Parlodel

Dosage Forms & Strengths

tablet (Parlodel)

• 2.5mg

capsule (Parlodel)

• 5mg

tablet (Cycloset)

• 0.8mg

Hyperprolactinemia-Associated Dysfunctions (Parlodel)

Indicated for treatment of dysfunctions associated with hyperprolactinemia including amenorrhea with or without galactorrhea, infertility or hypogonadism; also indicated in patients with prolactin-secreting adenomas

1.25-2.5 mg PO qDay initially; may increase by 2.5 mg/day q2-7Days until optimal therapeutic response achieved

Usual therapeutic dosage ranges from 2.5-15 mg/day

Up to 30 mg/day has been used in some patients with amenorrhea and/or galactorrhea

Parkinson Disease (Parlodel)

Indicated as adjunctive treatment to levodopa for the signs and symptoms of idiopathic/postencephalitic Parkinson disease

1.25 mg PO q12hr initially; may increase dose by 2.5 mg/day q2-4Weeks until optimal therapeutic response achieved

Safety >100 mg/day not established

Acromegaly (Parlodel)

Indicated for acromegaly

1.25-2.5 mg PO qHS for 3 days initially; may increase by 1.25-2.5 mg/day q3-7Days until optimal therapeutic response achieved

Not to exceed 100 mg/day

Type 2 Diabetes Mellitus (Cycloset)

Quick release formulation (Cycloset) is the only bromocriptine product indicated for diabetes mellitus type 2 as adjunct to diet and exercise to improve glycemic control

0.8 mg PO qDay initially; may increase by 0.8-mg increments qWeek as tolerated

Usual dosage ranges between 1.5-4.8 mg PO qDay; not to exceed 4.8 mg (6 tablets)/day

Note: Cycloset is not indicated for hyperprolactinemia, Parkinson disease, or acromegaly

see Dosage Modifications (Cycloset) and Administratio (Cycloset)

Neuroleptic Malignant Syndrome (Off-label, Parlodel)

2.5-5 mg PO 2-3 times/day; not to exceed 45 mg/day

[Strawn JR, Keck PE Jr, and Caroff SN, "Neuroleptic Malignant Syndrome," Am J Psychiatry, 2007, 164(6):870-6]

Dosage Modifications

Hepatic impairment: Safety and efficacy has not been established; dosage adjustment may be necessary due to extensive hepatic metabolism; use with caution

Renal impairment: Safety and efficacy has not been established

Cycloset

• Concomitant use with CYP3A4 inhibitor
  • Strong CYP3A4 inhibitor (eg, azole antimycotics, HIV protease inhibitors): Avoid use; ensure adequate washout of the strong CYP3A4 inhibitor drug before initiating Cycloset treatment
  • Moderate CYP3A4 inhibitor (eg, erythromycin): Dose should not exceed 1.6 mg PO qDay

Dosing Considerations

Dosage forms for Cycloset and Parlodel and not interchangeable

Cycloset

• Limitations of use
  • Not for treatment of type 1 diabetes or diabetic ketoacidosis
  • Limited efficacy data in combination with thiazolidinediones
  • Efficacy has not been confirmed in combination with insulin

Parlodel

• Patients treated with pituitary irradiation should be withdrawn from Parlodel therapy on a yearly basis to assess both the clinical effects of radiation on the disease process and effects of Parlodel therapy; usual withdrawal period range, 4-8 weeks; recurrence of the signs/symptoms or increases in growth hormone indicate the disease is still active and further courses of Parlodel should be considered

Dosage Forms & Strengths

tablet (Parlodel)

• 2.5mg

capsule (Parlodel)

• 5mg

Hyperprolactinemia (Parlodel)

≤10 years: Safety and efficacy not established

11-15 years: 1.25-2.5 mg PO qDay initially; therapeutic dosage ranges from 2.5-10 mg/day; may need to increase dose for optimal therapeutic response

≥16 years: Safety and efficacy not established

see Administration (Parlodel)

Parlodel is a prescription medication used to:

• treat the effects of hyperprolactinemia (high levels of a natural hormonal substance called prolactin) including lack of menstrual periods, discharge from the nipples, infertility and hypogonadism (low levels of certain natural substances needed for normal development and sexual function)
• shrink prolactin-secreting tumors which cause hyperprolactinemia
• treat acromegaly (condition in which there is too much growth hormone in the body)
• treat Parkinson's disease

This medication may be prescribed for more uses. Ask your doctor or pharmacist for more information.

Common side effects of Parlodel include:

Hyperprolactinemia

• Nausea
• Headache
• Dizziness
• Extreme tiredness 
• Lightheadedness
• Vomiting
• Stomach (abdomen) cramps 
• Stuffy nose
• Constipation
• Diarrhea
• Drowsiness

Acromegaly

• Nausea
• Constipation
• Certain forms of low blood pressure
• Loss of appetite
• Dry mouth
• Stuffy nose
• Acid indigestion
• Condition where blood vessels constrict
• Drowsiness
• Vomiting

Parkinson's disease

• Nausea
• Abnormal, uncontrolled movements
• Hallucinations
• Confusion
• "On-off" phenomenon which is a condition where patients switch between being able to move and unable to move
• Dizziness
• Drowsiness
• Fainting
• Vomiting
• Lack of energy
• Stomach (abdomen) discomfort
• Visual changes
• Loss of control of body movements
• Difficulty sleeping
• Depression
• Low blood pressure
• Shortness of breath
• Constipation
• Vertigo (feeling like your surroundings are spinning)

This is not a complete list of Parlodel side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before taking Parlodel tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• if you are allergic to Parlodel or to any of its ingredients
• if you are allergic to ergot alkaloids such as cabergoline (Dostinex), dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylates (Germinal, Hydergine), ergonovine (Ergotrate), ergotamine (Bellergal-S, Cafergot, Ergomar, Wigraine), methylergonovine (Methergine), methysergide (Sansert), and pergolide (Permax)
• you have high blood pressure or migraine headaches that cause fainting. Your doctor may tell you not to take Parlodel.
• have recently given birth
• have ever fainted
• have or have ever had a heart attack
• have a slow, fast, or irregular heartbeat
• have a mental illness
• have low blood pressure
• have ulcers or bleeding in the stomach or intestines
• have Raynaud's syndrome (condition in which the hands and feet become numb and cool when exposed to cold temperatures)
• have heart, kidney, or liver disease
• have any condition that prevents you from digesting foods containing sugar, starch, or dairy products normally
• are pregnant or plan to become pregnant.  If you become pregnant during your treatment with Parlodel, stop taking the medication and call your doctor.
• you are breastfeeding or planning on breasfeeding while you are taking Parlodel.
• are having surgery, including dental surgery

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Ask your doctor about the safe use of alcoholic beverages while you are taking Parlodel. Alcohol can make the side effects from Parlodel worse.

Ask your doctor what to do if you get sick, develop an infection or fever, experience unusual stress, or are injured. These conditions can affect your blood sugar and the amount of Parlodel you may need.

• Store below 25ºC (77ºF) in a tight, light-resistant container. 
• Keep this and all medicines out of the reach of children.

This medication guide provides information about the Parlodel brand of bromocriptine. Cycloset is another brand of bromocriptine that is not covered in this medication guide.

The Parlodel brand of bromocriptine is used to treat certain conditions caused by a hormone imbalance in which there is too much prolactin in the blood (hyperprolactinemia). Symptoms include lack of sexual development in adolescents. Women may have missed menstrual periods, loss of interest in sex, hot flashes, infertility, or unexpected breast milk production and leakage from the nipples. Men may have enlarged breasts, decreased libido, decreased facial or body hair, and loss of muscle. Parlodel is also used to treat these disorders when they are caused by brain tumors that can produce prolactin.

Parlodel is sometimes used together with surgery or radiation in treating acromegaly, a condition caused by a pituitary gland tumor that produces too much growth hormone. Parlodel is also used to treat symptoms of Parkinson's disease, such as stiffness, tremors, muscle spasms, and poor muscle control.

Bromocriptine may also be used for purposes not listed in this medication guide.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop taking this medicine and call your doctor at once if you have a serious side effect such as:

• vision problems, constant runny nose;

• chest pain, pain when you breathe, fast heart rate, rapid breathing, feeling short of breath (especially when lying down);

• back pain, swelling in your ankles or feet, urinating less than usual or not at all;

• confusion, hallucinations, feeling like you might pass out;

• low blood sugar (headache, hunger, weakness, sweating, tremors, irritability, trouble concentrating);

• muscle movements you cannot control, loss of balance or coordination;

• bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or

• dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).

Less serious side effects may include:

• dizziness, spinning sensation, mild drowsiness, feeling tired;

• mild headache, depressed mood, sleep problems (insomnia);

• dry mouth, stuffy nose;

• upset stomach, nausea, vomiting, stomach pain, loss of appetite, diarrhea, constipation; or

• cold feeling or numbness in your fingers.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Hyperprolactinemic Disorders

Treatment of male and female dysfunctions associated with hyperprolactinemia, including amenorrhea and/or galactorrhea, hypogonadism, and infertility.a b

Used in patients with prolactin-secreting adenomas (e.g., prolactinoma), including macroadenomas, to decrease tumor size; may be used prior to surgery in patients undergoing excision of the tumor (adenectomy).a b

Treatment of female infertility associated with hyperprolactinemia; used to induce ovulation in appropriately selected anovulatory women.b

Treatment of hypogonadism and galactorrhea that persist following radiation therapy or surgery in hyperprolactinemic males with prolactin-secreting adenomas and adequate testosterone concentrations.a b Some clinicians consider bromocriptine the treatment of choice for reduction of large tumors (macroadenomas).b

Parkinsonian Syndrome

Symptomatic management of idiopathic or postencephalitic parkinsonian syndrome.a b

Used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome in patients with advanced disease.111 112 a

Has been used as monotherapy for initial symptomatic management of parkinsonian syndrome†.111 Most clinicians would use levodopa for initial therapy in individuals >70 years of age (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.111 A dopamine receptor agonist may be preferred for initial therapy in patients ≤70 years of age.111

Acromegaly

Treatment of acromegaly, alone or as adjunctive therapy with pituitary irradiation or surgery.a b

Male Infertility

Has been used to increase sperm counts and restore fertility† in oligospermic men without hyperprolactinemia who are unresponsive to traditional drug therapy.b

Neuroleptic Malignant Syndrome

Has been used to relieve extrapyramidal reactions, hyperthermia, and hypertension of neuroleptic malignant syndrome† (NMS) associated with neuroleptic drug therapy (e.g., haloperidol, fluphenazine).b

Hepatic Encephalopathy

Has been used in the management of chronic hepatic encephalopathy†.b

Postpartum Breast Engorgement

Used in the past for prevention of postpartum breast engorgement†;106 b FDA has withdrawn approval of bromocriptine for this indication because the risk of serious, potentially fatal adverse effects100 102 104 107 108 outweigh the limited benefits associated with this use.101 103 (See Cardiovascular Effects under Cautions.)

General

• Individualize and adjust dosage carefully; evaluate frequently during dosage adjustment to determine lowest therapeutic dosage.a b

• Temporary dosage reduction or discontinuance may be necessary in patients developing intolerable adverse effects.b

• When bromocriptine is discontinued (i.e., during pregnancy) in patients being treated for hyperprolactinemic disorders, monitor patients for tumor progression or development.b (See Warnings: Pregnancy under Cautions.)

Hyperprolactinemic Disorders

• During initial therapy for female infertility, use a mechanical contraceptive in conjunction with bromocriptine therapy until normal ovulatory menstrual cycles have been restored; contraception can then be discontinued.a b

• If menstruation does not occur within 3 days of the expected date, discontinue bromocriptine and perform a pregnancy test.a b

Parkinsonian Syndrome

• Assess patient’s therapeutic response at 2-week intervals to ensure lowest effective dosage is not exceeded.a b

Acromegaly

• Determine serum growth hormone concentrations monthly, and adjust bromocriptine dosage based on the reduction in these concentrations and the patient’s clinical response.a b

• If an adequate response is not apparent after a brief trial with the drug and/or dosage adjustment and clinical evaluation, consider discontinuance of bromocriptine.a b

• Withdraw therapy (4- to 8-week period is usually adequate) annually in patients undergoing radiation therapy of the pituitary to determine if continued therapy with the drug and/or radiation is necessary.a b If signs and/or symptoms of acromegaly recur or growth hormone concentrations increase during this period, consider additional bromocriptine therapy.a b

Administration

Oral Administration

Administer orally with food.a b

Dosage

Available as bromocriptine mesylate; dosage expressed in terms of bromocriptine.a

Pediatric Patients

Children ≥11 years of age: Initially, 1.25–2.5 mg daily.a May increase as tolerated until therapeutic response achieved.a Usual dosage range is 2.5–10 mg daily.a

Adults

Initially, 1.25–2.5 mg daily.a b May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved.a Usual dosage range is 2.5–15 mg daily;a up to 30 mg daily has been required in some patients with amenorrhea and/or galactorrhea.b

Initially, 1.25–2.5 mg daily.a b May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved.a Usual dosage range is 2.5–15 mg daily;a up to 40 mg daily has been required in some patients.b

Initially, 1.25–2.5 mg daily.b May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved.a Usual dosage range is 2.5–15 mg daily.a

Initially, 1.25 mg twice daily with meals.a b If needed, may increase dosage by 2.5 mg daily every 14–28 days; do not exceed 100 mg daily.a b

If levodopa dosage reduced because of adverse effects, may increase daily dosage of bromocriptine gradually in 2.5-mg increments.a b

Initially, 1.25–2.5 mg at bedtime for 3 days.a b May increase dosage by 1.25–2.5 mg daily at 3- to 7-day intervals, as tolerated, until desired therapeutic benefit achieved.a b

Reevaluate patients monthly, adjust dosage based on reduction of growth hormone or clinical response.a b Usual dosage range is 20–30 mg daily; do not exceed 100 mg daily.a b Dosages of 20–60 mg have been administered daily in divided doses.b

2.5–5 mg 2–6 times daily.b

Initially, 1.25 mg daily; increase dosage by 1.25 mg daily every third day up to a total maintenance dosage of 15 mg daily.b

Prescribing Limits

Safety of dosages >100 mg daily not established.a b

Adults

Maximum 100 mg daily.a b Safety of therapy for >2 years not established.a b

Special Populations

Hepatic Impairment

Decreased clearance; dosage adjustment may be necessary.a (See Elimination under Pharmacokinetics)

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

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 Parlodel® (bromocriptine mesylate).

If pregnancy occurs during Parlodel administration, careful observation of these patients is mandatory. Prolactin-secreting adenomas may expand and compression of the optic or other cranial nerves may occur, emergency pituitary surgery becoming necessary. In most cases, the compression resolves following delivery. Reinitiation of Parlodel treatment has been reported to produce improvement in the visual fields of patients in whom nerve compression has occurred during pregnancy. The safety of Parlodel treatment during pregnancy to the mother and fetus has not been established.

Parlodel has been associated with somnolence, and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported. Patients must be informed of this and advised not to drive or operate machines during treatment with bromocriptine. Patients who have experienced somnolence and/or an episode of sudden sleep onset must not drive or operate machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Symptomatic hypotension can occur in patients treated with Parlodel for any indication. In postpartum studies with Parlodel, decreases in supine systolic and diastolic pressures of greater than 20 mm and 10 mm Hg, respectively, have been observed in almost 30% of patients receiving Parlodel. On occasion, the drop in supine systolic pressure was as much as 50-59 mm of Hg.

Since, especially during the first days of treatment, hypotensive reactions may occasionally occur and result in reduced alertness, particular care should be exercised when driving a vehicle or operating machinery.

While hypotension during the start of therapy with Parlodel occurs in some patients, in rare cases serious adverse events, including hypertension, myocardial infarction, seizures, stroke, have been reported in postpartum women treated with Parlodel for the inhibition of lactation. Hypertension have been reported, sometimes at the initiation of therapy, but often developing in the second week of therapy; seizures have also been reported both with and without the prior development of hypertension; stroke have been reported mostly in postpartum patients whose prenatal and obstetric courses had been uncomplicated. Many of these patients experiencing seizures (including cases of status epilepticus) and/or strokes reported developing a constant and often progressively severe headache hours to days prior to the acute event. Some cases of strokes and seizures were also preceded by visual disturbances (blurred vision, and transient cortical blindness). Cases of acute myocardial infarction have also been reported.

Although a causal relationship between Parlodel administration and hypertension, seizures, strokes, and myocardial infarction in postpartum women has not been established, use of the drug for prevention of physiological lactation, or in patients with uncontrolled hypertension is not recommended. In patients being treated for hyperprolactinemia, Parlodel should be withdrawn when pregnancy is diagnosed (see PRECAUTIONS, Hyperprolactinemic States). In the event that Parlodel is reinstituted to control a rapidly expanding macroadenoma (see PRECAUTIONS, Hyperprolactinemic States) and a patient experiences a hypertensive disorder of pregnancy, the benefit of continuing Parlodel must be weighed against the possible risk of its use during a hypertensive disorder of pregnancy. When Parlodel is being used to treat acromegaly or Parkinson's disease in patients who subsequently become pregnant, a decision should be made as to whether the therapy continues to be medically necessary or can be withdrawn. If it is continued, the drug should be withdrawn in those who may experience hypertensive disorders of pregnancy (including eclampsia, preeclampsia, or pregnancy-induced hypertension) unless withdrawal of Parlodel is considered to be medically contraindicated. Because of the possibility of an interaction between Parlodel and other ergot alkaloids, the concomitant use of these medications is not recommended. Periodic monitoring of the blood pressure, particularly during the first weeks of therapy is prudent. If hypertension, severe, progressive, or unremitting headache (with or without visual disturbance), or evidence of CNS toxicity develops, drug therapy should be discontinued and the patient should be evaluated promptly. Particular attention should be paid to patients who have recently been treated or are on concomitant therapy with drugs that can alter blood pressure. Their concomitant use in the puerperium is not recommended.

Among patients on Parlodel, particularly on long-term and high-dose treatment, pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis, have been reported. Patients with unexplained pleuropulmonary disorders should be examined thoroughly and discontinuation of Parlodel therapy should be considered. In those instances in which Parlodel treatment was terminated, the changes slowly reverted towards normal.

In a few patients on Parlodel, particularly on long-term and high-dose treatment, retroperitoneal fibrosis has been reported. To ensure recognition of retroperitoneal fibrosis at an early reversible stage it is recommended that its manifestations (e.g., back pain, edema of the lower limbs, impaired kidney function) should be watched in this category of patients. Parlodel medication should be withdrawn if fibrotic changes in the retroperitoneum are diagnosed or suspected.