Strategies for the Detection and Prevention of Idiosyncratic Haematological ADRS

STRATEGIES FOR THE DETECTION AND PREVENTION OF IDIOSYNCRATIC HAEMATOLOGICAL ADRS

INDIVIDUAL MONITORING

Regular full blood count (FBC) monitoring is clearly indicated when drugs associated with type A haematological ADR, such as cytotoxic agents, are prescribed. For idiosyncratic reactions, early warning rather than prevention is the main goal. For a small number of drugs with a significant risk of myelosup-pression, regular monitoring, as for cytotoxic therapy, is required or desirable (Table 34.3). Patient and carer education in the significance of symptoms sugges-tive of infection, bleeding and anaemia are again important. Monitoring may prevent a minor cytope-nia developing into a more severe aplasia by indi-cating the discontinuation of gold or penicillamine therapy where a prodromal gradual count reduction may precede a severe reaction. Monitoring itself will clearly not prevent a suddenly precipitate agranulocy-tosis with, e.g., antithyroid drugs, which may occur in between even quite frequent monitoring visits. It does however reinforce patient education in the potential complication, and their access to FBC increasing the likelihood of early detection.

The case for routine surveillance monitoring with antithyroid drugs is controversial (Drug and Therapeutics Bulletin, 1997a,b). A prospective study in Japan found a 0.4% incidence of agranulocyto-sis occurring within the first 3 months of treatment with methimazole or propylthiouracil, and 43 of 55 the affected patients were detected by routine moni-toring before the onset of symptoms (Tajiri et al., 1990). Counts recovered in all the patients, and 29 did not develop any infection. Monitoring clearly allowed the prevention of a potentially dangerous complication for a significant group of patients in this study, but the pharmacoeconomic justification for routine monitoring in this situation is not universally accepted.

INDIVIDUAL RISK-FACTOR IDENTIFICATION

In addition to FBC monitoring, pre-treatment assess-ment of TPMT either by enzyme activity or by genetic markers before azathioprine or 6-MP treatment and MTHFR status before MTX therapy, as discussed above, may assist prevention. It is likely that addi-tional predictive tests will become applicable as phar-macogenetic knowledge increases.

SPONTANEOUS REPORTING

The notification of suspected occurrences of drug-induced myelosuppression to national licensing authorities is an important contribution to prevention, and particularly important for idiosyncratic reactions to new agents. The UK ‘Yellow Card’ scheme informs an ADRs On-line Information Tracking (ADROIT) database that captures all reports for separate drugs and categorises haematological reactions into non-serious, serious and fatal categories. Whilst such data, which have no reliable numerator, cannot define inci-dences of reactions, they can highlight suspicions of new potentially significant reactions and follow trends in frequency and severity of established reactions.