QUINAGOLIDE SUMMARY SHEET TRADE NAME: Norprolac Licensed

This drug has been "archived" and will not be actively updated except for a compelling reason or request (August 2005).

QUINAGOLIDE

SUMMARY SHEET

TRADE NAME: Norprolac

Licensed Indication:

‘Hyperprolactinaemia (idiopathic or originating from a prolactin secreting pituitary microadenoma or macroadenoma)’

Background Information:

Hyperprolactinaemia is a relatively common endocrine disorder which occurs more frequently in women. The underlying causes are numerous including physiological causes, drug induced and idiopathic disease. Most commonly a primary tumour (micro- or macroadenoma) is responsible.1,2

Bromocriptine has formed the mainstay of treatment for hyperprolactinaemia for over 20 years. It significantly reduces serum prolactin levels, causes shrinkage of pituitary tumours and produces a rapid improvement of symptoms in most of these patients. Unfortunately, patients can be resistant to or intolerant of (up to 5%) bromocriptine. Recently both cabergoline and quinagolide, two long acting dopamine agonists, have been launched in the UK.2

Clinical Efficacy

Numerous studies in small groups of patients have confirmed the efficacy of quinagolide in the management of hyperprolactinaemia. In an open study, where the identity of the trial drug was known to both patients and investigators, conducted over 24 months, 24 women with hyperprolactinaemia were treated with quinagolide. The dose was titrated according to individual patient response. At 24 months only 15 patients were still receiving treatment, 5 withdrew due to pregnancy, 3 for social reasons and 1 due to treatment resistance. All 15 treated patients had normal serum prolactin levels, 13 had regular menstrual bleeding and 3 were still suffering with mild galactorrhoea. 7 of these women reported mild side effects.3

In a similarly open designed study the efficacy of 12 months quinagolide treatment in 128 patients with macroprolactinaemias was evaluated. Unfortunately the collective results have not been published. Where the separate studies are published, efficacy in reducing serum prolactin levels, relief from galactorrhoea, improved libido and potency and return of regular menses is reported in more than 50% of patients.4

A literature review evaluated the efficacy of quinagolide in bromocriptine intolerant or resistant patients with hyperprolactinaemia. 91 treatment episodes were identified. In 35% of resistant patients and 66% of intolerant patients, quinagolide treatment normalised the serum prolactin level. About 50% of patients suffered side effects but these were not serious enough to warrant treatment withdrawal.5

Comparative trials with bromocriptine, again in small groups of patients, of up to 12 months have demonstrated comparative efficacy in suppressing prolactin levels, relieving galactorrhoea, restoring regular menstrual cycles and fertility. The reported incidence and type of adverse effects was similar for both treatments although tolerability was considered to be improved with quinagolide.6,7,8

An open randomised crossover study compared 12 weeks treatment with cabergoline 0.5mg twice weekly and quinagolide 0.075mg once daily. 11 of 12 patients completed treatment with cabergoline and 10 of 12 treatment with quinagolide. Normalisation of the serum prolactin levels occurred in 10 patients on cabergoline and 6 on quinagolide, with no apparent difference in terms of effect on menstrual cycle. 5 patients on cabergoline and 9 on quinagolide reported side effects. These were usually mild and resolved in the first week of treatment. A larger trial with individual dose titration is required to clarify the possible difference in efficacy between these products.9

Adverse Effects

These are most common during the early stages of treatment and following dosage increases. Most frequently nausea, vomiting, headaches, dizziness and fatigue are seen. Hypotensive reactions including orthostatic hypotension can occur and lead to reduced alertness. Clinicians are advised to check patients blood pressure for the first few days after initiating quinagolide treatment and following any dosage increases.

Less frequently anorexia, abdominal pain, constipation, diarrhoea, insomnia, oedema, flushing and nasal congestion have been reported.

Sandoz have received reports of 13 cases of psychotic reactions following quinagolide treatment, in a total of 3001 patients. These reactions can occur in patients with no previous history of mental illness. Depression and anxiety are reported most frequently and are usually seen 6-12 months after commencing treatment. In all cases to-date, these reactions have been reversible upon discontinuation of quinagolide.10

No information is available on the long term safety of quinagolide in patients treated, or children conceived, following treatment. The company are currently aware of 176 pregnancies where quinagolide treatment was continued in pregnancy for a median duration of 37 days. Of the 176 pregnancies 115 children were delivered, 14 were terminated, 24 were spontaneously aborted, one was an ectopic pregnancy and there was one still birth. In the 115 delivered children, 9 had malformatioins of variable types diagnosed and 6 presented with various perinatal disorders. The outcome of the remaining pregnancies is unknown. None of these children has subsequently been followed up by the company. Quinagolide is currently contra-indicated in pregnancy due to insufficient evidence of safety.

Drug Interactions

No drug interactions have been identified to-date. Care is advised with drugs that act at the dopaminegic or serotonin receptors.

Health Economics

No useful economic data on the treatment of hyperprolactinaemia with quinagolide is apparent in the literature. Quinagolide 0.075mg once daily costs £53.20 for one month’s treatment at current prices.

Conclusion

Quinagolide has only been studied in small groups of patients for limited periods of time. However, it appears to be as effective as bromocriptine in the management of hyperprolactinaemia and may offer some advantage for patients who are intolerant or resistant to bromocriptine treatment. Of major concern is the lack of long term safety data in these patients and their children (if conceived during quinagolide treatment). This is required before widespread prescribing can be undertaken safely.

References

1. Jones TH. The Management of Hyperprolactinaemia. Br. J. Hosp. Med. 1995; 53: 374-378. 2. Sarapura V & Schlaff WD. Recent Advances in the Understanding of the Pathophysiology and Treatment of Hyperprolactinaemia. Curr. Opin. Obstet. Gynecol. 1993; 5: 360-367.

3. Rasmusson C, Brownell J & Bergh T. Clinical Response and Prolactin Concentration in Hyperprolactinemic Women during and after treatment for 24 months with the new Dopamine Agonist. CV205-502.

4. Anon. Norprolac. Product Information on the Clinical Efficacy of Norprolac on Macroadenomas. Sandoz Product Summary September 1994.

5. Vilar L & Burke CW. Quinagolide Efficacy and Tolerability in Hyperprolactinaemic patients who are Resistant to or Interolerant of Bromocriptine. Clin. Endocrinol. 1994; 41: 821-826.

6. Van der Heijden PFM, de Wit W, Brownell J, Schoermaker J & Rolland R. CV205-502, a New Dopamine Agonist versus Bromocriptine in the treatment of Hyperprolactinaemia. Eur. J. Obstet. Gynecol. Reprod. Biol. 1991; 40: 111-118.

7. Homburg R, West C, Brownell J & Jacobs H. A Double Blind Study Comparing a New Non-Ergot, Long-Acting Dopamine Agonist CV205-502 with Bromocriptine in Women with Hyperprolactinaemia. Clin. Endocrinol. 1990; 32: 565-571.

8. Verhelst JA, Froud AL, Touzel R, Wass JAH, Besser GM & Grossman AB. Acute and Long-Term Effects of Once-Daily Oral Bromocriptine and a New Long-Acting Non-Ergot Dopamine Agonist, Quinagolide in the Treatment of Hyperprolactinaemia: A Double-Blind Study. Acta. Endocrinologica 1991; 125: 385-391.

9. Giusti M, Porcella E, Carroro A, Cuttia M, Valenti S & Geiordano G. A Cross-over Study with the Two Novel Dopaminegic Drugs Cabergoline and Quinagolide in Hyperprolactinaemic Patients. J. Endocrinol. Invest. 1994; 17: 51-57.

10. Personal correspondence. Sandoz. November 1995.

Date: November 1995 SS95/14