Adverse reactions : תופעות לוואי

4.8   Undesirable effects

In controlled clinical trials in patients with moderate to severe motor fluctuations 'Sinemet CR' did not produce side-effects which were unique to the modified-release formulation.

The side-effect reported most frequently was dyskinesia (a form of abnormal involuntary movements). A greater incidence of dyskinesias was seen with 'Sinemet CR' than with 'Sinemet'.

Other side-effects that also were reported frequently (above 2%) were: nausea, hallucinations, confusion, dizziness, chorea and dry mouth.

Side effects occurring less frequently (1-2%) were: dream abnormalities, dystonia, somnolence, insomnia, depression, asthenia, vomiting and anorexia.

Other side effects reported in clinical trials or in post-marketing experience include: 
Infections and infestations: urinary tract infections (frequency: very common) 
Body as a whole: chest pain, syncope.

Cardiovascular: palpitation, orthostatic effects including hypotensive episodes.
Gastro-intestinal: constipation, diarrhoea, dyspepsia, gastro-intestinal pain, dark saliva.

Hypersensitivity: angioedema, urticaria, pruritus.

Metabolic: weight loss.
Nervous System/Psychiatric: neuroleptic malignant syndrome (see 4.4 ‘Special warnings and precautions for use’), agitation, anxiety, decreased mental acuity, paraesthesia, disorientation, fatigue, headache, extrapyramidal and movement disorders, falling, gait abnormalities, muscle cramps, on-off phenomenon, increased libido, psychotic episodes including delusions and paranoid ideation. Levodopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.

Respiratory: dyspnoea

Skin: flushing, alopecia, rash, dark sweat.
Special Senses: blurred vision.

Urogenital: dark urine.
Other side effects that have been reported with levodopa or levodopa/carbidopa combinations and may be potential side-effects with 'Sinemet CR' are listed below: 
Cardiovascular: cardiac irregularities, hypertension, phlebitis.

Gastro-intestinal: bitter taste, sialorrhoea, dysphagia, bruxism, hiccups, gastro-intestinal bleeding, flatulence, burning sensation of tongue, development of duodenal ulcer.

Haematologic: leucopenia, haemolytic and non-haemolytic anaemia, thrombocytopenia, agranulocytosis.

Nervous system/Psychiatric: ataxia, numbness, increased hand tremor, muscle twitching, blepharospasm, trismus, activation of latent Horner’s syndrome, euphoria, and dementia, depression with suicidal tendencies and Dopamine Dysregulation Syndrome.

Description of selected adverse reactions
Dopamine Dysregulation Syndrome (DDS) is an addictive disorder seen in some patients treated with carbidopa/ levodopa. Affected patients show a compulsive pattern of dopaminergic drug misuse above doses adequate to control motor symptoms, which may in some cases result in severe dyskinesias (see also section 4.4).

Impulse control disorders
Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including Sinemet CR (see section 4.4. ‘Special warnings and precautions for use’).

Skin: increased sweating.

Special senses: diplopia, dilated pupils, oculogyric crises.
Urogenital: urinary retention, urinary incontinence, priapism.

Miscellaneous: weight gain, oedema, weakness, faintness, hoarseness, malaise, hot flashes, sense of stimulation, bizarre breathing patterns, malignant melanoma (see 4.3 Contraindications), Henoch-Schonlein purpura.

Convulsions have occurred; however, a causal relationship with levodopa or levodopa/carbidopa combinations has not been established.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/