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.
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.
Liver disease The safety and efficacy of Ziagen has not been established in patients with significant underlying liver disorders. 2). Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy, and should be monitored according to standard practice.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered. Patients co-infected with chronic hepatitis B or C virus Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse reactions.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products. 2). Excipients Ziagen oral solution contains 340 mg/ml of sorbitol. When taken according to the dosage recommendations each 15 ml dose contains approximately 5 g of sorbitol.
Patients with rare hereditary problems of fructose intolerance should not take this medicine. Sorbitol can have a mild laxative effect. 6 kcal/g. Ziagen oral solution also contains methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed).
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’. Immune Reactivation Syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterium infections, and Pneumocystis carinii pneumonia.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to CART.
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement. Opportunistic infections Patients receiving Ziagen or any other antiretroviral therapy may still develop opportunistic infections and other complications of HIV infection.
Therefore patients should remain under close clinical observation by physicians experienced in the treatment of these associated HIV diseases. Myocardial Infarction Observational studies have shown an association between myocardial infarction and the use of abacavir.
Those studied were mainly antiretroviral experienced patients. Data from clinical trials showed limited numbers of […]