Adverse drug reactions rechallenge

Diplopia may be an early sign of generalized drug-induced muscle dysfunction. Altogether, 71 cases of diplopia, possibly related to various HMG-CoA inhibitors, have been collected from adverse drug reactions-report-ing databases. The information was mostly too scanty to judge a causal relation, but improvement occurred in 33 on withdrawal, and two patients had positive rechallenge data (52). 

Girard M. Conclusiveness of rechallenge in the interpretation of adverse drug reactions. Br J Clin Pharmacol 1987 23 73-9. 

In a review of definite or probable drug-associated pancreatitis spontaneously reported to the Dutch adverse drug reactions system during 1977-98, azathioprine was the suspected drug in four of 34 patients, two of whom had positive rechallenge (37). Although most of the carefully described reports of azathioprine-induced pancreatitis were found in patients with inflammatory bowel disease, transplant recipients can also suffer this complication. 

The relative contributions of amoxicillin and clavula-nate to co-amoxiclav-induced hepatotoxicity are incompletely understood. In patients with co-amoxiclav hepatotoxicity, previous use of amoxicillin and rechallenge with amoxicillin were both uneventful, pointing to clavulanic acid as the more likely culprit (16). In a report from the UK, the incidence of liver injury with amoxicillin alone was 0.3 per 10000 prescriptions versus 1.7 with co-amoxiclav (32). The risk increased after multiple use and with increasing age to 1 per 1000 prescriptions of co-amoxiclav. The main message is that the combination should be used with caution in elderly patients. A patient who has had documented hepatotoxicity related to co-amoxiclav should be well informed about this adverse drug reaction and any future use should be prohibited. 

A definite case of pancreatitis proven by positive rechallenge was also briefly cited in a review of drug-associated pancreatitis spontaneously reported to the Dutch adverse drug reactions system (261). 

Factors that indicate a causal association between triazolam and adverse behavioral reactions include corroborating case reports and sleep laboratory studies in the literature, reports of reactions in otherwise normal persons, acute onset and temporal relationship to reactions with initial dose, spontaneous recoveries and return to normalcy with drug discontinuation, and occurrences of positive rechallenge. Also, the high benzodiazepine receptor affinity with triazolam has been postulated as a possible biological mechanism. 

Many re-challenges occur accidentally and do not fulfil the full criteria mentioned above. Rechallenge should only be undertaken when the patient has recovered completely from the first reaction. Re-challenge means that precisely the same drug, in the same formulation, at the same dose is given to the patient again, for as long as is reasonable to re-produce the adverse effect. The aim is to see if the same effect is produced under controlled conditions. It is important to differentiate this from re-exposure. Re-exposure is an accidental event in... 

The most common adverse effects associated with enfuvirtide therapy are local injection site reactions. Hypersensitivity reactions may rarely occur, are of varying severity, and may recur on rechallenge. Eosinophilia has also been noted. In one prospective clinical trial, an increased rate of bacterial pneumonia was noted in patients receiving enfuvirtide. No interactions have been identified that would require the alteration of the dosage of other antiretroviral drugs. 

In rechallenge, the drug is given again to see if the adverse reaction can be repeated. 

The main varieties of adverse effects attributed to cimetidine relate to its antiandrogenic properties and its actions in sufficient concentrations on the central nervous system. There is also a spectrum of drug interactions, mainly attributable to inhibition of hepatic CYP isoforms, but they only have clinical consequences under special circumstances. Occasional adverse effects, which are generally minor, include bradycardia and conduction defects, thrombocytopenia, neutropenia, interstitial nephritis, mild hepatic dysfunction, and headache. Intestinal infection due to loss of the gastric acid barrier also occurs, and myalgia, fever, monoamine oxidase-Uke interactions, and neuropathies have been well documented occasionally. Allergic reactions, such as bronchospasm, have rarely been described. Anaphylaxis with recurrence on rechallenge is on record, as are asthma and skin effects. 

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