HIV-1 perinatal transmission, presumptive treatment; higher risk (3-drug regimen) (HHS [perinatal 2020]):
Note: In general, empiric therapy should be initiated as soon as possible after birth; however, neonatal raltegravir administration should be delayed to 24 to 48 hours after birth if the mother received raltegravir within 2 to 24 hours prior to delivery and other antiretrovirals should be started as soon as possible. If HIV infection is confirmed in the neonate, transition to a treatment and monitoring regimen for confirmed infection. Recommended in combination with lamivudine and zidovudine for empiric treatment of HIV in neonates at higher risk of perinatal transmission; see guidelines for additional information on high-risk definitions. Duration of therapy undefined; some experts suggest a full 6 weeks of therapy, and others suggest that raltegravir (but not zidovudine) can be discontinued after 2 weeks in certain situations (ie, negative nucleic acid test [NAT], specific maternal factors) (HHS [perinatal 2021]).
Term neonate (≥37 weeks GA) and weighing ≥2 kg:
PNA ≤7 days: Oral: Oral suspension (10 mg/mL):
Weight-directed dosing: 1.5 mg/kg/dose once daily.
Fixed dosing:
2 to <3 kg: 4 mg once daily.
3 to <4 kg: 5 mg once daily.
4 to <5 kg: 7 mg once daily.
PNA 8 to 28 days: Oral: Oral suspension (10 mg/mL):
Weight-directed dosing: 3 mg/kg/dose twice daily.
Fixed dosing:
2 to <3 kg: 8 mg twice daily.
3 to <4 kg: 10 mg twice daily.
4 to <5 kg: 15 mg twice daily.
PNA 29 to 42 days (≥4 to 6 weeks of age): Oral: Oral suspension (10 mg/mL):
Weight-directed dosing: 6 mg/kg/dose twice daily.
Fixed dosing:
3 to <4 kg: 25 mg twice daily.
4 to <6 kg: 30 mg twice daily.
6 to <8 kg: 40 mg twice daily.
HIV-1 infection, treatment: Note: Use in combination with other antiretroviral (ARV) agents. Gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.
Term neonate (≥37 weeks GA) and weighing ≥2 kg:
PNA ≤7 days: Oral: Oral suspension (10 mg/mL): Note: If the mother received raltegravir 2 to 24 hours prior to delivery, the initial neonatal dose should be delayed until 24 to 48 hours after birth. Other ARVs should be started as soon as possible (HHS [perinatal 2021]).
Weight-directed dosing: 1.5 mg/kg/dose once daily.
Fixed dosing:
2 to <3 kg: 4 mg once daily.
3 to <4 kg: 5 mg once daily.
4 to <5 kg: 7 mg once daily.
PNA 8 to 28 days: Oral: Oral suspension (10 mg/mL):
Weight-directed dosing: 3 mg/kg/dose twice daily.
Fixed dosing:
2 to <3 kg: 8 mg twice daily.
3 to <4 kg: 10 mg twice daily.
4 to <5 kg: 15 mg twice daily.
Note: Raltegravir film-coated tablets (including Isentress HD) and chewable tablets or oral suspension are not bioequivalent and are not substitutable on a mg/mg basis.
HIV-1 infection, treatment: Note: Use in combination with other antiretroviral (ARV) agents. Gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.
Oral suspension (10 mg/mL):
Infants and Children weighing <20 kg:
Weight-directed dosing: Oral: 6 mg/kg/dose twice daily; maximum dose: 100 mg/dose.
Fixed dosing: Oral:
3 to <4 kg: 25 mg twice daily.
4 to <6 kg: 30 mg twice daily.
6 to <8 kg: 40 mg twice daily.
8 to <11 kg: 60 mg twice daily.
11 to <14 kg: 80 mg twice daily.
14 to <20 kg: 100 mg twice daily.
Chewable tablets: Note: The film-coated tablets are preferred in children and adolescents weighing ≥25 kg who are able to swallow a tablet whole.
Infants, Children, and Adolescents weighing ≥3 kg:
Weight-directed dosing: Oral: 6 mg/kg/dose twice daily; maximum dose: 300 mg/dose.
Fixed dosing: Oral:
3 to <6 kg: 25 mg twice daily.
6 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.
Film-coated tablets:
Isentress: 400 mg tablets: Children and Adolescents ≥25 kg: Oral: 400 mg twice daily.
Isentress HD: 600 mg tablets: Children and Adolescents ≥40 kg: Oral: 1,200 mg once daily. Note: Regimen appropriate for treatment-naive patients, or patients virologically suppressed on an initial regimen of raltegravir 400 mg twice daily.
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (HHS [nPEP] 2016): 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: Oral suspension (10 mg/mL): 6 mg/kg/dose twice daily.
Children ≥2 years: Oral:
Chewable tablets:
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: Isentress 400 mg tablet: Children ≥6 years weighing >25 kg who are able to swallow a tablet whole: 400 mg twice daily.
Adolescents: Oral: Film-coated tablet: Isentress 400 mg tablet: 400 mg twice daily for 28 days.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents:
Mild, moderate, or severe impairment: No dosage adjustment required.
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): Dose after dialysis on dialysis days.
Film-coated tablet (400 mg formulation at standard twice-daily dose), chewable tablet, oral suspension:
Infants, Children, and Adolescents:
Mild to moderate hepatic impairment: No dosage adjustment required.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Film-coated tablet (600 mg formulation [Isentress HD]): Pediatric patients ≥40 kg: Use is not recommended in any degree of hepatic impairment (has not been studied).
(For additional information see "Raltegravir: Drug information")
HIV-1 infection, treatment: Oral: Note: Do not use raltegravir in combination with darunavir and ritonavir in patients with HIV RNA >100,000 copies/mL and/or CD4 count <200 cells/mm3, or in combination with abacavir and lamivudine in patients with HIV RNA >100,000 copies/mL (HHS [adult] 2019).
Treatment- naive patients: Film-coated tablet: 400 mg twice daily or 1,200 mg once daily (2 x 600 mg tablet). Note: Patients virologically suppressed on an initial regimen of raltegravir 400 mg twice daily may switch to 1,200 mg (2 x 600 mg tablet) once daily. Once daily dosing is not recommended for use during pregnancy (HHS [perinatal] 2020).
Treatment- experienced patients: Film-coated tablet: 400 mg twice daily.
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 concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild, moderate, and severe impairment: No dosage adjustment necessary.
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): Dose after dialysis on dialysis days.
Film-coated tablet (400 mg formulation), chewable tablet, oral suspension:
Mild-to-moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in manufacturer’s labeling (has not been studied).
Film-coated tablet (600 mg formulation): Use is not recommended (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Packet, Oral:
Isentress: 100 mg (1 ea [DSC], 60 ea) [contains polyethylene glycol; banana flavor]
Tablet, Oral:
Isentress: 400 mg
Isentress HD: 600 mg
Tablet Chewable, Oral:
Isentress: 25 mg [contains aspartame, saccharin sodium; orange banana flavor]
Isentress: 100 mg [scored; contains aspartame, saccharin sodium; orange banana flavor]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Isentress: 400 mg [contains polyethylene glycol]
Isentress HD: 600 mg
Tablet Chewable, Oral:
Isentress: 25 mg, 100 mg [contains aspartame, saccharin sodium]
Oral: May be administered without regard to meals.
Chewable tablets: May be chewed, crushed (25 mg), or swallowed whole; 100 mg chewable tablet can be split in half.
Patients unable to chew the chewable tablet: The 25 mg tablet may be crushed by placing tablet and ~5 mL of liquid (eg, water, juice, breast milk) in a small cup; the tablet should break apart within 2 minutes; crush any remaining pieces of undispersed tablet with a spoon and administer the entire mixture immediately. If any dose remains in cup, add ~5 mL of liquid, swirl, and administer immediately.
Film-coated tablets: Must be swallowed whole.
Oral suspension: Administer dose (at a concentration of 10 mg/mL) within 30 minutes of reconstitution.
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: Using provided mixing cup, pour packet contents into 10 mL water, close lid and swirl in a circular motion for 45 seconds; do not shake. Do not turn the mixing cup upside down. Once mixed, measure recommended suspension dose with an oral syringe (concentration of suspension is 10 mg/mL). Administer within 30 minutes of mixing with water. Discard any remaining suspension in the trash.
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).
Film-coated and 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.
Treatment of HIV-1 infection in combination with other antiretroviral agents (Isentress: FDA approved in pediatric patients weighing ≥2 kg and adults; Isentress HD: FDA approved in pediatric patients weighing ≥40 kg and adults). Note: HIV regimens consisting of three antiretroviral agents from at least two classes strongly recommended. Has also been used for HIV-1 nonoccupational postexposure prophylaxis (nPEP) and in the management of newborns with perinatal HIV exposure.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Hepatic: Increased serum ALT (1% to 11%; incidence higher with hepatitis B and/or C coinfection)
1% to 10%:
Central nervous system: Headache (≤4%), insomnia (≤4%), abnormal dreams (≥2%), nightmares (≥2%), dizziness (≤2%), fatigue (≤2%), depression (<2%; particularly in subjects with a preexisting history of psychiatric illness), suicidal ideation (<2%), suicidal tendencies (<2%), psychomotor agitation (children and adolescents), abnormal behavior (children and adolescents)
Dermatologic: Allergic rash (children and adolescents: 1%)
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 (≤5%), increased serum amylase (≤4%), nausea (≤3%), decreased appetite (≥2%), diarrhea (≥2%), flatulence (≥2%), abdominal pain (<2%), dyspepsia (<2%), gastritis (<2%), vomiting (<2%)
Genitourinary: Herpes genitalis (<2%)
Hematologic & oncologic: Decrease in absolute neutrophil count (1% to 4%), thrombocytopenia (≤3%), decreased hemoglobin (≤1%)
Hepatic: Increased serum AST (≤9%; incidence higher with hepatitis B and/or C coinfection), hyperbilirubinemia (≤6%; incidence slightly higher with hepatitis B and/or C coinfection), increased serum alkaline phosphatase (≤2%), hepatitis (<2%)
Hypersensitivity: Hypersensitivity reaction (<2%)
Infection: Herpes zoster (<2%)
Neuromuscular & skeletal: Increased creatine phosphokinase (1% to 4%), weakness (<2%)
Renal: Nephrolithiasis (<2%), renal failure (<2%), increased serum creatinine (≤1%)
Frequency not defined:
Hematologic & oncologic: Malignant neoplasm
Neuromuscular & skeletal: Myopathy, rhabdomyolysis
<1%, postmarketing, and/or case reports: Anxiety, cerebellar ataxia, DRESS syndrome (Perry 2013), hepatic failure, immune reconstitution syndrome, paranoia, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Hypersensitivity to raltegravir or any other component of the formulation
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, constitutional symptoms, organ dysfunction) have also been reported. Discontinue immediately if a severe skin reaction or hypersensitivity symptoms develop. Monitor clinical status, including liver transaminases.
Dosage form specific issues:
• Chewable tablet: Contains phenylalanine; avoid or use with caution in patient with phenylketonuria.
• 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.
At birth, the enzyme responsible for the metabolism of raltegravir (UGT1A1) is low and raltegravir elimination in neonates may be prolonged. The activity of UGT1A1 increases rapidly over the first 4 to 6 weeks of life (HHS [perinatal 2021]). Raltegravir also competes with bilirubin for albumin protein-binding sites and may increase unconjugated bilirubin concentrations, which could be particularly concerning in neonates due to kernicterus risk in the presence of high raltegravir concentrations. However, in vitro data suggest that this effect is unlikely to be significant at typical serum concentrations (Clarke 2013; HHS [pediatric 2021]). Additionally, in 42 neonates who received ≤6 weeks of raltegravir therapy and were followed for 24 weeks, there were only 2 cases of nonserious bilirubin elevations for which no treatment was necessary and no drug-related clinical adverse reactions were observed.
In perinatally HIV-exposed neonates and infants, the sensitivity of diagnostic virologic assays, particularly HIV RNA assays, may be decreased by combination antiretroviral therapy in the neonate or infant. All neonates and infants with perinatal HIV exposure (regardless of risk) should undergo standard virologic testing at PNA 14 to 21 days, 1 to 2 months of life, and 4 to 6 months of life. For neonates and infants at higher risk of perinatal HIV transmission, additional testing is recommended at birth and 2 to 6 weeks after cessation of antiretroviral agents (HHS [perinatal 2021]).
Substrate of UGT1A1
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. Risk X: Avoid combination
Calcium Carbonate: May decrease the serum concentration of Raltegravir. Management: Use of once-daily raltegravir with calcium carbonate is not recommended; dose separation does not appear to be adequate to minimize the significance of this interaction. Use of other raltegravir products do not require any dose change. Risk D: Consider therapy modification
Etravirine: May decrease the serum concentration of Raltegravir. Management: Concurrent use of etravirine with once-daily raltegravir (Isentress HD) is not recommended. Concurrent use of other raltegravir products with etravirine does not require any dose change. Risk C: Monitor therapy
Fibric Acid Derivatives: Raltegravir may enhance the myopathic (rhabdomyolysis) effect of Fibric Acid Derivatives. Risk C: Monitor therapy
Fosamprenavir: May decrease the serum concentration of Raltegravir. Raltegravir may decrease the serum concentration of Fosamprenavir. Risk X: Avoid combination
HMG-CoA Reductase Inhibitors (Statins): Raltegravir may enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: 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. Risk X: Avoid combination
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Polyvalent Cation Containing Products: May decrease the serum concentration of Raltegravir. Management: Administer raltegravir 2 hours before or 6 hours after administration of the polyvalent cations. Dose separation may not adequately minimize the significance of this interaction. Risk D: Consider therapy modification
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. Risk C: 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. Concurrent use of rifampin with once-daily raltegravir (Isentress HD) is not recommended. Risk D: Consider therapy modification
Rifapentine: May increase the serum concentration of Raltegravir. Rifapentine may decrease the serum concentration of Raltegravir. Risk C: Monitor therapy
Tipranavir: May decrease the serum concentration of Raltegravir. Management: Concurrent use of tipranavir/ritonavir with once-daily raltegravir (Isentress HD) is not recommended. Risk C: Monitor therapy
Zidovudine: Raltegravir may enhance the myopathic (rhabdomyolysis) effect of Zidovudine. Risk C: Monitor therapy
Variable absorption depending upon meal type (low- vs high-fat meal) and dosage form. Management: Raltegravir was administered without regard to meals in clinical trials.
Some products may contain phenylalanine; avoid or use with caution in patient with phenylketonuria.
The Health and Human Services (HHS) Perinatal HIV Guidelines consider raltegravir a preferred integrase strand transfer inhibitor for patients living with HIV who are not yet pregnant but are trying to conceive.
Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in patients of all genders who are living with HIV and planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception.
Health care providers caring for couples planning a pregnancy when one or both partners are living with HIV may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2020).
Raltegravir has high transfer across the human placenta.
No increased risk of overall teratogenic effects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
The Health and Human Services (HHS) Perinatal HIV Guidelines consider raltegravir a preferred integrase strand transfer inhibitor (INSTI) for pregnant patients living with HIV who are antiretroviral-naive, who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking raltegravir may continue if viral suppression is effective and the regimen is well tolerated. Raltegravir is an alternative component of a regimen when acute HIV infection is detected during pregnancy. INSTIs can rapidly suppress viral load. A regimen with raltegravir may be useful when drug interactions or the potential for preterm delivery with protease inhibitors are a concern. In addition, use of raltegravir, may be beneficial in patients with HIV who are not on ART and present for care late in pregnancy. Based on limited data, raltegravir may also be used as a fourth drug in pregnant patients with high viral loads, or as part of a new regimen for a patient experiencing virologic failure on ART.
The pharmacokinetics of raltegravir are variable. Dose adjustments are not required in pregnant patients; however, once daily dosing is not recommended until more data in pregnancy are available.
ART is recommended for all patients who are pregnant and living with HIV to maintain the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART should be continued postpartum for all patients living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant patients who are living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2020).
HIV: General recommendations: Management of HIV infection requires extensive monitoring; refer to current guidelines (https://aidsinfo.nih.gov) for additional guidance. Antiretroviral (ARV) drug-resistance testing is recommended before initiation of therapy in treatment-naive patients. After initiation of or change in ARV therapy regimen, pediatric patients should be evaluated for clinical adverse effects and treatment adherence at 1 to 2 weeks, and laboratory testing for drug toxicity should occur at 2 to 4 weeks; monitor for therapy adherence, effectiveness, and toxicities every 3 to 4 months.
Drug-specific monitoring: Frequency may vary based on several factors including age, concomitant therapy, and clinical response; refer to current guidelines for additional information.
Bilirubin (at baseline and periodically during therapy during the first month of life), hepatic function tests (aminotransferases) and bilirubin (baseline, periodically during therapy for patients with underlying liver disease or concomitant hepatotoxic medications, and if clinical presentation indicates need for others), creatine phosphokinase (periodically during therapy or if clinical presentation indicates need), platelets (if clinical presentation indicates need).
Desired trough concentration: >20 ng/mL; based on data from adults in which patients receiving once-daily dosing with trough concentrations <20 ng/mL were at the highest risk of treatment failure (HHS [pediatric 2021]); in the evaluation of neonatal raltegravir dosing in IMPACT P1110, the target exposure for efficacy was trough concentration >33 ng/mL, and the target exposures for safety were Cmax ≤8.7 mg/L, AUC24 12 to 40 mg•hour/L, and AUC12 6 to 20 mg•hour/L (Clarke 2019).
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.
Note: The pharmacokinetic profile of raltegravir in pediatric patients receiving recommended doses was similar to that observed in adults.
Absorption: Film-coated tablet (400 mg formulation): 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
Protein binding: ~83%
Metabolism: Primarily hepatic glucuronidation mediated by UGT1A1
Bioavailability: 600 mg film-coated tablet, chewable tablet, and oral suspension have higher bioavailability compared to 400 mg film-coated tablet; dosage forms are not interchangeable.
Half-life elimination: ~9 hours
Time to peak, plasma: Film-coated tablet (400 mg formulation): ~3 hours; film-coated tablet (600 mg formulation): ~1.5 to 2 hours
Excretion: Feces (~51%, as unchanged drug); urine (~32%; 9% as unchanged drug)
Pediatric: At birth, the enzyme responsible for the metabolism of raltegravir (UGT1A1) is low and raltegravir elimination in neonates may be prolonged. The activity of UGT1A1 increases rapidly over the first 4 to 6 weeks of life (HHS [perinatal 2021]). Raltegravir also competes with bilirubin for albumin protein-binding sites and may increase unconjugated bilirubin concentrations (HHS [perinatal 2021]).
Chewable (Isentress Oral)
25 mg (per each): $2.28
100 mg (per each): $9.11
Pack (Isentress Oral)
100 mg (per each): $9.11
Tablets (Isentress HD Oral)
600 mg (per each): $36.43
Tablets (Isentress Oral)
400 mg (per each): $36.43
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