Quinagolide efficacy and tolerability in hyperprolactinaemic patients who are resistant to or intolerant of bromocriptine

Abstract

Objective: To audit the efficacy of quinagolide (CV205-502, Norprolac, Sandoz) in lowering prolactin, and its tolerability, in patients with bromocriptine resistance (BCR) or bromocriptine intolerance (BCI), in view of the paucity of results published in patients specifically with BCR or BCI, by collating results in our own patients with the reports in the literature.

Design: Open prospective, uncontrolled administration of quinagolide in patients with BCR (defined for this report as failure to attain normal prolactin levels after 4 months of bromocriptine at maximum tolerated doses), or BCI (defined as a patient request to cease bromocriptine treatment because of side-effects at doses that were required, or failed, to normalize PRL levels).

Measurements: Prolactin levels, menses or pregnancy, and side-effects.

Patients: Six with BCR, and six with BCI (microprolactinoma in 7, macroprolactinoma in 5), treated with quinagolide 75 micrograms nightly increasing incrementally to a maximum of 450 micrograms. One patient who had taken part in a multicentre study of quinagolide in macroprolactinomas had BCI, and 11 further patients in the endocrine clinic who had BCR or BCI were offered quinagolide therapy under named-patient compassionate arrangements.

Results: Normal prolactin in 4/5 with BCR (3/6 with side-effects, none of them quinagolide intolerant), and normal prolactin in 2/6 with BCI (4/6 with side-effects, two of them quinagolide intolerant).

Conclusions: Results in our 12 patients are broadly in line with those in 51 patients with bromocriptine resistance and 39 with bromocriptine intolerance extracted from various published reports, which together suggest that prolactin can be normalized in 16% of patients with bromocriptine resistance by quinagolide in doses of 225 micrograms or less, and in a further 20% by higher doses up to 600 micrograms. In bromocriptine intolerance, prolactin was normalized by quinagolide in doses of 225 micrograms or less in 58% of published cases and in 3 more patients by higher doses up to 1050 micrograms. About half the patients with bromocriptine resistance or bromocriptine intolerance who are treated with quinagolide experience side-effects, and around 7% are quinagolide intolerant. Doses need not exceed 225 micrograms, until failure to respond at this dose level is demonstrated.