Bromocriptine is used in males and females for the treatment of dysfunctions associated with hyperprolactinemia including amenorrhea, with or without galactorrhea; hypogonadism; and infertility. The drug is used in patients with prolactin-secreting adenomas (e.g., prolactinoma), including macroadenomas; this tumor may be the basic underlying endocrinopathy contributing to dysfunctions associated with hyperprolactinemia. The drug has decreased tumor size in both males and females with macroadenomas and may be used to reduce tumor size prior to surgery in patients undergoing excision of the tumor (adenectomy).
Amenorrhea and Galactorrhea
Bromocriptine mesylate is used for the short-term treatment of amenorrhea and/or galactorrhea associated with hyperprolactinemia of various etiologies. Bromocriptine reduces serum prolactin concentrations in patients with prolactin-secreting adenomas; however, use of the drug in these patients does not obviate the need for radiotherapy or surgery when indicated. Although bromocriptine may be effective in restoring menses in some patients with prolactin-secreting tumors and may decrease tumor growth during pregnancy in patients who have had partial surgical tumor removal, the risks associated with the use of the drug in these patients should be considered.
(See Cautions: Pregnancy and Lactationand also Carcinogenicity.)Bromocriptine is not effective in patients with ovarian failure or inadequate concentrations of gonadotropin. Bromocriptine is not indicated in patients with normal prolactin concentrations although it is effective in the treatment of amenorrhea and/or galactorrhea in some of these patients. Treatment with bromocriptine mesylate is not curative. Following discontinuance of bromocriptine therapy, the recurrence rate of amenorrhea and/or galactorrhea is 70-80%.
Male Hypogonadism and Galactorrhea
Bromocriptine has been used effectively in hyperprolactinemic males with prolactin-secreting adenomas (e.g., prolactinoma) and adequate concentrations of testosterone to treat hypogonadism and galactorrhea which persisted following radiation therapy or surgery. Recent studies indicate that bromocriptine therapy, in addition to relieving symptoms of the disease, also results in a reduction in the size of prolactin-secreting adenomas in most patients. Some clinicians suggest that bromocriptine may be the treatment of choice for hyperprolactinemic males with large tumors (macroadenomas).
Bromocriptine is used to induce ovulation in appropriately selected anovulatory women desiring pregnancy. Although the manufacturer states that bromocriptine is indicated in the treatment of female infertility associated with hyperprolactinemia in the absence of a demonstrable pituitary tumor, some clinicians state that bromocriptine is the treatment of choice to restore fertility in selected patients with prolactin-secreting adenomas. Bromocriptine restores ovulation without ovarian hyperstimulation and the risk of multiple ovulations with resulting plural gestations. However, bromocriptine probably should be reserved for patients who are not responsive to clomiphene, menotropins with chorionic gonadotropin, or estrogens. In some anovulatory women requiring concomitant treatment with 100-150 mg of clomiphene citrate and chorionic gonadotropin to induce ovulation, bromocriptine and a lower dosage of clomiphene have been used effectively to induce ovulation.
Bromocriptine is used for the treatment of idiopathic or postencephalitic parkinsonian syndrome.
Dopamine receptor agonists (bromocriptine mesylate, pramipexole dihydrochloride, pergolide mesylate, ropinirole hydrochloride) are used as adjuncts to levodopa for the symptomatic management of parkinsonian syndrome in patients with advanced disease. Dopamine receptor agonists also are used as monotherapy for the initial symptomatic management of parkinsonian syndrome. Levodopa currently is the most effective drug for relieving the symptoms of parkinsonian syndrome and traditionally has been considered the drug of choice for the initial symptomatic management of idiopathic parkinsonian syndrome. However, long-term administration of levodopa is associated with motor complications. One strategy to reduce the risk of motor complications and to improve long-term outcome is to initiate symptomatic therapy with a dopamine receptor agonist and to add levodopa as supplemental therapy when dopamine receptor agonist monotherapy no longer provides adequate symptom control. However, clinical studies evaluating this strategy are limited both in number and duration, and it remains to be determined whether initiating therapy with a dopamine receptor agonist rather than levodopa results in a more favorable long-term outcome. Factors to consider when choosing an agent for the initial symptomatic management of idiopathic parkinsonian syndrome include patient age, cognitive status, disease severity, and cost. Most clinicians would use levodopa for initial therapy in individuals older than 70 years of age since these individuals are less likely than younger individuals to develop levodopa-related motor complications and because of concerns about cognitive dysfunction, in patients with cognitive impairment, and in those with severe disease. A dopamine receptor agonist may be preferred for initial therapy in patients 70 years of age or younger.
In controlled, double-blind studies in patients receiving optimum treatment of parkinsonian syndrome which included levodopa therapy, addition of bromocriptine allowed a gradual reduction in levodopa (with or without carbidopa) dosage. When used in conjunction with levodopa (alone or with a peripheral decarboxylase inhibitor), bromocriptine may provide additional therapeutic benefits in patients who are currently maintained on optimal dosages of levodopa, patients who are beginning to develop tolerance to levodopa, and patients who are experiencing ''end-of-dose failure'' on levodopa therapy. In several controlled studies, bromocriptine was as effective as levodopa (with or without carbidopa) when bromocriptine was substituted for levodopa in patients who were well controlled on levodopa therapy. Patients unresponsive to levodopa are poor candidates for bromocriptine therapy. Data are insufficient to evaluate the potential benefits of bromocriptine in patients with newly diagnosed parkinsonian syndrome. A higher incidence of adverse effects (e.g., nausea, hallucinations, confusion, hypotension) have been reported in patients receiving bromocriptine than in patients receiving levodopa and carbidopa; however, bromocriptine has a longer duration of action and causes the ''on-off'' phenomenon less often than does levodopa. Bromocriptine may be useful in patients who are unable to tolerate levodopa's adverse effects or when levodopa is ineffective; however, continued efficacy of bromocriptine for more than 2 years has not been established and long-term or high-dose bromocriptine therapy has caused adverse effects such as erythromelalgia and psychosis.
(See Cautions: Nervous System Effects.)Further study is required to determine the precise role of bromocriptine in the treatment of parkinsonian syndrome and to establish safety and efficacy of the drug during long-term administration.
Bromocriptine is used in the treatment of acromegaly. Although bromocriptine is not effective in all patients with acromegaly, the drug has reduced growth hormone concentrations in some patients. Reduction in growth hormone concentrations in these patients is associated with abolition of excessive sweating, reduction in soft tissue thickening, improvement in facial features, improvement in glucose tolerance, and reduction in urinary hydroxyproline excretion. However, further studies are required to determine the long-term effectiveness of bromocriptine in the treatment of acromegaly and to determine which patients may respond to the drug.
Although bromocriptine had been used to prevent lactation after stillbirth or abortion or when breast-feeding was contraindicated or the mother elected not to breast-feed, such use has been controversial (e.g., because of the low incidence of substantial painful engorgement, cost considerations, efficacy of appropriate supportive therapy, and concerns about potentially fatal toxicity) despite efficacy of the drug in inhibiting lactogenesis and the subsequent development of secretion, congestion, and engorgement. In addition, such use of bromocriptine no longer is recommended because of the risks of serious adverse effects (e.g., hypertension, seizures, myocardial infarction, cerebrovascular accidents, which may be fatal) nor is it included in the current US labeling for the drug. In 1994, the US Food and Drug Administration (FDA) proposed formally to withdraw approval of this indication based on accumulating reports of potentially fatal, serious adverse effects. The manufacturer of the drug (Sandoz) subsequently agreed voluntarily to withdraw the mentioned use for lactation prevention from their labeling, and FDA's approval withdrawal was finalized in February 1995. Although the absolute incidence and relative risk of associated serious effects remain to be clearly defined, the decision of FDA to seek withdrawal was based, in part, on conclusions by FDAs Fertility and Maternal Health Drugs Advisory Committee that the possible risks of serious adverse effects outweigh the limited benefits associated with the use of bromocriptine in postpartum breast engorgement, a temporary condition, that can be managed by more conservative treatments (e.g., cold packs, compression bandages, analgesics).
Bromocriptine has been used to relieve premenstrual breast symptoms (e.g., swelling, discomfort, discharge), edema, weight gain, migraine headache, and changes in mood.
Bromocriptine has been used to restore fertility in oligospermic men without hyperprolactinemia. Unlike traditional therapy with fluoxymesterone, testosterone, or chorionic gonadotropin, bromocriptine may increase sperm counts both during and after treatment. However, unless these patients are unresponsive to traditional drug therapy, bromocriptine should not be used since safety and efficacy of the drug for the management of this condition have not been established.
Bromocriptine has been used with some success in the treatment of neuroleptic malignant syndrome (NMS) associated with neuroleptic drug therapy (e.g., haloperidol, fluphenazine). In a limited number of patients, bromocriptine has relieved extrapyramidal reactions, hyperthermia, and hypertension associated with NMS.
In a limited number of patients, bromocriptine has been used effectively in the management of Cushing's disease or chronic hepatic encephalopathy.
Bromocriptine is not effective in the management of Huntington's chorea.