Data from FDA - Curated by Toby Galbraith - Last updated 23 February 2017
FDA (Food and Drug Administration, USA)
4 CONTRAINDICATIONS Abacavir and Lamivudine tablets are contraindicated in patients: • who have the HLA?B * 5701 allele [see Warnings and Precautions (5.1)].
• with prior hypersensitivity reaction to abacavir [see Warnings and Precautions (5.1)] or lamivudine.
•Presence of HLA-B * 5701 allele.
(4) •Prior hypersensitivity reaction to abacavir or lamivudine.
(4) •Moderate or
•Lactic acidosis and
•Exacerbations of hepatitis B [see Boxed
•Hepatic decompensation in patients co-infected with HIV-1 and Hepatitis C [see Warnings and Precautions (5.4)].
•Immune reconstitution syndrome [see Warnings and Precautions (5.5)].
•Fat redistribution [see Warnings and Precautions (5.6)].
•Myocardial infarction [see Warnings and Precautions (5.7)].
The most commonly reported
(6.1) To report SUSPECTED
6.1 Clinical Trials Experience in Adult Subjects Because clinical trials are conducted under widely
These reactions have been characterized by 2 or more of the following signs or symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including
Almost all abacavir hypersensitivity reactions include fever and/or rash as part of the syndrome.
Other signs and symptoms have included
Physical findings have included lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and maculopapular or urticarial rash (although some patients had other types of rashes and
There were reports of erythema multiforme.
Treatment?emergent (All Causality)
experienced a significantly higher incidence of
Five percent (5 %) of subjects receiving ZIAGEN 600 mg once
Two percent (2 %) of subjects receiving ZIAGEN 600 mg once
bCNA30024 was a multi?center, double-blind,
CNA30024 used double?blind ascertainment of suspected hypersensitivity reactions.
The frequencies of treatment?emergent laboratory
The frequency of Grade 3 and 4
One event of Grade 4 hepatitis in the once-daily cohort was considered as
6.3 Postmarketing Experience The following
Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to
Abacavir Cardiovascular: Myocardial infarction.
Skin: Suspected Stevens?Johnson syndrome (SJS) and
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,
There have also been reports of erythema multiforme with abacavir use [see
Abacavir and Lamivudine Body as a Whole: Redistribution/accumulation of body fat [see Warnings and Precautions (5.6)].
Endocrine and Metabolic: Hyperglycemia.
Hemic and Lymphatic: Aplastic anemia, anemia (including
cell aplasia and
progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic: Lactic acidosis and hepatic steatosis [see Warnings and Precautions (5.2)], posttreatment
Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria.
Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome.
2 DOSAGE AND ADMINISTRATION •Before initiating Abacavir and Lamivudine tablets, screen for the HLA?B * 5701 allele because Abacavir and Lamivudine tablets contain abacavir.
(2.1) •Adults: One tablet orally once daily.
(2.2) •Pediatric patients weighing at least 25 kg: One tablet daily.
(2.3) •Because Abacavir and Lamivudine tablets are a fixed-dose tablet and can not be dose
(2.4, 4) 2.1 Screening for HLAB * 5701 Allele prior to Starting Abacavir and Lamivudine Tablets Screen for the HLA?B * 5701 allele prior to initiating therapy with Abacavir and Lamivudine tablets [see Boxed
Before prescribing Abacavir and Lamivudine tablets, pediatric patients should be assessed for the
Abacavir and Lamivudine tablets are contraindicated in
Use of EPIVIR® (lamivudine) oral solution or tablets and ZIAGEN® (abacavir) oral solution may be considered.
8 USE IN SPECIFIC POPULATIONS •Lactation: Breastfeeding not
(8.2) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Abacavir and Lamivudine tablets during pregnancy.
Abacavir produced fetal malformations and other embryonic and fetal toxicities in
Lamivudine produced embryonic toxicity in rabbits at a dose that produced similar human exposures to the
The relevance of animal findings to human pregnancy registry data is not known.
Data Human Data: Abacavir: Based on prospective reports from the Antiretroviral Pregnancy Registry of over 2,000 exposures to abacavir during pregnancy resulting in live births (including over 900
The prevalence of
Lamivudine: Based on prospective reports from the Antiretroviral Pregnancy Registry of over 11,000 exposures to lamivudine during pregnancy resulting in live births (including over 4,300
The prevalence of
Lamivudine pharmacokinetics were studied in pregnant women during 2 clinical trials conducted in South Africa.
The trials assessed pharmacokinetics in 16 women at 36 weeks gestation using 150 mg lamivudine twice daily with zidovudine, 10 women at 38 weeks gestation using 150 mg lamivudine twice daily with zidovudine, and 10 women at 38 weeks gestation using lamivudine 300 mg twice daily
These trials were not designed or powered to provide efficacy information.
Lamivudine pharmacokinetics in pregnant women were similar to those seen in non-pregnant adults and in postpartum women.
Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples.
In a subset of subjects, amniotic fluid specimens were collected following
Animal Data: Abacavir: Studies in pregnant
Fetal malformations (
In the rabbit,
Reproduction studies with orally administered lamivudine have been performed in
Evidence of early embryolethality was seen in the rabbit at exposure levels similar to those observed in humans, but there was
Because of the
8.4 Pediatric Use The dosing
In pediatric patients weighing less than 25 kg, use of abacavir and
8.5 Geriatric Use Clinical trials of abacavir and lamivudine did not include
If a dose reduction of lamivudine, a component of Abacavir and Lamivudine tablets, is
If a dose reduction of abacavir, a component of Abacavir and Lamivudine tablets, is
Class C) hepatic
|Agency product number||2T8Q726O95|
|Date Last Revised||29-02-2016|
|Type||HUMAN PRESCRIPTION DRUG|
|Marketing authorisation holder||Prasco Laboratories|
HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND
Patients who carry the HLA?
B * 5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA?
B * 5701 allele [see Warnings and Precautions (5.1)].
Abacavir and Lamivudine tablets are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA?
B * 5701-positive patients [see Contraindications (4), Warnings and Precautions (5.1)].
All patients should be screened for the HLA?
B * 5701 allele prior to initiating therapy with Abacavir and Lamivudine tablets or reinitiation of therapy with Abacavir and Lamivudine tablets, unless patients have a previously documented HLA?
B * 5701 allele assessment.
Following a hypersensitivity reaction to Abacavir and Lamivudine tablets, NEVER restart Abacavir and Lamivudine tablets or any other abacavir?
containing product because
Lactic Acidosis and
Lamivudine tablets if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.2)].
1) and have
1 and HBV.
hepatitis B therapy may be warranted [see Warnings and Precautions (5.3)].
HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND
(5.1) • Hypersensitivity to abacavir is a multi-organ clinical syndrome.
(5.1) • Patients who carry the HLA-B * 5701 allele are at a higher risk of experiencing a hypersensitivity reaction to abacavir.
(5.1) • Abacavir and Lamivudine tablets are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B * 5701-positive patients.
Regardless of HLA-B * 5701 status,
(5.1) • Following a hypersensitivity reaction to Abacavir and Lamivudine tablets, NEVER restart Abacavir and Lamivudine tablets or any other abacavir-containing product.
(5.1) Lactic Acidosis and