Bromocriptine (Systemic)


VA CLASSIFICATION
Primary: AU900
Secondary: HS900

Commonly used brand name(s): Alti-Bromocriptine; Apo-Bromocriptine; Parlodel; Parlodel SnapTabs.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Dopamine agonist—

antihyperprolactinemic—

infertility therapy adjunct—

lactation inhibitor—

antidyskinetic—

growth hormone suppressant (acromegaly)—

neuroleptic malignant syndrome therapy—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Prolactinomas, pituitary (treatment)—Bromocriptine is indicated in the treatment of prolactin–secreting pituitary tumors in men and women {27} {28} {65}. Bromocriptine is usually considered to be the treatment of choice for microadenomas and for macroadenomas including those with visual defects {06} {07} {12} {18} {22} {28} {33} {65} {95}. However, surgery may be required to treat macroadenomas in those patients who either cannot take bromocriptine or who exhibit a poor therapeutic response to bromocriptine {12}. Bromocriptine may also be used as an adjunct to radiotherapy when the tumor is inoperable {28} {65}.
—[Bromocriptine is used by some clinicians in the treatment of visual field defects that develop during pregnancy {33} . Visual field defects that respond to bromocriptine are secondary to pituitary adenoma enlargement. {33}]1

Amenorrhea, secondary, due to hyperprolactinemia (treatment) or {27} {28} {29} {30}
Galactorrhea due to hyperprolactinemia (treatment) or {27} {28} {29} {30}
Hypogonadism, male, due to hyperprolactinemia (treatment) or {29} {30}
Infertility due to hyperprolactinemia (treatment) {27} {28}—Bromocriptine is indicated in the short-term symptomatic treatment of amenorrhea and/or galactorrhea or male or female infertility associated with hyperprolactinemia. {29} {30} Its usefulness in normoprolactinemic amenorrhea or anovulation is controversial {65}.

[Lactation, after second- or third-trimester pregnancy loss (prophylaxis)]1 {29} {30}—Bromocriptine can be used in selected individuals for the prevention of physiological lactation and breast engorgement after stillbirth, neonatal death, or abortion. {48} {49} {50} {52} {54} {55} {58} {89} However, in many patients, breast engorgement is a benign, self-limited condition, which may respond to breast support and mild analgesics, such as acetaminophen and ibuprofen. {42} {89} Once bromocriptine has been discontinued, 18 to 40% of patients experience rebound symptoms of breast secretion, congestion, or engorgement. {31} {42} {89} {95} Also, the relative risk of all of bromocriptine"s rare, severe, or life-threatening side effects, which have included strokes, seizures, and myocardial infarction, has yet to be determined. {42} {55} {89} {95}

Parkinsonism (treatment)—Bromocriptine is indicated, usually as an adjunct to levodopa/carbidopa therapy, in the treatment of the signs and symptoms of idiopathic or postencephalic parkinsonism. {27} {28} {43} {46} {47} {89}

Acromegaly (treatment)—Bromocriptine is indicated in the treatment of some cases of acromegaly, usually as an adjunct to surgery or radiotherapy. {27} {28} {37} There are some reports that patients who respond may have elevated prolactin as well as elevated growth hormone concentrations. {43}

[Neuroleptic malignant syndrome (treatment) ]1—Although controlled clinical trials have not been conducted, bromocriptine is sometimes used as adjunctive therapy in the treatment of neuroleptic malignant syndrome {44} {59} {61} {71} {72} {73} {74} {75} {76} {77} {78} {79} {80} {81} {82} {83} {84} {85} {86} {87} {88} {89} {97}. Individual case reports and the known pharmacological activity of bromocriptine indicate that it may have some utility in the treatment of this disorder, as well as a lower incidence of side effects, as compared with other modes of therapy for this condition {59} {71} {72} {73} {74} {75} {76} {77} {78} {79} {80} {81} {82} {83} {84} {85} {86} {87} {88} {89}.

Unaccepted
The routine use of bromocriptine for suppression of postpartum lactation is not recommended {29} {30} {58} {89} {95}.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Bromocriptine is an ergot alkaloid derivative {27} {28}.
Molecular weight—
    750.70 {32}

Mechanism of action/Effect:

Dopamine agonist

Antihyperprolactinemic

Infertility therapy adjunct and

Lactation inhibitor—Reduction of serum prolactin concentrations by direct inhibition of release of prolactin from the anterior pituitary gland through binding to dopamine type 2 (D 2) receptors {14} {15} {16} {27} {28} {34}, resulting in restoration of testicular or ovarian function and suppression of lactation {34} {43} {44} {46} {47}.


Antidyskinetic—In high doses, stimulation of post-synaptic dopamine type 2 (D 2) receptors in the neostriatum of the central nervous system (CNS); {28} {34} {43} {44} {46} {47} may also decrease dopamine turnover {28} {34}. At low doses, bromocriptine may worsen dyskinesia by stimulating presynaptic dopamine receptors {34} {43} {44} {46} {47} {51}. Is most effective when used concurrently with levodopa, as stimulation of D 1 receptors by levodopa enhances the antidyskinetic effects of postsynaptic D 2 receptor stimulation by bromocriptine {34} {43} {44} {46} {47} {51}.


Growth hormone suppressant (acromegaly)—Suppression of secretion and reduction of elevated growth hormone serum concentrations {27} {90} {91}.


Neuroleptic malignant syndrome therapy—Some evidence exists that neuroleptic malignant syndrome may result from depletion of dopamine or blockade of dopamine receptors in the nigrostriatal, hypothalamic, and mesolimbic cortical pathways. Bromocriptine stimulates these dopamine receptors {71} {72} {73} {74} {76} {77} {78} {79} {80} {81} {85} {86} {87} {88}.


Absorption:

Approximately 28% of an oral dose is absorbed from the gastrointestinal tract, but because of first-pass metabolism, only 6% reaches the systemic circulation unchanged {27} {28} {68} {69}.

Protein binding:

Very high (90 to 96% to serum albumin {27} {28}).

Biotransformation:

Hepatic {27} {28} {66} {67} {68} {69}.

Half-life:


Biphasic:

4 to 4.5 hours (alpha phase).

15 hours (terminal) {53}.


Onset of action:


Single dose:

Serum prolactin–lowering effect: 2 hours.

Antiparkinsonism effect: 30 to 90 minutes.

Growth hormone–lowering effect: 1 to 2 hours.


Time to peak concentration:

1 to 3 hours.

Time to peak effect:

Serum prolactin–lowering effect—8 hours (after a single dose).

Note: The maximum obtainable reduction in serum prolactin occurs after approximately 4 weeks of continuous therapy. The average duration of therapy required to reinitiate menses is 6 to 8 weeks. In the treatment of galactorrhea, a significant reduction in lactation usually occurs within 6 to 7 weeks, with cessation of lactation occurring by 12 to 13 weeks {17}. Suppression of postpartum lactation requires 2 to 3 weeks of therapy; some clinicians believe that 3 weeks of therapy is necessary to prevent rebound lactation.


Antiparkinsonism effect—2 hours (after a single dose).

Growth hormone–lowering effect—A clinical response occurs within 4 to 8 weeks with continuous therapy.

Duration of action:

Serum prolactin–lowering effect—Approximately 24 hours (after a single dose).

Note: Serum prolactin concentrations usually return to pretreatment levels within 2 months after bromocriptine is discontinued {17}.


Growth hormone–lowering effect—4 to 8 hours.

Elimination:
    As metabolites—

• Biliary: Approximately 95% {27}.


• Renal: 2.5 to 5.5% {27} {28}.



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other ergot derivatives may be sensitive to this medication also {27} {28}.

Pregnancy/Reproduction
Fertility—
Restoration of fertility may result in pregnancy with possible enlargement of a pituitary adenoma, leading to visual field defects, headaches, and excessive nausea and vomiting in the mother {65}.

In general, use of a nonhormonal contraceptive is recommended in patients being treated for hyperprolactinemia until normal ovulatory menstrual cycles are established {27}. At that time, contraception can be discontinued in patients desiring pregnancy, with careful monitoring to avoid inadvertent administration of bromocriptine after pregnancy is diagnosed {01} {27} {45} {50}.

Pregnancy—
Bromocriptine is not generally recommended for use during pregnancy; however, it has been used in the treatment of acromegaly, Parkinson's disease, or prolactinoma in pregnant patients when deemed medically necessary. For patients who develop pregnancy-related hypertension or have recently developed hypertensive disorders of pregnancy, withdrawal of bromocriptine is recommended, unless discontinuation is considered medically contraindicated {101}.

Large and long-term studies performed in humans have found no increased incidence of birth defects {43} {45} {52} {65}. In clinical use, successful pregnancies have occurred in humans taking bromocriptine both before conception and {17} for periods ranging from the first 2 to 3 weeks to {01} the full length of the pregnancy {45}.

FDA Pregnancy Category B.

Postpartum —
Bromocriptine should not be used during the postpartum period in women with a history of coronary artery disease or other severe cardiovascular conditions, unless withdrawal of bromocriptine is considered medically contraindicated {101}. If bromocriptine is used during the postpartum period, the patient should be monitored for adverse events. Although causal relationship between bromocriptine and these adverse events has not been established, serious events that have occurred during bromocriptine treatment are seizures with or without hypertension, stroke, and myocardial infarction. Many postpartum patients who had seizures or strokes during bromocriptine therapy experienced severe headaches with possible visual disturbances for hours or days before the event occurred {101}.

Breast-feeding

This medication should not be administered to mothers who intend to breast-feed, since bromocriptine interferes with lactation.

Pediatrics

Appropriate studies on the relationship of age to the effects of bromocriptine have not been performed in the pediatric population. Safety and efficacy have not been established {29}.



Adolescents

Appropriate studies performed to date have not demonstrated adolescent-specific problems that would limit the use of bromocriptine in adolescents 15 years of age and older. However, appropriate studies to establish safety and efficacy in adolescents younger than 15 years of age have not been performed {29} {48}.


Geriatrics


Appropriate studies on the relationship of age to the effects of bromocriptine have not been performed in the geriatric population. However, clinical experience with the use of bromocriptine has shown that CNS effects may occur more frequently in the elderly.


Dental

Use of large doses of bromocriptine (for example, in the treatment of acromegaly or parkinsonism) may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort {11}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Alcohol{54}    (disulfiram-like reaction may occur, including chest pain, confusion, fast or pounding heartbeat, flushing or redness of face, sweating, nausea, vomiting, throbbing headache, blurred vision, and severe weakness {17} {23} {25} {27} {54})


Clarithromycin or
» Erythromycin or
Troleandomycin    (concurrent use of erythromycin caused a 268% increase in bromocriptine's area under the plasma concentration–time curve (AUC) when standardized to body weight and a 4.7-fold increase in the peak bromocriptine plasma concentration (C max). Patients should be monitored for bromocriptine toxicity if erythromycin is used concurrently. Although not reported, similar increases may be expected for clarithromycin or troleandomycin {102})


» Ergot alkaloids, other, or derivatives, including{58}
Dihydroergotamine
Ergonovine
Methylergonovine
Methysergide    (although there is no conclusive evidence of a drug interaction, rarely occurring cases of hypertension associated with the use of bromocriptine may be aggravated with use of ergot alkaloids or its derivatives {03} {18})


Haloperidol or
Loxapine or
Methyldopa or
Metoclopramide or
Molindone or
Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline or
Phenothiazines or
Pimozide{101} or
Reserpine or
» Risperidone{100} or
Thioxanthenes    (may increase serum prolactin concentrations and interfere with effects of bromocriptine; dosage adjustment of bromocriptine may be necessary)


Hypotension-producing medications, other (See Appendix II )    (concurrent use may result in additive hypotensive effects; antihypertensive dosage adjustment may be necessary {27})


Levodopa    (bromocriptine may produce additive effects, allowing reduction in levodopa dosage {34})


» Ritonavir    (bromocriptine serum concentrations can increase threefold when given with ritonavir; 50% reduction of bromocriptine dose is recommended if the combination is necessary {103} {104})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Growth hormone    (plasma concentrations may be transiently increased in individuals with normal concentrations, paradoxically reduced in patients with acromegaly {27})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Hepatic function impairment    (metabolism may be reduced; dosage reduction may be required {27})


Hypertension, or history of or{58}{95}
Hypertension, pregnancy-induced, history of{58}{62}{64}{95}    (may be aggravated; cautious use and monitoring of blood pressure are indicated with these conditions {03} {27} {28} {62} {64} {95})


Psychiatric disorders    (may be exacerbated)


Sensitivity to bromocriptine or other ergot alkaloids

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Blood pressure measurements    (recommended especially when used for suppression of postpartum lactation; commonly decreases or rarely increases {01} {03} {04} {05} {06} {07})


» Imaging studies of sella turcica{13}{65}{95}{99}    (recommended prior to initiation of therapy for all patients with hyperprolactinemia, {50} to rule out possible pituitary tumor {27}, and once a year during therapy to detect enlargement of a tumor; after one or two years of therapy, this examination may be performed less frequently in asymptomatic patients {24} {58} {65})


» Pregnancy test{65}    (recommended in patients being treated for amenorrhea once menses resumes, whenever a menstrual period is missed {18})


» Prolactin, serum{65}    (measurement of serum concentrations is recommended monthly during initial treatment and twice yearly during maintenance treatment of hyperprolactinemia to assess effectiveness of bromocriptine)


Visual field assessment    (recommended if clinically indicated during pregnancy after treatment with bromocriptine in case of enlargement of a previously detected macroadenoma {17} {35} {58})


For treatment of female infertility
Anterior pituitary function{54}    (complete evaluation may be warranted prior to initiation of treatment for infertility {54})


» Evaluation of ovulation, including:{58}
Daily basal body temperature and/or{33}{58}
Progesterone, serum and/or{33}{41}{58}{92}{93}
Use of ovulation prediction test kits{58} and
» Prolactin, serum{54}    (measurement of baseline serum prolactin concentration is recommended, with subsequent measurements as needed, along with other tests as may be appropriate for the evaluation and treatment of female infertility {54})


For treatment of male infertility
FSH, serum and
LH, serum and
Prolactin, serum and
Testosterone, serum    (baseline serum concentration measurements recommended to rule out other causes of infertility and at 3- to 6-month intervals thereafter {39} {40})


Prolactin, serum    (measurement of serum concentrations is recommended at 4- to 6-week intervals until normal levels are established, then at 3- to 6-month intervals {39} {40})


Sperm counts    (recommended at periodic intervals beginning 3 months after initiation of treatment)


For treatment of acromegaly
» Growth hormone or
Insulin-like growth factor I concentrations (IGF-I), serum{17}{19}{20}{36}{37}{57}    (measurement of serum concentrations is recommended at periodic intervals to assess efficacy and aid in dosage adjustment {01} {27} {37})


Physical examination    (periodic examination, especially assessing changes in ring size, heel pad thickness, or soft-tissue volume {37} {38})




Side/Adverse Effects

Note: The most common side effects occur on initiation of therapy. Most side effects occurring with continuous therapy are dose-related {58} {89}.
Long-term treatment (6 to 36 months) with bromocriptine mesylate has rarely been associated with pulmonary infiltrates, pleural effusion, and thickening of the pleura {01} {03} {09} {11} {12} {27} {28} {89}. These occurred in a few patients taking doses ranging from 20 to 100 mg per day {01} {03} {09} {11} {12} {27} {28} {89}. When bromocriptine was discontinued, the changes slowly reversed toward normal {01} {03} {09} {11} {12} {27} {28} {89}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Confusion{27}{47}
    
dyskinesia {27}{47}{51}(uncontrolled movements of the body, such as the face, tongue, arms, hands, head, and upper body)
    
hallucinations{47}

Note: Confusion, dyskinesia, or hallucinations are usually associated with use of high doses but may occur in 20 to 25% of patients being treated for parkinsonism, even at low doses, and may persist for a week or more after bromocriptine is withdrawn {02}.


Incidence rare
    
Myocardial infarction (severe chest pain{47}; fainting; fast heartbeat; increased sweating; continuing or severe nausea and vomiting; nervousness; unexplained shortness of breath; weakness){43}
    
seizures{43}{60}{63} or strokes{43}{60} {58}{60}{63}(atypical headache; vision changes, such as blurred vision or temporary blindness; sudden weakness)

Note: There have been a few reports of myocardial infarction occurring in patients treated with bromocriptine, including patients that were treated with bromocriptine to suppress lactation, although a direct causal relationship has not been established {03} {04} {06} {27} {43} {48}.
There have been a number of reports of postpartum hypertension, seizures, and strokes as well as reports of fatalities occurring in patients treated with bromocriptine to suppress lactation {48} {60}; however, further studies are being conducted to determine if a causal relationship exists between the incidence of hypertension, strokes, and seizures and the use of bromocriptine for suppression of lactation {48}. Mean onset of the reactions was 9 days postpartum. The cases of cerebrovascular accident were all associated with hypertension {03} {04} {05} {07} {10} {48}. Use of bromocriptine should be re-evaluated in those patients who experience unexplained headaches and therapy discontinued if headache is severe and atypical {58} {60} {95} {98}.

With high doses
    
Cerebrospinal fluid rhinorrhea (continuing runny nose)—in patients treated for pituitary macroadenomas{01}{27}
    
fainting —has also occurred with low doses used in postpartum patients
    
gastrointestinal hemorrhage or peptic ulcer {27}(black, tarry stools; blood in vomit; severe or continuing stomach pain)
    
retroperitoneal fibrosis (continuing or severe abdominal or stomach pain; increased frequency of urination; continuing loss of appetite; lower back pain; continuing or severe nausea and vomiting; weakness)—with long-term use{03}{08}{09}{27}{28}




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Hypotension, especially orthostatic hypotension {27}{47}(dizziness or lightheadedness, especially when getting up from a lying or sitting position)
    
nausea{27}

Note: Hypotension occurs frequently, but is symptomatic only in 1 to 5% of patients (8% of postpartum patients). Rarely, hypotension may be severe. A ``first-dose phenomenon'' has been reported.


Incidence less frequent
—more frequent with high doses (for example, when used for acromegaly or parkinsonism)    
Constipation{27}
    
diarrhea
    
drowsiness or tiredness{01}{27}
    
dry mouth{11}{27}
    
leg cramps at night
    
loss of appetite{27}
    
mental depression{27}
    
Raynaud's phenomenon {27}{47}(tingling or pain in fingers or toes when exposed to cold)
    
stomach pain{27}
    
stuffy nose{27}
    
vomiting{27}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Bromocriptine (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to bromocriptine or other ergot alkaloids

Pregnancy—Use is not generally recommended





Breast-feeding—Will prevent lactation in mothers who intend to breast-feed





Use in the elderly—CNS effects may occur more frequently





Dental—Reduced salivary flow caused by large doses may contribute to dental disorders
Other medications, especially alcohol, ergot alkaloids or derivatives, erythromycin, risperidone, or ritonavir

Proper use of this medication
Taking with meals or milk to reduce gastrointestinal irritation; taking dose at bedtime or the first doses vaginally to better tolerate nausea

» Proper dosing
Missed dose: Taking if remembered within 4 hours; otherwise not taking at all; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress

» Caution when driving or doing jobs requiring alertness because of possible drowsiness or dizziness

Dizziness may be more likely to occur after initial dose; taking first dose at bedtime or lying down; getting up slowly from sitting or lying position; taking first dose vaginally, if necessary

» Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks

Checking with physician before reducing dosage or discontinuing medication

» Possibility of disulfiram-like reaction with alcohol

For treatment of acromegaly, amenorrhea, infertility, galactorrhea, or pituitary prolactinomas in females of child-bearing potential
Advisability of using nonhormonal contraception during therapy or, when using bromocriptine for female infertility, until normal menstrual cycle is established; patients desiring pregnancy should discuss with physician proper time to discontinue use of contraception; telling physician immediately if pregnancy is suspected

» Telling physician right away if symptoms of enlargement of pituitary tumor (blurred vision, sudden headache, severe nausea and vomiting) occur


Side/adverse effects
Signs of potential side effects, especially CNS effects, fainting, myocardial infarction, seizures, gastrointestinal hemorrhage, peptic ulcer, retroperitoneal fibrosis, rhinorrhea, and strokes


General Dosing Information
Incidence and severity of side effects (especially nausea) may be reduced by initiating therapy at a low dose (for example, 1.25 mg at bedtime) and increasing gradually (increments of 2.5 mg every 14 to 28 days for parkinsonism and 3 to 7 days for other indications) to the minimum effective dose, and by administering bromocriptine with food {27} {65}. Also, dizziness and nausea may be better tolerated by administering some or all of the dose at bedtime or by administering one or more of the initial doses intravaginally. Since no first-pass effect occurs with a vaginal dose, a reduced first dose may be warranted in some cases and certainly with subsequent doses because higher serum concentrations may result. {01} {03} {58} {65} {66} {67} {68} {69} {70}

Bromocriptine is used rarely to prevent postpartum lactation because of the risk of significant hypotension and other adverse effects. If it is used, the medication should be given only after the patient's vital signs are stable and no sooner than 4 hours after delivery {27}.

Treatment of hyperprolactinemia with bromocriptine may be symptomatic rather than curative {21}. Following withdrawal, rebound amenorrhea usually occurs within 4 to 24 weeks and galactorrhea within 2 to 12 weeks. Pituitary adenoma regrowth and increase in serum prolactin concentrations may occur after withdrawal of bromocriptine {01} {17} {19} {21}. Elevated growth hormone concentrations will also return when the medication is withdrawn if the cause of acromegaly is not eliminated.


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

BROMOCRIPTINE MESYLATE CAPSULES USP

Note: For doses less than 5 mg, use Bromocriptine Mesylate Tablets USP {48}.


Usual adult dose
Amenorrhea, secondary, due to hyperprolactinemia or
Galactorrhea due to hyperprolactinemia or
Hypogonadism, male, due to hyperprolactinemia or
Infertility due to hyperprolactinemia
Initial: Oral, 1.25 to 2.5 mg at bedtime with a snack. Dosage may be increased by 2.5 mg every three to seven days as needed to a total of 5 to 7.5 mg a day taken in divided doses with meals {27} {28} {29} {30} {65}.

Maintenance: Oral, 2.5 mg two or three times a day with meals. Doses of up to 15 mg have been used {28} {65}.

Prolactinomas, pituitary
Initial: Oral, 1.25 mg two or three times a day with meals. Dosage adjustment is gradual over several weeks to 10 to 20 mg a day taken in divided doses with meals {28} {29} {30} {58} {65}. Occasionally, higher doses may be required {58}.

Maintenance: Oral, 2.5 to 20 mg a day taken in divided doses with meals {29} {30}.

Parkinsonism
Initial: Oral, 1.25 mg one or two times a day with meals; for single doses, at bedtime with a snack is preferred. Dosage may be increased by 2.5 mg increments every fourteen to twenty-eight days {28} {29}.

Maintenance: Oral, 2.5 to 40 mg a day, taken in divided doses with meals. Although higher doses have been used, safety and efficacy have not been established with doses greater than 100 mg a day {28} {29} {30}.

Acromegaly
Initial: Oral, 1.25 to 2.5 mg at bedtime with a snack for 3 days; dosage may be increased by 1.25 or 2.5 mg every three to seven days up to 30 mg a day taken in divided doses with meals or at bedtime with a snack {27} {28} {29} {30}.

Maintenance: Oral, 10 to 30 mg a day taken in divided doses with meals or at bedtime with a snack. Up to 100 mg per day has been used {01} {03} {27} {28} {29} {30}.

[Lactation suppression]1
Initial: Oral, 2.5 mg twice a day taken with meals. Patient may begin medication only after vital signs stabilize and no sooner than four hours after delivery {31}.

Maintenance: Oral, 2.5 to 7.5 mg a day taken in divided doses with meals or at bedtime with a snack for fourteen days. Has been used for up to twenty-one days if needed {31}.

[Neuroleptic malignant syndrome]1
Initial: Oral, 5 mg once a day taken at bedtime with a snack; dosage adjustment titrated according to patient response by 2.5 mg increments a day as needed, taken in divided doses with meals or at bedtime with a snack {71} {72} {73} {76} {77} {79} {80} {82} {83} {85} {89}.

Maintenance: Oral, up to 20 mg a day taken in divided doses with meals or at bedtime with a snack {71} {72} {73} {75} {76} {79} {80} {81} {83} {87} {88} {89}.


Usual adult prescribing limits
Parkinsonism—40 mg a day {29} {30}.

Other indications—20 mg a day {29} {30}.

Note: Although higher doses have been used, safety and efficacy have not been established with doses greater than 100 mg a day {28} {29}.


Usual pediatric dose
Children up to 15 years of age: Dosage has not been established {29}.

Children 15 years of age and older: See Usual adult dose {29}.

Strength(s) usually available
U.S.—


5 mg (Rx) [Parlodel (lactose) (sodium bisulfite){27}{29}]

Canada—


5 mg (Rx) [Parlodel (lactose){28}{30}]

Packaging and storage:
Store below 25 °C (77 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • Take with meals or milk {27}.
   • May cause drowsiness.

Note: Unit-dose repackaging by any process involving heat is not recommended.



BROMOCRIPTINE MESYLATE TABLETS USP

Note: For doses 5 mg or greater, consider using Bromocriptine Mesylate Capsules USP.


Usual adult dose
See Bromocriptine Mesylate Capsules USP .

Usual pediatric dose
See Bromocriptine Mesylate Capsules USP .

Strength(s) usually available
U.S.—


2.5 mg (Rx) [Parlodel SnapTabs (scored) (lactose){27}{29}][Generic]

Canada—


2.5 mg (Rx) [Alti-Bromocriptine] [Apo-Bromocriptine] [Parlodel (scored) (lactose){28}{30}][Generic]

Packaging and storage:
Store below 25 °C (77 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Avoid alcoholic beverages. {27}
   • Take with meals or milk {27} {28}.
   • May cause drowsiness {27}.

Note: Unit-dose repackaging by any process involving heat is not recommended.




Revised: 08/20/1997



References
  1. Parlodel package inserts (Sandoz—US), Rev 10/1/85 and Rev 6/10/86, Rec 6/87 and 5/86.
  1. Panel comment, 1986 revision.
  1. Parlodel (Sandoz), Rev 8/3/87. In: PDR Physicians' desk reference. 42nd ed. 1988. Oradell, NJ: Medical Economics Company, 1988: 1876-8.
  1. FDA Advisory Panel Meeting—Fertility and Maternal Health Drugs, 6/2-3/88.
  1. Katz M, Kroll D, Pak I, et al. Puerperal hypertension, stroke and seizures after suppression of lactation with bromocriptine. Obstet Gynecol 1985; 66(6) 822-4.
  1. Iffy L, TenHove W, Frisoli G. Acute myocardial infarction in the puerperium in patients receiving bromocriptine. Am J Obstet Gynecol 1986; 155(2): 371-2.
  1. Postpartum hypertension, seizures, strokes reported with bromocriptine. FDA Drug Bull 1984; 14(1): 3-4.
  1. Bowler JV, Ormerod IF, Legg NJ. Retroperitoneal fibrosis and bromocriptine. Lancet 1986 Aug 23; 2: 466.
  1. Wiggins J, Skinner C. Bromocriptine induced pleuropulmonary fibrosis. Thorax 1986 Apr; 41(4): 328-30.
  1. Phillips P. Drug triggers postpartum rise. Med World News 1988 Jun; 29(11): 45.
  1. Davies DM, editor. Textbook of adverse drug reactions. 3rd ed. New York: Oxford University Press, 1985.
  1. Dukes MNG, editor. Meyler's side effects of drugs. An encyclopedia of adverse reactions and interactions. 11th ed. Amsterdam: Elsevier, 1987.
  1. Panelist comment, 8/6/87.
  1. Panelist comments., 8/6/87.
  1. Gilman AG, Goodman LS, Rall TW, Murad F, editors. Goodman and Gilman's the pharmacological basis of therapeutics. 7th ed. New York: Macmillan, 1985: 473.
  1. Williams RH, editor. Textbook of endocrinology. 6th ed. Philadelphia: W.B. Saunders Company, 1981.
  1. Panelist comment, 8/6/87.
  1. Manufacturer comment, 8/6/87.
  1. Panelist comment, 8/6/87.
  1. Wallach J. Interpretation of diagnostic tests: a synopsis of laboratory medicine. 4th ed. Boston: Little, Brown and Company, 1986.
  1. Panelist comment, 8/6/87.
  1. Berkowitz RL, Coustan DR, Mochizuki TK. Handbook for prescribing medications during pregnancy. 2nd ed. Boston: Little, Brown and Company, 1986.
  1. The Medical Letter on Drugs and Therapeutics. Handbook of adverse drug reactions. New Rochelle, NY, 1985.
  1. Panelist comment, 8/6/87.
  1. Panelist comment, 8/6/87.
  1. Parlodel PM (Sandoz, Canada), Rev 1988. In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988: 686-8.
  1. Parlodel package insert (Sandoz—US), Rev 5/15/88, Rec 10/31/88.
  1. Parlodel product monograph (Sandoz), Rev 1988. In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988: 686-8.
  1. Parlodel SnapTabs package insert (Sandoz—US), Rev 3/95, Rec 4/95.
  1. Parlodel product monograph (Sandoz—Canada), Rev 11/94, Rec 3/95.
  1. Parlodel SnapTabs package insert (Sandoz—US), Rev 4/91, Rec 3/95.
  1. Fleeger CA, editor. USP dictionary of USAN and international drug names 1995. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 100.
  1. Panel comments, 8/18/88.
  1. Panel comment, 8/18/88.
  1. Panel comment, 8/18/88.
  1. Manufacturer comment, 8/18/88.
  1. Wyngaarden JB, Smith LH, editors. Cecil's textbook of medicine. 18th ed. Philadelphia: W.B. Saunders Company, 1988: 1301.
  1. Panel comment, 8/18/88.
  1. Panel comment, 8/18/88.
  1. Panel comment, 8/18/88.
  1. Panel comment, 8/18/88.
  1. FDA Fertility and Maternal health drugs advisory committee meetings, June 1-2 1989. Bethesda, MD.
  1. Ho Ky, Thorner Mo. Therapeutic applications of bromocriptine in endocrine and neurological diseases. Drugs 1988; 36: 67-82.
  1. Harpe C, Stoudemire A. Aetiology and treatment of neuroleptic malignant syndrome. Med Toxicol 1987; 2: 166-76.
  1. Krupp P, Monka C. Bromocriptine in pregnancy: Safety aspects. Klin Wochenschr 1987; 65: 823-7.
  1. Fischer P-A. Antiparkinson drugs. Drugs Today 1987; 23(2): 87-99.
  1. Lieberman AN, Goldstein M. Bromocriptine in parkinson disease. Pharmacol Rev 1985; 37(2): 217-27.
  1. Panel comment, 7/13/89.
  1. Panelist comment, 7/13/89.
  1. Panelist comment, 7/13/89.
  1. Panelist comment, 7/13/89.
  1. Panelist comment, 7/13/89.
  1. Panelist comment, 7/13/89.
  1. Panel comments, 4/16/90.
  1. Panel comments, 3/90 and 4/90.
  1. Panel comments, panel meeting and ballot 3/90 and 4/90.
  1. Panel comments, panel meeting and ballot 3/90 and 4/90.
  1. Panel comments. Obstetrics and Gynecology Panel meeting, 11/91.
  1. Panel comments. Psychiatric Disease Panel meeting, 5/91.
  1. Kulig K, Moore LL, Kirk M, et al. Bromocriptine-associated headache: Possible life-threatening sympathomimetic interaction. Obstet Gynecol 1991; 78(5 Pt 2): 941-3.
  1. Nierenberg D, Disch M, Manheimer E, et al. Facilitating prompt diagnosis and treatment of the neuroleptic malignant syndrome. Clin Pharmacol Ther 1991; 50 (5 Pt 1): 580-6.
  1. Watson DL, Bhatia RK, Norman GS, et al. Bromocriptine mesylate for lactation suppression: a risk for postpartum hypertension. Obstet Gynecol 1989; 74(4): 573-6.
  1. Gittelman DK. Bromocriptine associated with postpartum hypertension, seizures, and pituitary hemorrhage. Gen Hosp Psychiatry 1991; 13: 278-80.
  1. Bakht FR, Kirshon B, Baker T, et al. Postpartum cardiovascular complications after bromocriptine and cocaine use. Am J Obstet Gynecol 1990; 162: 1065-6.
  1. The American Fertility Society. Guideline for practice: The use of bromocriptine. Birmingham: American Fertility Society, 1991.
  1. Vermesh M, Fossum GT, Kletzky OA. Vaginal bromocriptine: Pharmacology and effect on serum prolactin in normal women. Obstet Gynecol 1988; 72(5); 693-8.
  1. Kletzky OA, Vermesh M. Effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia. Fertil Steril 1989; 51(2): 269-72.
  1. Katz E, Schran HF, Adashi EY. Successful treatment of a prolactin-producing pituitary macroadenoma with intravaginal bromocriptine mesylate: a novel approach to intolerance of oral therapy. Obstet Gynecol 1989; 73(3 Part 2): 517-20.
  1. Katz E, Weiss,BE, Hassell A, et al. Increased circulating levels of bromocriptine after vaginal compared with oral administration. Fertil Steril 1991; 55(5): 882-4.
  1. Ginsburg J, Hardiman P, Thomas M. Vaginal bromocriptine [letter]. Lancet 1991 Nov 9; 338: 1205-6.
  1. Janati A, Webb RT. Successful treatment of neuroleptic malignant syndrome with bromocriptine. South Med J 1986; 79(12): 1567-73.
  1. Rampertaap MP. Neuroleptic malignant syndrome [review]. South Med J 1986; 79(3): 331-6.
  1. Abbott RJ, Loizou LA. Neuroleptic malignant syndrome [review]. Br J Psychiatry 1986; 148: 47-51.
  1. Hamburg P, WJeilburg JB, Cassem NH, et al. Relapse of neuroleptic malignant syndrome with early discontinuation of amantadine therapy. Compr Psychiatry 1986; 27(4): 272-5.
  1. Schulz P, Dick P. Therapeutic rounds [case]. Clin Ther 1986; 8(6): 605-6, 722-3.
  1. Haggerty JJ, Bentsen BS, Gillette GM. Neuroleptic malignant syndrome superimposed on tardive dyskinesia. Br J Psychiatry 1987; 150: 104-5.
  1. Sullivan CF. A possible variant of the neuroleptic malignant syndrome [case]. Br J Psychiatry 1987; 151: 689-90.
  1. Allsop P, Twigley AJ. The neuroleptic malignant syndrome: case report and review of the literature. Anaesthesia 1987; 42: 49-53.
  1. Patterson JF. Neuroleptic malignant syndrome associated with metoclopramide. South Med J 1988; 81(5): 674-5.
  1. Guerrero RM, Shifrar KA. Diagnosis and treatment of neuroleptic malignant syndrome [case]. Clin Pharm 1988; 7: 697-701.
  1. Dhib-Jalbut S, Hesselbrock R, Mouradian MM, et al. Bromocriptine treatment of neuroleptic malignant syndrome. J Clin Psych 1987; 48: 69-73.
  1. Schvehla TJ, Herjanic M. Neuroleptic malignant syndrome, bromocriptine, and anticholinergic drugs [letter]. J Clin Psychiatry 1988; 49(7): 283-4.
  1. Goldwasser HD, Hooper JF, Spears NM. Concomitant treatment of neuroleptic malignant syndrome and psychosis. Br J Psych 1989; 154: 102-4.
  1. Singh SP, Giridhar C, Avasthi A. Neuroleptic malignant syndrome with trifluperidol [case]. Br J Psychiatry 1989; 155: 561-3.
  1. Adityanjee PD, Chawla HM. Neuroleptic malignant syndrome and psychotic illness. Br J Psychiatry 1989; 155: 852-4.
  1. Langlow JR, Alarcon RD. Trimipramine-induced neuroleptic malignant syndrome after transient psychogenic polydipsia in one patient [case]. J Clin Psychiatry 1989; 50(4): 144-5.
  1. Epperley TD, McGlaughlin VG, Leo KU. A hazardous side effect of neuroleptics: diagnosis and treatment [review]. Geriatrics 1990; 45(8); 58-62.
  1. Baca L, Martinelli L. Neuroleptic malignant syndrome: a unique association with a tricyclic antidepressant [case]. Neurology 1990; 40: 1797-8.
  1. Panel consensus, 3/3/92.
  1. Panel comment, 3/3/92.
  1. Panel comment, 3/3/92.
  1. Panel comment, 3/3/92.
  1. Panel comment, 3/3/92.
  1. Reviewer comment, 4/16/93.
  1. Obstetrics and Gynecology Advisory Panel Meeting Memo #14, 1/93.
  1. Obstetrics and Gynecology Advisory Panel Meeting Memo #20, 6/94.
  1. Panel comment, 6/94.
  1. Panelist comment, 3/02/92.
  1. Panel comment, 6/94.
  1. Freeman HL. Drug development report (11): clinical issues in the use of risperidone. J Drug Dev 1994; 6(4): 153-7.
  1. Parlodel package insert (Sandoz—US), Rev 11/96, Rec 5/97.
  1. Nelson MV, Berchou RC, Kareti D, et al. Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine in normal subjects. Clin Pharmacol Ther 1990; 47(6): 694-7.
  1. Norvir package insert (Ritonavir, Abbott—US), Rec 5/97, Rev 11/96.
  1. Bertz JF, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997 Mar; 32(3): 210-58.
  1. Kulig K, Moore LH, Kirk M, et al. Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction. Obstet Gynecol 1991; 78(5 Pt 2): 941-3.
  1. Chan JCN, Critchley AJH, Cockram CS. Postpartum hypertension, bromocriptine and phenylpropanolamine. Drug Invest 1994; 8(4): 254-6.
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