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Drugline nr 22657

Publicerat 2005-06-17

Question

Is cabergoline (Dostinex) therapy compatible with pregnancy and lactation?

A 32-year-old woman is pregnant. Her first day of the last menstruation period was six weeks ago. She is currently treated for at prolactinoma with cabergoline (Dostinex) 0.25 mg once weekly.

Answer

Cabergoline is a dopamine agonist used in hyperprolactinemic states. Teratology testing has been performed in mice and rabbits, and no increase in congenital malformations was found at maternal doses up to 8.0 mg/kg/day. A report on 226 pregnancies occurring in 205 women treated with cabergoline has appeared. Follow-up on 204 of these pregnancies showed 24 miscarriages and five fetuses or infants with major malformations. These figures do not suggest an increase compared to general population rates and no pattern of malformations was evident. In 107 babies followed for at least a month (61 for at least a year), there was no evidence of abnormal development (1). Adequate and well controlled studies in humans have not been done (2). Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed (3).

A study of 2587 pregnancies, in which bromocriptine was given in the first weeks indicated a slight increase in the rate of early miscarriages, but there was no increase in the rate of birth defects. Because most women stop therapy as soon as pregnancy is confirmed, this study also suggests that continuing hyperprolcatinemia has no adverse effect on the developing fetus (4).

After conception, the medication as a rule should be discontinued. However, continuing treatment is neither ground for a termination of pregnancy nor for invasive diagnostic procedures (4).

Dopamine agonists reduce the milk production (5).

Based on data collected using a radio labelled form of cabergoline administered to lactating rats, this compound may be accumulated in milk. A maximum milk plasma ratio of six was found in this study (1). The experience, up to now, on tolerance in the infant is insufficient for a risk assessment (6).

Following a dosage of 2.5 mg bromocriptine, less than 0.1 ug/l can be expected to appear in the mothers milk. This represents 0.04% of the maternal weight-related dosage. Intolerance in the breast fed infant, even with prolactinoma treatment, has not been observed. If treatment with a dopamine agonist during breast feeding is necessary, bromocriptine would be the drug of choice (6).

Ending the treatment with dopamine agonist should be done with caution, as there is a risk of growth of the prolactinoma during pregnancy (7). The effect of breast feeding on the growth of the prolactinoma appears to be more limited than that of the pregnancy, so that an interruption of dopamine agonist treatment during breast feeding can be considered (6,8).

Conclusion

No teratogen effect has been seen in laboratory animals or humans when cabergoline is given during pregnancy, but the human material is sparse. There exist more documentation in regard to the use of bromocriptine during pregnancy. If possible, it is recommended to withdraw the treatment during pregnancy.

Dopamine agonists reduce the amount of milk. Cabergoline should not be used during lactation, as it is found in the milk in considerable concentration. Bromocriptine is only found in small amounts in the milk and can be used during lactation, if treatment is necessary.

Change of drug or withdrawal of treatment requires special knowledge, as there is a risk that the prolactinoma might grow.

Damkier P
Brodbaek H

References

  1. Cabergoline. REPROTOX(R) in Reprorisk System. Thomson MICROMEDEX, Greenwood Village, Colorado (Edition expires 05/06).
  2. Cabergoline (Systemic). In: USP DI(R) Drug Information for the Health Care Professional. Thomson MICROMEDEX, Greenwood Village, Colorado (Cited 05-06-20).
  3. Dostinex Tablets (Pharmacia & Upjohn). In: Physician´s Desk Reference(R). Thomson MICROMEDEX, Greenwood Village, Colorado (Edition expires 06/05).
  4. Schaefer C, editor. Drugs during pregnancy and lactation. Handbook of prescription drugs and comparative risk assessment. Amsterdam: Elsevier; 2001:134.
  5. Schaefer C, editor. Drugs during pregnancy and lactation. Handbook of prescription drugs and comparative risk assessment. Amsterdam: Elsevier; 2001:259.
  6. Schaefer C, editor. Drugs during pregnancy and lactation. Handbook of prescription drugs and comparative risk assessment. Amsterdam: Elsevier; 2001:284.
  7. Prolactinomer og hyperprolactinæmi. Instruks fra Endokrinologisk Afdeling, Herlev Sygehus. Citeret fra www.endoherlev.dk (Cited 05-06-21).
  8. Holmgren U, Bergstrand G, Hagenfeldt K, Werner S. Women with prolactinoma--effect of pregnancy and lactation on serum prolactin and tumour growth. Acta Endocrinol. 1986;111(4):452-9.

Senast ändrad 2018-09-20