Dosing & Uses
Dosage Forms & Strengths
tablet, film-coated
- 400mg (Isentress)
- 600mg (Isentress HD)
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
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
- ≥40 kg and treatment naïve or virologically suppressed on an initial regimen: 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 adults and children weighing at least 40 kg
- ≥40 kg and treatment naïve or virologically suppressed on an initial regimen:1200 mg PO qDay
Chewable tablet
- <4 weeks: Safety and efficacy not established
- ≥4 weeks
- Not to exceed daily dose is 300 mg PO BID; dosing recommendations are based on ~6 mg/kg/dose
- 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
- Preterm neonates: Safety and efficacy not established
- 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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10% (STARMARK trial)
Serum alanine aminotransferase, Grade 2-4 (2-11%)
Serum aspartate aminotransferase, Grade 2-4 (1-8%)
1-10% (STARTMRK trial)
Fasting serum glucose test, Grade 2-4 (7%)
Total serum bilirubin, Grade 2-4 (≤5%)
Headache (4%)
Insomnia (4%)
Nausea (3%)
ANC, Grade 2-4 (1-3%)
Serum alkaline phosphate, Grade 2-4 (≤3%)
Dizziness (2%) Fatigue (2%)
Creatinine (≤1%)
Hemoglobin, Grade 2-4 (≤1%)
Platelet count, Grade 2-3 (≤1%)
1-10% (ONCEMRK trial)
Lipase, Grade 2-4 (≤2-7%)
Creatine kinase, Grade 2-4 (≤2-4%)
Serum aspartate aminotransferase, Grade 2-4 (≤5%)
Serum alanine aminotransferase, Grade 2-4 (≤4%)
Serum alkaline phosphate, Grade 2-4 (≤1%)
ANC, Grade 2-4 (≤2%)
Platelet count, Grade 2-3 (≤1%)
Total serum bilirubin, Grade 2-4 (≤3%)
Headache (1%)
Nausea (1%)
Postmarketing Reports
Blood and lymphatic system disorders: Thrombocytopenia
Gastrointestinal Disorders: Diarrhea
Hepatobiliary disorders: Hepatic failure (with and without associated hypersensitivity) in patients with underlying liver disease and/or concomitant medications
Musculoskeletal and connective tissue disorders: Rhabdomyolysis
Nervous system disorders: Cerebellar ataxia
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
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.
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 and 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)
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
Images
Patient Handout
Formulary
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.
