This paper reviews the epidemiology and pathogenesis of clozapine-associated agranulocytosis. According to present clinical experience, granulocytopenia can be expected in approximately 3% of patients during clozapine treatment. The risk of serious sequelae of granulocytopenia can be minimised by regular white blood cell count monitoring. Although research suggests that some patient groups may be at higher risk of developing this serious adverse reaction, we cannot yet predict the susceptible patients, so all patients exposed to clozapine should receive regular blood monitoring throughout treatment. Because of the risk of agranulocytosis, clozapine should only be used in schizophrenic patients who are resistant to, or intolerant of, conventional antipsychotic medications. Unless compliance with blood monitoring is assured, clozapine treatment should not be recommended.
Since Bromocriptine is used to restore fertility in hyperprolactinemic women, its safety in pregnancy and the offspring was investigated in a stepwise approach: (i) the first survey in pregnancy was based on spontaneous reporting, (ii) the second investigation was conducted at 33 clinics as an intensive monitoring project and, (iii) the third study consisted in a full examination of children up to the age of 9 years who had been exposed to Bromocriptine in utero. The data collated in this program includes information on 2587 pregnancies in 2437 women treated with Bromocriptine during some stage of gestation, and follow-up examinations for 988 infants. The results show that the use of Bromocriptine in the treatment of infertility in women is not associated with an increased risk of spontaneous abortion, multiple pregnancy or the occurrence of congenital malformation in their progeny. Moreover, exposure to this drug in utero has no adverse influence on the postnatal development.
This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to-moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential.
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