nucleoside reverse transcriptase inhibitors
integrase strand transfer inhibitors instis
Treatment of HIV infection in combination with other agents.
- Lamivudine– After intracellular conversion to its active form (lamivudine-5-triphosphate), inhibits viral DNA synthesis by inhibiting the enzyme reverse transcriptase.
- Raltegravir Inhibits HIV-1 integrase, which is required for viral replication.
- Slows the progression of HIV infection and decreases the occurrence of its sequelae.
- Increases CD4 cell counts and decreases viral load.
Absorption: Lamivudine– Well absorbed after oral administration (86% in adults, 66% in infants and children); raltegravir– Unknown.
Distribution: Lamivudine– Distributes into the extravascular space. Some penetration into CSF; remainder of distribution unknown; raltegravir–
Metabolism and Excretion: Lamivudine– Mostly excreted unchanged in urine; <5% metabolized by the liver; raltegravir– Mostly metabolized by the uridine diphosphate glucuronosyltransferase (UGT) A1A enzyme system; 23% excreted in urine as parent drug and metabolite.
Half-life: Lamivudine–– Adults– 3.7 hr; children– 2 hr; raltegravir– 9 hr.
TIME/ACTION PROFILE (blood levels)
|lamivudine PO||unknown||0.9 hr†||12 hr|
|ratltegravir PO||unknown||3 hr||12 hr|
- Concurrent use of other antiretroviral combination products containing lamivudine or raltegravir
- CCr <50 mL/min
- Lactation: Breastfeeding not recommended for HIV positive mothers.
Use Cautiously in:
- Women, prolonged exposure, obesity, history of liver disease (↑ risk of lactic acidosis and severe hepatomegaly with steatosis);
- Coinfection with hepatitis B (hepatitis may recur after discontinuation of lamivudine);
- Concurrent use of medications associated with rhabdomyolysis/myopathy (may ↑ risk);
- Geri: Choose dose carefully, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function;
- OB: Use in pregnancy only if maternal benefit outweighs fetal risk;
- Pedi: Safe and effective use in children <6 yr or <30 kg not established.
Exercise Extreme Caution in:
Pedi: Pediatric patients with a history of or significant risk factors for pancreatitis (use only if no alternative).
Adverse Reactions/Side Effects
CNS: SEIZURES, fatigue, headache, insomnia, malaise, depression, dizziness
GI: HEPATOMEGALY WITH STEATOSIS, PANCREATITIS (↑ IN PEDIATRIC PATIENTS), anorexia, diarrhea, nausea, vomiting, abdominal discomfort, ↑ liver enzymes, dyspepsia
Derm: skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis , alopecia, erythema multiforme, rash, urticaria
F and E: lactic acidosis
Hemat: anemia, neutropenia, pure red cell aplasia
MS: musculoskeletal pain, arthralgia, muscle weakness, myalgia, rhabdomyolysis
Misc: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, fever (↑ in children), immune reconstitution syndrome,
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Trimethoprim/sulfamethoxazole ↑ levels (dose alteration may be necessary in renal impairment).
- ↑ risk of pancreatitis with concurrent use of other drugs causing pancreatitis.
- ↑ risk of neuropathy with concurrent use of other drugs causing neuropathy.
- Combination therapy with tenofovir and abacavir may lead to virologic nonresponse and should not be used.
- 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 or aluminum ↓ absorption of raltegravir; separate administration of raltegravir and magnesium- or aluminum-containing antacids by ≥6 hr.
PO: (Adults and Children ≥16 yr and children 6–16 yr weighing ≥ 30 kg): Lamivudine 150 mg/ raltegravir 300 mg twice daily.
Tablets: lamivudine 150 mg/ raltegravir potassium 325.8 mg (equivalent to 300 mg raltegravir)
- 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.
- Assess patient, especially pediatric patients, for signs of pancreatitis (nausea, vomiting, abdominal pain) periodically during therapy. May require discontinuation of therapy.
- Monitor patient for signs and symptoms of peripheral neuropathy (tingling, burning, numbness, or pain in hands or feet); may be difficult to differentiate from peripheral neuropathy of severe HIV disease. May require discontinuation of therapy.
- Upon discontinuation, monitor ALT and for signs and symptoms of hepatitis B for several mo. Discontinuation of lamivudine has caused exacerbations of hepatitis B.
Lab Test Considerations: Monitor viral load and CD4 levels before and periodically during therapy.
- Monitor serum amylase, lipase, and triglycerides periodically during therapy. Elevated serum levels may indicate pancreatitis and require discontinuation.
- Monitor liver function. May cause ↑ levels of AST, ALT, CPK, bilirubin, and alkaline phosphatase, which usually resolve after interruption of therapy. Lactic acidosis may occur with hepatic toxicity causing hepatic steatosis; may be fatal, especially in women.
- May rarely cause neutropenia and anemia.
- PO: Administer 1 tablet twice daily without regard to food, with other antiretroviral agents.
- Emphasize the importance of taking Dutrebis 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 before starting therapy and with each Rx refill in case of changes.
- Instruct patient that Dutrebis 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 Dutrebis does not cure AIDS or prevent associated or opportunistic infections. Dutrebis 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 Dutrebis 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 (Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, or tuberculosis). Notify health care professional if symptoms occur.
- Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
- Rep: Instruct females using hormonal contraceptives to use an alternative nonhormonal method of contraception. Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. If pregnant patient is exposed to Dutrebis, register patient in Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
- Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
- Decrease in viral load and improvement in CD4 cell counts.
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