Ziagen Adverse Reactions

For many adverse reactions reported, it is unclear whether they are related to Ziagen, to the wide range of medicinal products used in the management of HIV infection or as a result of the disease process.
Many of the adverse reactions listed as follows occur commonly (nausea, vomiting, diarrhoea, fever, lethargy, rash) in patients with abacavir hypersensitivity. Therefore, patients with any of these symptoms should be carefully evaluated for the presence of this hypersensitivity (see Warnings). Very rarely cases of erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported where abacavir hypersensitivity could not be ruled out. In such cases medicinal products containing abacavir should be permanently discontinued.
Many of the adverse reactions have not been treatment limiting. The following convention has been used for their classification: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000), very rare (<1/10,000).
Metabolism and nutrition disorders: Common: anorexia.
Very rare: lactic acidosis.
Nervous system disorders: Common: headache.
Gastrointestinal disorders: Common: nausea, vomiting, diarrhoea.
Rare: pancreatitis.
Skin and subcutaneous tissue disorders: Common: rash (without systemic symptoms).
Very rare: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
General disorders and administration site conditions: Common: fever, lethargy, fatigue.
Description of Selected Adverse Reactions: Abacavir hypersensitivity reactions: The signs and symptoms of this HSR are listed as follows. These have been identified either from clinical studies or post marketing surveillance. Those reported in at least 10% of patients with a hypersensitivity reaction are in bold text.
Almost all patients developing hypersensitivity reactions will have fever and/or rash (usually maculopapular or urticarial) as part of the syndrome, however reactions have occurred without rash or fever. Other key symptoms include gastrointestinal, respiratory or constitutional symptoms such as lethargy and malaise.
Skin: Rash (usually maculopapular or urticarial).
Gastrointestinal tract: Nausea, vomiting, diarrhoea, abdominal pain, mouth ulceration.
Respiratory tract: Dyspnoea, cough, sore throat, adult respiratory distress syndrome, respiratory failure.
Miscellaneous: Fever, lethargy, malaise, oedema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis.
Neurological/Psychiatry: Headache, paraesthesia.
Haematological: Lymphopenia.
Liver/pancreas: Elevated liver function tests, hepatitis, hepatic failure.
Musculoskeletal: Myalgia, rarely myolysis, arthralgia, elevated creatine phosphokinase.
Urology: Elevated creatinine, renal failure.
Symptoms related to this HSR worsen with continued therapy and can be life-threatening and in rare instance, have been fatal.
Restarting abacavir following an abacavir HSR results in a prompt return of symptoms within hours. This recurrence of the HSR is usually more severe than on initial presentation, and may include life-threatening hypotension and death. Similar reactions have also occurred infrequently after restarting abacavir in patients who had only one of the key symptoms of hypersensitivity (see as previously mentioned) prior to stopping abacavir; and on very rare occasions have also been seen in patients who have restarted therapy with no preceding symptoms of a HSR (i.e., patients previously considered to be abacavir tolerant).
Metabolic parameters: Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see Precautions).
Immune reactivation syndrome: In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART) an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. 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 (see Precautions).
Osteonecrosis: Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see Precautions).
Changes in laboratory chemistries: In controlled clinical studies laboratory abnormalities related to Ziagen treatment were uncommon, with no differences in incidence observed between Ziagen treated patients and the control arms.
Paediatric population: 1206 HIV-infected paediatric patients aged 3 months to 17 years were enrolled in the ARROW Trial (COL105677), 669 of whom received abacavir and lamivudine either once or twice daily (see Pharmacology: Pharmacodynamics under Actions). No additional safety issues have been identified in paediatric subjects receiving either once or twice daily dosing compared to adults.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.