Raltegravir Potassium

Pronunciation

Pronunciation: ral-TEG-ra-vir poe-TAS-ee-um
Class: Antiretroviral, Integrase inhibitor

Trade Names

Isentress
- Tablets, oral 400 mg
- Tablets, chewable, oral 25 mg
- Tablets, chewable, oral 100 mg

Pharmacology

Raltegravir is an HIV-1 antiviral agent that blocks the enzyme HIV-1 integrase that is needed for viral replication.

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Pharmacokinetics

Absorption

T max is approximately 3 h postdose. AUC and C max increase dose proportionally. Steady state is reached in approximately 2 days. Food appears to increase pharmacokinetic variability relative to fasting.

Distribution

Human plasma protein binding is approximately 83%.

Metabolism

Raltegravir is metabolized to raltegravir-glucuronide by the enzyme UGT1A1.

Elimination

The half-life is approximately 9 h. Approximately 51% and 32% of an administered dose is excreted in the feces and urine, respectively.

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.

Hepatic Function Impairment

No clinically important pharmacokinetic differences were observed between subjects with moderate hepatic impairment and healthy subjects. Effect of severe hepatic impairment has not been studied.

Elderly

The effect of age on the pharmacokinetics of raltegravir was evaluated in the composite analysis. No dosage adjustment is necessary.

Children

The pharmacokinetic profile of raltegravir in children was similar to that observed in adults receiving 400 mg twice daily.

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.

Race

The effect of race on the pharmacokinetics of raltegravir was evaluated in the composite analysis. No dosage adjustment is necessary.

Indications and Usage

Treatment of HIV-1 infection in combination with other antiretroviral agents.

Contraindications

None well documented.

Dosage and Administration

Chewable Tablet
Children 2 to younger than 12 y

PO For weight 10 to 13 kg, 75 mg twice daily; for weight 14 to 19 kg, 100 mg twice daily; for weight 20 to 27 kg, 150 mg twice daily; for weight 28 to 39 kg, 200 mg twice daily; for weight 40 kg or more, 300 mg twice daily (max, 600 mg/day).

Coadministration With Rifampin
Adults

PO 800 mg twice daily.

Film-Coated Tablet
Adults and children 6 y and older with weight 25 kg or more

PO 400 mg twice daily.

Adults and children 6 y and older with weight 24 kg or less

PO Use the chewable tablet.

General Advice

  • Administer with or without food. Chewable tablets may be chewed or swallowed whole. Film-coated tablets must be swallowed whole.
  • Because the formulations are not bioequivalent, do not substitute the chewable tablet for the film-coated tablet.

Storage/Stability

Store between 59° and 86°F. Store chewable tablets in the original package with the bottle tightly closed. Keep desiccant in the bottle to protect from moisture.

Drug Interactions

Darunavir

The risk of a rash may be increased. Instruct patients to contact their health care provider if a rash develops.

Drugs that are strong inducers of UGT1A1 (eg, rifampin)

Raltegravir plasma levels may be reduced. The recommended dosage of raltegravir is 800 mg twice daily during coadministration with rifampin. Coadminister with caution.

Drugs that inhibit UGT1A1 (eg, atazanavir, atazanavir/ritonavir)

Raltegravir plasma levels may be increased; however, dosage adjustments are not needed with coadministration of atazanavir/ritonavir. Monitor the response of the patient.

Efavirenz, etravirine

Raltegravir plasma concentrations may be reduced. The clinical importance has not been assessed. Monitor the response of the patient.

Fosamprenavir

Plasma concentrations of fosamprenavir and raltegravir may be reduced, decreasing the pharmacologic effects. Close clinical and laboratory monitoring is warranted.

Omeprazole

Raltegravir plasma concentrations may be increased because of increased solubility at higher pH. Dosage adjustments do not appear to be necessary. Monitor the response of the patient.

Ritonavir

Raltegravir plasma concentrations may be reduced. However, the magnitude of the changes is not expected to warrant a dose adjustment.

Tenofovir

Raltegravir plasma concentrations may be increased. Monitor the response of the patient.

Tipranavir/Ritonavir

Raltegravir plasma concentrations may be reduced. No dosage adjustment is recommended. Monitor the response of the patient.

Adverse Reactions

Adverse reactions are for raltegravir in a combination regimen.

CNS

Insomnia (4%); headache (2%); asthenia, depression including suicidal ideation and behaviors, dizziness, fatigue (less than 2%); abnormal behavior; psychomotor hyperactivity; anxiety, cerebellar ataxia, paranoia (postmarketing).

Dermatologic

Rash, Stevens-Johnson syndrome (postmarketing).

GI

Abdominal pain, dyspepsia, gastritis, nausea, vomiting (less than 2%); diarrhea (postmarketing).

Genitourinary

Genital herpes, nephrolithiasis, renal failure (less than 2%).

Hepatic

Hepatitis (less than 2%); elevated AST and ALT; hepatic failure in patients with underlying liver disease and/or concomitant medications (postmarketing).

Hypersensitivity

Hypersensitivity (less than 2%).

Lab Tests

Decreased Hgb, neutrophils, triglycerides, and platelets; increased serum alkaline phosphatase, ALT, AST, bilirubin, creatine kinase, fasting glucose, HDL cholesterol, lipase, LDL cholesterol, total cholesterol, and pancreatic amylase.

Musculoskeletal

Myopathy; rhabdomyolysis.

Miscellaneous

Herpes zoster (less than 2%); thrombocytopenia (postmarketing).

Precautions

Monitor

Monitor CD4+ cell count and HIV-1 RNA load.


Pregnancy

Category C .

Lactation

Undetermined; however, HIV-infected women should not breast-feed.

Children

Safety and effectiveness in children younger than 2 y have not been established.

Elderly

Select dose with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Hypersensitivity

Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure.

Special Risk Patients

Use with caution in patients at risk of myopathy or rhabdomyolysis.

Dermatologic effects

Severe, potentially life-threatening and fatal skin reactions have been reported, including Stevens-Johnson syndrome and TEN.

Immune reconstitution syndrome

During the initial phase of treatment, patients may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium complex), which may require further evaluation and treatment.

Phenylketonurics

The chewable tablets contain phenylalanine, a component of aspartame.

Overdosage

Symptoms

No information is available.

Patient Information

  • Inform patients that severe and potentially life-threatening rash has been reported. Advise patients to immediately contact their health care provider if they develop a rash. Instruct patients to immediately stop taking raltegravir and other suspect agents and seek medical attention if they develop a rash associated with any of the following symptoms because it may be a sign of a more serious reaction, such as Stevens-Johnson syndrome, TEN, or severe hypersensitivity: fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters; oral lesions; eye inflammation; facial swelling; swelling of the eyes, lips, or mouth; breathing difficulty; and/or signs and symptoms of liver problems (eg, yellowing of the skin or whites of the eyes, dark or tea-colored urine, pale-colored stools/bowel movements, nausea, vomiting, loss of appetite, pain or aching sensitivity on the right side below the ribs).
  • Inform patients that this medication is not a cure for HIV infection or AIDS. Inform patients that sustained decreases in plasma HIV RNA have been associated with a reduced risk of progression to AIDS and death. Patients should remain on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses. Also tell them that people taking raltegravir may still get infections or other conditions common in people with HIV (opportunistic infections).
  • Emphasize to patients, families, and significant others that this medication does not reduce the risk of transmitting HIV to others through sexual contact or blood contamination.
  • Instruct patients that if they miss a dose, they should take it as soon as they remember. If they do not remember until it is time for the next dose, instruct them to skip the missed dose and go back to the regular schedule. Patients should not double their next dose or take more than the prescribed dose.
  • Inform patients that the chewable tablet can be chewed or swallowed whole, but the film-coated tablet should only be swallowed whole.
  • Inform patients with phenylketonuria that raltegravir chewable tablets contain phenylalanine.
  • Advise women not to breast-feed while taking this medicine.

Copyright © 2009 Wolters Kluwer Health.

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