Source: Υπουργείο Υγείας (CY) Revision Year: 2026 Publisher: Remedica Ltd, Aharnon Street, Limassol Industrial Estate 3056 Limassol, Cyprus, EU
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Non-selective monoamine oxidase (MAO) inhibitors are contraindicated for use with Credanil. These inhibitors must be discontinued at least two weeks before starting Credanil. Credanil may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selective MAO type B (e.g. selegiline hydrochloride). (see section 4.5).
Credanil is contraindicated in patients with narrow-angle glaucoma and in patients with known hypersensitivity to any component of this medication.
Because levodopa may activate a malignant melanoma, it should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma (see also section 4.6).
Use in patients with severe psychoses.
Credanil is not recommended for the treatment of drug-induced extrapyramidal reactions.
Credanil should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease (because of the possibility of upper gastro-intestinal haemorrhage).
Care should be exercised when Credanil is administered to patients with a history of myocardial infarction who have residual atrial nodal, or ventricular arrhythmias. Cardiac function should be monitored with particular care in such patients during the period of initial dosage adjustment.
Levodopa has been associated with somnolence and episodes of sudden sleep onset. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with levodopa. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore a reduction of dosage or termination of therapy may be considered.
All patients should be monitored carefully for the development of mental changes, depression with suicidal tendencies, and other serious antisocial behaviour. Patients with current psychoses should be treated with caution.
Dyskinesias may occur in patients previously treated with levodopa alone because carbidopa permits more levodopa to reach the brain and, thus, more dopamine to be formed. The occurrence of dyskinesias may require dosage reduction.
As with levodopa, Credanil may cause involuntary movements and mental disturbances. Patients with a history of severe involuntary movements or psychotic episodes when treated with levodopa alone should be observed carefully when Credanil is substituted. These reactions are thought to be due to increased brain dopamine following administration of levodopa, and use of Credanil may cause a recurrence. A syndrome resembling the neuroleptic malignant syndrome including muscular rigidity, elevated body temperature, mental changes and increased serum creatine phosphokinase has been reported with the abrupt withdrawal of antiparkinsonian agents. Therefore, any abrupt dosage reduction or withdrawal of Credanil should be carefully observed, particularly in patients who are also receiving neuroleptics.
Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of Credanil than with levodopa. Transient abnormalities include elevated levels of blood urea, AST (SGOT), ALT (SGPT), LDH, bilirubin, and alkaline phosphatase.
Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.
Positive Coombs' tests have been reported, both with Credanil and levodopa alone.
Credanil may cause a false positive result when a dipstick is used to test for urinary ketone; and this reaction is not altered by boiling the urine. The use of glucose oxidase methods may give false negative results for glycosuria.
Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including 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 Credanil. Review of treatment is recommended if such symptoms develop.
Dopamine Dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some patients treated with carbidopa/levodopa. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing DDS (see also section 4.8).
Concomitant administration of psycho-active drugs such as phenothiazines or butyrophenones should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect. Patients with a history of convulsions should be treated with caution.
As with levodopa, periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function are recommended during extended therapy.
Patients with chronic wide-angle glaucoma may be treated cautiously with Credanil, provided the intra-ocular pressure is well controlled and the patient monitored carefully for changes in intra-ocular pressure during therapy.
If general anaesthesia is required, therapy with Credanil may be continued for as long as the patient is permitted to take fluids and medication by mouth. If therapy has to be stopped temporarily, Credanil may be restarted as soon as oral medication can be taken at the same daily dosage as before.
Epidemiological studies have shown that patients with Parkinson's disease have a higher risk of developing melanoma than the general population (approximately 2-6 fold higher). It is unclear whether the increased risk observed was due to Parkinson's disease, or other factors such as drugs used to treat Parkinson's disease. Therefore patients and providers are advised to monitor for melanomas on a regular basis when using Credanil for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
Caution should be exercised when the following drugs are administered concomitantly with Credanil.
Postural hypotension can occur when Credanil is added to the treatment of patients already receiving antihypertensive drugs. Dosage adjustment of the antihypertensive agent may be required.
Rarely, reactions including hypertension and dyskinesia have been reported with the concomitant use of tricyclic antidepressants (see section 4.3 Contraindications for patients receiving MAOIs).
Anticholinergics may affect the absorption and thus the patient's response.
Studies demonstrate a decrease in the bioavailability of carbidopa and/or levodopa when it is ingested with ferrous sulphate or ferrous gluconate.
To date there has been no indication of interactions that would preclude concurrent use of standard antiparkinsonian drugs.
Dopamine D2 receptor antagonists (e.g. phenothiazines, butyrophenones and risperidone) and isoniazid, may reduce the therapeutic effect of levodopa. The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with Credanil should be carefully observed for loss of therapeutic response.
Use of Credanil with dopamine-depleting agents (e.g. tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.
Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone (see section 4.3).
Since levodopa competes with certain amino acids, the absorption of Credanil may be impaired in some patients on a high protein diet.
The effect of simultaneous administration of antacids with Credanil on the bioavailability of levodopa has not been studied.
Credanil may be given to patients with Parkinson's disease and syndrome who are taking vitamin preparations that contain pyridoxine hydrochloride (Vitamin B6).
Although the effects of Credanil on human pregnancy are unknown, both levodopa and combinations of carbidopa and levodopa have caused visceral and skeletal malformations in rabbits. Therefore, the use of Credanil in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards should pregnancy occur.
It is not known whether carbidopa or levodopa is excreted in human milk. In a study of one nursing mother with Parkinson's disease, excretion of levodopa in human breast milk was reported. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in infants, a decision should be made whether to discontinue breastfeeding or discontinue the use of Credanil, taking into account the importance of the drug to the mother.
Individual responses to medication may vary and certain side effects that have been reported with Credanil may affect some patients' ability to drive or operate machinery. Patients treated with levodopa and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines), until such recurrent episodes and somnolence have resolved (see also section 4.4).
Side effects that occur frequently with Credanil are those due to the central neuropharmacological activity of dopamine. These reactions can usually be diminished by dosage reduction. The most common are dyskinesias including choreiform, dystonic and other involuntary movements and nausea. Muscle twitching and blepharospasm may be taken as early signs to consider dosage reduction.
Other serious side effects reported in clinical trials or in post-marketing experience include:
Body as a whole: Syncope, chest pain, anorexia.
Cardiovascular: Cardiac irregularities and/or palpitations, orthostatic effects including hypotensive episodes, hypertension, phlebitis.
Gastro-intestinal: Vomiting, gastro-intestinal bleeding, development of duodenal ulcer, diarrhoea, dark saliva.
Hematologic: Leucopenia, haemolytic and non-haemolytic anaemia, thrombocytopenia, agranulocytosis.
Hypersensitivity: Angioedema, urticaria, pruritus, Henoch-Schonlein purpura.
Nervous System/Psychiatric: Neuroleptic malignant syndrome (see section 4.3), bradykinetic episodes (the "on-off" phenomenon), dizziness, paraesthesia, psychotic episodes including delusions, hallucinations and paranoid ideation, depression with or without development of suicidal tendencies, dementia, dream abnormalities, agitation, confusion, increased libido. Levodopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.
Respiratory: Dyspnoea.
Skin: Alopecia, rash, dark sweat.
Urogenital: Dark urine.
Rarely convulsions have occurred; however, a causal relationship with Credanil has not been established.
Other side effects that have been reported with levodopa or levodopa/carbidopa combinations and may be potential side effects with Credanil include:
Nervous System/Psychiatric: Asthenia, decreased mental acuity, disorientation, ataxia, numbness, increased hand tremor, muscle cramp, trismus, activation of latent Horner's syndrome, insomnia, anxiety, euphoria, falling and gait abnormalities.
Frequency "not known": Dopamine dysregulation syndrome.
Gastro-intestinal: Dyspepsia, dry mouth, bitter taste, sialorrhoea, dysphagia, bruxism, hiccups, abdominal pain and distress, constipation, diarrhoea, flatulence, burning sensation of the tongue.
Metabolic: Weight gain or loss, oedema.
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 Credanil (see section 4.4).
Skin: Flushing, increased sweating.
Special senses: Diplopia, blurred vision, dilated pupils, oculogyric crises.
Urogenital: Urinary retention, urinary incontinence, priapism.
Infections and Infestations: Urinary tract infections (frequency: very common)
Miscellaneous: Weakness, faintness, fatigue, headache, hoarseness, malaise, hot flushes, sense of stimulation, bizarre breathing patterns, malignant melanoma (see section 4.3).
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).
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Cyprus: Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Tel: +357 22608607, Fax: +357 22608669, Website: www.moh.gov.cy/phs/
Not applicable.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.