2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Added:
Excipients:
Each 50 microgram tablet contains 273.3mg of lactose as lactose monohydrate.
Each 250 microgram tablet contains 271.8mg of lactose as lactose monohydrate.
Each 1000 microgram tablet contains 272.1mg of lactose as lactose monohydrate
For a full list of excipients, see section 6.1.
4. CLINICAL PARTICULARS
4.4 Special warnings and precautions for use
Changes shown in bold and deleted text in strikethrough:
· Cardiac failure; cases of valvular and pericardial fibrosis have often manifested as cardiac failure. Therefore, valvular fibrosis (and constrictive pericarditis) should be excluded if such symptoms occur.
· Cardiac failure, as cases of valvular fibrosis have often manifested as cardiac failure; valvular fibrosis should be excluded if such symptoms appear.
Additional appropriate investigations such as erythrocyte sedimentation rate, chest x-ray and serum creatinine measurements should be performed if necessary to support a diagnosis of a fibrotic disorder.
Hypotension
Patients and their families should be informed of the common adverse consequences of the use of pergolide mesilate and the risk of hypotension. Patients should be warned to begin therapy with low doses and to increase dosage in carefully adjusted increments over a period of 3 to 4 weeks (see section 4.2) to minimise the risk of symptomatic postural and/or sustained hypotension. With gradual dosage titration, tolerance to the hypotension usually develops (but see section 4.5).
Hallucinations and Psychosis
In controlled trials, pergolide mesilate with l-dopa caused hallucinosis in about 14 percent of patients, as opposed to 3 percent taking placebo with l-dopa. This was of sufficient severity to cause discontinuation of treatment in about 3 percent of those enrolled. Tolerance to this untoward effect was not observed. Pergolide should only be administered with caution in patients with a history of psychosis, since pre-existing states of confusion and hallucination may be exacerbated.
Cardiac Disease/Arrhythmia
Caution should be exercised when administering pergolide to patients prone to cardiac dysrhythmias or with significant underlying cardiac disease.
Added following paragraphs:
Patients should be advised to tell their doctor if they become pregnant or intend to become pregnant during therapy. They should also tell their doctor if they are breast-feeding.
Pathological gambling, increased libido and hypersexuality
Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson’s disease, including pergolide.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Deleted:
Patients and their families should be informed of the common adverse consequences of the use of pergolide mesilate and the risk of hypotension.
Patients should be advised to tell their doctor if they become pregnant or intend to become pregnant during therapy. They should also tell their doctor if they are breast-feeding.
4.8 Undesirable effects
Changes shown in bold and deleted text in strikethrough:
There have been reports of fibrotic and serosal inflammatory conditions, such as pleuritis, pleural effusion, pleural fibrosis, pulmonary fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy (including restrictive valvular heart disease and pulmonary hypertension), and retroperitoneal fibrosis, in patients taking pergolide (see section 4.4).
Other events that have been reported include insomnia, confusion, dizziness, constipation, diarrhoea, abnormal liver function tests, postural hypotension, syncope, palpitation, atrial premature contractions, sinus tachycardia, peripheral vasospasm, rash, fever, Raynaud’s phenomenon and neuroleptic malignant syndrome (with rapid detitration of pergolide), and Raynaud’s phenomenon
Patients treated with dopamine agonists for treatment of Parkinson’s disease, including pergolide, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose or treatment discontinuation.
5. PHARMACOLOGICAL PROPERTIES
5.2 Pharmacokinetic properties
Changes shown in bold text:
Studies in male healthy volunteers have shown that pergolide appears to be active at the pituitary, as measured by attenuation of plasma prolactin levels, 2 hours post dosing. Suppression of prolactin following a dose of 50 micrograms may be complete and can last for at least 24 hours. In Parkinson’s disease patients, pergolide appears to be active at the pituitary within 30 minutes of oral dosing, as measured by time to attenuation of plasma prolactin levels. Complete suppression of prolactin occurs 2 hours post-dose.
Because pergolide mesilate is approximately 90 percent associated with plasma proteins, caution should be exercised if it is co-administered with other drugs known to affect protein binding.
5.3 Preclinical safety data
Changes shown in bold text:
Furthermore, no increased risk of uterine malignancies has been identified among patients receiving pergolide.
6. PHARMACEUTICAL PARTICULARS
6.2 Incompatibilities
Changed from ‘Not known’ to ‘Not applicable’.
6.3 Shelf-life
Deletion in strikethrough text.
Two years. when stored appropriately.
6.4 Special precautions for storage
New text in bold and deleted text in strikethrough.
Keep tightly closed.
Protect from light.
Do not store above 25°C. Keep the blister in the outer carton.
6.5 Nature and contents of container
Added:
Starter Pack (adjunctive treatment): 81 tablets containing 75 x 50 microgram tablets and 6 x 250 microgram tablets.
Starter Pack (monotherapy): 166 tablets containing 109 x 50 microgram tablets and 57 x 250 microgram tablets.
Not all pack sizes may be marketed
6.6 Special precautions for disposal
Changed the heading of 6.6 from ‘Instruction for use/handling’ to above and deleted the following statement:
For oral use.
Added:
No special requirements.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Changes in bold:
Date of first authorisation: 6 November 1990
Date of last renewal of authorisation: 10 October 2006
10. DATE OF REVISION OF THE TEXT
New date:
July 2007
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