raltegravir (Rx)

Brand and Other Names:Isentress, Isentress HD
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet, film-coated

  • 400mg (Isentress)
  • 600mg (Isentress HD)
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HIV-1 Infection

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

Also see Administration

Treatment-naïve or virologically suppressed

  • Treatment-naïve patients or patients who are virologically suppressed on an initial regimen of 400 mg BID
  • Isentress (400-mg tab): 400 mg PO BID
  • Isentress HD (600-mg tab): 1200 (two 600-mg tabs) PO qDay

Treatment-experienced

  • 400 mg PO BID

Dosage Modifications

Coadministration with rifampin

  • Treatment-naïve or treatment-experienced when coadministered with rifampin
  • 800 mg (two 400-mg tabs) PO BID

Hepatic impairment

  • Isentress
    • Mild-to-moderate (Child Pugh A and B): No dose adjustment required
    • Severe (Child Pugh C): Not studied
  • Isentress HD
    • Safety and efficacy not established; administration is not recommended

Renal impairment

  • No dosage adjustment required for any degree of renal impairment
  • Dialysis: Unknown if drug is removed by dialysis; avoid dosing before dialysis session

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

Do not substitute chewable tablets or oral suspension for film-coated tablets; these are not bioequivalent, and therefore, are not interchangeable

Do not switch between film-coated 400 mg and 600 mg tablet if prescribed dose is 1200 mg

Dosage Forms & Strengths

tablet, film-coated

  • 400mg (Isentress)
  • 600mg (Isentress HD)

tablet, chewable

  • 25mg
  • 100mg (scored)

powder for oral suspension

  • 100mg/packet
more...

HIV-1 Infection

Film-coated tablet, Isentress 400-mg tab

  • Indicated in combination with other antiretroviral agents for HIV-1
  • ≥25 kg to <40 kg: 400 mg PO BID
  • Treatment naïve or virologically suppressed on an initial regimen
    • ≥40 kg: 400 mg PO BID
    • See Dosing Modifications

Film-coated tablet, Isentress HD 600-mg tab

  • Indicated in combination with other antiretroviral agents for HIV-1 infection in children and adults weighing
  • ≥40 kg: 1200 mg PO qDay

Chewable tablet (NIH Guidelines)

  • Not to exceed daily dose is 300 mg PO BID
  • 11 to <14 kg: 75 mg PO BID (3 x 25 mg tablets)
  • 14 to <20 kg: 100 mg PO BID (1 x 100 mg tablet)
  • 20 to <28 kg: 150 mg PO BID (1.5 x 100 mg tablets)
  • 28 to <40 kg: 200 mg PO BID (2 x 100 mg tablet)
  • ≥40 kg: 300 mg PO BID (3 x 100 mg tablets)

Oral suspension

  • Not to exceed 100 mg PO BID; see age and weight-based dosing listed below
  • For full-term neonates (birth to 1 week)
    • Dosing recommendations are based on ~1.5 mg/kg/dose
    • 2 to <3 kg: 4 mg (0.4 mL) PO qDay
    • 3 to <4 kg: 5 mg (0.5 mL) PO qDay
    • 4 to <5 kg: 7 mg (0.7 mL) PO qDay
  • For full-term neonates (1 to 4 weeks)
    • Dosing recommendations are based on ~3 mg/kg/dose
    • 2 to <3 kg: 8 mg (0.8 mL) PO qDay
    • 3 to <4 kg: 10 mg (1 mL) PO qDay
    • 4 to <5 kg: 15 mg (1.5 mL) PO qDay
  • Age at least 4 weeks and weight 3-20 kg
    • 3 to <4 kg: 25 mg (2.5 mL) PO BID
    • 4 to <6 kg: 30 mg (3 mL) PO BID
    • 6 to <8 kg: 40 mg (4 mL) PO BID
    • 8 to <11 kg: 60 mg (6 mL) PO BID
    • 11 to <14 kg: 80 mg (8 mL) PO BID
    • 14 kg to <20 kg: 100 mg (10 mL) PO BID

Dosage Modifications

Hepatic impairment

  • Isentress
    • Mild-to-moderate (Child Pugh A and B): No dose adjustment required
    • Severe (Child Pugh C): Not studied
  • Isentress HD
    • Safety and efficacy not established; administration is not recommended

Renal impairment

  • No dosage adjustment required for any degree of renal impairment
  • Dialysis: Unknown if drug is removed by dialysis; avoid dosing before dialysis session

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

Do not substitute chewable tablets or oral suspension for film-coated tablets; these are not bioequivalent, and therefore, are not interchangeable

Do not switch between film-coated 400 mg and 600 mg tablet if prescribed dose is 1200 mg

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Interactions

Interaction Checker

and raltegravir

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse 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

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            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

            Drug interactions overview

            • Coadministration of raltegravir with drugs that inhibit UGT1A1 (eg, rifampin) may reduce plasma levels of raltegravir (see Dosage Modifications)
            • Coadministration with other strong inducers (eg, carbamazepine, phenobarbital, phenytoin) of drug metabolizing enzymes on raltegravir is unknown and therefore not recommended
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            Pregnancy & Lactation

            Pregnancy

            There is a pregnancy exposure registry that monitors pregnancy outcomes in women; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1- 800-258-4263  

            Available data from APR show no difference in rate of overall birth defects for raltegravir compared to background rate for major birth defects of 2.7% in U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP); the rate of miscarriage is not reported in the APR; the MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation

            In animal reproduction studies in rats and rabbits, no evidence of adverse developmental outcomes observed with oral administration during organogenesis at doses that produced exposures up to approximately 4 times maximal recommended human dose (MRHD) of 1200 mg

            Lactation

            The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers in United States not breastfeed infants to avoid risking postnatal transmission of HIV-1 infection

            No data are available on presence of raltegravir in human milk, effects on breastfed infant, or on milk production; when administered to lactating rats, raltegravir was present in milk

            Owing to the potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV- positive infants), and adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving therapy

            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.

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            Pharmacology

            Mechanism of Action

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

            Absorption

            Fasted state

            • Peak plasma concentration: 4.5 mcg/mL (400 mg PO BID); 15.7 mcg/mL (1200 mg PO qDay)
            • Peak plasma time: ~3 hr (400 mg PO BID)
            • Peak plasma time: ~1.5 – 2 hr (1200 mg PO qDay)
            • Steady state: 2 days

            Effect of food

            • Low fat
              • AUC ratio: 0.54 (400 mg PO BID); 0.58 (1200 mg PO BID)
              • Peak plasma concentration ratio: 0.48 (400 mg PO BID); 0.48 (1200 mg PO qDay)
            • Moderate fat
              • AUC ratio: 1.13 (400 mg PO BID)
              • Peak plasma concentration ratio: 1.05 (400 mg PO BID)
            • High fat
              • AUC ratio: 2.11 (400 mg PO BID); 1.02 (1200 mg PO BID); 0.94 (chewable tablet)
              • Peak plasma concentration ratio: 1.96 (400 mg PO BID); 0.72 (1200 mg PO qDay); 0.38 (chewable tablet)

            Distribution

            Protein Bound: ~83%

            Metabolism

            Primarily metabolized by UGT1A1-mediated glucuronidation

            Elimination

            Half-Life: ~9 hr

            Excretion: 51% (feces); 32% (urine)

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            Administration

            Oral Suspension Preparation

            Combine and mix 10 mL of water and 1 packet (100 mg) of the oral suspension

            Gently swirl mixing cup for 45 seconds in a circular motion to mix powder into a uniform suspension; final concentration (10 mg/mL); do not shake

            Once mixed, measure prescribed dose volume with a syringe and administer the dose orally

            Administer dose within 30 minutes of mixing

            Discard any remaining suspension into the trash

            Oral Administration

            May administer with or without food

            Do not substitute chewable tablets or oral suspension for film-coated tablets; these are not bioequivalent, and therefore, are not interchangeable

            Film-coated tablet: Must be swallowed whole

            Chewable tablet: May be chewed or swallowed whole

            Storage

            Oral suspension

            • Store at room temperature between 68-77°F (20-25°C)
            • Store in the original container
            • Do not open foil packet until ready for use

            Chewable tablets

            • Store at room temperature between 68-77°F (20-25°C)
            • Store in the original package with the bottle tightly closed
            • Keep the drying agent (desiccant) in bottle to protect from moisture

            Film-coated tablets

            • Store at room temperature between 68-77°F (20-25°C)
            • Store in the original package with the bottle tightly closed
            • Keep the drying agent (desiccant) in bottle to protect from moisture
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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