Dosing and uses of Dutrebis (lamivudine/raltegravir)
Adult dosage forms and strengths
lamivudine/raltegravir
tablet
- 150mg/300mg
- Approved, but not commercially available in the United States
HIV Infection
Indicated for use in combination with other antiretroviral products for the treatment of HIV-1 infection in adults and pediatric patients aged ≥6 yr weighing at ≥30 kg
1 tablet (150 mg/300 mg) PO BId
Dosage modifications
Renal impairment
- CrCl <50 mL/min: Should not be used with moderate-to-severe renal impairment
Hepatic impairment
- Mild-to-moderate: No dose adjustment required
- Decompensated liver disease: Safety and efficacy not established
- Severe: Not studied
Pediatric dosage forms and strengths
lamivudine/raltegravir
tablet
- 150mg/300mg
- Approved, but not commercially available in the United States
HIV Infection
Indicated for use in combination with other antiretroviral products for the treatment of HIV-1 infection in adults and pediatric patients aged ≥6 yr weighing at ≥30 kg
<6 years: Safety and efficacy not established
≥6 years and weight ≥30 kg: 1 tablet (150 mg/300 mg) PO BId
Dosage modifications
Renal impairment
- CrCl <50 mL/min: Should not be used with moderate-to-severe renal impairment
Hepatic impairment
- Mild-to-moderate: No dose adjustment required
- Decompensated liver disease: Safety and efficacy not established
- Severe: Not studied
Dutrebis (lamivudine/raltegravir) adverse (side) effects
>10% Lamivudine
Cough
Diarrhea
Fatigue and malaise
Fever (pediatric)
Headache
Musculoskeletal pain
Nausea
Nervous system neuropathy
Pancreatitis
Peripheral neuropathy
Nasal S/s
Vomiting
>10% Raltegravir
Total cholesterol increased (16%)
1-10% Lamivudine
Abdominal cramps, abdominal pain
Anorexia and/or decreased appetite
Arthralgia
Chills
Depression
Dizziness
Dyspepsia
Insomnia
Myalgia
Rash
Thrombocytopenia
Creatine phosphokinase increased
1-10% Raltegravir
AST increased (9%)
Glucose increased (9%)
Hyperbilirubinemia (9%)
Fatigue (8%)
Nasopharyngitis (6%)
Abdominal pain (5%)
Cough (5%)
Rash (5%)
Dizziness (4%)
Insomnia (4%)
Vomiting (4%)
Arthralgia (3%)
Extremity pain (3%)
Influenza (3%)
Nausea
Diarrhea
Pyrexia
<1% Raltegravir
Asthenia GI disorders
Lipodystrophy
Skin disorders
Drug related hypersensitivity
Thrombocytopenia
Renal failure
Suicidal ideation
Frequency not defined Lamivudine
Body fat redistribution
Elevated amylase
Neutropenia
Hepatitis B exacerbation
Postmarketing Reports Raltegravir
Cerebellar ataxia
Diarrhea
Hepatic failure
Thrombocytopenia
Rhabdomyolysis
Psychiatric disorders: anxiety, depression (particularly in patients with a pre-existing history of psychiatric illness), including suicidal ideation and behaviors, paranoia
Skin: rash, Steven’s-Johnson syndrome
Warnings
Contraindications
Hypersensitivity
Cautions
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of NRTIs alone or in combination, including lamivudine and other antiretrovirals
Post-treatment exacerbations of hepatitis in patients with HIV-1 and hepatitis B virus coinfection reported
Pancreatitis reported; use with caution in pediatric patients with a history or prior antiretroviral nucleoside exposure, a history of pancreatitis, or other risk factors for pancreatitis; discontinue immediately if signs or symptoms of pancreatitis occur
Hepatic decompensation reported with used with interferon- or ribavirin-based regimens; ribavirin can reduce the phosphorylation of pyrimidine NRTIs such as lamivudine
Severe, potentially life-threatening, and fatal skin reactions reported with raltegravir, including Stevens-Johnson syndrome and toxic epidermal necrolysis; hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure; discontinue if signs or symptoms occur
Immune reconstitution syndrome reported with combination antiretroviral therapy and may include an inflammatory response to indolent or residual opportunistic infections or emergence of autoimmune disorders (eg, Grave disease, polymyositis, Guillain-Barré syndrome)
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” reported with ARTs
Not recommended in combination with products containing the individual components (ie, lamivudine and raltegravir) or emtricitabine
Pregnancy
Pregnancy category: C
Lactation: Breastfeeding is not recommended while taking lamivudine/raltegravir; additionally it is recommended that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dutrebis (lamivudine/raltegravir)
Mechanism of action
Lamivudine: Nucleoside reverse transcriptase inhibitor (NRTI); following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog
Raltegravir: Integrase inhibitor; inhibits catalytic activity of HIV-1 integrase, an HIV encoded enzyme required for viral replication
Pharmacokinetics
Bioavailability: 60% (raltegravir, fasting)
Peak plasma time: 1 hr (raltegravir, fasting)
Once absorbed, lamivudine and raltegravir distribution, metabolism, and excretion are similar to those of the reference components administered individually as described
Administration
Instructions
May take with or without food
