raltegravir


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raltegravir

Pharmacologic class: Human immunodeficiency virus (HIV) integrasestrand transfer inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category C

Action

Rapidly blocks HIV integrase (enzyme needed for HIV replication), leading to viral load reduction and increased CD4+ count

Availability

Tablets (chewable): 25 mg, 100 mg

Tablets (film-coated): 400 mg

Indications and dosages

HIV-1 infection in adults used in combination with other antiretrovirals

Adults and adolescents ages 12 and older: 400 mg film-coated tablet P.O. b.i.d.

Children age 6 to younger than age 12 weighing at least 25 kg (55 lb): One 400-mg film-coated tablet P.O. b.i.d. or chewable tablets, weight based to maximum of 300 mg P.O. b.i.d.

Children age 6 to younger than age 12 weighing less than 25 kg (55 lb): Chewable tablets, weight based to maximum of 300 mg P.O. b.i.d.

Children age 2 to younger than age 6 weighing at least 10 kg (22 lb): Chewable tablets, weight based to maximum of 300 mg P.O. b.i.d.

Contraindications

None

Precautions

Use cautiously in:
• treatment-naive adults (safety and efficacy not established)
• increased risk of myopathy or rhabdomyolysis (such as with concomitant use of drugs known to cause these conditions)
• elderly patients
• pregnant patients
• breastfeeding patients (use not recommended)
• children younger than age 2 (safety and efficacy not established).

Administration

• Administer with or without food.
• Be aware that film-coated tablets can't be substituted with chewable tablets.

Adverse reactions

CNS: headache, fatigue, asthenia, dizziness, insomnia

CV: myocardial infarction

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

GU: toxic nephropathy, renal failure, renal tubular necrosis

Hematologic: anemia, neutropenia

Hepatic: hepatitis

Musculoskeletal: myopathy, rhabdomyolysis

Skin: lipodystrophy, Stevens-Johnson syndrome, toxic epidermal necrolysis

Other: fever, herpes simplex, immune reconstitution syndrome, hypersensitivity reaction

Interactions

Drug-drug.Strong UGT1A1 inducers (such as rifampin): reduced raltegravir blood level

UGT1A1 inhibitors (such as atazanavir): increased raltegravir blood level

Drug-diagnostic tests.Absolute neutrophil count, hemoglobin, platelets: decreased levels

ALP, ALT, AST, blood glucose, creatine kinase, lipase, pancreatic enzymes, total bilirubin: increased levels

Patient monitoring

• Monitor renal function tests.
• Be aware that immune reconstitution syndrome has occurred in patients receiving drug with combination antiretroviral therapy. During initial phase of therapy, patient whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, or tuberculosis), which may necessitate further evaluation and treatment.
• Be aware that severe, potentially life-threatening and fatal skin reactions have been reported, including Stevens-Johnson syndrome, hypersensitivity reaction, and toxic epidermal necrolysis. Immediately discontinue drug if severe hypersensitivity, severe rash, or rash with systemic symptoms or liver aminotransferase elevations develops. Closely monitor clinical status, including liver aminotransferases.

Patient teaching

• Tell patient drug may be taken with or without food.
• Inform patient with phenylketonuria that chewable tablets contain phenylalanine.
• Inform patient that drug doesn't cure HIV infection or reduce risk of passing it to others through sexual contact, needle sharing, or blood exposure.

Advise patient to immediately report muscle weakness, urinary problems, new infections, rash, fever, general malaise, swelling of face or throat, or chest pain.
• Instruct female patient to notify prescriber if she is pregnant or intends to become pregnant.
• Caution breastfeeding patient to discontinue breastfeeding while taking drug, because of potential HIV transmission and adverse reactions in infants.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

raltegravir

(ral-teg-ra-veer) ,

Isentress

(trade name)

Classification

Therapeutic: antiretrovirals
Pharmacologic: integrase strand transfer inhibitors instis
Pregnancy Category: C

Indications

HIV-1 infection (with other antiretrovirals) in treatment-experienced or treatment-naïve patients.

Action

Inhibits HIV-1 integrase, which is required for viral replication.

Therapeutic effects

Evidence of decreased viral replication and reduced viral load with slowed progression of HIV and its sequelae.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Metabolism and 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 (blood levels)

ROUTEONSETPEAKDURATION
POunknown3 hr12 hr

Contraindications/Precautions

Contraindicated in: Lactation: Breast feeding not recommended in HIV-infected patients.
Use Cautiously in: Concurrent use of medications associated with rhabdomyolysis/myopathy (may ↑ risk);Phenylketonuria (chewable tablets contain phenylalanine) Geriatric: Choose dose carefully, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function; Obstetric: Use in pregnancy only if maternal benefit outweighs fetal risk; Pediatric: Children <4 wk (safety and effectiveness not established).

Adverse Reactions/Side Effects

Central nervous system

  • suicidal thoughts (life-threatening)
  • headache (most frequent)
  • depression
  • dizziness
  • fatigue
  • insomnia
  • weakness

Cardiovascular

  • myocardial infarction

Gastrointestinal

  • diarrhea (most frequent)
  • abdominal pain
  • gastritis
  • hepatitis
  • nausea
  • vomiting

Genitourinary

  • renal failure/impairment

Hematologic

  • anemia
  • neutropenia

Metabolic

  • lipodystrophy

Dermatologic

  • stevens johnson syndrome (life-threatening)
  • toxic epidermal necrolysis (life-threatening)
  • rash

Musculoskeletal

  • rhabdomyolysis (life-threatening)
  • ↑ creatine kinase
  • myopathy

Miscellaneous

  • hypersensitivity reactions
  • immune reconstitution syndrome
  • fever (most frequent)

Interactions

Drug-Drug interaction

Concurrent use with strong inducers of the UGT A1A enzyme system including rifampin may ↓ blood levels and effectiveness.Concurrent use with strong inhibitors of the UGT A1A enzyme system including atazanavir may ↑ blood levels.↑ risk of rhabomyolysis/myopathy HMG-CoA reductase inhibitors.Proton pump inhibitors may ↑ levels.Efavirenz, etravirine, and tipranavir/ritonavir may ↓ levels.Administration with antacids, containing magnesium, aluminum, or calcium ↓ absorption of tipranavir; separate administration of tipranavir and magnesium- or aluminum-containing antacids by ≥2 hr.

Route/Dosage

Oral (Adults) 400 mg twice daily; ↑ dose to 800 mg twice daily when used with rifampin.
Oral (Children ≥4 wk and ≥25 kg) Tablet—400 mg twice daily; Chewable tablets (if unable to swallow tablet)—25–28 kg: 150 mg twice daily; 28–39.9 kg: 200 mg twice daily; ≥40 kg: 300 mg twice daily
Oral (Children ≥4 wk and 20–<25 kg) Chewable tablets—150 mg twice daily
Oral (Children ≥4 wk and 14–<20 kg) Oral suspension—100 mg twice daily; Chewable tablets—100 mg twice daily
Oral (Children ≥4 wk and 11–<14 kg) Oral suspension—80 mg twice daily; Chewable tablets—75 mg twice daily
Oral (Children ≥4 wk and 8–<11 kg) Oral suspension—60 mg twice daily
Oral (Children ≥4 wk and 6–<8 kg) Oral suspension—40 mg twice daily
Oral (Children ≥4 wk and 4–<6 kg) Oral suspension—30 mg twice daily
Oral (Children ≥4 wk and 3–<4 kg) Oral suspension—20 mg twice daily

Availability

Tablets: 400 mg
Chewable tabletsorange-banana: 25 mg, 100 mg
Packet for oral suspension: 100 mg

Nursing implications

Nursing 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 Stevens-Johnson syndrome. 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 casue ↓ ANC, hemoglobin, and platelet counts.
    • May cause ↑ serum glucose, AST, ALT, GGT, total bilirubin, alkaline phosphatase, pancreatic amylase, serum lipase, and creatinine kinase concentrations.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Tablets are not interchangeable with chewable tablets or packets for oral suspension.
  • Oral: May be administered without regard to meals.
    • Swallow tablets whole; do not break, crush, or chew.
    • Chewable tablets may be chewed or swallowed.
    • Pour packet for oral solution into 5 mL of water and mix. 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 prescription renewal in case changes have been made.
  • 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.
  • Advise patients to notify health care professional if pregnancy is planned or suspected. Breast feeding should be avoided during therapy.
  • Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and improvement in CD4 cell counts.

raltegravir

an antiretroviral.
indication This drug is used to treat HIV in combination with other retrovirals.
contraindications Breastfeeding and known hypersensitivity to this drug prohibit its use.
adverse effects Adverse effects of this drug include fatigue, fever, dizziness, nausea, vomiting, diarrhea, abdominal pain, asthenia, gastritis, rash, urticaria, pruritus, pain or phlebitis at IV site, unusual sweating, alopecia, hyperamylasia, hyperglycemia, and myopathy. Life-threatening side effects include hepatitis, oliguria, proteinuria, hematuria, glomerulonephritis, acute renal failure, renal tubular necrosis, anemia, neutropenia, and rhabdomyolysis.

raltegravir

An HIV-1 integrase inhibitor drug that is expected to become an important component of combined therapy for AIDS. Integrase is one of three enzymes essential for HIV replication.
References in periodicals archive ?
Nachman S, Zheng N, Acosta EP, et al Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years.
Yin: Evidence is emerging for avoidance of TDF and possibly PIs in favor of raltegravir in patients with prior fracture and osteoporosis.
Other options would be the integrase-inhibitor raltegravir [36] or the non-nucleoside reverse transcriptase inhibitor rilpivirine.
Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study.
In addition, two small, nonrandomized studies showed no significant decline in cell-associated HIV DNA or unspliced RNA in the gastrointestinal tract following intensification with raltegravir (n = 7) and no change in HIV RNA in the CSF following intensification with maraviroc, lopinavir/ritonavir or enfurvitide (n = 10)
Washington, Sep 24 (ANI): A drug approved in 2007 for the treatment of AIDS- raltegravir or Isentress-could also play a role in preventing the herpes virus, found a new study.
The researchers then soaked the crystals in solutions of the integrase inhibiting drugs Raltegravir (also known as Isentress) and Elvitegravir and observed for the first time how these antiretroviral drugs bind to and inactivate integrase.
Recent intensification studies with raltegravir added to apparently effective therapy, have failed to make an impact on this background viral release, when monitoring with ultra-sensitive viral load assays.
It is important for patients at any stage of HIV to have treatment options like raltegravir that are effective and have a demonstrated tolerability profile in order to help them manage their disease.
The three new drugs in these classes are etravirine, maraviroc, and raltegravir (6).
The updated recommendations also give a boost for using recently-approved drugs, including raltegravir, maraviroc and etravirine, in combination with older treatments to keep down viral levels and boost CD4 counts.
Studies show that 75 per cent of patients receiving the drug raltegravir have a reduction in HIV viral load in their blood, compared with 40 per cent taking a dummy drug.