Ziagen Adverse Reactions

For many of the other adverse events reported, it is unclear whether they are related to ZIAGEN, to the wide range of medicinal products used in the management of HIV disease or as a result of the disease process.
Many of those listed as follows (nausea, vomiting, diarrhoea, fever, fatigue, rash) occur commonly as part of ZIAGEN hypersensitivity. Therefore, patients with any of these symptoms should be carefully evaluated for the presence of this hypersensitivity reaction. If ZIAGEN has been discontinued in patients due to experiencing any one of these symptoms and a decision is made to restart ZIAGEN, this should be done only under direct medical supervision (see "Special considerations following an interruption of ZIAGEN therapy" under Precautions).
The majority of the adverse reactions listed as follows have not been treatment limiting. The following convention has been used for their classification: very common (more than 1/10), common (more than 1/100, less than 1/10), uncommon (more than 1/1,000, less than 1/100), rare (more than 1/10,000, less than 1/1,000) very rare (less than 1/10,000).
Clinical Trial Data: Metabolism and nutrition disorders: Common: anorexia.
Nervous system disorders: Common: headache.
Gastrointestinal disorders: Common: nausea, vomiting, diarrhoea.
General disorders and administration site disorders: Common: fever, lethargy, fatigue.
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: The safety database to support abacavir once daily dosing in paediatric patients comes from the ARROW Trial (COL105677) in which 669 HIV-1 infected paediatric subjects received abacavir and lamivudine either once or twice daily (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). No additional safety issues have been identified in paediatric subjects receiving either once or twice daily dosing compared to adults.
Postmarketing Data: Metabolism and nutrition disorders: Common: hyperlactataemia. Rare: lactic acidosis (see Precautions).
Gastrointestinal disorders: Rare: pancreatitis has been reported, but a causal relationship to ZIAGEN treatment is uncertain.
Skin and subcutaneous tissue disorders: Common: rash (without systemic symptoms). Very rare: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Description of Selected Adverse Reactions: Hypersensitivity (see Precautions): Abacavir hypersensitivity reaction (HSR) has been identified as a common adverse reaction with abacavir therapy. The signs and symptoms of this hypersensitivity reaction 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, fatigue, malaise, oedema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis.
Neurological/Psychiatry: Headache, paraesthesia.
Haematological: Lymphopenia.
Liver/pancreas: Elevated liver function tests, hepatic failure.
Musculoskeletal: Myalgia, rarely myolysis, arthralgia, elevated creatine phosphokinase.
Urology: Elevated creatinine, renal failure.
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. Reactions have also occurred infrequently after restarting abacavir in patients who had only one of the key symptoms of hypersensitivity (see 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).
For details of clinical management in the event of a suspected abacavir HSR see Precautions.