ABACAVIR ACCORD

Abacavir should be prescribed by physicians experienced in the management of HIV infection. Abacavir can be taken with or without food. To ensure administration of the entire dose, the tablet(s) should ideally be swallowed without crushing.

Abacavir may also be available as an oral solution for use in children over three months of age and weighing less than 14 kg and for those patients for whom the tablets are inappropriate. 2).

Adults, adolescents and children (weighing at least 25 kg):

The recommended dose of Abacavir is 600 mg daily. 1).

Children (weighing less than 25 kg):

Dosing according to weight bands is recommended for Abacavir tablets.

Children weighing ≥ 20 kg to < 25 kg:

The recommended dose is 450 mg daily. This may be administered as either one 150 mg (one half of a tablet) taken in the morning and 300 mg (one whole tablet) taken in the evening, or 450 mg (one and a half tablets) taken once daily.

Children weighing 14 to < 20 kg:

The recommended dose is 300 mg daily. This may be administered as either 150 mg (one half of a tablet) twice daily or 300 mg (one whole tablet) once daily. 2). Patients changing from the twice daily dosing regimen to the once daily dosing regimen should take the recommended once daily dose (as described above) approximately 12 hours after the last twice daily dose, and then continue to take the recommended once daily dose (as described above) approximately every 24 hours.

When changing back to a twice daily regimen, patients should take the recommended twice daily dose approximately 24 hours after the last once daily dose. Special populations Renal impairment No dosage adjustment of Abacavir is necessary in patients with renal dysfunction.

2). Hepatic impairment Abacavir is primarily metabolised by the liver. No definitive dose recommendation can be made in patients with mild hepatic impairment (Child- Pugh score 5-6). In patients with moderate or severe hepatic impairment, no clinical data are available, therefore the use of abacavir is not recommended unless judged necessary.

8 Description of selected adverse reactions). Restarting abacavir in such patients must be done in a setting where medical assistance is readily available. Mitochondrial dysfunction following exposure in utero Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues; these have predominantly concerned treatment with regimens containing zidovudine. The main adverse reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipasemia).

These events have often been transitory. Late-onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are transient or permanent is currently unknown. These findings should be considered for any child exposed in utero to nucleotide and nucleotide analogues, who presents with severe clinical findings of unknown etiology, particularly neurologic findings.

These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV. Weight and metabolic parameters An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy.

Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring of blood lipids and glucose reference is made to established HIV treatment guidelines.

Lipid disorders should be managed as clinically appropriate. Pancreatitis Pancreatitis has been reported, but a causal relationship to abacavir treatment is uncertain. 1). There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when abacavir was combined with tenofovir disoproxil fumarate and lamivudine as a once daily regimen.

8) characterised by fever and/or rash with other symptoms indicating multi-organ involvement. HSRs have been observed with abacavir, some of which have been life- threatening, and in rare cases fatal, when not managed appropriately.

The risk for abacavir HSR to occur is high for patients who test positive for the HLA- B*5701 allele. However, abacavir HSRs have been reported at a lower frequency in patients who do not carry this allele. Therefore the following should be adhered to: • HLA-B*5701 status must always be documented prior to initiating therapy.

g. abacavir/lamivudine, abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine). • Abacavir must be stopped without delay, even in the absence of the HLA- B*5701 allele, if an HSR is suspected. Delay in stopping treatment with abacavir after the onset of hypersensitivity may result in a life-threatening reaction.

g. abacavir/lamivudine, abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine) must never be re-initiated. • Restarting abacavir containing products following a suspected abacavir HSR can result in a prompt return of symptoms within hours.

This recurrence is usually more severe than on initial presentation, and may include life- threatening hypotension and death. • In order to avoid restarting abacavir, patients who have experienced a suspected HSR should be instructed to dispose of their remaining Abacavir Accord tablets.

Clinical description of abacavir HSR Abacavir HSR has been well characterised through clinical studies and during post marketing follow-up. Symptoms usually appeared within the first six weeks (median time to onset 11 days) of initiation of treatment with abacavir, although these reactions may occur at any time during therapy.

Almost all HSR to abacavir include fever and/or rash. 8 (Description of selected adverse reactions), including respiratory and gastrointestinal symptoms. Importantly, such symptoms may lead to misdiagnosis of HSR as respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis.

1. 8.