BROMOCRIPTINE MESYLATE- bromocriptine mesylate_tablet

CLINICAL PHARMACOLOGY
Bromocriptine mesylate is a dopamine receptor agonist, which activates post-synaptic dopamine receptors. The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor (thought to be dopamine); in the corpus striatum the dopaminergic neurons are involved in the control of motor function. Clinically, bromocriptine mesylate significantly reduces plasma levels of prolactin in patients with physiologically elevated prolactin as well as in patients with hyperprolactinemia. The inhibition of physiological lactation as well as galactorrhea in pathological hyperprolactinemic states is obtained at dose levels that do not affect secretion of other tropic hormones from the anterior pituitary. Experiments have demonstrated that bromocriptine induces long-lasting stereotyped behavior in rodents and turning behavior in rats having unilateral lesions in the substantia nigra. These actions, characteristic of those produced by dopamine, are inhibited by dopamine antagonists and suggest a direct action of bromocriptine on striatal dopamine receptors. Absorption 1 max 2 3 max 4 Distribution In vitro Metabolism In vitro 5 see PRECAUTIONS, drug interactions section 6 max Excretion 5 1 2 3 4 5 6 in vitro Effect of Renal Impairment see PRECAUTIONS, general Effect of Hepatic Impairment (see PRECAUTIONS, general Clinical Studies Galactorrhea may take longer to control depending on the degree of stimulation of the mammary tissue prior to therapy. At least a 75% reduction in secretion is usually observed after 8 to 12 weeks. Some patients may fail to respond even after 12 months of therapy.
Pharmacokinetics
Absorption 1 max 2 3 max 4 Distribution In vitro Metabolism In vitro 5 see PRECAUTIONS, drug interactions section 6 max Excretion 5 1 2 3 4 5 6 in vitro

Hyperprolactinemia-Associated Dysfunctions hyperprolactinemia amenorrhea galactorrhea, infertility or hypogonadism prolactin-secreting adenomas, Reduction tumor size Acromegaly Parkinson’s Disease

General Hyperprolactinemic Indications see Pediatric Use Acromegaly Parkinson’s Disease

ADVERSE REACTIONS
Hyperprolactinemic Indications Acromegaly Parkinson’s Disease The following adverse reactions have been reported during postapproval use of bromocriptine mesylate (All Indications Combined). Because adverse reactions from spontaneous reports are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Psychiatric disorders: Nervous system disorders: Eye disorders: Ear and labyrinth disorders: Cardiac disorders: Vascular disorders: Respiratory, thoracic and mediastinal disorders: Gastrointestinal disorders: Skin and subcutaneous tissue disorders: Musculoskeletal and connective tissue disorders: General disorders and administration site conditions: see Precautions Postpartum Patients (see above Warnings).
Adverse Reactions from Clinical Trials
Hyperprolactinemic Indications Acromegaly Parkinson’s Disease
Adverse Reactions from Postmarketing Experience
The following adverse reactions have been reported during postapproval use of bromocriptine mesylate (All Indications Combined). Because adverse reactions from spontaneous reports are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Psychiatric disorders: Nervous system disorders: Eye disorders: Ear and labyrinth disorders: Cardiac disorders: Vascular disorders: Respiratory, thoracic and mediastinal disorders: Gastrointestinal disorders: Skin and subcutaneous tissue disorders: Musculoskeletal and connective tissue disorders: General disorders and administration site conditions: see Precautions
Adverse Events Observed in Other Conditions
Postpartum Patients (see above Warnings)

Hypersensitivity to bromocriptine or to any of the excipients of bromocriptine mesylate, uncontrolled hypertension and sensitivity to any ergot alkaloids. In patients being treated for hyperprolactinemia, bromocriptine mesylate should be withdrawn when pregnancy is diagnosed ( see PRECAUTIONS, Hyperprolactinemic States see PRECAUTIONS, Hyperprolactinemic States

Specific Populations
Effect of Renal Impairment see PRECAUTIONS, general Effect of Hepatic Impairment (see PRECAUTIONS, general Clinical Studies Galactorrhea may take longer to control depending on the degree of stimulation of the mammary tissue prior to therapy. At least a 75% reduction in secretion is usually observed after 8 to 12 weeks. Some patients may fail to respond even after 12 months of therapy.
Pregnancy
Category B: Of these 1276 pregnancies, there were 1088 full-term deliveries (4 stillborn), 145 spontaneous abortions (11.4%), and 28 induced abortions (2.2%). Moreover, 12 extrauterine gravidities and 3 hydatidiform moles (twice in the same patient) caused early termination of pregnancy. These data compare favorably with the abortion rate (11% - 25%) cited for pregnancies induced by clomiphene citrate, menopausal gonadotropin, and chorionic gonadotropin.
Nursing Mothers
Bromocriptine mesylate should not be used during lactation in postpartum women.
Pediatric Use
The safety and effectiveness of bromocriptine for the treatment of prolactin-secreting pituitary adenomas have been established in patients age 16 to adult. No data are available for bromocriptine use in pediatric patients under the age of 8 years. A single 8-year-old patient treated with bromocriptine for a prolactin-secreting pituitary macroadenoma has been reported without therapeutic response.
Geriatric Use
Clinical studies for bromocriptine mesylate did not include sufficient numbers of subjects aged 65 and over to determine whether the elderly respond differently from younger subjects. However, other reported clinical experiences, including postmarketing reporting of adverse events, have not identified differences in response or tolerability between elderly and younger patients. Even though no variation in efficacy or adverse reaction profile in geriatric patients taking bromocriptine mesylate has been observed, greater sensitivity of some elderly individuals cannot be categorically ruled out. In general, dose selection for an elderly patient should be cautious, starting at the lower end of the dose range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy in this population.

The risk of using bromocriptine mesylate in combination with other drugs has not been systematically evaluated, but alcohol may potentiate the side effects of bromocriptine mesylate. Bromocriptine mesylate may interact with dopamine antagonists, butyrophenones, and certain other agents. Compounds in these categories result in a decreased efficacy of bromocriptine mesylate: phenothiazines, haloperidol, metoclopramide, and pimozide. Bromocriptine is a substrate of CYP3A4. Caution should therefore be used when co-administering drugs which are strong inhibitors of this enzyme (such as azole antimycotics, HIV protease inhibitors). The concomitant use of macrolide antibiotics such as erythromycin was shown to increase the plasma levels of bromocriptine (mean AUC and C max 1 4

WARNINGS
Since hyperprolactinemia with amenorrhea/galactorrhea and infertility has been found in patients with pituitary tumors, a complete evaluation of the pituitary is indicated before treatment with bromocriptine mesylate. see PRECAUTIONS, Hyperprolactinemic States see PRECAUTIONS, Hyperprolactinemic States
Carcinogenesis,Mutagenesis, Impairment of Fertility
A 74-week study was conducted in mice using dietary levels of bromocriptine mesylate equivalent to oral doses of 10 and 50 mg/kg/day. A 100-week study in rats was conducted using dietary levels equivalent to oral doses of 1.7, 9.8, and 44 mg/kg/day. The highest doses tested in mice and rats were approximately 2.5 and 4.4 times, respectively, the maximum human dose administered in controlled clinical trials (100 mg/day) based on body surface area. Malignant uterine tumors, endometrial and myometrial, were found in rats as follows: 0/50 control females, 2/50 females given 1.7 mg/kg daily, 7/49 females given 9.8 mg/kg daily, and 9/50 females given 44 mg/kg daily. The occurrence of these neoplasms is probably attributable to the high estrogen/progesterone ratio which occurs in rats as a result of the prolactin-inhibiting action of bromocriptine mesylate. The endocrine mechanisms believed to be involved in the rats are not present in humans. There is no known correlation between uterine malignancies occurring in bromocriptine-treated rats and human risk. In contrast to the findings in rats, the uteri from mice killed after 74 weeks of treatment did not exhibit evidence of drug-related changes. in vitro in vivo in vivo
OVERDOSAGE
The most commonly reported signs and symptoms associated with acute bromocriptine mesylate overdose are: nausea, vomiting, constipation, diaphoresis, dizziness, pallor, severe hypotension, malaise, confusion, lethargy, drowsiness, delusions, hallucinations, and repetitive yawning. The lethal dose has not been established and the drug has a very wide margin of safety. However, one death occurred in a patient who committed suicide with an unknown quantity of bromocriptine mesylate and chloroquine.

Bionpharma Inc.

• Founded in:

  2014-11-07 00:00:00

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