Idiosyncratic effects

Sulfasalazine is associated with various adverse effects, most of which are thought to be due to the sulfapyridine component. Common adverse effects that may be dose related include headache, dyspepsia, nausea, vomiting, and fatigue.19 Idiosyncratic effects include bone marrow suppression, reduction in sperm counts in males, hepatitis, and pulmonitis. Hypersensitivity reactions may occur in patients allergic to sulfonamide-containing medications. 

The adverse, toxic effects of drugs can be divided into one of two t5rpes, A and B. Type A adverse reactions are due to the pharmacological (therapeutic) effect of the drug and are therefore usually predictable and related to the dose. They are usually exaggerated therapeutic effects. Type B are unexpected, idiosyncratic effects. 

The authors of a case report suggested that pegylated hposomal doxorubicin was the probable cause of hepatic failure in a patient who, 2 weeks after treatment with pegylated liposomal doxorubicin 10 mg/m (cumulative dose 20 mg/m ) (15), developed jaundice and ascites (31). Despite withdrawal of other potentially hepato-toxic drugs, the patient died of hepatorenal failure 12 weeks later. This may have been an idiosyncratic effect augmented by hepatitis B viral infection (15,32), as there have been no other reports of hepatorenal failure (14,33). 

Gastric upset from CBZ may be diminished by taking the drug after meals. Common toxicities include blurred vision, dizziness, drowsiness, and ataxia. Tremor, depression, hyponatremia, and cardiac disturbances are seen at high serum concentrations. Idiosyncratic rashes are common rarer severe idiosyncratic effects include aplastic anemia, agranulocytosis, thrombocytopenia, and jaundice. Therefore, patients receiving CBZ should have periodic blood count determinations and liver function tests. Both CBZ and oxcarbazepine can reduce plasma 25-hydroxy vitamin D levels (45). CBZ increases levels of phenytoin and decreases levels of... 

Erythromycin is a known inhibitor of the cytochrome P450 isoenzyme CYP3A4. However, this isoenzyme has only a minor role in the metabolism of warfarin , (p.358), specifically the less active R-isomer of warfarin. Consequently, only minor increases in the levels of warfarin have been seen in pharmacokinetic studies, which would generally not be expected to be clinically relevant. However, it is possible that even these small changes might be important in a very few patients, particularly those with a low prothrombin complex aetivity. Other macrolides (azithromycin, clarithromycin, dirithromycin, roxithromycin) have less effect on CYP3A4 than erythromycin, and consequently would be expected to have even less effect on the pharmacokinetics of warfarin or acenocoumarol, which is borne out in the few studies available. Nevertheless, cases of interactions have been reported for nearly all these macrolides. Moreover, one cohort study found that clarithromycin increased the risk of an interaction and erythromycin did not. It is possible that there is some other, as yet unidentified, mechanism involved. Alternatively, it is equally possible that the relatively few cases just represent idiosyncratic effects attributable to other factors, and not to any interaction (see also Coumarins -i- Antibacterials , p.365). 

Other Precautions Special considerations for use are identified in this field. These may include, for example, common idiosyncratic effects (e.g., allergic reactions), adverse effects that may be undesirable but are not typically dangerous, or other conditions that require some specific caution, as stated. 

Idiosyncratic psychomimetic effects have been reported in the literature once previously. It is postulated to be a GABAergic effect. Etomidate binds to GABA subunit p2 to produce sedation and p3 to produce hypnosis and immobility. An idiosyncratic effect of agitation and movement may also be seen. Midazolam was ineffective as, also being a GABA receptor blocker it may produce an additive effect to etomidate. 

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