Plot 6, Abimbola Way, Isolo, P.M.B. 1120, Apapa, Lagos, Nigeria., km 32, Lagos Bad, Exp/way, Agbara
Tel: 01-7901401 - 8 (8 lines)
Fax: 01-7912722, 01-7912732
Cipla Ltd.,Mumbai, India.
Dosage Form, Composition & NAFDAC Registration Number (NRN)
Tablet (NRN: 04-6228): Abacavir sulphate 300 mg
Pack size: 60's.
Oral solution (NRN: A4-4268): Abacavir sulphate 20 mg per mL
Pack size: 240 mL.
Abacavir is a synthetic nucleoside analogue and it is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5'-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3'-OH group in the incorporated nucleotide analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.
Abavir tablets and oral solution in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
Abavir is contraindicated in patients with:
- previously demonstrated hypersensitivity to abacavir or any other component of the products. Never restart Abavir or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA-B*5701 status.
- moderate or severe hepatic impairment
Serious and sometimes fatal hypersensitivity reactions have been associated with Abavir and other abacavir-containing products. Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended; this approach has been found to decrease the risk of a hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended and should be considered only with close medical supervision and under exceptional circumstances when the potential benefit outweighs the risk.
HLA-B*5701-negative patients may develop a hypersensitivity reaction to abacavir; however, this occurs significantly less frequently than in HLA-B*5701-positive patients. Regardless of HLA-B*5701 status, permanently discontinue Abavir if hypersensitivity cannot be ruled out, even when other diagnoses are possible.
Important information on signs and symptoms of hypersensitivity, as well as clinical management, is presented below.
Signs and Symptoms of Hypersensitivity:
Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups.
Group 1: Fever
Group 2: Rash
Group 3: Gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain).
Group 4: Constitutional (including generalized malaise, fatigue, or achiness).
Group 5: Respiratory (including dyspnea, cough, or pharyngitis).
Clinical Management of Hypersensitivity:
Discontinue Abavir as soon as a hypersensitivity reaction is suspected. To minimize the risk of a life-threatening hypersensitivity reaction, permanently discontinue Abavir if hypersensitivity cannot be ruled out, 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).
Following a hypersensitivity reaction to abacavir, Never restart Abavir or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death.
When therapy with Abavir has been discontinued for reasons other than symptoms of a hypersensitivity reaction, and if reinitiation of Abavir or any other abacavir-containing product is under consideration, carefully evaluate the reason for discontinuation of Abavir to ensure that the patient did not have symptoms of a hypersensitivity reaction. If the patient is of unknown HLA-B*5701 status, screening for the allele is recommended prior to reinitiation of Abavir.
If hypersensitivity cannot be ruled out, Do not reintroduce Abavir or any other abacavir-containing product. Even in the absence of the HLA-B*5701 allele, it is important to permanently discontinue abacavir and not rechallenge with abacavir if a hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe or even fatal reaction.
If symptoms consistent with hypersensitivity are not identified, reintroduction can be undertaken with continued monitoring for symptoms of a hypersensitivity reaction. Make patients aware that a hypersensitivity reaction can occur with reintroduction of Abavir or any other abacavir-containing product and that reintroduction of Abavir or any other abacavir-containing product needs to be undertaken only if medical care can be readily accessed by the patient or others.
Risk Factor: HLA-B*5701 Allele: Trials have shown that carriage of the HLA-B*5701 allele is associated with a significantly increased risk of a hypersensitivity reaction to abacavir.
Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure.
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 Abavir twice daily (twice the currently recommended dose), oral methadone clearance increased. 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.
Serious and sometimes fatal hypersensitivity reaction. In one trial, once-daily dosing of abacavir was associated with more severe hypersensitivity reactions, Lactic acidosis and severe hepatomegaly, Immune reconstitution syndrome, Fat redistribution and Myocardial infarction.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of Abavir. 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 Abavir.
Body as a whole: Redistribution/accumulation of body fat.
Cardiovascular: Myocardial infarction.
Hepatic: Lactic acidosis and hepatic steatosis.
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.
Dosage & Administration
The recommended oral dose of Abavir for adults is 600 mg daily, administered as either 300 mg twice daily or 600 mg once daily, in combination with other antiretroviral agents.
The recommended oral dose of Abavir Oral Solution in HIV-1-infected pediatric patients aged 3 months and older is 8 mg/kg twice daily (up to a maximum of 300 mg twice daily) in combination with other antiretroviral agents.
Before prescribing Abavir Tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow Abavir Tablets, the oral solution formulation should be prescribed.
Patients with Hepatic Impairment
The recommended dose of Abavir in patients with mild hepatic impairment (Child-Pugh score 5 to 6) is 200 mg twice daily. To enable dose reduction, Abavir 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, Abavir is contraindicated in these patients.
Abacavir tablets should be stored between 20-25oC and protected from light.
Keep all medicines out of the reach of children.