Raltegravir Potassium

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

Trade Names

Isentress
- Tablets 400 mg

Pharmacology

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

Pharmacokinetics

Absorption

T _max is approximately 3 h postdose. AUC and C _max increase dose proportionally. Steady state is reached in approximately 2 days. Administration with a high-fat meal increases the AUC and C _max by approximately 2-fold. Administration with a low-fat meal decreased the AUC and C _max 46% and 52%, respectively.

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 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.

Age, gender, race

No dosage adjustments are needed.

Indications and Usage

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

Contraindications

None well documented.

Dosage and Administration

Adults

PO 400 mg twice daily.

Coadministration of Rifampin
Adults

PO 800 mg twice daily.

General Advice

• May be given with or without food.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

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.

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.

Tipranavir/Ritonavir

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

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Insomnia (4%); abnormal dreams, dizziness (less than 2%); asthenia; fatigue; headache; anxiety, depression, paranoia, suicidal ideation and behavior (postmarketing).

Dermatologic

Rash, Stevens-Johnson syndrome (postmarketing).

GI

Abdominal pain, gastritis (less than 2%); nausea.

Genitourinary

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

Hepatic

Hepatitis (less than 2%).

Hypersensitivity

Hypersensitivity (less than 2%).

Lab Tests

Decreased hemoglobin, 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.

Miscellaneous

Herpes zoster (less than 2%).

Precautions

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

Pregnancy

Category C .

Lactation

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

Children

Safety and effectiveness not 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.

Hepatic Function

Effect of severe hepatic impairment has not been studied.

Immune reconstitution syndrome

During 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.

Overdosage

Symptoms

No information is available.

Patient Information

• Advise patient to read the patient information leaflet before using product the first time and with each refill.
• Inform patient that this medication is not a cure for HIV infection or AIDS.
• Emphasize to patient, family, and significant others that this medication does not reduce the risk of transmitting HIV to others through sexual contact or blood contamination.
• Advise patients to take this medication exactly as prescribed, with or without food.
• Warn patients not to alter dose or discontinue medication without consulting health care provider.
• Explain that the long-term effects of this medication are not known.
• Inform patients to report symptoms of unexplained muscle pain, tenderness, or weakness to health care provider.
• Advise breast-feeding women not to breast-feed while taking this medicine.

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