"The U.S. Food and Drug Administration today approved Tivicay (dolutegravir), a new drug to treat HIV-1 infection.
Tivicay is an integrase strand transfer inhibitor that interferes with one of the enzymes necessary for HIV to multiply. "...
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Hematologic toxicity, including neutropenia and anemia [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Symptomatic myopathy [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Lactic acidosis and severe hepatomegaly with steatosis [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The frequency and severity of adverse reactions associated with the use of RETROVIR are greater in patients with more advanced infection at the time of initiation of therapy.
Table 3 summarizes events reported at a statistically significant greater incidence for patients receiving RETROVIR in a monotherapy study.
Table 3: Percentage (%) of Patients With Adverse Reactionsa
in Asymptomatic HIV-1Infection (ACTG 019)
|Adverse Reaction||RETROVIR 500 mg/day
(n = 428)
|Body as a whole|
|aReported in ≥5% of study population.
b 193 Not statistically significant versus placebo.
In addition to the adverse reactions listed in Table 3, adverse reactions observed at an incidence of ≥5% in any treatment arm in clinical studies (NUCA3001, NUCA3002, NUCB3001, and NUCB3002) were abdominal cramps, abdominal pain, arthralgia, chills, dyspepsia, fatigue, insomnia, musculoskeletal pain, myalgia, and neuropathy. Additionally, in these studies hyperbilirubinemia was reported at an incidence of ≤0.8%.
Selected laboratory abnormalities observed during a clinical study of monotherapy with RETROVIR are shown in Table 4.
Table 4: Frequencies of Selected (Grade 3/4) Laboratory
Abnormalities in Patients With Asymptomatic HIV-1 Infection (ACTG 019)
|Test (Abnormal Level)||RETROVIR 500 mg/day
(n = 428)
|Anemia (Hgb < 8 g/dL)||1%||< 1%|
|Granulocytopenia ( < 750 cells/mm³)||2%||2%|
|Thrombocytopenia (platelets < 50,000/mm³)||0%||< 1%|
|ALT (>5 x ULN)||3%||3%|
|AST (>5 x ULN)||1%||2%|
|ULN = Upper limit of normal.|
The clinical adverse reactions reported among adult recipients of RETROVIR may also occur in pediatric patients.
Study ACTG 300: Selected clinical adverse reactions and physical findings with a ≥5% frequency during therapy with EPIVIR® (lamivudine) Oral Suspension 4 mg/kg twice daily plus RETROVIR 160 mg/m² 3 times daily compared with didanosine in therapy-naive (≤56 days of antiretroviral therapy) pediatric patients are listed in Table 5.
Table 5: Selected Clinical Adverse Reactions and Physical
Findings (≥5% Frequency) in Pediatric Patients in Study ACTG 300
|Adverse Reaction||EPIVIR plus RETROVIR
(n = 236)
(n = 235)
|Body as a whole|
|Nausea & vomiting||8%||7%|
|Abnormal breath sounds/wheezing||7%||9%|
|Ear, Nose, and Throat|
|Signs or symptoms of earsa||7%||6%|
|Nasal discharge or congestion||8%||11%|
|a Includes pain, discharge, erythema, or swelling of an ear.|
Selected laboratory abnormalities experienced by therapy-naive ( < 56 days of antiretroviral therapy) pediatric patients are listed in Table 6.
Table 6: Frequencies of Selected (Grade 3/4) Laboratory
Abnormalities in Pediatric Patients in Study ACTG 300
|Neutropenia (ANC < 400 cells/mm³)||8%||3%|
|Anemia (Hgb < 7.0 g/dL)||4%||2%|
|Thrombocytopenia (platelets < 50,000/mm³)||1%||3%|
|ALT (>10 x ULN)||1%||3%|
|AST (>10 x ULN)||2%||4%|
|Lipase (>2.5 x ULN)||3%||3%|
|Total amylase (>2.5 x ULN)||3%||3%|
|ULN = Upper limit of normal.
ANC = Absolute neutrophil count.
Macrocytosis was reported in the majority of pediatric patients receiving RETROVIR 180 mg/m every 6 hours in open-label studies. Additionally, adverse reactions reported at an incidence of < 6% in these studies were congestive heart failure, decreased reflexes, ECG abnormality, edema, hematuria, left ventricular dilation, nervousness/irritability, and weight loss.
Use for the Prevention of Maternal-Fetal Transmission of HIV-1
In a randomized, double-blind, placebo-controlled trial in HIV-1-infected women and their neonates conducted to determine the utility of RETROVIR for the prevention of maternal-fetal HIV-1 transmission, RETROVIR Syrup at 2 mg/kg was administered every 6 hours for 6 weeks to neonates beginning within 12 hours following birth. The most commonly reported adverse reactions were anemia (hemoglobin < 9.0 g/dL) and neutropenia ( < 1,000 cells/mm3). Anemia occurred in 22% of the neonates who received RETROVIR and in 12% of the neonates who received placebo.The mean difference in hemoglobin values was less than 1.0 g/dL for neonates receiving RETROVIR compared with neonates receiving placebo. No neonates with anemia required transfusion and all hemoglobin values spontaneously returned to normal within 6 weeks after completion of therapy with RETROVIR. Neutropenia in neonates was reported with similar frequency in the group that received RETROVIR (21%) and in the group that received placebo (27%). The long-term consequences of in utero and infant exposure to RETROVIR are unknown.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of RETROVIR. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to RETROVIR.
Body as a Whole: Back pain, chest pain, flu-like syndrome, generalized pain, redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].
Eye: Macular edema.
Skin: Changes in skin and nail pigmentation, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweat, urticaria. Special Senses: Amblyopia, hearing loss, photophobia, taste perversion. Urogenital: Urinary frequency, urinary hesitancy.
Read the Retrovir (zidovudine) Side Effects Center for a complete guide to possible side effects
Concomitant use of zidovudine with stavudine should be avoided since an antagonistic relationship has been demonstrated in vitro.
Nucleoside Analogues Affecting DNA Replication
Concomitant use of zidovudine with doxorubicin should be avoided since an antagonistic relationship has been demonstrated in vitro.
Hematologic/Bone Marrow Suppressive/Cytotoxic Agents
Coadministration of ganciclovir, interferon alfa, ribavirin, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.
Read the Retrovir Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/21/2012
This monograph has been modified to include the generic and brand name in many instances.
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