet NA Weight-based dosing twice daily (see Table 3 ) NA If at least 4 weeks of age and weighing 3 kg to less than 25 kg NA NA Weight-based dosing twice daily (see Table 4 ) Weight-based dosing twice daily up to 20 kg (see Table 4 ) From birth to 4 weeks (28 days) weighing at least 2 kg NA NA NA Weight-based dosing once daily or twice daily (see Table 5 ) Table 3: Alternative Dosage The weight-based dosing recommendation for the chewable tablet is based on approximately 6 mg/kg/dose twice daily. with ISENTRESS Chewable Tablets for Pediatric Patients Weighing at Least 25 kg Body Weight (kg) Dose Number of 100 mg Chewable Tablets 25 to less than 28 150 mg twice daily 1.5 × 100 mg The 100 mg chewable tablet can be divided into equal halves. twice daily 28 to less than 40 200 mg twice daily 2 × 100 mg twice daily At least 40 300 mg twice daily 3 × 100 mg twice daily Table 4: Recommended Dosage The weight-based dosing recommendation for the chewable tablet and oral suspension is based on approximately 6 mg/kg/dose twice daily. for ISENTRESS For Oral Suspension and Chewable Tablets in Pediatric Patients at Least 4 Weeks of Age and Weighing at Least 3 kg and Less than 25 kg Body Weight (kg) Volume (Dose) of Suspension to be Administered Number of Chewable Tablets The chewable tablets are available as 25 mg and 100 mg tablets. 3 to less than 4 2.5 mL (25 mg) twice daily 1 × 25 mg twice daily May be administered as a crushed tablet(s); see General Dosing Recommendations for guidance. 4 to less than 6 3 mL (30 mg) twice daily 6 to less than 8 4 mL (40 mg) twice daily 2 × 25 mg twice daily 8 to less than 10 6 mL (60 mg) twice daily 10 to less than 14 8 mL (80 mg) twice daily 3 × 25 mg twice daily 14 to less than 20 10 mL (100 mg) twice daily 1 × 100 mg twice daily 20 to less than 25 Not applicable 1.5 × 100 mg The 100 mg chewable tablet can be divided into equal halves. twice daily For full-term neonates (birth to 4 weeks [28 days] of age): Weight-based dosing of the oral suspension as specified in Table 5. No data are available in pre-term neonates. The use of ISENTRESS is not recommended in pre-term neonates.

Table 5: Recommended Dose for ISENTRESS For Oral Suspension in Full-Term Neonates (Birth to 4 Weeks [28 days] of Age) Body Weight (kg) Volume (Dose) of Suspension to be Administered Note: If the mother has taken ISENTRESS or ISENTRESS HD 2-24 hours before delivery, the neonate's first dose should be given between 24-48 hours after birth. Birth to 1 Week - Once daily dosing The dosing recommendations are based on approximately 1.5 mg/kg/dose. 2 to less than 3 0.4 mL (4 mg) once daily 3 to less than 4 0.5 mL (5 mg) once daily 4 to less than 5 0.7 mL (7 mg) once daily 1 to 4 Weeks - Twice daily dosing The dosing recommendations are based on approximately 3 mg/kg/dose. 2 to less than 3 0.8 mL (8 mg) twice daily 3 to less than 4 1 mL (10 mg) twice daily 4 to less than 5 1.5 mL (15 mg) twice daily