raltegravir

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Mostly metabolized by the uridine diphosphate glucuronosyltransferase (UGT) A1A enzyme system; 23% excreted in urine as parent drug and metabolite.

Half-Life: 9 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Lactation: Breastfeeding not recommended in women with HIV.

Use Cautiously in:

Phenylketonuria (chewable tablets contain phenylalanine);
OB: Considered a preferred integrase strand transfer inhibitor for pregnant patients living with HIV who are antiretroviral-naive, who have had antiretroviral therapy in the past but are restarting, or who require a new antiretroviral therapy regimen;
Pedi: Preterm neonates (safety and effectiveness not established);
Geri: Choose dose carefully in older adults, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function.

Adv. Reactions/Side Effects ⬆ ⬇

CV: MI

Derm: rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS

GI: diarrhea, abdominal pain, gastritis, hepatitis, nausea, vomiting

GU: renal failure/impairment

Hemat: anemia, neutropenia

Metab: lipodystrophy

MS: ↑creatine kinase, myopathy, RHABDOMYOLYSIS

Neuro: headache, depression, dizziness, fatigue, insomnia, SUICIDAL THOUGHTS, weakness

Misc: fever, immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with strong inducers of the UGT A1A enzyme system, including rifampin, may ↓ levels and effectiveness.
Concurrent use with strong inhibitors of the UGT A1A enzyme system, including atazanavir, may ↑ levels and the risk of toxicity.
↑risk of rhabomyolysis/myopathy with HMG-CoA reductase inhibitors.
Proton pump inhibitors may ↑ levels and the risk of toxicity.
Efavirenz, etravirine, and tipranavir/ritonavir may ↓ levels and effectiveness.
Administration with antacids, containing magnesium or aluminum↓ absorption of raltegravir; separate administration of raltegravir and magnesium- or aluminum-containing antacids by ≥6 hr.

Route/Dosage ⬆ ⬇

Do not substitute the chewable tablets or oral suspension for the film-coated tablets.

PO (Adults ): Treatment-naive patients or patients who are virologically suppressed on an initial regimen of raltegravir 400 mg twice daily: Two 600-mg tablets (1200 mg) once daily or 400 mg twice daily; Treatment-experienced patients: 400 mg twice daily; Concurrent use of rifampin (either treatment-naive or treatment-experienced patients): 800 mg twice daily.
PO (Children ≥40 kg and either treatment-naive or virologically suppressed on an initial regimen of raltegravir 400 mg twice daily): Tablet: Two 600-mg tablets (1200 mg) once daily or 400 mg twice daily; Chewable tablets: 300 mg twice daily.
PO (Children 28–39 kg): Tablet: 400 mg twice daily; Chewable tablets (if unable to swallow tablet): 200 mg twice daily.
PO (Children 25–27 kg): Tablet: 400 mg twice daily; Chewable tablets (if unable to swallow tablet): 150 mg twice daily.
PO (Children ≥4 wk and 20–<25 kg): Chewable tablets: 150 mg twice daily.
PO (Children ≥4 wk and 14–19 kg): Oral suspension: 100 mg twice daily; Chewable tablets: 100 mg twice daily.
PO (Children ≥4 wk and 10–13 kg): Oral suspension: 80 mg twice daily; Chewable tablets: 75 mg twice daily.
PO (Children ≥4 wk and 8–9 kg): Oral suspension: 60 mg twice daily; Chewable tablets: 50 mg twice daily.
PO (Children ≥4 wk and 6–7 kg): Oral suspension: 40 mg twice daily; Chewable tablets: 50 mg twice daily.
PO (Children ≥4 wk and 4–5 kg): Oral suspension: 30 mg twice daily; Chewable tablets: 25 mg twice daily.
PO (Children ≥4 wk and 3–<4 kg): Oral suspension: 25 mg twice daily; Chewable tablets: 25 mg twice daily.
PO (Neonates 1–4 wk and 4–<5 kg): Oral suspension: 15 mg twice daily.
PO (Neonates 1–4 wk and 3–<4 kg): Oral suspension: 10 mg twice daily.
PO (Neonates 1–4 wk and 2–<3 kg): Oral suspension: 8 mg twice daily.
PO (Neonates 0–1 wk and 4–<5 kg): Oral suspension: 7 mg once daily.
PO (Neonates 0–1 wk and 3–<4 kg): Oral suspension: 5 mg once daily.
PO (Neonates 0–1 wk and 2–<3 kg): Oral suspension: 4 mg once daily.

Availability ⬆ ⬇

Tablets: 400 mg; 600 mg
Chewable tabletsorange-banana: 25 mg; 100 mg
Packet for oral suspensionbanana flavor: 100 mg/pkt

Assessment ⬆ ⬇

Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
Monitor for anxiety, depression (especially in patients with a history of psychiatric illness), suicidal ideation, and paranoia during therapy.
Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.

Lab Test Considerations:

Monitor viral load and CD4 counts regularly during therapy.
- May cause ↓ absolute neutrophil count, hemoglobin, and platelet counts.
- May cause ↑ serum glucose, AST, ALT, GGT, total bilirubin, alkaline phosphatase, pancreatic amylase, serum lipase, and CK concentrations.

Implementation ⬆ ⬇

Tablets are not interchangeable with chewable tablets or packets for oral suspension.
PO: May be administered without regard to meals.
- DNC: Swallow tablets whole; do not break, crush, or chew.
- Chewable tablets may be chewed or swallowed. For children with difficulty chewing the 25 mg chewable tablet, tablet may be crushed. Place the tablet(s) in a small, clean cup. For each tablet, add a teaspoonful (5 mL) of liquid (water, juice, breast milk). Within 2 min, tablet(s) will absorb liquid and fall apart. Using a spoon, crush any remaining pieces of the tablet(s). Immediately administer the entire dose orally. If any portion of dose is left in the cup, add another teaspoonful (5 mL) of liquid, swirl and administer immediately.
- Oral suspension: Pour packet for oral solution into 10 mL of water and mix in provided mixing cup. Gently swirl for 45 sec until mix is uniform; do not shake. Once mixed, administer with syringe orally within 30 min of mixing. Discard unused solution.

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of taking raltegravir as directed, at evenly spaced times throughout day. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered unless almost time for next dose. Do not double doses. Advise patient to read Patient Information sheet before starting therapy and with each Rx renewal in case of changes.
Instruct patient that raltegravir should not be shared with others.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Inform patient that raltegravir does not cure AIDS or prevent associated or opportunistic infections. Raltegravir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of raltegravir are unknown at this time.
Advise patient to notify health care professional if they develop any unusual symptoms, if any known symptom persists or worsen, or if signs and symptoms of rhabdomyolysis (unexplained muscle pain, tenderness, weakness), rash, or depression or suicidal thoughts occur.
Immune reconstitution syndrome may trigger opportunistic infections or autoimmune disorders. Notify health care professional if symptoms occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected. Inform pregnant women about the pregnancy exposure registry to monitor pregnancy outcomes. Enroll patient in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise female patient to avoid breastfeeding during therapy.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇