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raltegravir (Isentress)

 

Classes: HIV, Integrase Inhibitors

Dosing and uses of Isentress (raltegravir)

 

Adult dosage forms and strengths

tablet, film-coated

  • 400mg

 

HIV-1 Infection

Indicated in combination with other antiretroviral agents for HIV-1 infection

400 mg PO BID with or without food

 

Dosage modifications

Coadministration with rifampin: 800 mg PO BId

 

Dosing Considerations

Combination regimen is based on analyses of plasma HIV-1 RNA levels in 3 double-blind controlled studies; 2 of these studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, NRTI, PI) treatment-experienced adults through 96 wk and 1 study was conducted in treatment-naïve adults through 240 wk

The use of other active agents with raltegravir is associated with a greater likelihood of treatment response

 

Pediatric dosage forms and strengths

tablet, film-coated

  • 400mg

tablet, chewable

  • 25mg
  • 100mg (scored)

powder for oral suspension

  • 100mg/packet

 

HIV-1 Infection

Indicated in combination with other antiretroviral agents for HIV-1 infection in children and adolescents aged 4 weeks or older

Film-coated tablet (weight ≥25 kg): 400 mg PO BId

Chewable tablet

  • 10 to <14 kg: 75 mg PO BID
  • 14 to <20 kg: 100 mg PO BID
  • 20 to <28 kg: 150 mg PO BID
  • 28 to <40 kg: 200 mg PO BID
  • ≥40 kg: 300 mg PO BID

Powder for oral suspension

  • Age at least 4 weeks and weight 3-20 kg
  • 3 to <4 kg: 20 mg (1 mL) PO BID
  • 4 to <6 kg: 30 mg (1.5 mL) PO BID
  • 6 to <8 kg: 40 mg (2 mL) PO BID
  • 8 to <11 kg: 60 mg (3 mL) PO BID
  • 11 to <14 kg: 80 mg (4 mL) PO BID
  • 14 kg to <20 kg: 100 mg (5 mL) PO BID

 

Dosing Considerations

Combination regimen is based on safety, tolerability, pharmacokinetic parameters, and efficacy data through at least 24-wk in a multicenter, open-label, noncomparative study in HIV-1 infected children and adolescents aged 4 wk to 18 yr

 

Administration

May administer with or without food

Chewable tablets and film-coated tablets are not bioequivalent; and therefore, are not interchangeable

Powder for oral suspension

  • Suspend 1 packet (100 mg) in 5 mL of water; final concentration of 20 mg/mL
  • Administer suspension within 30 minutes of mixing
  • Discard any remaining suspension

 

Isentress (raltegravir) adverse (side) effects

>10%

Total cholesterol increased (16%)

 

1-10%

AST increased (9%)

Glucose increased (9%)

Hyperbilirubinemia (9%)

Fatigue (8%)

Nasopharyngitis (6%)

Abdominal pain (5%)

Cough (5%)

Rash (5%)

Dizziness (4%)

Insomnia (4%)

Vomiting (4%)

Arthralgia (3%)

Extremity pain (3%)

Influenza (3%)

Nausea

Diarrhea

Pyrexia

 

<1%

Asthenia

GI disorders

Lipodystrophy

Skin disorders

Drug related hypersensitivity

Thrombocytopenia

Renal failure

Suicidal ideation

 

Postmarketing Reports

Cerebellar ataxia

Diarrhea

Hepatic failure

Thrombocytopenia

Rhabdomyolysis

Psychiatric disorders: anxiety, depression (particularly in patients with a pre-existing history of psychiatric illness), including suicidal ideation and behaviors, paranoia

Skin: rash, Steven’s-Johnson syndrome

 

Warnings

Contraindications

None

 

Cautions

Risk of immune reconstitution syndrome if used with HAARt

Autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment

Concomitant medications known to increase risk of myopathy or rhabdomyolysis

Coadministration with drugs that are strong inducers of UGT1A1 may result in reduced plasma concentrations of raltegravir

Drug rash with eosinophilia and systemic symptoms (DRESS) reported

Severe, potentially life-threatening and fatal skin reactions reported; skin reactions include cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis; immediately discontinue treatment if severe hypersensitivity, severe rash, or rash with systemic symptoms or liver aminotransferase elevations develops and monitor clinical status, including liver aminotransferases closely

Phenylketonurics: Chewable tablets contain phenylalanine, a component of aspartame

 

Pregnancy and lactation

Pregnancy category: C

Lactation: HIV+ women shouldn't breastfeed

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Isentress (raltegravir)

Mechanism of action

Inhibits catalytic activity of HIV-1 integrase, an HIV encoded enzyme required for viral replication

 

Absorption

Peak Plasma Time: 3 hr in fasted state

 

Distribution

Protein Bound: 83%

 

Metabolism

Liver

 

Elimination

Half-Life: 9 hr

Excretion: Feces 51%; urine 32%