"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:
Serious and sometimes fatal hypersensitivity reaction. In one trial, once-daily dosing of abacavir was associated with more severe hypersensitivity reactions [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Lactic acidosis and severe hepatomegaly [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Acute exacerbations of hepatitis B [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Hepatic decompensation in patients co-infected with HIV-1 and Hepatitis C [see WARNINGS AND PRECAUTIONS].
- Immune reconstitution syndrome [see WARNINGS AND PRECAUTIONS].
- Fat redistribution [see WARNINGS AND PRECAUTIONS].
- Myocardial infarction [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 clinical practice.
Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a ≥ 5% frequency during therapy with ZIAGEN 600 mg once daily or ZIAGEN 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily, are listed in Table 1.
Table 1: Treatment-Emergent (All Causality) Adverse
Reactions of at Least Moderate Intensity (Grades 2-4, ≥ 5%
Frequency) in Therapy-Naive Adults (CNA30021) Through 48 Weeks of Treatment
|Adverse Event||ZIAGEN 600 mg q.d. plus EPIVIR plus Efavirenz
(n = 384)
|ZIAGEN 300 mg b.i.d. plus EPIVIR plus Efavirenz
(n = 386)
|a Subjects receiving ZIAGEN 600 mg once daily,
experienced a significantly higher incidence of severe drug hypersensitivity
reactions and severe diarrhea compared with subjects who received ZIAGEN 300 mg
twice daily. Five percent (5%) of subjects receiving ZIAGEN 600 mg once daily
had severe drug hypersensitivity reactions compared with 2% of subjects
receiving ZIAGEN 300 mg twice daily. Two percent (2%) of subjects receiving
ZIAGEN 600 mg once daily had severe diarrhea while none of the subjects
receiving ZIAGEN 300 mg twice daily had this event.
b CNA30024 was a multi-center, double-blind, controlled trial in which 649 HIV-1-infected, therapy-naive adults were randomized and received either ZIAGEN (300 mg twice daily), EPIVIR (150 mg twice daily), and efavirenz (600 mg once daily); or zidovudine (300 mg twice daily), EPIVIR (150 mg twice daily), and efavirenz (600 mg once daily). CNA30024 used double-blind ascertainment of suspected hypersensitivity reactions. During the blinded portion of the trial, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 subjects in the abacavir group and 3% of 325 subjects in the zidovudine group.
Laboratory abnormalities observed in clinical trials of ZIAGEN were anemia, neutropenia, liver function test abnormalities, and elevations of CPK, blood glucose, and triglycerides. Additional laboratory abnormalities observed in clinical trials of EPIVIR were thrombocytopenia and elevated levels of bilirubin, amylase, and lipase.
The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in CNA30021.
Other Adverse Events
In addition to adverse reactions listed above, other adverse events observed in the expanded access program for abacavir were pancreatitis and increased GGT.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of abacavir, lamivudine, and/or EPZICOM. 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 abacavir, lamivudine, and/or EPZICOM.
Cardiovascular: Myocardial infarction.
Skin: Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases.
There have also been reports of erythema multiforme with abacavir use.
Abacavir and Lamivudine
Body as a Whole: Redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS]
Endocrine and Metabolic: Hyperglycemia.
Respiratory: Abnormal breath sounds/wheezing.
Read the Epzicom (abacavir sulfate and lamivudine tablets) Side Effects Center for a complete guide to possible side effects
- No drug interaction trials have been conducted using EPZICOM Tablets [see CLINICAL PHARMACOLOGY].
Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure [see CLINICAL PHARMACOLOGY].
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 subjects, hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected subjects receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].
The addition of methadone has no clinically significant effect on the pharmacokinetic properties of abacavir. In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased [see CLINICAL PHARMACOLOGY]. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.
No change in dose of either drug is recommended [see CLINICAL PHARMACOLOGY]. 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 Epzicom Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/4/2012
This monograph has been modified to include the generic and brand name in many instances.
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