ISENTRESS

ISENTRESS- raltegravir potassium tablet, film coated
Dispensing Solutions, Inc.

1 INDICATIONS AND USAGE

1.1 Adults

ISENTRESS® is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection.

This indication is based on analyses of plasma HIV-1 RNA levels in three double-blind controlled studies of ISENTRESS. Two of these studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, NRTI, PI) treatment-experienced adults through 96 weeks and one was conducted in treatment-naïve adults through 156 weeks.

The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response [see Clinical Studies (14)].

1.2 Pediatrics

ISENTRESS is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in children and adolescents 2 years of age and older and weighing at least 10 kg [see Use in Specific Populations (8.4)].

This indication is based on the evaluation of safety, tolerability, pharmacokinetic parameters and efficacy of ISENTRESS through at least 24-weeks in a multi-center, open-label, noncomparative study in HIV-1 infected children and adolescents 2 to 18 years of age [see Clinical Studies (14.3)].

The safety and efficacy of ISENTRESS have not been established in children less than 2 years of age.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Recommendations

• ISENTRESS Film-Coated Tablets and Chewable Tablets can be administered with or without food [see Clinical Pharmacology (12.3)].
• Maximum dose of chewable tablets is 300 mg twice daily.
• ISENTRESS Chewable Tablets may be chewed or swallowed whole.
• ISENTRESS Film-Coated Tablets must be swallowed whole.
• Because the formulations are not bioequivalent, do not substitute chewable tablets for the 400 mg film-coated tablet.
• During coadministration of ISENTRESS 400 mg film-coated tablets with rifampin, the recommended dosage of ISENTRESS is 800 mg twice daily in adults. There are no data to guide co-administration of ISENTRESS with rifampin in patients below 18 years of age [see Drug Interactions (7)].

2.2 Adults

For the treatment of adult patients with HIV-1 infection, the dosage of ISENTRESS is one 400 mg film-coated tablet administered orally, twice daily.

2.3 Pediatrics

For the treatment of children and adolescents with HIV-1 infection, the dosage of ISENTRESS is as follows:

• 12 years of age and older: One 400 mg film-coated tablet orally, twice daily
• 6 to less than 12 years of age:
  If at least 25 kg in weight:
  • One 400 mg film-coated tablet orally, twice daily OR
  • Chewable tablets: weight based to maximum dose 300 mg, twice daily as specified in Table 1
  If less than 25 kg in weight:
  • Chewable tablets: weight based to maximum dose 300 mg, twice daily as specified in Table 1
• 2 to less than 6 years of age: If at least 10 kg in weight:
  • Chewable tablets: weight based to maximum dose 300 mg, twice daily as specified in Table 1

Table 1: Recommended Dose * for ISENTRESS Chewable Tablets in Pediatric Patients 2 to Less Than 12 Years of Age

Body Weight(kg)	Dose	Number of Chewable Tablets
* The weight-based dosing recommendation for the chewable tablet is based on approximately 6 mg/kg/dose twice daily. † The 100 mg chewable tablet can be divided into equal halves.
10 to less than 14	75 mg twice daily	3 × 25 mg twice daily
14 to less than 20	100 mg twice daily	1 × 100 mg twice daily
20 to less than 28	150 mg twice daily	1.5 × 100 mg † 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

3 DOSAGE FORMS AND STRENGTHS

• Film-coated Tablets
  400 mg pink, oval-shaped, film-coated tablets with “227” on one side.
• Chewable Tablets
  100 mg pale orange, oval-shaped, orange-banana flavored, chewable tablets scored on both sides and imprinted on one face with the Merck logo and “477” on opposite sides of the score.25 mg pale yellow, round, orange-banana flavored, chewable tablets with the Merck logo on one side and “473” on the other side.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Severe Skin and Hypersensitivity Reactions

Severe, potentially life-threatening, and fatal skin reactions have been reported. These include cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure. Discontinue ISENTRESS and other suspect agents immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema). Clinical status including liver aminotransferases should be monitored and appropriate therapy initiated. Delay in stopping ISENTRESS treatment or other suspect agents after the onset of severe rash may result in a life-threatening reaction.

5.2 Immune Reconstitution Syndrome

​ Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including ISENTRESS. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia, tuberculosis), which may necessitate further evaluation and treatment.

​ Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

5.3 Phenylketonurics

ISENTRESS Chewable Tablets contain phenylalanine, a component of aspartame. Each 25 mg ISENTRESS Chewable Tablet contains approximately 0.05 mg phenylalanine. Each 100 mg ISENTRESS Chewable Tablet contains approximately 0.10 mg phenylalanine. Phenylalanine can be harmful to patients with phenylketonuria.

6 ADVERSE REACTIONS

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.