Abacavir Tablets ®

Abacavir (ABC) is an antiretroviral medication used to prevent and treat HIV/AIDS. Viral strains that are resistant to zidovudine (AZT) or lamivudine (3TC) are generally, but not always, sensitive to abacavir.

Abacavir should always be used in combination with other antiretroviral agents. Abacavir should not be added as a single agent when antiretroviral regimens are changed due to loss of virologic response.

Contents

Name

Abacavir (ABC)

Chemical Name

{(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol

Mechanism of action

ABC a chiral purine carbocyclic nucleoside, is a prodrug of the guanosine analog carbovir. Its target is the viral reverse transcriptase enzyme. ABC is converted intracellularly to the triphosphate of carbovir which competes with guanosine triphosphate for incorporation into the DNA strand. When reverse transcriptase incorporates the ABC product carbovir triphosphate, transcription is terminated because there is no 3' hydroxyl group on the molecule to make a phosphodiester bond to the next nucleotide in the DNA sequence.

Medical Uses

Treatment And Prevention OF AIDS

Brand Names

زياجين ziagen ®

Abamune Cipla Limited Tablet 300mg اباميون
Abavir Genix Pharma Ltd Tablet 300mg ابافير

Abcavir Taj Pharmaceuticals Ltd Tablet 300mg V ابكافير

Abec Emcure Pharmaceuticals Ltd. Tablet 300mg ابيك

Abmune Cipla Limited Tablet 300mg ابميون
Virol فيرول

Use In Pregnancy and Lactaion

Pregnancy

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: Not assigned. Risk summary: Malformative risk with use of this drug in pregnant women is unlikely. Comments: A pregnancy exposure registry is available.

Animal studies (high-dose) have revealed evidence of embryonic and fetal toxicity, including developmental toxicity, fetal anasarca, skeletal malformations, and increased incidence of stillbirth. Placental transfer has been observed in humans. There are no controlled data in human pregnancy; however, based on observed outcomes (more than 800 after first-trimester exposure and more than 1000 after second-/third-trimester exposure), the malformative risk is unlikely in humans. To monitor maternal-fetal outcome of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com The APR has received prospective reports of over 2000 exposures to this drug (over 900 exposed in the first trimester) resulting in live births; there was no difference between abacavir and overall birth defects compared with the background birth defect rate of 2.7% in the reference population. The prevalence of defects in the first trimester was 3% for abacavir. No increased risk of major birth defects observed for this drug compared to background rate. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decision and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Lactation

Breast milk from 15 women and blood samples from 9 of their partially or exclusively breastfed infants were collected about 1 month postpartum; the mothers were using abacavir 300 mg twice a day (with lamivudine and zidovudine). Breast milk was obtained right before a dose; whole breast milk abacavir levels averaged 0.057 mg/L (about 85% of maternal blood levels). Infant blood was obtained 11 to 18 hours after the last maternal dose and about 1 hour (range: 6 minutes to 35 hours) after the last breastfeeding; plasma drug levels were undetectable (less than 16 mcg/L) in 8 of 9 infants.

Breastfeeding is not recommended during use of this drug; if replacement feeding is not an option, a different drug may be preferred. Excreted into human milk: Yes Comments: -The effects in the nursing infant are unknown. -The US CDC, American Academy of Pediatrics, and manufacturer advise HIV-infected women not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected. -Local guidelines should be consulted if replacement feeding is not an option.

Side Effects

Common reactions include nausea, headache, fatigue, vomiting, hypersensitivity reaction, diarrhea, fever/chills, depression, rash, anxiety, URI, ALT, AST elevated, hypertriglyceridemia, and lipodystrophy.[4]

Patients with liver disease should be cautious about using abacavir because of the possibility that it can aggravate the condition. The use of nucleoside drugs such as abacavir can very rarely cause lactic acidosis. Resistance to abacavir has developed in laboratory versions of HIV which are also resistant to other HIV-specific antiretrovirals such as lamivudine, didanosine and zalcitabine. HIV strains that are resistant to protease inhibitors are not likely to be resistant to abacavir.

Abacavir is contraindicated for use in infants under 3 months of age.

Little is known about the effects of Abacavir overdose. Overdose victims should be taken to a hospital emergency room for treatment.

Babies and Children

Dose should be adjusted

Can not be used in babies less than 3 months old

Legal Status

Prescription only medicine

Adminstration

Oral

Tablets

Solution

Excretion

Renal (1.2% abacavir, 30% 5'-carboxylic acid metabolite, 36% 5'-glucuronide metabolite, 15% unidentified minor metabolites). Fecal (16%)

Bioavailability

83%

Metabolism

Hepatic

It is capable of crossing the blood–brain barrier.

Dosage

Usual Adult Dose for HIV Infection

300 mg orally twice a day or 600 mg orally once a day

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Usual Adult Dose for Nonoccupational Exposure

US CDC recommendations: 300 mg orally twice a day or 600 mg orally once a day
Duration of therapy: 28 days

Comments:
-Recommended as part of alternative regimens (NNRTI-based, protease inhibitor-based, or triple NRTI) for nonoccupational postexposure prophylaxis of HIV infection
-Prophylaxis should be started as soon as possible, within 72 hours of exposure.
-Current guidelines should be consulted for additional information.

Usual Adult Dose for Occupational Exposure

US Public Health Service working group recommendations: 300 mg orally twice a day or 600 mg orally once a day
Duration of therapy: 28 days, if tolerated

Comments:
-Only with expert consultation, as part of an alternative regimen for use as HIV postexposure prophylaxis
-Prophylaxis should be started as soon as possible, preferably within hours after exposure.
-The optimal duration of prophylaxis is unknown and may differ based on institution protocol.
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose for HIV Infection

3 months or older:
Oral solution: 8 mg/kg orally twice a day or 16 mg/kg orally once a day
Maximum dose: 600 mg/day

Tablets:
14 to less than 20 kg: 150 mg orally twice a day or 300 mg orally once a day
20 to less than 25 kg: 150 mg orally in the morning and 300 mg in the evening, or 450 mg orally once a day
25 kg or more: 300 mg orally twice a day or 600 mg orally once a day

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection