Sifrol Special Precautions

Renal impairment: When prescribing SIFROL in a patient with renal impairment a reduced dose is suggested in line with section Dosage & Administration.
Hallucinations and abnormal behaviour: Hallucinations and confusion are known side effects of treatment with dopamine agonists and levodopa in Parkinson's disease patients. Hallucinations were more frequent when SIFROL was given in combination with levodopa in Parkinson's disease patients with advanced disease than in monotherapy in Parkinson's disease patients with early disease.
Within the RLS clinical development program for registration, one case of hallucinations has been reported. Patients should be informed that (mostly visual) hallucinations can occur.
Patients should be made aware of the fact that hallucinations can occur and may adversely affect their ability to drive.
Patients with psychotic disorders: Patients with psychotic disorders should be treated with dopamine agonists only if the potential benefits outweigh the risks. Co-administration of antipsychotic medicinal products with pramipexole dihydrochloride monohydrate is not recommended, e.g. if dopamine-antagonistic effects can be expected.
Patients and caregivers should be made aware of the fact that abnormal behavior (reflecting symptoms of impulse control disorders and compulsive behaviors) such as binge eating, compulsive shopping, hypersexuality, and pathological gambling have been reported in patients treated with dopaminergic drugs. Dose reduction/tapered discontinuation should be considered.
Retinal changes in albino rats: Pathologic changes (degeneration and loss of photoreceptor cells) were observed in the retina of albino rats in the 2-years carcinogenicity study. Evaluation of the retinas of albino mice, pigmented rats, monkeys, and minipigs did not reveal similar changes. The potential significance of this effect in humans has not been established, but cannot be disregarded because disruption of a mechanism that is universally present in vertebrates (i.e. disk shedding) may be involved.
Postural hypotension: In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of postural hypotension associated with dopaminergic therapy.
Sudden onset of sleep and somnolence: Patients should be alerted to the potential sedating effects associated with SIFROL, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Since somnolence is a frequent adverse event with potentially serious consequences, patients should neither drive a car nor operate other complex machinery until they have gained sufficient experience with SIFROL to gauge whether or not it affects their mental and/or motor performance adversely. Patients should be advised that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., conversations, eating, etc.) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities and should contact their physician.
Melanoma: Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanoma when using pramipexole dihydrochloride monohydrate or other dopaminergic drugs.
Treatment discontinuation in Parkinson's disease: Symptoms suggestive of a neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy (see Dosage & Administration). Augmentation in RLS: Reports in the literature that indicate treatment of RLS with dopaminergic medications can result in augmentation.
Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other extremities. Augmentation was specifically investigated in a controlled clinical trial over 26 weeks. Kaplan-Meier analysis of time to augmentation showed no significant difference between pramipexole dihydrochloride monohydrate (N = 152) and placebo groups (N = 149).
Remnants in stool: Some patients have reported the occurrence of remnants in faeces which may resemble intact SIFROL prolonged-release tablets. If patients report such an observation, the physician should reassess patient's response to therapy.
Effects on Ability to Drive and Use Machines: Patients should be aware of the fact that hallucinations can occur and may adversely affect their ability to drive.
Patients should be alerted to the potential sedating effects associated with SIFROL, including somnolence and the possibility of falling asleep while engaged in activities of daily living (see Precautions).
Since somnolence is a frequent adverse event with potentially serious consequences, patients should neither drive a car nor operate other complex machinery until they have gained sufficient experience with SIFROL to gauge whether or not it affects their mental and/or motor performance adversely.