"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:
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.
Lamivudine Plus Zidovudine Administered As Separate Formulations
In 4 randomized, controlled trials of EPIVIR 300 mg per day plus RETROVIR 600 mg per day, the following selected adverse reactions and laboratory abnormalities were observed (see Tables 1 and 2).
Table 1: Selected Clinical Adverse Reactions ( ≥ 5% Frequency)
in 4 Controlled Clinical Trials With EPIVIR 300 mg/day and RETROVIR 600 mg/day
|Adverse Reaction||EPIVIR plus RETROVIR
(n = 251)
|Body as a whole|
|Malaise & fatigue||27%|
|Fever or chills||10%|
|Nausea & vomiting||13%|
|Anorexia and/or decreased appetite||10%|
|Insomnia & other sleep disorders||11%|
|Nasal signs & symptoms||20%|
Pancreatitis was observed in 9 of the 2,613 adult patients (0.3%) who received EPIVIR in controlled clinical trials [see WARNINGS AND PRECAUTIONS].
Selected laboratory abnormalities observed during therapy are listed in Table 2.
Table 2: Frequencies of Selected Laboratory Abnormalities
Among Adults in 4 Controlled Clinical Trials of EPIVIR 300 mg/day plus RETROVIR
|Test (Abnormal Level)||EPIVIR plus RETROVIR %
|Neutropenia (ANC < 750/mm³)||7.2% (237)|
|Anemia (Hgb < 8.0 g/dL)||2.9% (241)|
|Thrombocytopenia (platelets < 50,000/mm³)||0.4% (240)|
|ALT ( > 5.0 x ULN)||3.7% (241)|
|AST ( > 5.0 x ULN)||1.7% (241)|
|Bilirubin ( > 2.5 x ULN)||0.8% (241)|
|Amylase ( > 2.0 x ULN)||4.2% (72)|
|ULN = Upper limit of normal.
ANC = Absolute neutrophil count.
n = Number of patients assessed.
a Frequencies of these laboratory abnormalities were higher in patients with mild laboratory abnormalities at baseline.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during post-approval use of EPIVIR, RETROVIR, and/or COMBIVIR. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to EPIVIR, RETROVIR, and/or COMBIVIR.
Body as a Whole: Redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].
Gastrointestinal: Oral mucosal pigmentation, stomatitis.
General: Vasculitis, weakness.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Respiratory: Abnormal breath sounds/wheezing.
Read the Combivir (lamivudine, zidovudine) Side Effects Center for a complete guide to possible side effects
No drug interaction studies have been conducted using COMBIVIR Tablets [see CLINICAL PHARMACOLOGY].
Zalcitabine: Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of COMBIVIR in combination with zalcitabine is not recommended.
Stavudine: Concomitant use of COMBIVIR with stavudine should be avoided since an antagonistic relationship with zidovudine has been demonstrated in vitro .
Nucleoside Analogues Affecting DNA Replication: Some nucleoside analogues affecting DNA replication, such as ribavirin, antagonize the in vitro antiviral activity of zidovudine against HIV-1; concomitant use of such drugs should be avoided.
Concomitant use of COMBIVIR with doxorubicin should be avoided since an antagonistic relationship with zidovudine 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.
Interferon- and Ribavirin-Based Regimens
Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV-1/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].
No change in dose of either drug is recommended. There is no information regarding the effect on lamivudine pharmacokinetics of higher doses of TMP/SMX such as those used to treat PCP.
Read the Combivir Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 12/16/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Combivir Information
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Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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