abacavir (as abacavir sulfate) 300 MG Oral Tablet
DRUG INTERACTIONS
7 Methadone: An increased methadone dose may be required in a small number of patients.
( 7.1) 7.1 Methadone In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of abacavir twice daily (twice the currently recommended dose), oral methadone clearance increased [see Clinical Pharmacology (12.3)] .
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.
OVERDOSAGE
10 There is no known specific treatment for overdose with abacavir.
If overdose occurs, the patient should be monitored and standard supportive treatment applied as required.
It is not known whether abacavir can be removed by peritoneal dialysis or hemodialysis.
DESCRIPTION
11 Abacavir sulfate is a synthetic carbocyclic nucleoside analogue with inhibitory activity against HIV-1.
The chemical name of abacavir sulfate is (1 S,cis)-4-[2-amino-6-(cyclopropylamino)-9 H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1).
Abacavir sulfate is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring.
It has a molecular formula of (C 14H 18N 6O) 2•H 2SO 4 and a molecular weight of 670.76 g per mol.
It has the following structural formula: Abacavir sulfate USP is a white to off-white solid and is soluble in water.
Abacavir tablets USP are for oral administration.
Each tablet contains abacavir sulfate USP equivalent to 300 mg of abacavir as active ingredient and the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.
The tablets are coated with a film that is made of hypromellose, iron oxide yellow, polysorbate 80, titanium dioxide, and triacetin.
In vivo, abacavir sulfate dissociates to its free base, abacavir.
Dosages are expressed in terms of abacavir.
Chemical Structure
CLINICAL STUDIES
14 14.1 Adult Trials Therapy-Naive Adults CNA30024 was a multicenter, double-blind, controlled trial in which 649 HIV-1-infected, therapy-naive adults were randomized and received either abacavir (300 mg twice daily), lamivudine (150 mg twice daily), and efavirenz (600 mg once daily); or zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), and efavirenz (600 mg once daily).
The duration of double-blind treatment was at least 48 weeks.
Trial participants were male (81%), white (51%), black (21%), and Hispanic (26%).
The median age was 35 years; the median pretreatment CD4+ cell count was 264 cells per mm 3, and median plasma HIV-1 RNA was 4.79 log 10 copies per mL.
The outcomes of randomized treatment are provided in Table 7.
Table 7.
Outcomes of Randomized Treatment through Week 48 (CNA30024) Outcome Abacavir plus Lamivudine plus Efavirenz (n = 324) Zidovudine plus Lamivudine plus Efavirenz (n = 325) Responder Subjects achieved and maintained confirmed HIV-1 RNA less than or equal to 50 copies per mL (less than 400 copies per mL) through Week 48 (Roche AMPLICOR Ultrasensitive HIV-1 MONITOR® standard test 1 PCR).
69% (73%) 69% (71%) Virologic failures Includes viral rebound, insufficient viral response according to the investigator, and failure to achieve confirmed less than or equal to 50 copies per mL by Week 48.
6% 4% Discontinued due to adverse reactions 14% 16% Discontinued due to other reasons Includes consent withdrawn, lost to follow up, protocol violations, those with missing data, clinical progression, and other.
10% 11% After 48 weeks of therapy, the median CD4+ cell count increases from baseline were 209 cells per mm 3 in the group receiving abacavir and 155 cells per mm 3 in the zidovudine group.
Through Week 48, 8 subjects (2%) in the group receiving abacavir (5 CDC classification C events and 3 deaths) and 5 subjects (2%) on the zidovudine arm (3 CDC classification C events and 2 deaths) experienced clinical disease progression.
CNA3005 was a multicenter, double-blind, controlled trial in which 562 HIV-1-infected, therapy-naive adults were randomized to receive either abacavir (300 mg twice daily) plus COMBIVIR ® (lamivudine 150 mg/zidovudine 300 mg twice daily), or indinavir (800 mg 3 times a day) plus COMBIVIR twice daily.
The trial was stratified at randomization by pre-entry plasma HIV-1 RNA 10,000 to 100,000 copies per mL and plasma HIV-1 RNA greater than 100,000 copies per mL.
Trial participants were male (87%), white (73%), black (15%), and Hispanic (9%).
At baseline the median age was 36 years; the median baseline CD4+ cell count was 360 cells per mm 3, and median baseline plasma HIV-1 RNA was 4.8 log 10 copies per mL.
Proportions of subjects with plasma HIV-1 RNA less than 400 copies per mL (using Roche AMPLICOR HIV-1 MONITOR Test) through 48 weeks of treatment are summarized in Table 8.
Table 8.
Outcomes of Randomized Treatment through Week 48 (CNA3005) Outcome Abacavir plus Lamivudine/Zidovudine (n = 262) Indinavir plus Lamivudine/Zidovudine (n = 265) Responder Subjects achieved and maintained confirmed HIV-1 RNA less than 400 copies per mL.
49% 50% Virologic failure Includes viral rebound and failure to achieve confirmed less than 400 copies per mL by Week 48.
31% 28% Discontinued due to adverse reactions 10% 12% Discontinued due to other reasons Includes consent withdrawn, lost to follow up, protocol violations, those with missing data, clinical progression, and other.
11% 10% Treatment response by plasma HIV-1 RNA strata is shown in Table 9.
Table 9.
Proportions of Responders through Week 48 by Screening Plasma HIV-1 RNA Levels (CNA3005) Screening HIV-1 RNA (copies/mL) Abacavir plus Lamivudine/Zidovudine (n = 262) Indinavir plus Lamivudine/Zidovudine (n = 265) <400 copies/mL n 100,000 50% 48% 166 96 48% 52% 165 100 In subjects with baseline viral load greater than 100,000 copies per mL, percentages of subjects with HIV-1 RNA levels less than 50 copies per mL were 31% in the group receiving abacavir versus 45% in the group receiving indinavir.
Through Week 48, an overall mean increase in CD4+ cell count of about 150 cells per mm 3 was observed in both treatment arms.
Through Week 48, 9 subjects (3.4%) in the group receiving abacavir (6 CDC classification C events and 3 deaths) and 3 subjects (1.5%) in the group receiving indinavir (2 CDC classification C events and 1 death) experienced clinical disease progression.
CNA30021 was an international, multicenter, double-blind, controlled trial in which 770 HIV-1-infected, therapy-naive adults were randomized and received either abacavir 600 mg once daily or abacavir 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily.
The double-blind treatment duration was at least 48 weeks.
Trial participants had a mean age of 37 years; were male (81%), white (54%), black (27%), and American Hispanic (15%).
The median baseline CD4+ cell count was 262 cells per mm 3 (range: 21 to 918 cells per mm 3) and the median baseline plasma HIV-1 RNA was 4.89 log 10 copies per mL (range: 2.6 to 6.99 log 10 copies per mL).
The outcomes of randomized treatment are provided in Table 10.
Table 10.
Outcomes of Randomized Treatment through Week 48 (CNA30021) Outcome Abacavir 600 mg q.d.
plus EPIVIR ® plus Efavirenz (n = 384) Abacavir 300 mg b.i.d.
plus EPIVIR plus Efavirenz (n = 386) Responder Subjects achieved and maintained confirmed HIV-1 RNA less than 50 copies per mL (less than 400 copies per mL) through Week 48 (Roche AMPLICOR Ultrasensitive HIV-1 MONITOR standard test version 1).
64% (71%) 65% (72%) Virologic failure Includes viral rebound, failure to achieve confirmed less than 50 copies per mL (less than 400 copies per mL) by Week 48, and insufficient viral load response.
11% (5%) 11% (5%) Discontinued due to adverse reactions 13% 11% Discontinued due to other reasons Includes consent withdrawn, lost to follow up, protocol violations, clinical progression, and other.
11% 13% After 48 weeks of therapy, the median CD4+ cell count increases from baseline were 188 cells per mm 3 in the group receiving abacavir 600 mg once daily and 200 cells per mm 3 in the group receiving abacavir 300 mg twice daily.
Through Week 48, 6 subjects (2%) in the group receiving abacavir 600 mg once daily (4 CDC classification C events and 2 deaths) and 10 subjects (3%) in the group receiving abacavir 300 mg twice daily (7 CDC classification C events and 3 deaths) experienced clinical disease progression.
None of the deaths were attributed to trial medications.
14.2 Pediatric Trials Therapy-Experienced Pediatric Subjects CNA3006 was a randomized, double-blind trial comparing abacavir 8 mg per kg twice daily plus lamivudine 4 mg per kg twice daily plus zidovudine 180 mg per m 2 twice daily versus lamivudine 4 mg per kg twice daily plus zidovudine 180 mg per m 2 twice daily.
Two hundred and five therapy-experienced pediatric subjects were enrolled: female (56%), white (17%), black (50%), Hispanic (30%), median age of 5.4 years, baseline CD4+ cell percent greater than 15% (median = 27%), and median baseline plasma HIV-1 RNA of 4.6 log 10 copies per mL.
Eighty percent and 55% of subjects had prior therapy with zidovudine and lamivudine, respectively, most often in combination.
The median duration of prior nucleoside analogue therapy was 2 years.
At 16 weeks the proportion of subjects responding based on plasma HIV-1 RNA less than or equal to 400 copies per mL was significantly higher in subjects receiving abacavir plus lamivudine plus zidovudine compared with subjects receiving lamivudine plus zidovudine, 13% versus 2%, respectively.
Median plasma HIV-1 RNA changes from baseline were -0.53 log 10 copies per mL in the group receiving abacavir plus lamivudine plus zidovudine compared with -0.21 log 10 copies per mL in the group receiving lamivudine plus zidovudine.
Median CD4+ cell count increases from baseline were 69 cells per mm 3 in the group receiving abacavir plus lamivudine plus zidovudine and 9 cells per mm 3 in the group receiving lamivudine plus zidovudine.
Additional pediatric use information for patients aged 3 months and above is approved for ViiV Healthcare Company’s ZIAGEN ® (abacavir sulfate) tablets.
However, due to ViiV Healthcare Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
HOW SUPPLIED
16 /STORAGE AND HANDLING Abacavir tablets USP, containing abacavir sulfate equivalent to 300 mg abacavir, are yellow colored, biconvex, capsule shaped, coated tablet, debossed with ‘D’ and ‘88’ on either side of the score line on one side and plain with a score line on other side.
They are packaged as follows: Unit dose packages of 30 (3 x 10) NDC 68084-021-21 Store at 20° to 25° C (68° to 77° F); excursions permitted to 15° to 30° C (59° to 86° F) [ see USP Controlled Room Temperature] .
FOR YOUR PROTECTION: Do not use if blister is torn or broken.
RECENT MAJOR CHANGES
Warnings and Precautions, Related Products that are Not Recommended (5.6) Removed 03/2017
GERIATRIC USE
8.5 Geriatric Use Clinical trials of abacavir did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
In general, caution should be exercised in the administration of abacavir in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
DOSAGE FORMS AND STRENGTHS
3 Abacavir tablets, containing abacavir sulfate equivalent to 300 mg abacavir, are yellow colored, biconvex, capsule shaped, coated tablet, debossed with ‘D’ and ‘88’ on either side of the score line on one side and plain with a score line on other side.
Tablets: 300 mg scored (3)
MECHANISM OF ACTION
12.1 Mechanism of Action Abacavir is an antiretroviral agent [see Microbiology (12.4)] .
INDICATIONS AND USAGE
1 Abacavir tablets, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
Abacavir tablets, a nucleoside analogue human immunodeficiency virus (HIV-1) reverse transcriptase inhibitor, are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
( 1)
PEDIATRIC USE
8.4 Pediatric Use The safety and effectiveness of abacavir have been established in pediatric patients aged 3 months and older.
Use of abacavir is supported by pharmacokinetic trials and evidence from adequate and well-controlled trials of abacavir in adults and pediatric subjects [see Dosage and Administration (2.2), Adverse Reactions (6.2), Clinical Pharmacology (12.3), Clinical Studies (14.2)].
PREGNANCY
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir during pregnancy.
Healthcare Providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
Risk Summary Available data from the APR show no difference in the overall risk of birth defects for abacavir compared with the background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population [see Data].
The APR uses the MACDP as the U.S.
reference population for birth defects in the general population.
The MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks gestation.
The rate of miscarriage is not reported in the APR.
The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S.
general population is 15% to 20%.
The background risk for major birth defects and miscarriage for the indicated population is unknown.
In animal reproduction studies, oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the recommended clinical daily dose.
However, no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis, at exposures approximately 9 times the human exposure (AUC) at the recommended clinical dose [see Data].
Data Human Data: Based on prospective reports to the APR of over 2,000 exposures to abacavir during pregnancy resulting in live births (including over 1,000 exposed in the first trimester), there was no difference between the overall risk of birth defects for abacavir compared with the background birth defect rate of 2.7% in the U.S.
reference population of the MACDP.
The prevalence of defects in live births was 2.9% (95% CI: 2.0% to 4.1%) following first trimester exposure to abacavir-containing regimens and 2.7% (95% CI: 1.9% to 3.7%) following second/third trimester exposure to abacavir-containing regimens.
Abacavir has been shown to cross the placenta and concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery [see Clinical Pharmacology (12.3)] .
Animal Data: Abacavir was administered orally to pregnant rats (at 100, 300, and 1,000 mg per kg per day) and rabbits (at 125, 350, or 700 mg per kg per day) during organogenesis (on gestation Days 6 through 17 and 6 through 20, respectively).
Fetal malformations (increased incidences of fetal anasarca and skeletal malformations) or developmental toxicity (decreased fetal body weight and crown-rump length) were observed in rats at doses up to 1,000 mg per kg per day, resulting in exposures approximately 35 times the human exposure (AUC) at the recommended daily dose.
No developmental effects were observed in rats at 100 mg per kg per day, resulting in exposures (AUC) 3.5 times the human exposure at the recommended daily dose.
In a fertility and early embryo-fetal development study conducted in rats (at 60, 160, or 500 mg per kg per day), embryonic and fetal toxicities (increased resorptions, decreased fetal body weights) or toxicities to the offspring (increased incidence of stillbirth and lower body weights) occurred at doses up to 500 mg per kg per day.
No developmental effects were observed in rats at 60 mg per kg per day, resulting in exposures (AUC) approximately 4 times the human exposure at the recommended daily dose.
Studies in pregnant rats showed that abacavir is transferred to the fetus through the placenta.
In pregnant rabbits, no developmental toxicities and no increases in fetal malformations occurred at up to the highest dose evaluated, resulting in exposures (AUC) approximately 9 times the human exposure at the recommended dose.
BOXED WARNING
WARNING: HYPERSENSITIVITY REACTIONS, and LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir.
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 is 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 or reinitiation of therapy with abacavir, unless patients have a previously documented HLA-B*5701 allele assessment.
Discontinue abacavir immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible [see Contraindications (4), Warnings and Precautions (5.1)].
Following a hypersensitivity reaction to abacavir, NEVER restart abacavir or any other abacavir-containing product because more severe symptoms, including death can occur within hours.
Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity [see Warnings and Precautions (5.1)] .
Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals.
Discontinue abacavir if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.2)] .
WARNING: HYPERSENSITIVITY REACTIONS, and LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS See full prescribing information for complete boxed warning.
Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir.
( 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 is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients.
( 4) Discontinue abacavir as soon as a hypersensitivity reaction is suspected.
Regardless of HLA-B *5701 status, permanently discontinue abacavir if hypersensitivity cannot be ruled out, even when other diagnoses are possible.
( 5.1) Following a hypersensitivity reaction to abacavir, NEVER restart abacavir or any other abacavir-containing product.
( 5.1) Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues.
( 5.2)
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Immune reconstitution syndrome and redistribution/accumulation of body fat have been reported in patients treated with combination antiretroviral therapy.
( 5.3, 5.4) 5.1 Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir.
These hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment [see Adverse Reactions (6.1)] .
Patients who carry the HLA-B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA-B*5701 allele have developed hypersensitivity reactions.
Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA-B*5701 screening was not performed.
The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA-B*5701 allele were excluded.
In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making.
Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir: All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir or reinitiation of therapy with abacavir, unless patients have a previously documented HLA-B*5701 allele assessment.
Abacavir is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients.
Before starting abacavir, review medical history for prior exposure to any abacavir-containing product.
NEVER restart abacavir or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA-B*5701 status.
To reduce the risk of a life-threatening hypersensitivity reaction, regardless of HLA-B*5701 status, discontinue abacavir immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications).
If a hypersensitivity reaction cannot be ruled out, do not restart abacavir or any other abacavir-containing products because more severe symptoms which may include life-threatening hypotension and death, can occur within hours.
If a hypersensitivity reaction is ruled out, patients may restart abacavir.
Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy.
Therefore, reintroduction of abacavir or any other abacavir-containing product is recommended only if medical care can be readily accessed.
A Medication Guide and Warning Card that provide information about recognition of hypersensitivity reactions should be dispensed with each new prescription and refill.
5.2 Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals.
A majority of these cases have been in women.
Obesity and prolonged nucleoside exposure may be risk factors.
Caution should be exercised when administering abacavir to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors.
Treatment with abacavir should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
5.3 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including abacavir.
During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment.
5.4 Fat Redistribution Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy.
The mechanism and long-term consequences of these events are currently unknown.
A causal relationship has not been established.
5.5 Myocardial Infarction In a published prospective, observational, epidemiological trial designed to investigate the rate of myocardial infarction (MI) in patients on combination antiretroviral therapy, the use of abacavir within the previous 6 months was correlated with an increased risk of MI.
In a sponsor-conducted pooled analysis of clinical trials, no excess risk of MI was observed in abacavir-treated subjects as compared with control subjects.
In totality, the available data from the observational cohort and from clinical trials are inconclusive.
As a precaution, the underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide).
Hypersensitivity Reactions Inform patients: that a Medication Guide and Warning Card summarizing the symptoms of the abacavir hypersensitivity reaction and other product information will be dispensed by the pharmacist with each new prescription and refill of abacavir, and instruct the patient to read the Medication Guide and Warning Card every time to obtain any new information that may be present about abacavir.
The complete text of the Medication Guide is reprinted at the end of this document.
to carry the Warning Card with them.
how to identify a hypersensitivity reaction [see Warnings and Precautions (5.1), Medication Guide] .
that if they develop symptoms consistent with a hypersensitivity reaction they should call their healthcare provider right away to determine if they should stop taking abacavir.
that a hypersensitivity reaction can worsen and lead to hospitalization or death if abacavir is not immediately discontinued.
to not restart abacavir or any other abacavir-containing product following a hypersensitivity reaction because more severe symptoms can occur within hours and may include life-threatening hypotension and death.
that if they have a hypersensitivity reaction, they should dispose of any unused abacavir to avoid restarting abacavir.
that a hypersensitivity reaction is usually reversible if it is detected promptly and abacavir is stopped right away.
that if they have interrupted abacavir for reasons other than symptoms of hypersensitivity (for example, those who have an interruption in drug supply), a serious or fatal hypersensitivity reaction may occur with reintroduction of abacavir.
to not restart abacavir or any other abacavir-containing product without medical consultation and only if medical care can be readily accessed by the patient or others.
Lactic Acidosis/Hepatomegaly with Steatosis Advise patients that lactic acidosis and severe hepatomegaly with steatosis have been reported with use of nucleoside analogues and other antiretrovirals.
Advise patients to stop taking abacavir if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Boxed Warning, Warnings and Precautions (5.2)] .
Immune Reconstitution Syndrome Advise patients to inform their healthcare provider immediately of any signs and symptoms of infection as inflammation from previous infection may occur soon after combination antiretroviral therapy, including when abacavir is started [see Warnings and Precautions (5.3)].
Redistribution/Accumulation of Body Fat Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time [see Warnings and Precautions (5.4)] .
Pregnancy Registry Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir during pregnancy [see Use in Specific Populations (8.1)] .
Lactation Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk [see Use in Specific Populations (8.2)] .
Missed Dose Instruct patients that if they miss a dose of abacavir, to take it as soon as they remember.
Advise patients not to double their next dose or take more than the prescribed dose [see Dosage and Administration (2)] .
Availability of Medication Guide Instruct patients to read the Medication Guide before starting abacavir and to re-read it each time the prescription is renewed.
Instruct patients to inform their physician or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens.
DOSAGE AND ADMINISTRATION
2 Before initiating abacavir, screen for the HLA-B*5701 allele.
( 2.1) Adults: 600 mg daily, administered as either 300 mg twice daily or 600 mg once daily.
( 2.2) Pediatric Patients Aged 3 Months and Older: Administered twice daily.
Dose should be calculated on body weight (kg) and should not exceed 600 mg daily.
( 2.3) Patients with Hepatic Impairment: Mild hepatic impairment – 200 mg twice daily.
( 2.4) 2.1 Screening for HLA-B*5701 Allele prior to Starting Abacavir Tablets Screen for the HLA-B*5701 allele prior to initiating therapy with abacavir tablets [see Boxed Warning, Warnings and Precautions (5.1)] .
2.2 Recommended Dosage for Adult Patients The recommended dosage of abacavir tablets for adults is 600 mg daily, administered orally as either 300 mg twice daily or 600 mg once daily, in combination with other antiretroviral agents.
2.3 Recommended Dosage for Pediatric Patients Abacavir tablets are available as scored tablet for HIV-1-infected pediatric patients weighing greater than or equal to 14 kg for whom a solid dosage form is appropriate.
Before prescribing abacavir tablets, children should be assessed for the ability to swallow tablets.
If a child is unable to reliably swallow abacavir tablets, the oral solution formulation should be prescribed.
The recommended oral dosage of abacavir tablets for HIV-1-infected pediatric patients is presented in Table 1.
Table 1.
Dosing Recommendations for Abacavir Scored Tablets in Pediatric Patients Weight (kg) Twice-Daily Dosing Regimen AM Dose PM Dose Total Daily Dose 14 to 20 to <25 ½ tablet (150 mg) 1 tablet (300 mg) 450 mg ≥ 25 1 tablet (300 mg) 1 tablet (300 mg) 600 mg Additional pediatric use information for patients aged 3 months and above is approved for ViiV Healthcare Company’s ZIAGEN ® (abacavir sulfate) tablets.
However, due to ViiV Healthcare Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
2.4 Recommended Dosage for Patients with Hepatic Impairment The recommended dose of abacavir tablets in patients with mild hepatic impairment (Child-Pugh Class A) is 200 mg twice daily.
To enable dose reduction, abacavir oral solution (10 mL twice daily) should be used for the treatment of these patients.
The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate to severe hepatic impairment; therefore, abacavir tablets are contraindicated in these patients.