Permax (Pergolide Mesylate) is an ergot derivative dopamine receptor agonist at both D₁ and D₂ receptor sites. Pergolide mesylate is chemically designated as 8B-[(Methylthio)methyl]-6-propylergoline monomethanesulfonate.

The formula weight of the base is 314.5; 1 mg of base corresponds to 3.18 µmol. Permax is provided for oral administration in tablets containing 0.05 mg (0.159 µmol), 0.25 mg (0.795 µmol), or 1 mg (3.18 µmol) pergolide as the base. The tablets also contain croscarmel lose sodium, iron oxide, lactose, magnesium stearate, and povidone. The 0.05-mg tablet also contains methionine, and the 0.25mg tablet also contains FD&C Blue No.2.

Last updated on RxList: 12/8/2004

Permax is indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson†s disease.

Evidence to support the efficacy of pergolide mesylate as an antiparkinsonian adjunct was obtained in a multicenter study enrolling 376 patients with mild to moderate Parkinson†s disease who were intolerant to l-dopa/carbidopa as manifested by moderate to severe dyskinesia and/or on-off phenomena. On average, the patients evaluated had been on l-dopa/carbidopa for 3.9 years (range, 2 days to 16.8 years). The administration of pergolide mesylate permitted a 5% to 30% reduction in the daily dose of l/dopa. On average, these patients treated with pergolide mesylate maintained an equivalent or better clinical status than they exhibited at baseline.

Administration of Permax should be initiated with a daily dosage of 0.05 mg for the first 2 days. The dosage should then be gradually increased by 0.1 or 0.15 mg/day every third day over the next 12 days of therapy. The dosage may then be increased by 0.25 mg/day every third day until an optimal therapeutic dosage is achieved.

Permax is usually administered in divided doses 3 times per day. During dosage titration, the dosage of concurrent l-dopa/carbidopa may be cautiously decreased.

In clinical-studies, the mean therapeutic daily dosage of Permax was 3 mg/day. The average concurrent daily dosage of l-dopa/carbidopa (expressed as l-dopa) was approximately 650 mg/day. The efficacy of Permax at doses above 5 mg/day has not been systematically evaluated.

Tablets (scored):

0.05 mg, ivory, debossed with A615, (UC5336)-(RxPak* of 30) NDC 59075-615-30
0.25 mg, green, debossed with A625, (UC5337)-(RxPak of 100) NDC 59075-625-10
1 mg, pink, debossed with A630, (UC5338)--(RxPak of 100) NDC 59075-630-10

*All RxPaks (prescription packages, Lilly) have safety closures.

Store at controlled room temperature, 59 to 86° F (15 to 30° C ).

CAUTION-Federal (USA) law prohibits dispensing without prescription.

Updated Apr 08, 2003

Last updated on RxList: 12/8/2004

Commonly Observed

In premarketing clinical trials, the most commonly observed adverse events associated with use of pergolide mesylate which were not seen at an equivalent incidence among placebo-treated patients were:

• nervous system complaints, including dyskinesia, hallucinations, somnolence, insomnia;
• digestive complaints, including nausea, constipation, diarrhea, dyspepsia; and
• respiratory system complaints, including rhinitis.

Associated With Discontinuation of Treatment

Twenty-seven percent (27%) of approximately 1,200 patients receiving pergolide mesylate for treatment of Parkinson†s disease in premarketing clinical trials in the US and Canada discontinued treatment due to adverse events. The events most commonly causing discontinuation were related to the nervous system (15.5%), primarily hallucinations (7.8%) and confusion (1.8%).

Fatalities-See WARNINGS.

Incidence in Controlled Clinical Trials

The table that follows enumerates adverse events that occurred at a frequency of 1% or more among patients taking pergolide mesylate who participated in the premarketing controlled clinical trials comparing pergolide mesylate with placebo. In a double-blind, controlled study of 6 month†s duration, patients with Parkinson†s disease were continued on l-dopa/carbidopa and were randomly assigned to receive either pergolide mesylate or placebo as additional therapy.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.

Incidence of Treatment-Emergent Adverse Experiences in the

Placebo-Controlled Clinical Trial Percentage of Patients Reporting Events

Body System/Adverse Event*	Pergolide Mesylate	Placebo
	N= 189	N= 187
Body as a Whole
Pain	7.0	2.1
Abdominal pain	5.8	2.1
Injury, accident	5.8	7.0
Headache	5.3	6.4
Asthenia	4.2	4.8
Chest pain	3.7	2.1
Flu syndrome	3.2	2.1
Neck pain	2.7	1.6
Back pain	1.6	2.1
Surgical procedure	1.6	< 1
Chills	1.1	0
Face edema	1.1	0
Infection	1.1	0
Cardiovascular
Postural hypotension	9.0	7.0
Vasodilatation	3.2	< 1
Palpitation	2.1	< 1
Hypotension	2.1	< 1
Syncope	2.1	1.1
Hypertension	1.6	1.1
Arrhythmia	1.1	< 1
Myocardial infarction	1.1	< 1
Digestive
Nausea	24.3	12.8
Constipation	10.6	5.9
Diarrhea	6.4	2.7
Dyspepsia	6.4	2.1
Anorexia	4.8	2.7
Dry mouth	3.7	< 1
Vomiting	2.7	1.6
Hemic and Lymphatic
Anemia	1.1	< 1
Metabolic and Nutritional
Peripheral edema	7.4	4.3
Edema	1.6	0
Weight gain	1.6	0
Musculoskeletal
Arthralgia	1.6	2.1
Bursitis	1.6		< 1
Myalgia	1.1		< 1
Twitching	1.1		0
Nervous System
Dyskinesia	62.4		24.6
Dizziness	19.1		13.9
Hallucinations	13.8		3.2
Dystonia	11.6		8.0
Confusion	11.1		9.6
Somnolence	10.1		3.7
Insomnia	7.9		3.2
Anxiety	6.4		4.3
Tremor	4.2		7.5
Depression	3.2		5.4
Abnormal dreams	2.7		4.3
Personality disorder	2.1		< 1
Psychosis	2.1		0
Abnormal gait	1.6		1.6
Akathisia	1.6		0
Extrapyramidal syndrome	1.6		1.1
Incoordination	1.6		< 1
Paresthesia	1.6		3.2
Akinesia	1.1		1.1
Hypertonia	1.1		0
Neuralgia	1.1		< 1
Speech disorder	1.1		1.6
Respiratory System
Rhinitis	12.2		5.4
Dyspnea	4.8		1.1
Epistaxis	1.6		< 1
Hiccup	1.1		0
Skin and Appendages
Rash	3.2		2.1
Sweating .	2.1		2.7
Special Senses
Abnormal vision	5.8		5.4
Diplopia	2.1		0
Taste perversion	1.6		0
Eye disorder	1.1		0
Urogenital Svstem
Urinary frequency	2.7		6.4
Urinary tract infection	2.7		3.7
Hematuria	1.1		< 1

 *Events reported by at least 1% of patients receiving pergolide mesylate are included.

Events Observed During the Premarketing Evaluation of Permax

This section reports event frequencies evaluated as of October 1988 for adverse events occurring in a group of approximately 1,800 patients who took multiple doses of pergolide mesylate. The conditions and duration of exposure to pergolide mesylate varied greatly, involving well-controlled studies as well as experience in open and uncontrolled clinical settings. In the absence of appropriate controls in some of the studies, a causal relationship between these events and treatment with pergolide mesylate cannot be determined.

The following enumeration by organ system describes events in terms of their relative frequency of reporting in the data base. Events of major clinical importance are also described in the Warnings and Precautions sections.

The following definitions of frequency are used: frequent adverse events are defined as those occurring in at least 1/100 patients; infre-quent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in fewer than l/1,000 patients.

Body as a Whole - Frequent: headache asthenia, accidental injury, pain, abdominal pain, chest pain, back pain, flu syndrome, neck pain, fever; Infrequent: facial edema, chills, enlarged abdomen, malaise, neoplasm, hernia, pelvic pain, sepsis, cellulitis, moniliasis, abscess, jaw pain, hypothermia; Rare: acute abdominal syndrome, LE syndrome

Cardiovascular System - Frequent: postural hypotension, syncope, hypertension, palpitations, vasodilatations, congestive heart failure; Infrequent: myocardial infarction, tachycardia, heart arrest, abnormal electrocardiogram, angina pectoris, thrombophlebitis, bradycardia, ventricular extrasystoles, cerebrovascular accident, ventricular tachycardia, cerebral ischemia, atrial fibrillation, varicose vein, pulmonary embolus, AV block, shock; Rare: vasculitis, pulmonary hypertension, pericarditis, migraine, heart block, cerebral hemorrhage

Digestive System - Frequent: nausea, vomiting, dyspepsia, diarrhea, constipation, dry mouth, dysphagia; Infrequent: flatulence, abnormal liver function tests, increased appetite, salivary gland enlargement, thirst, gastroenteritis, gastritis, periodontal abscess, intestinal obstruction, nausea and vomiting, gingivitis, esophagitis, cholelithiasis, tooth caries, hepatitis, stomach ulcer, melena, hepatomegaly, hematemesis, eructation; Rare: sialadenitis, peptic ulcer, pancreatitis, jaundice, glossitis, fecal incontinence, duodenitis, colitis, cholecystitis, aphthous stomatitis, esophageal ulcer

Endocrine System - Infrequent: hypothyroidism, adenoma, diabetes mellitus, ADH inappropriate; Rare: endocrine disorder, thyroid adenoma

Hemic and Lymphatic System - Frequent: anemia; Infrequent: leukopenia, lymphadenopathy, leukocytosis, thrombocytopenia, petechia, megaloblastic anemia, cyanosis; Rare: purpura, lymphocytosis, eosinophilia, thrombocythemia, acute lymphoplastic leukemia, polycythemia, splenomegaly

Metabolic and Nutritional System - Frequent: peripheral edema, weight loss, weight gain; Infrequent: dehydration, hypokalemia, hypoglycemia, iron deficiency anemia, hyperglycemia, gout, hyper-cholesteremia; Rare: electrolyte imbalance, cachexia, acidosis, hyperuricemia

Musculoskeletal System - Frequent: twitching, myalgia, arthralgia; Infrequent: bone pain, tenosynovitis, myositis, bone sarcoma, arthritis; Rare: osteoporosis, muscle atrophy, osteomyelitis

Nervous System - Frequent: dyskinesia, dizziness, hallucinations, confusion, somnolence, insomnia, dystonia, paresthesia, depression, anxiety, tremor, akinesia, extrapyramidal syndrome, abnormal gait, abnormal dreams, incoordination, psychosis, personality disorder, nervousness, choreoathetosis, amnesia, paranoid reaction, abnormal thinking; Infrequent: akathisia, neuropathy, neuralgia, hypertonia, delusions, convulsion, libido increased, euphoria, emotional lability, libido decreased, vertigo, myoclonus, coma, apathy, paralysis, neurosis, hyperkinesia, ataxia, acute brain syndrome, torticollis, meningitis, manic reaction, hypokinesia, hostility, agitation, hypotonia; Rare: stupor, neuritis, intracranial hypertension, hemiplegia, facial paralysis, brain edema, myelitis, hallucinations and confusion after abrupt discontinuation

Respiratory System - Frequent: rhinitis, dyspnea, pneumonia, pharyngitis, cough increased; Infrequent: epistaxis, hiccup, sinusitis, bronchitis, voice alteration, hemoptysis, asthma, lung edema, pleural effusion, laryngitis, emphysema, apnea, hyperventilation; Rare: pneumothorax, lung fibrosis, larynx edema, hypoxia, hypoventilation, hemothorax, carcinoma of lung

Skin and Appendages System - Frequent: sweating, rash; Infrequent: skin discoloration, pruritus, acne, skin ulcer, alopecia, dry skin, skin carcinoma, seborrhea, hirsutism, herpes simplex, eczema, fungal dermatitis, herpes zoster; Rare: vesiculobullous rash, subcutaneous nodule, skin nodule, skin benign neoplasm, lichenoid dermatitis

Special Senses System - Frequent: abnormal vision, diplopia; Infrequent: otitis media, conjunctivitis, tinnitus, deafness, taste perversion, ear pain, eye pain, glaucoma, eye hemorrhage, photophobia, visual field defect; Rare: blindness, cataract, retinal detachment, retinal vascular disorder

Urogenital System - Frequent: urinary tract infection, urinary frequency, urinary incontinence, hematuria, dysmenorrhea; Infrequent: dysuria, breast pain, menorrhagia, impotence, cystitis, urinary retention, abortion, vaginal hemorrhage, vaginitis, priapism, kidney calculus, fibrocystic breast, lactation, uterine hemorrhage, urolithiasis, salpingitis, pyuria, metrorrhagia, menopause, kidney failure, breast carcinoma, cervical carcinoma; Rare: amenorrhea, bladder carcinoma, breast engorgement, epididymitis, hypogonadism, leukorrhea, nephrosis, pyelonephritis, urethral pain, uricaciduria, withdrawal bleeding.

Postintroduction Reports - Voluntary reports of adverse events temporally associated with pergolide that have been received since market Introduction and which may have no causal relationship with the drug, include the following: neuroleptic malignant syndrome.

Dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthines ) or metoclopramide, ordinarily should not be administered concurrently with Permax (a dopamine agonist); these agents may diminish the effectiveness of Permax. Because pergolide mesylate is approximately 90% bound to plasma proteins, caution should be exercised if pergolide mesylate is coadministered with other drugs known to affect protein binding.

Last updated on RxList: 12/8/2004

Symptomatic Hypotension

In clinical trials, approximately 10 % of patients taking pergolide mesylate with l-dopa versus 7% taking placebo with l-dopa experienced symptomatic orthostatic and/or sustained hypotension, especially during initial treatment. With gradual dosage titration, tolerance to the hypotension usually develops. It is therefore important to warn patients of the risk, to begin therapy with low doses, and to increase the dosage in carefully adjusted increments over a period of 3 to 4 weeks (see DOSAGE AND ADMININSTRATION).

Hallucinosis

In controlled trials, pergolide mesylate with l-dopa caused hallucinosis in about 14% of patients as opposed to 3% taking placebo with l-dopa. This was of sufficient severity to cause discontinuation of treatment in about 3% of those enrolled; tolerance to this untoward effect was not observed.

Fatalities

In the placebo-controlled trial, 2 of 187 patients treated with placebo died as compared with 1 of 189 patients treated with pergolide mesylate. Of the 2,299 patients treated with pergolide mesylate in premarketing studies evaluated as of October 1988, 143 died while on the drug or shortly after discontinuing it. Because the patient population under evaluation was elderly, ill, and at high risk for death, it seems unlikely that pergolide mesylate played any role in these deaths, but the possibility that pergolide shortens survival of patients cannot be excluded with absolute certainty.

In particular, a case-by-case review of the clinical course of the patients who died failed to disclose any unique set of signs, symptoms, or laboratory results that would suggest that treatment with pergolide caused their deaths. Sixty-eight percent (68%) of the patients who died were 65 years of age or older. No death (other than a suicide) occurred within the first month of treatment; most of the patients who died had been on pergolide for years. A relative frequency of the causes of death by organ system are:

• Pulmonary failure/Pneumonia, 35%;
• Cardiovascular, 30%;
• Cancer, 11%;
• Unknown, 8.4%;
• Infection, 3.5%;
• Extrapyramidal syndrome, 3.5%;
• Stroke, 2.1%;
• Dysphagia, 2.1%;
• Injury, 1 .4 %;
• Suicide, 1.4%;
• Dehydration, 0.7%;
• Glomerulonephritis, 0.7%.

Serious Inflammation and Fibrosis

There have been rare reports of pleuritis, pleural effusion, cardiac valvulopathy involving one or more valves, pleural fibrosis, pericarditis, pericardial effusion or retroperitoneal fibrosis in patients taking pergolide. In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of pergolide. Some patients had experienced similar events while taking the ergot derivative bromocriptine. Pergolide should be used with caution in patients with a history of these conditions, particularly those patients who experienced the events while taking ergot derivatives. Patients with a history of such events should be carefully monitored clinically and with appropriate radiographic and laboratory studies while taking pergolide.

General

Caution should be exercised when administering pergolide mesylate to patients prone to cardiac dysrhythmias.

In a study comparing pergolide mesylate and placebo, patients taking pergolide mesylate were found to have signifiscantly more episodes premature contractions (PACs) and sinus tachycardia.

The use of pergolide mesylate in patients on l-dopa may cause and/or exacerbate preexisting states of confusion and hallucinations (see WARNINGS) and preexisting dyskinesia. Also, the abrupt discontinuation of pergolide mesylate in patients receiving it chronically as an adjunct to l-dopa may precipitate the onset of hallucinations and confusion; these may occur within a span of several days. Discontinuation of pergolide should be undertaken gradually whenever possible, even if the patient is to remain on l-dopa.

A symptom complex resembling the neuroleptic malignant syndrome (NMS) (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology has been reported in association with rapid dose reduction, with drawal of, or changes in antiparkinsonian therapy, including pergolide.

Information for Patients

Patients and their families should be informed of the common adverse consequences of the use of pergolide mesylate (see ADVERSE REACTIONS) and the risk of hypotension (see WARNINGS ). Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be advised to notify their physician if they are breast feeding an infant.

Laboratory Tests

No specific laboratory tests are deemed essential for the management of patients on Permax. Periodic routine evaluation of all patients, however, is appropriate.

Drug Interactions

Dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthines ) or metoclopramide, ordinarily should not be administered concurrently with Permax (a dopamine agonist); these agents may diminish the effectiveness of Permax. Because pergolide mesylate is approximately 90% bound to plasma proteins, caution should be exercised if pergolide mesylate is coadministered with other drugs known to affect protein binding.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

A 2-year carcinogenicity study was conducted in mice using dietary levels of pergolide mesylate equivalent to oral doses of 0.6, 3.7, and 36.4 mg/kg/day in males and 0.6, 4.4, and 40.8 mg/kg/day in females. A 2-year study in rats was conducted using dietary levels equivalent to oral doses of 0.04, 0.18, and 0.88 mg/kg/day in males and 0.05, 0.28, and 1.42 mg/kg/day in females. The highest doses tested in the mice and rats were approximately 340 and 12 times the maximum human oral dose administered in controlled clinical trials (6 mg/day equivalent to 0.12 mg/kg/day).

A low incidence of uterine neoplasms occurred in both rats and mice. Endometrial adenomas and carcinomas were observed in rats. Endometrial sarcomas were observed in mice. The occurrence of these neoplasms is probably attributable to the high estrogen/progesterone ratio that would occur in rodents as a result of the prolactin-inhibiting action of pergolide mesylate. The endocrine mechanisms believed to be involved in the rodents are not present in humans. However, even though there is no known correlation between uterine malignancies occurring in pergolide-treated rodents and human risk, there are no human data to substantiate this conclusion.

Pergolide mesylate was evaluated for mutagenic potential in a battery of tests that included an Ames bacterial mutation assay, a DNA repair assay in cultured rat hepatocytes, an in vitro mammalian cell-point- mutation assay in cultured L5178Y cells, and a determination of chromosome alteration in bone marrow cells of Chinese hamsters. A weak mutagenic response was noted in the mammalian cell-point-mutation assay only after metabolic activation with rat liver microsomes. No mutagenic effects were obtained in the 2 other in vitro assays and in the in vivo assay. The relevance of these findings in humans is unknown.

A fertility study in male and female mice showed that fertility was maintained at 0.6 and 1.7 mg/kg/day but decreased at 5.6 mg/kg/day. Prolactin has been reported to be involved in stimulating and maintaining progesterone levels required for implantation in mice and therefore, the impaired fertility at the high dose may have occurred because of decressed prolactin levels.

Usage in Pregnancy

Pregnancy Category B: Reproduction studies were conducted in mice at doses of 5, 16, and 45 mg/kg/day and in rabbits at doses of 2, 6, and 16 mg/kg/day. The highest doses tested in mice and rabbits were 375 and 133 times the 6 mg /day maximum human dose administered in controlled clinical trials. In these studies, there was no evidence of harm to the fetus due to pergolide mesylate.

There are, however, no adequate and well-controlled studies in pregnant women. Among women who received pergolide mesylate for endocrine disorders in premarketing studies, there were 33 pregnancies that resulted in healthy babies and 6 pregnancies that resulted in congenital abnormalities (3 major, 3 minor); a causal relationship has not been established. Because human data are limited and because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. The pharmacologic action of pergolide mesylate suggests that it may interfere with lactation. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions to pergolide mesylate in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Last updated on RxList: 12/8/2004

There is no clinical experience with massive overdosage. The largest overdose involved a young hospitalized adult patient who was not being treated with pergolide mesylate but who intentionally took 60 mg of the drug. He experienced vomiting, hypotension, and agitation. Another patient receiving a daily dosage of 7 mg of pergolide mesylate unintentionally took 19 mg/day for 3 days, after which his vital signs were normal but he experienced severe hallucinations. Within 36 hours of resumption of the prescribed dosage level, the hallucinations stopped. One patient unintentionally took 14 mg/day for 23 days instead of her prescribed 1.4 mg/day dosage. She experienced severe involuntary movements and tingling in her arms and legs. Another patient who inadvertently received 7 mg instead of the prescribed 0.7 mg experienced palpitations, hypotension, and ventricular extrasystoles. The highest total daily dose (prescribed for several patients with refractory Parkinson†s disease) has exceeded 30 mg.

Symptoms

Animal studies indicate that the manifestations of over-dosage in man might include nausea, vomiting, convulsions, decreased blood pressure, and CNS stimulation. The oral median lethal doses in mice and rats were 54 and 15 mg/kg respectively.

Treatment

To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

Management of overdosage may require supportive measures to maintain arterial blood pressure. Cardiac function should be monitored; an antiarrhythmic agent may be necessary. If signs of CNS stimulation are present, a phenothiazine or other butvronhenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdose has not been assessed.

Protect the patient†s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient†s vital signs, blood gases, serum electrolytes, etc.. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient†s airway when employing gastric emptying or charcoal.

There is no experience with dialysis or hemoperfusion, and these procedures are unlikely to be of benefit.

Pergolide mesylate is contraindicated in patients who are hypersensitive to this drug or other ergot derivatives.

Last updated on RxList: 12/8/2004

Pharmacodynamic Information

Pergolide mesylate is a potent dopamine receptor agonist. Pergolide is 10 to 1,000 times more potent than bromocriptine on a milligram per milligram basis in various in vitro and in vivo test systems. Pergolide mesylate inhibits the secretion of prolactin in humans; it causes a transient rise in serum concentrations of growth hormone and a decrease in serum concentrations of luteinizing hormone. In Parkinson†s disease, pergolide mesylate is believed to exert its therapeutic effect by directly stimulating postsynaptic dopamine receptors in the nigrostriatal system.

Pharmacokinetic Information (Absorption, Distribution, Metabolism, and Elimination)

Information on oral systemic bioavailability of pergolide mesylate is unavailable because of the lack of a sufficiently sensitive assay to detect the drug after the administration of a single dose. However, following oral administration of ¹⁴C radiolabeled pergolide mesylate, approximately 55% of the administered radioactivity can be recovered from the urine and 5% from expired CO₂, suggesting that a significant fraction is absorbed. Nothing can be concluded about the extent of presystemic clearance, if any.

Data on postabsorption distribution of pergolide are unavailable.

At least 10 metabolites have been detected, including N-despropyl-pergolide, pergolide sulfoxide, and pergolide sulfone. Perolide sulfoxide and pergolide sulfone are dopamine agonists in animals. The other detected metabolites have not been identified and it is not known whether any other metabolites are active pharmacologically.

The major route of excretion is the kidney.

Pergolide is approximately 90% bound to plasma proteins. This extent of protein binding may be important to consider when pergolide mesylate is coadministered with other drugs known to affect protein binding.

Last updated on RxList: 12/8/2004

Patients and their families should be informed of the common adverse consequences of the use of pergolide mesylate (see ADVERSE REACTIONS) and the risk of hypotension (see WARNINGS ). Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be advised to notify their physician if they are breast feeding an infant.

Last updated on RxList: 12/8/2004

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

PERGOLIDE - ORAL

(PURR-go-lide)

COMMON BRAND NAME(S): Permax

USES: This medication is used to treat Parkinson's disease. It can improve your ability to move and decrease shakiness (tremor), stiffness, slowed movement, and unsteadiness. It may also decrease the number of episodes of not being able to move ("on-off syndrome").

Pergolide is an ergot medication that works by helping to restore the balance of a certain natural substance (dopamine) in the brain.

This medication has been withdrawn from the U.S. market due to safety problems (see Side Effects-heart valve problems). Do not stop taking this medication suddenly (see How To Use section). Talk to your doctor or pharmacist about other treatment options (e.g., pramipexole, ropinirole).

HOW TO USE: Take this medication by mouth with or without food, usually 3 times a day or as directed by your doctor. Taking this medication with food may reduce nausea. To decrease the risk of side effects (e.g., drowsiness, low blood pressure) when you first start taking pergolide, your doctor will slowly increase your dosage until the best dose for you is reached. Take this medication exactly as prescribed. Do not increase your dose or take it more often than directed.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day. If you are taking levodopa or a carbidopa/levodopa combination, your doctor may direct you to decrease your levodopa dose after you start taking pergolide. Follow your doctor's directions carefully.

Do not stop taking this medication without your doctor's approval. If you suddenly stop taking this drug, withdrawal reactions may occur. Such reactions can include fever, muscle stiffness, confusion, and hallucinations. Report any such reactions to your doctor immediately. When stopping extended, regular treatment with this drug, gradually reducing the dosage as directed will help prevent withdrawal reactions. Consult your doctor or pharmacist for more details.

The dosage is based on your medical condition and response to treatment. It may take a few weeks for you to notice the full effects of this medication.

Tell your doctor if your symptoms do not improve or if they worsen.

SIDE EFFECTS: Nausea, dizziness, drowsiness, trouble sleeping, diarrhea, heartburn, runny nose, constipation, headache, or dry mouth may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fainting, mental/mood changes (e.g., confusion, depression, hallucinations, memory problems), increased difficulty moving/walking, muscle cramps/spasm, restlessness, decreased sexual function.

Some people taking pergolide have reported falling asleep suddenly during their usual daily activities (e.g., watching television, driving). In some cases, sleep occurred without any feelings of drowsiness beforehand. This sleep effect may occur any time during treatment with pergolide, including up to 1 year after starting the medication. Therefore, you should not drive or take part in other possibly dangerous activities until you are certain that this medication will not cause drowsiness or sudden sleep. If you experience increased sleepiness or fall asleep during the day, do not drive or take part in other possibly dangerous activities until you have discussed this effect with your doctor. Your risk is increased with use of alcohol or other medications that can make you drowsy.

You may also develop a sudden drop in blood pressure, which can cause dizziness, nausea, sweating, and fainting. This is more likely when you are first starting the medication, when your dose is increased, or when you get up suddenly. To lower your risk, get up slowly from a sitting or lying position.

In rare cases, this medication may cause very serious heart valve problems or swelling around the heart and lungs (e.g., pleural fibrosis/effusion, pericarditis). Tell your doctor immediately if you develop any of the following symptoms: difficult/painful breathing, chest pain, unusually slow/fast/irregular heartbeat, swelling of the ankles/feet, unusual weakness.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking pergolide, tell your doctor or pharmacist if you are allergic to it; or to other ergot medications (e.g., bromocriptine); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, heart problems (e.g., fast/ irregular heartbeat, heart failure, heart valve problems), kidney problems, lung problems (e.g., pulmonary fibrosis), mental/mood disorders (e.g., confusion, hallucinations, psychosis, schizophrenia), sleep disorder (e.g., sleep apnea, narcolepsy).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Avoid alcoholic beverages.

To reduce dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at greater risk for side effects such as dizziness and hallucinations.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. It may affect milk production. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: ergot alkaloids (e.g., ergonovine).

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting pergolide.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antipsychotic medication (e.g., haloperidol, pimozide, thiothixene), metoclopramide.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., phenytoin), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, nortriptyline, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., blood pressure, radiographic studies, kidney function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.