(ral TEG ra vir)
- Raltegravir Potassium
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Isentress: 100 mg (1 ea, 60 ea) [contains polyethylene glycol; banana flavor]
Isentress: 400 mg [contains polyethylene glycol]
Tablet Chewable, Oral:
Isentress: 25 mg [contains aspartame, saccharin sodium; orange banana flavor]
Isentress: 100 mg [scored; contains aspartame, saccharin sodium; orange banana flavor]
Brand Names: U.S.
- Antiretroviral, Integrase Inhibitor (Anti-HIV)
Incorporation of viral DNA into the host cell’s genome is required to produce a self-replicating provirus and propagation of infectious virion particles. The viral cDNA strand produced by reverse transcriptase is subsequently processed and inserted into the human genome by the enzyme HIV-1 integrase (encoded by the pol gene of HIV). Raltegravir inhibits the catalytic activity of integrase, thus preventing integration of the proviral gene into human DNA.
Film-coated tablet: AUC increased twofold with high-fat meal; Chewable tablet: AUC decreased by ~6% with high-fat meal (not clinically significant); Oral suspension: The effect of food was not studied.
Primarily hepatic glucuronidation mediated by UGT1A1
Feces (~51%, as unchanged drug); urine (~32%; 9% as unchanged drug)
Time to Peak
Film-coated tablet: ~3 hours
Special Populations: Renal Function Impairment
No clinically important pharmacokinetic differences were observed between subjects with severe renal impairment and healthy subjects. Because the extent to which raltegravir is dialyzable is unknown, avoid dosing before dialysis.
Special Populations: Gender
A study of the pharmacokinetics of raltegravir was performed in healthy adult men and women. Additionally, the effect of gender was evaluated in a composite analysis of pharmacokinetic data from 103 healthy subjects and 28 HIV-1 infected subjects receiving raltegravir monotherapy with fasted administration. No dosage adjustment is necessary.
Use: Labeled Indications
US labeling: Treatment of HIV-1 infection in combination with other antiretroviral agents in patients 4 weeks and older and weighing at least 3 kg
Canadian labeling: Treatment of HIV-1 infection in combination with other antiretroviral agents in patients ≥2 years of age
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Hypersensitivity to raltegravir or any other component of the formulation
HIV-1 treatment: Oral: Film-coated tablet: 400 mg twice daily. Note: Raltegravir is a component of a recommended initial regimen with tenofovir plus emtricitabine (or lamivudine) or tenofovir alafenamide plus emtricitabine in ART-naive patients (HHS [adult] 2016); may also be used in combination with darunavir and ritonavir as part of a nucleoside-sparing regimen in ART-naïve patients with HIV-1 viral load <100,000 copies/mL and CD4 count >200 cells/mm3 (HHS [adult] 2016; Raffi 2014; Taiwo 2011).
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use): Oral: Film-coated tablet: 400 mg twice daily for 28 days in combination with other antiretroviral agents. Initiate therapy within 72 hours of exposure (HHS [nPEP] 2016).
HIV-1 occupational postexposure, prophylaxis (oPEP) (off-label use): Oral: Film-coated tablet: 400 mg twice daily for 4 weeks with concomitant emtricitabine/tenofovir. Initiate therapy as soon as possible after occupational exposure (and within 72 hours) (Kuhar 2013).
Dosage adjustment for rifampin coadministration: 800 mg twice daily
Refer to adult dosing.
HIV-1 treatment: Oral:
Note: Raltegravir film-coated tablets and chewable tablets or oral suspension are not bioequivalent and are not substitutable on a mg/mg basis
Infants ≥4 weeks and Children (≥3 to <25 kg): Weight-based dosing based on ~6 mg/kg/dose twice daily (maximum dose: 600 mg/day [chewable tablet]; 200 mg/day [oral suspension]).
3 to <4 kg: 20 mg twice daily (oral suspension)
4 to <6 kg: 30 mg twice daily (oral suspension)
6 to <8 kg: 40 mg twice daily (oral suspension)
8 to <11 kg: 60 mg twice daily (oral suspension)
11 to <14 kg: 80 mg twice daily (oral suspension) or 75 mg twice daily (chewable tablet) (see "Note")
14 to <20 kg: 100 mg twice daily (oral suspension or chewable tablet) (see "Note")
20 to <25 kg: 150 mg twice daily (chewable tablet)
Note: Infants and Children ≥4 weeks who are between 11 and <20 kg may use either the chewable tablet or the oral suspension. Patients can remain on the oral suspension as long as their weight is <20 kg.
Children and Adolescents ≥25 kg:
Film-coated tablet: Refer to adult dosing.
Chewable tablet: Weight-based dosing based on ~6 mg/kg/dose twice daily (maximum dose: 600 mg/day).
25 to <28 kg: 150 mg twice daily (see "Note")
28 to <40 kg: 200 mg twice daily (see "Note")
≥40 kg: 300 mg twice daily (see "Note")
Note: May use either weight-based dosing (chewable tablet) or adult dosing (film-coated tablet).
Canadian labeling: Chewable tablet: Children 2 to <12 years (maximum dose: 600 mg/day):
7 to <10 kg: 50 mg twice daily
10 to <14 kg: 75 mg twice daily
14 to <20 kg: 100 mg twice daily
20 to <28 kg: 150 mg twice daily
28 to <40 kg: 200 mg twice daily
≥40 kg: 300 mg twice daily
Dosage adjustment for rifampin coadministration: There are no data to guide dose adjustment in patients <18 years.
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use) (HHS [nPEP] 2016): Oral: Note: Initiate therapy within 72 hours of exposure and continue for 28 days; use in combination with other antiretroviral agents.
Infants and Children <2 years: Oral suspension: 6 mg/kg/dose twice daily
Children ≥2 years:
11 to <14 kg: 75 mg twice daily
14 to <20 kg: 100 mg twice daily
20 to <28 kg: 150 mg twice daily
28 to <40 kg: 200 mg twice daily
≥40 kg: 300 mg twice daily
Film-coated tablet: Children ≥ 6 years weighing >25 kg who are able to swallow a tablet whole: 400 mg twice daily
Adolescents: Oral: Film-coated tablet: Refer to adult dosing.
Dosing: Renal Impairment
Mild, moderate, and severe impairment: No dosage adjustment necessary.
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): Dose after dialysis on dialysis days.
Dosing: Hepatic Impairment
Mild-to-moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in manufacturer’s labeling (has not been studied).
May be administered without regard to meals.
Chewable tablets: May be chewed or swallowed whole; the 100 mg chewable tablet may be divided into equal halves.
Film-coated tablets: Must be swallowed whole.
Oral suspension: Open foil packet of drug (100 mg). Measure 5 mL water in provided mixing cup. Pour packet contents into 5 mL water, close lid and swirl for 30-60 seconds. Do not turn the mixing cup upside down. Once mixed, measure recommended suspension dose with an oral syringe. Administer within 30 minutes of mixing with water. Discard any remaining suspension in the trash.
Some products may contain phenylalanine.
Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Chewable tablets: Store in the original package; keep desiccant in the bottle to protect from moisture.
Oral suspension: Store in the original container; do not open foil packet until ready for reconstitution and use.
Aluminum Hydroxide: May decrease the serum concentration of Raltegravir. Management: Avoid the use of oral / enteral aluminum hydroxide with raltegravir. No dose separation schedule has been established that adequately reduces the magnitude of interaction. Avoid combination
Fibric Acid Derivatives: Raltegravir may enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. Monitor therapy
Fosamprenavir: May decrease the serum concentration of Raltegravir. Raltegravir may decrease the serum concentration of Fosamprenavir. Consider therapy modification
HMG-CoA Reductase Inhibitors: Raltegravir may enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Magnesium Salts: May decrease the serum concentration of Raltegravir. Management: Avoid the use of oral / enteral magnesium salts with raltegravir. No dose separation schedule has been established that adequately reduces the magnitude of interaction. Avoid combination
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy
Proton Pump Inhibitors: May increase the serum concentration of Raltegravir. Monitor therapy
Rifabutin: May decrease the serum concentration of Raltegravir. Specifically, minimum serum concentrations (Cmin) may be reduced. Total raltegravir exposure (i.e., AUC) may be increased. Monitor therapy
RifAMPin: May decrease the serum concentration of Raltegravir. Management: Increase raltegravir dose to 800 mg twice daily (adult dose) when used concomitantly with rifampin. Consider therapy modification
Rifapentine: May increase the serum concentration of Raltegravir. Rifapentine may decrease the serum concentration of Raltegravir. Monitor therapy
Tipranavir: May decrease the serum concentration of Raltegravir. Monitor therapy
Zidovudine: Raltegravir may enhance the myopathic (rhabdomyolysis) effect of Zidovudine. Monitor therapy
Hepatic: Increased serum ALT (1% to 11%; incidence higher with hepatitis B and/or C coinfection)
2% to 10%:
Central nervous system: Insomnia (4%), headache (2% to 4%), dizziness (2%), fatigue (2%)
Endocrine & metabolic: Increased serum glucose (126 to 250 mg/dL: 7% to 10%; 251 to 500 mg/dL: 2% to 3%)
Gastrointestinal: Increased serum lipase (2% to 5%), increased serum amylase (2% to 4%), nausea (3%)
Hematologic: Abnormal absolute neutrophil count (2% to 3%), thrombocytopenia (1% to 3%)
Hepatic: Increased serum AST (1% to 9%; incidence higher with hepatitis B and/or C coinfection), hyperbilirubinemia (<1% to 6%), increased serum alkaline phosphatase (<1% to 2%)
Neuromuscular & skeletal: Increased creatine phosphokinase (10 to 19.9 x ULN: 4%; ≥20 x ULN: 3%)
<2% (Limited to important or life-threatening): Anemia, cerebellar ataxia, depression (particularly in subjects with a pre-existing history of psychiatric illness), drug rash with eosinophilia and systemic symptoms (DRESS; Perry, 2013), gastritis, hepatic failure, hepatitis, hypersensitivity, myopathy, nephrolithiasis, psychomotor agitation (children; grade 3), renal failure, rhabdomyolysis, Stevens-Johnson syndrome, suicidal ideation, toxic epidermal necrolysis
Concerns related to adverse effects:
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Myopathy: Grade 2 to 4 creatine kinase (CK) increases have been observed and myopathy and rhabdomyolysis have been reported; use caution in patients with a history of rhabdomyolysis, myopathy, or increased serum creatine kinase or who have risk factors for CK elevations and/or skeletal muscle abnormalities, including taking other drugs known to cause myopathy or rhabdomyolysis.
• Skin and hypersensitivity reactions: Severe, life-threatening or fatal cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Hypersensitivity reactions (rash [may occur with fever, fatigue, malaise, conjunctivitis, or other constitutional symptoms], organ dysfunction and/or hepatic failure) have also been reported. Discontinue immediately if a severe skin reaction or hypersensitivity symptoms develop. Monitor liver transaminases and start supportive therapy.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Dosage form specific issues:
• Chewable tablet: Contains phenylalanine.
• Tablets and oral suspension: Raltegravir film-coated tablets and chewable tablets or oral suspension are not bioequivalent and are not substitutable on a mg/mg basis.
• Appropriate use: Raltegravir plus darunavir/ritonavir should not be used in adolescent and adult HIV-1 patients with a pre-ART CD4 count <200 cells/mm3 and/or HIV RNA >100,000 copies/mL (HHS [adult] 2015).
Viral load, CD4 count, signs of skin rash, signs/symptoms of depression and suicidal ideation
HIV occupational postexposure prophylaxis (PEP) (Kuhar, 2013): Documented HIV test (at baseline and 6 weeks, 12 weeks and 6 months after exposure); if confirmation that a fourth generation HIV p2 antigen-HIV antibody test is being used, monitor at baseline, 6 weeks and 4 months after exposure. CBC, renal and hepatic function assessments at baseline and 2 weeks after exposure (minimum recommendations, others dictated by clinical assessment)
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Raltegravir has high transfer across the human placenta and can be detected in neonatal serum after delivery. Data collected by the antiretroviral pregnancy registry are insufficient to evaluate human teratogenic risk. Maternal antiretroviral therapy may increase the risk of preterm delivery, although available information is conflicting possibly due to variability of maternal factors (disease severity; initiation of therapy); however, maternal antiretroviral medication should not be withheld due to concerns of preterm birth. Information related to stillbirth, low birth weight, and small for gestational age infants is limited. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should begin as soon as possible after diagnosis. The Health and Human Services (HHS) Perinatal HIV Guidelines consider raltegravir to be the preferred integrase inhibitor for initial use in antiretroviral-naive pregnant patients and is useful when drug interactions with protease inhibitors are a concern. Because of its ability to rapidly suppress viral load, raltegravir may be useful in women who present late in pregnancy with high viral loads. Dose adjustments are not required in pregnant women. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated. Monitoring during pregnancy is more frequent than in non-pregnant adults; cART should be continued postpartum. Reversible elevation of liver enzymes occurred in a patient who initiated raltegravir late in pregnancy; monitor liver enzymes if used during pregnancy.
For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s) and expert consultation is recommended; modification of therapy (if needed) and optimization of the woman’s health should be done prior to conception. HIV-infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.
Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal], 2016).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience insomnia, headache, dizziness, or nausea. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), muscle pain, joint pain, severe loss of strength and energy, muscle weakness, bruising, bleeding, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: integrase strand transfer inhibitor
Other brands: Isentress