"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 with 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 adverse reactions reported at a statistically significant greater incidence for subjects receiving oral RETROVIR in a monotherapy trial.
Table 3: Percentage (%) of Subjects with Adverse
Reactions (Greater than or Equal to 5% Frequency) in Asymptomatic HIV-1
Infection (ACTG 019)
|Adverse Reaction||RETROVIR 500 mg/day
(n = 453)
(n = 428)
|Body as a whole|
|aNot statistically significant versus placebo.|
In addition to the adverse reactions listed in Table 3, adverse reactions observed at an incidence of greater than or equal to 5% in any treatment arm in clinical trials (NUCA3001, NUCA3002, NUCB3001, and NUCB3002) were abdominal cramps, abdominal pain, arthralgia, chills, dyspepsia, fatigue, insomnia, musculoskeletal pain, myalgia, and neuropathy. Additionally, in these trials hyperbilirubinemia was reported at an incidence of less than or equal to 0.8%.
Selected laboratory abnormalities observed during a clinical trial of monotherapy with oral RETROVIR are shown in Table 4.
Table 4: Frequencies of
Selected (Grade 3/4) Laboratory Abnormalities in Subjects with Asymptomatic
HIV-1 Infection (ACTG 019)
|Test (Abnormal Level)||RETROVIR 500 mg/day
(n = 453)
(n = 428)
|Anemia (Hgb < 8 g/dL)||1%||< 1%|
|Granulocytopenia ( < 750 cells/mm )||2%||2%|
|Thrombocytopenia (platelets < 50,000/mm )||0%||< 1%|
|ALT ( > 5 x ULN)||3%||3%|
|AST ( > 5 x ULN)||1%||2%|
|ULN = Upper limit of normal.|
The adverse reactions reported during IV administration of RETROVIR injection are similar to those reported with oral administration; neutropenia and anemia were reported most frequently. Long-term IV administration beyond 2 to 4 weeks has not been studied in adults and may enhance hematologic adverse reactions. Local reaction, pain, and slight irritation during IV administration occur infrequently.
The clinical adverse reactions reported among adult recipients of RETROVIR may also occur in pediatric patients.
Trial ACTG 300: Selected clinical adverse reactions and physical findings with a greater than or equal to 5% frequency during therapy with EPIVIR® (lamivudine) oral suspension 4 mg per kg twice daily plus RETROVIR 160 mg per m² 3 times daily compared with didanosine in therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 5.
Table 5: Selected Clinical Adverse Reactions and
Physical Findings (Greater than or Equal to 5% Frequency) in Pediatric Subjects
in Trial 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%|
|aIncludes pain, discharge, erythema, or swelling of an ear.|
Selected laboratory abnormalities experienced by therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 6.
Table 6: Frequencies of Selected (Grade 3/4)
Laboratory Abnormalities in Pediatric Subjects in Trial ACTG 300
|Test (Abnormal Level)||EPIVIR plus RETROVIR||Didanosine|
|Neutropenia (ANC < 400 cells/mm³)||8%||3%|
|Anemia (Hgb < 7.0 g/dL)||4%||2%|
|Thrombocytopenia (platelets < 50,000/mm )||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 subjects receiving RETROVIR 180 mg per m² every 6 hours in open-label trials. Additionally, adverse reactions reported at an incidence of less than 6% in these trials 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 per 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 less than 9.0 g per dL) and neutropenia (less than 1,000 cells per 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 per 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.
The following adverse reactions have been identified during postmarketing use of RETROVIR. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole: Back pain, chest pain, flu-like syndrome, generalized pain, redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].
Reproductive System and Breast: Gynecomastia.
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
Read the Retrovir Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 1/20/2015
This monograph has been modified to include the generic and brand name in many instances.
Additional Retrovir Information
Retrovir - User Reviews
Retrovir User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
Get breaking medical news.