Summary of Product Characteristics (SmPC) - Precifit 5 mg/1.25 mg dispersible tablet for dose Dispenser
1 NAME OF THE MEDICINAL PRODUCT
Precifit 5 mg/1.25 mg dispersible tablet for dose dispenser
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One dispersible tablet contains: levodopa 5 mg and carbidopa monohydrate corresponding to carbidopa 1.25 mg.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Dispersible tablet for dose dispenser.
White, spherical tablets with a diameter of about 3 mm.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Precifit is indicated for treatment of adult patients with idiopathic Parkinson's disease and syndrome.
4.2 Posology and method of administration
Posology
Treatment with Precifit primarily focuses on individualized therapy using either the pre-filled dose dispenser OraFID or the dose dispenser MyFID. The optimum daily dosage of levodopa/carbidopa must be determined by careful titration in each patient.
Precifit is available as small dose tablets, in a ratio of 1:4 of carbidopa to levodopa, to facilitate precise dosage for each patient.
General Considerations
Studies show that the peripheral dopa-decarboxylase is fully inhibited (saturated) by carbidopa at doses between 70 and 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.
Standard antiparkinsonian drugs, other than levodopa alone, may be continued while carbidopa/levodopa is being administered, although their dosage may have to be adjusted.
Patients should be carefully monitored during the dosage adjustment period. Involuntary movements, particularly blepharospasm, are a useful early sign of excess dosage in some patients.
Dosage may be best initiated with a 100/25 dose three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by 50/12.5-100/25 mg of Precifit every day or every other day, as necessary, maximum until a dosage equivalent of 800/200 mg of Precifit a day is reached.
Response has been observed in one day, and sometimes after one dose. Fully effective doses usually are reached within seven days as compared to weeks or months with levodopa alone.
Precifit tablets may be used for dosage titration according to the needs of the individual patient.
Maintenance
Therapy with Precifit should be individualized and adjusted gradually according to response. Patients who experience fluctuations in response and end of dose effect (wearing-off) may be helped by dividing the dosage into smaller, more frequent dosing without, however, altering the total daily dose.
If necessary, the dosage of Precifit may be increased to a maximum of 2000/500 mg a day. Experience with a total daily dosage greater than 200 mg carbidopa is limited.
Patients receiving levodopa with another decarboxylase inhibitor
Begin with a dosage of Precifit that will provide the same amount of levodopa as contained in the other levodopa/decarboxylase inhibitor combination.
Patients receiving other antiparkinsonian agents
Current evidence indicates that other antiparkinsonian agents may be continued when carbidopa/levodopa is introduced, although dosage may have to be adjusted in line with manufacturer’s recommendations.
Use in the elderly
There is wide experience in the use of levodopa/carbidopa in elderly patients. The recommendations set out above reflect the clinical data derived from this experience.
Patients with renal impairment
Impact of renal function on levodopa/carbidopa clearance is limited. Precifit should be administered cautiously to patients with renal impairment. The dose should be titrated individually.
Patients with hepatic impairment
Precifit should be administered cautiously to patients with mild to moderate hepatic impairment. The dose should be titrated individually.
Paediatric population
The safety of Precifit in patients under 18 years has not been established.
There is no relevant use of Precifit in children and adolescents in the indication of patients with idiopathic Parkinson's disease.
Method of administration
Oral use. The tablets should be dissolved in half a glass of water. When dissolved, a whitish dispersion is formed within a few minutes. Intake should be done immediately after dissolution.
The tablets (small tablets, each with a low dose of levodopa/carbidopa) are administered either by a pre-filled dose dispenser called OraFID or with a separately provided dose dispenser, called MyFID. Both dose dispensers deliver individualized dose based on the number of tablets dispensed.
Precifit in a pre-filled dose dispenser, OraFID
OraFID dispenses the correct number of tablets as long as there are tablets needed for a full dose left in the container. The OraFID container is disposable and should not be refilled. OraFID contains 2 250 dispersible tablets.
The dose dispenser can dispense 1-20 tablets per withdrawal. With a total daily dosage of 300–400 mg levodopa, the OraFID pre-filled dose dispenser will last about four to five weeks.
Precifit cartridges in MyFID dose dispenser
The MyFID dose dispenser is loaded with a cartridge containing 750 dispersible tablets.
The MyFID dose dispenser has a reminder function to facilitate dosage compliance. The dose dispenser is also equipped with a system for dose recording and symptom rating from which data can be transmitted to the treating physician.
At total daily dosages of 300–400 mg levodopa one cartridge lasts for about a week and a half.
When the cartridge is empty, it can easily be replaced by the patient.
For further information, see the manual of the dose dispenser.
Intake with food and drink: If possible, Precifit should be taken 30 minutes before or 1 hour after meals. Intake of Precifit with protein-rich food can reduce the effect.
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Non-selective monoamine oxidase (MAO) inhibitors and selective MAO type A inhibitors are contraindicated for use with Precifit.
These inhibitors must be discontinued at least two weeks before starting therapy with Precifit. Precifit may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g. selegiline hydrochloride). (See section 4.5 'Interaction with other medicinal products and other forms of interaction'.)
Precifit is contraindicated in patients with narrow-angle glaucoma.
Since levodopa may activate a malignant melanoma, it should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.
Conditions in which adrenergics are contraindicated, e.g. pheochromocytoma, hyperthyroidism, Cushing's syndrome, as well as psychosis.
4.4 Special warnings and precautions for use
Precifit is not recommended for the treatment of drug-induced extrapyramidal reactions.
Precifit 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 Precifit 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. A dosage reduction of antihypertensive treatment may be necessary.
If a COMT inhibitor is added to Precifit, it can be necessary to lower the dose of Precifit.
Precifit may induce orthostatic hypotension. Therefore Precifit should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension.
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.
As with levodopa, Precifit 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 Precifit is substituted. These reactions are thought to be due to increased brain dopamine following administration of levodopa, and use of Precifit may cause a recurrence.
At abrupt withdrawal of anti-Parkinsonian agents (especially during concomitant treatment with neuroleptics), Neuroleptic Malignant Syndrome including muscular rigidity, elevated body temperature, mental changes and elevated serum creatinine phosphokinase values have been reported. Therefore, patients should be closely monitored if the dosage of Precifit is abruptly reduced or the treatment is discontinued, especially when receiving concurrent treatment with neuroleptics.
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.
Impulse control disorders
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 Precifit. Review of treatment is recommended if such symptoms develop.
Concomitant administration of antipsychotics with dopamine receptor blocking properties, particularly D2 receptor antagonists should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect or worsening of parkinsonian symptoms.
Patients with a history of convulsions should be treated with caution.
As with levodopa, periodic evaluation of hepatic, haematopoetic, cardiovascular and renal function are recommended during extended therapy.
Patients with chronic wide-angle glaucoma may be treated cautiously with Precifit 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 Precifit 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, carbidopa/levodopa 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 medicinal products used to treat Parkinson's disease. Therefore, patients and providers are advised to monitor for melanomas on a regular basis when using Precifit for any indication. Periodic skin examinations performed by appropriately qualified individuals such as dermatologists, should be considered.
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).
Effect on laboratory tests
Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of carbidopa/levodopa 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 carbidopa/levodopa and levodopa alone.
Precifit 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.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with Precifit. The following interactions are known from generic combination of levodopa/carbidopa.
The following combination is contraindicated:
Non-selective MAO inhibitors and selective MAO-A inhibitors should not be given concomitantly with Precifit and must be discontinued at least two weeks prior to initiation of the treatment, see Section 4.3.
The following combinations with Precifit may require dose adjustment:
Butyrophenone derivatives: Butyrophenone derivatives counteract the effect of levodopa by blocking dopamine receptors in the brain.
Phenothiazines substituted with dimethylaminopropyl link/piperazine ring: Phenothiazines counteracts the effects of levodopa by blocking dopamine receptors in the brain. Phenothiazines with piperidine chain (thioridazine and pericyazine) have relatively weak dopamine receptor blocking properties.
Ferrous iron, oral preparations: Concomitant administration of single doses of ferrous sulphate and levodopa to healthy volunteers reduces the bioavailability of levodopa by 50%, probably because of chelating. Also, the bioavailability of carbidopa is reduced (by 75%). The agents should be given with the longest possible time intervals.
Pimozide: pimozide counteracts the effect of levodopa by blocking dopamine receptors in the brain.
Tetrabenazin counteracts the effect of levodopa and reduces its effect. Use of Precifit together with tetrabenazine or other medicinal products that reduce dopamine and other monoamines in the central nervous system should be avoided.
Pyridoxin accelerates the systemic metabolism of levodopa. Carbidopa inhibits this effect.
Other medications: D2 dopamine receptor antagonists (e.g., phenothiazines, butyrophenones, and risperidone) and isoniazid may reduce the therapeutic effect of levodopa. Additionally, there have been reports that phenytoin and papaverine might alter the effect of levodopa. Any potential loss of therapeutic response should be closely monitored when patients are receiving these medications concurrently with Precifit.
Concomitant therapy with MAO-B inhibitors such as rasagiline and selegiline with carbidopa/levodopa has been associated with severe orthostatic hypotension not attributed to carbidopa/levodopa only.
Metoclopramide, a dopamine -receptor antagonist, can reduce the effect of levodopa treatment by blocking postsynaptic dopamine receptors.
The concurrent use of catechol-O-methyltransferase inhibitors (COMT inhibitors) and levodopa/decarboxylase inhibitors can increase the bioavailability of levodopa. It may become necessary to reduce the dosage of the levodopa/decarboxylase inhibitor.
A protein-rich diet can reduce the absorption of levodopa.
Rarely, reactions including hypertension and dyskinesia have been reported with the concomitant use of tricyclic antidepressants.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of carbidopa/levodopa in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Precifit is not recommended during pregnancy or in women of childbearing potential not using contraception unless the benefits for the mother outweigh the possible risk to the fetus.
Breastfeeding
It is not known whether carbidopa or its metabolites are excreted in human milk. Animal studies have shown excretion of carbidopa in breast milk. Levodopa and possibly levodopa metabolites are excreted in human milk. There is insufficient information on the effects of carbidopa/levodopa or their metabolites in newborns/infants. Breastfeeding should be discontinued during treatment with Precifit.
Fertility
There are no data on the effects of carbidopa/levodopa on human fertility. No adverse effect on fertility has been observed in animal studies with levodopa alone. Fertility studies in animals have not been conducted with the combination of carbidopa and levodopa.
4.7 Effects on ability to drive and use machines
Precifit may have major influence on the ability to drive and use machines.
Individual responses to medication may vary and certain side effects that have been reported with carbidopa/levodopa 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 'Special warnings and precautions for use').
4.8 Undesirable effects
Summary of the safety profile
Side effects that occur frequently with carbidopa/levodopa 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.
Tabulated list of adverse reactions
Adverse events classified by MedDRA convention and frequency;
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); no known frequency (cannot be estimated from the available data).
MedDRA System Organ Class | Very common (≥1/10) | Common (≥ 1/100 to < 1/10) | Uncommo n (>1/1,000 to <1/100) | Rare (>1/10,000 to <1/1,000) | Very rare (<1/10,000) |
not known (cannot be estimated from the available data)
| Infections and Infestations | Urinary tract infections | ||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Malignant melanoma | ||||
Blood and lymphatic system disorders | Leukopenia, haemolytic and non- haemolytic anaemia, thrombocytope nia | Agranulocyt osis | |||
| Immune system disorders | Hypersensitivi ty reactions including angioedema | ||||
| Metabolism and nutrition disorders | Anorexia | Weight gain or loss | |||
| Psychiatric disorders | Hallucinations, anxiety, confusion, sleepiness, insomnia, depression with or without suicide tendencies, euphoria, psychotic episodes including | Agitation, dream abnormaliti es | Reduced thinking capacity, disorientation, increased libido, bruxism |
Dopamine dysregulatio syndrome, gambling mania
MedDRA System Organ Class | Very common (≥1/10) | Common (≥ 1/100 to < 1/10) | Uncommo n (>1/1,000 to <1/100) | Rare (>1/10,000 to <1/1,000) | Very rare (<1/10,000) |
not known (cannot be estimated from the available data)
delusions and paranoid ideation, feeling of stimulation | |||||
| Nervous system disorders | Dyskinesia, chorea, dizziness, dystonia, extrapyramidal and movement disorders, bradykinetic episodes (the “on-off” phenomenon), inclination to faint | Ataxia, increased hand tremor, headache, syncope | Malignant neuroleptic syndrome (see sec 4.4.), paraesthesia, epileptic seizures, dementia | Levodopa/ca rbidopa is associated with somnolence (see sec 4.4.) and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes, numbness | |
| Eye disorders | Blurred vision, blepharospasm , activation of a latent Horner's syndrome, diplopia, dilated pupils, and oculogyric crises. | ||||
| Cardiac disorders | Palpitations, irregular heartbeat | ||||
| Vascular disorders | Orthostatic hypotension including hypotensive episodes | Hypertensi on, hot flashes | Phlebitis, blushing | ||
| Respiratory, thoracic and mediastinal | Hoarseness, abnormal breathing | Dyspnoea, hiccups |
MedDRA System Organ Class | Very common (≥1/10) | Common (≥ 1/100 to < 1/10) | Uncommo n (>1/1,000 to <1/100) | Rare (>1/10,000 to <1/1,000) | Very rare (<1/10,000) |
not known (cannot be estimated from the available data)
| disorders | pattern | ||||
| Gastrointestin al disorders | Nausea, vomiting, bitter taste | Constipatio n, diarrhoea, sialorrhoea, dysphagia, flatulence, gastrointest inal pain and discomfort, dry mouth | Dyspepsia, dark saliva, gastrointestina l bleeding, burning sensation of the tongue, duodenal ulceration | ||
Skin and subcutaneous tissue disorders | Hypersensitivi ty reactions including urticaria, pruritus, facial redness, hair loss, rash, increased sweating, dark sweat and Henoch- Schonlein purpura | ||||
Musculoskelet al and connective tissue disorders | Muscle spasms, convulsions , muscle twitching | Trismus |
Muscle twitching
Renal and urinary disorders | Dark urine | Urinary retention, urinary incontinence | |||
Reproductive system and breast disorders | Priapism | ||||
General disorders and administration site conditions | Asthenia, weakness, malaise, oedema, fatigue | Chest pain |
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).
Disturbed impulse control
Pathological gambling, increased libido, hypersexuality, compulsive spending of money, and compulsive buying behaviour, binge eating, and compulsive eating may occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa, such as Precifit (see section 4.4)
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. Healthcare professionals are asked to report any suspected adverse reactions via
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
Toxicity: 100 mg to a 2-year-old gave after charcoal no symptoms. 5 g to adult resulted in moderate intoxication.
Symptoms: Nausea, vomiting, restlessness, abnormal movements, agitation, dyskinesia, choreiform movements. Possibly hallucinations, seizures, sinus tachycardia, hypertension possibly followed by postural hypotension. Possibly electrolyte imbalances. Rhabdomyolysis and renal failure in rare cases.
ECG monitoring should be instituted and the patient should be carefully monitored for the possible development of arrhythmias. If required, anti-arrhythmic therapy should be given.
Treatment:
Management of acute overdosage with Precifit is basically the same as management of acute overdosage with levodopa; however pyridoxine is not effective in reversing the actions of Precifit. ECG monitoring should be instituted, and the patient carefully observed for the possible development of arrhythmias; if required, appropriate anti-arrhythmic therapy should be given. The possibility that the patient may have taken other medicinal products as well as Precifit should be taken into consideration. To date, no experience has been reported with dialysis, and hence its value in the treatment of overdosage is not known. The terminal half-life of levodopa is about two hours in the presence of carbidopa.
If justified ventricular drainage, charcoal. In case of hypotonia, intravenous fluid administration. If necessary, inotropic agents. Benzodiazepines are administered in cases of dyskinesia and choreiform movements in patients with Parkinson's disease. For individuals without Parkinson's disease, Haldol may be prescribed instead. Symptomatic treatment such as sedation, ventilatory support, and muscle relaxation may be necessary.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-Parkinson drugs, dopaminergic agents, ATC code: N04BA02
Mechanism of action
Levodopa is a precursor of dopamine and is given as replacement therapy in Parkinson's disease.
Carbidopa is a peripheral dopa decarboxylase inhibitor. It prevents metabolism of levodopa to dopamine in the peripheral circulation, ensuring that a higher proportion of the dose reaches the brain, where dopamine acts. A lower dose of levodopa can be used, reducing the incidence and severity of side effects.
Pharmacodynamic effects
Carbidopa/levodopa is useful in relieving many of the symptoms of parkinsonism, particularly rigidity and bradykinesia. It is frequently helpful in the management of tremor, dysphagia, sialorrhoea, and postural instability associated with Parkinson's disease and syndrome.
Clinical efficacy and safety
When response to levodopa alone is irregular, and signs and symptoms of Parkinson's disease are not controlled evenly throughout the day, substitution of carbidopa/levodopa usually reduces fluctuations in response. By reducing some of the adverse reactions produced by levodopa alone, carbidopa/levodopa permits more patients to obtain adequate relief from the symptoms of Parkinson's disease.
5.2 Pharmacokinetic properties
Absorption
Levodopa is rapidly and completely absorbed but undergoes extensive first pass metabolism. The bioavailability of levodopa is approximately 30% without co-administration of carbidopa. Levodopa is co-administered with carbidopa, a decarboxylase inhibitor, which increases the bioavailability and decreases clearance for levodopa. Following administration of a single dose of Precifit, the maximum plasma concentration of levodopa occurs approximately after 30 minutes.
A clinical study showed that at a dose of 45 mg given at 2.5-hour intervals (after a bolus dose of 75 mg, 6 doses in total) gave a more consistent plasma concentration of levodopa than tablets with levodopa/ carbidopa/entacapone, 100 mg levodopa, given every six hours (3 doses in total).
Distribution
Volume of distribution for levodopa is 0.9-1.6 l/kg, when given together with a decarboxylase inhibitor. The partitioning ratio for levodopa between erythrocytes and plasma is approximately 1. The protein binding of levodopa in plasma is negligible (about 10%-30%). Levodopa is transported into the brain by the carrier mechanism for large neutral amino acids.
Carbidopa is approximately 36% bound to plasma protein. Carbidopa does not cross the blood-brain barrier.
Biotransformation and Elimination
Levodopa is eliminated completely through metabolism and the metabolites formed are excreted mainly in the urine. Four metabolic pathways are known, but levodopa is mainly eliminated via metabolism by the aromatic amino acid decarboxylase (AAAD) and the catechol-O-methyl-transferase (COMT) enzymes. Other routes of metabolism are transamination and oxidation. The decarboxylation of levodopa to dopamine by AAAD is the major enzymatic pathway when no enzyme inhibitor is co-administered. When levodopa is co-administered with carbidopa, the decarboxylase enzyme is inhibited, so that metabolism via catechol-O-methyl-transferase (COMT) becomes the dominant metabolic pathway. O-methylation of levodopa by COMT forms 3-O-methyldopa. Clearance for levodopa is 0.3 l/hour/kg, when given together with a decarboxylase inhibitor. When administered with carbidopa, the elimination half-life for levodopa is approximately 1.5 hours.
Carbidopa is metabolized to two main metabolites (α-methyl-3-methoxy-4-hydroxyphenylpropionic acid and α-methyl-3,4-dihydroxyphenylpropionic acid). These 2 metabolites are primarily eliminated in the urine unchanged or as glucuronide conjugates. Unchanged carbidopa accounts for 30% of the total urinary excretion. The elimination half-life of carbidopa is approximately 2 hours.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeat-dose toxicity, genotoxicity and carcinogenic potential. In reproductive toxicity studies both levodopa and the combination of carbidopa and levodopa have caused visceral and skeletal malformations in rabbits.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Cellulose microcrystalline
Silica, colloidal anhydrous
Corn starch
Sodium starch glycolate
Magnesium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
4 years.
6.4 Special precautions for storage
Store in the original package in order to protect from light and moisture.
Precifit in OraFID pre-filled dose dispenser
Once the foil bag is opened the dispersible tablets should be used within 3 months and be stored below 30°C.
Precifit in cartridges for MyFID dose dispenser
Once the foil bag is opened the dispersible tablets should be used within 3 months and be stored below 30°C.
6.5 Nature and contents of container
Precifit in OraFID pre-filled dose dispenser
The pre-filled dose dispenser, OraFID, is a non-transparent container consisting of polypropylene. The container has 2 250 dispersible tablets and has an integrated dose dispenser.
The dose dispenser can dispense 1-20 tablets per withdrawal. It is packed in a sealed aluminium foil/polyethylene/polyester bag which contains a desiccant.
Pack size: 2 250 tablets.
Precifit in cartridges for MyFID dose dispenser
The dose-dispenser cartridge of polypropylene contains 750 dispersible tablets for dose dispenser.
Each cartridge is packaged in a sealed aluminium foil/polyethylene/polyester bag and each box has 10 cartridges.
The cartridge should only be used with MyFID dose dispenser. The dispenser is provided separately from the Precifit tablet.
Pack size: 10 x 750 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
See instructions for use in the separate package leaflets for the two dose dispensers OraFID and MyFID, respectively.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland
8 MARKETING AUTHORISATION NUMBER(S)
PL 27925/0134
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
25/07/2016
10 DATE OF REVISION OF THE TEXT
15/04/2026