Active ingredients: Melevodopa, Carbidopa
SIRIO 25 mg + 250 mg effervescent tablets
SIRIO 12.5 mg + 125 mg effervescent tablets
SIRIO 25 mg + 100 mg effervescent tablets
Why is Sirio used? What is it for?
SIRIO contains two active ingredients, melevodopa and carbidopa.
SIRIO is a medicine indicated in adults in the treatment of Parkinson's disease, a disease of the central nervous system which causes problems in the movement of muscles and is manifested for example by tremor, muscle stiffness, slowing of movement, difficulty in maintaining balance.
Treatment with SIRIO is particularly indicated in patients with movement disorders called akinesias (akinesias on awakening, in the afternoon, at the end of the dose).
Contraindications When Sirio should not be used
Do not take SIRIO
- if you are allergic to melevodopa, carbidopa or any of the other ingredients of this medicine (listed in section 6);
- if you are in a condition in which the administration of sympathomimetic amines (such as adrenaline and noradrenaline) is contraindicated;
- if you suffer from severe eye disease characterized by increased pressure of the fluid contained in the eye (narrow angle glaucoma);
- if you have recently had a heart attack (myocardial infarction);
- if you have a suspected skin lesion or if you have ever had skin cancer (melanoma);
- if you are taking non-selective monoamine oxidase inhibitor and monoamine oxidase A inhibitor medicines, used to treat depression;
- if you are under 18;
- if you are pregnant or breast-feeding.
Precautions for use What you need to know before taking Sirio
Talk to your doctor before taking SIRIO:
- if you are also taking other medicines used to treat Parkinson's disease;
- if you suffer from movement disorders caused by another medicine you are taking. SIRIO can in fact cause involuntary movements;
- if you have or have suffered in the past from mental disorders (including psychosis), suicidal depression or other severe antisocial behavior;
- if you suffer from bronchial asthma or severe heart or lung disease, if you suffer from kidney, liver or hormonal disorders;
- if you have ever had a heart attack (myocardial infarction) or suffer from heart rhythm disturbances (atrial, nodal or ventricular arrhythmias);
- if you have ever had stomach (peptic ulcer) and / or bowel injuries. After taking SIRIO there is a greater chance of bleeding from the stomach and / or intestines;
- if you have a bone disease known as osteomalacia;
- if you have suffered from involuntary body movements (convulsions);
- if you suffer from an eye disease characterized by increased pressure of the fluid contained in the eye (chronic open-angle glaucoma);
- if you have an urge or desire to behave in ways that are unusual or you cannot resist the urge or temptation to engage in certain activities that could harm you and others. These behaviors are called impulse control disorders and can include gambling addiction. "gambling, overeating, overspending, abnormal and exaggerated sexual desire or an increase in sexual thoughts.
In all these cases, consult your doctor who will be able to prescribe an appropriate therapy.
Tell your doctor if you experience excessive sleepiness or sudden sleep attacks during treatment with SIRIO (see section 4 "Possible side effects"). The dosage may need to be decreased.
Interactions Which drugs or foods can modify the effect of Sirio
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, especially:
- Antihypertensives (medicines to treat high blood pressure): you may experience a drop in blood pressure from sitting to standing (systemic postural hypotension) when SIRIO is given to a patient who is already being treated with antihypertensive medicines.
- Antidepressants (such as non-selective monoamine oxidase A inhibitors): therapy with these medicines should be stopped at least two weeks before starting therapy with SIRIO. Undesirable effects, including increased blood pressure and difficulty moving, have been reported rarely. resulting from the concomitant use of antidepressants and medicines such as SIRIO.
- Phenothiazines (medicines for the treatment of mental disorders and allergies) and butyrophenones (medicines for the treatment of mental disorders and nausea): can reduce the effects of the levodopa contained in SIRIO.
- Phenytoin and papaverine (medicines to treat epilepsy and muscle spasms): can reduce the therapeutic effects of SIRIO.
- if you are following a high protein diet.
- Vitamin B6: do not take it in medium or high doses together with SIRIO as it counteracts the effects of SIRIO. This contrast effect does not occur in the case of vitamin B6 in low doses, such as those in preparations containing vitamins.
Warnings It is important to know that:
Laboratory tests
If you take SIRIO for a long time, your doctor will have frequent blood tests.
Your laboratory tests may be altered during treatment with SIRIO.
For example: decreased hemoglobin (a protein that carries oxygen from blood to tissues) and blood cell numbers (hematocrit), increased blood sugar and white blood cells (a type of blood cell) have been reported. blood) and the presence of blood and bacteria in the urine.
Pregnancy and breastfeeding
Do not take SIRIO if you are pregnant, think you may be pregnant or if you are breast-feeding (see section 2, "Do not take SIRIO").
Driving and using machines
During treatment with SIRIO, take special care while driving or using machines.
If you experience excessive sleepiness or sudden sleep attacks, refrain from driving and using machines and contact your doctor.
SIRIO contains lactose and sodium
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
SIRIO 25 mg + 250 mg effervescent tablets contain 50.2 mg of sodium per dose. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
SIRIO 12.5 mg + 125 mg effervescent tablets contain 25 mg of sodium per dose. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
SIRIO 25 mg + 100 mg effervescent tablets contain 24.23 mg of sodium per dose. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
Dosage and method of use How to use Sirio: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you.
If in doubt, consult your doctor or pharmacist.
The recommended starting dose in patients not on previous treatment with levodopa plus carbidopa is one effervescent tablet of SIRIO 25 mg + 100 mg three times a day. The dosage can be increased by one effervescent tablet per day, or every other day.
The recommended starting dose of SIRIO 12.5 mg + 125 mg and 25 mg + 250 mg is one effervescent tablet once or twice a day, increasing if necessary by one effervescent tablet a day or every other day until a response is achieved. optimal.
In patients already taking levodopa plus carbidopa and replacing the previous therapy with SIRIO, the doctor will establish the SIRIO dosage based on the previous treatment.
A maximum maintenance dose of 3 to 6 effervescent tablets per day can be administered in most patients.
The effervescent tablets, at the 3 available dosages, can be administered separately or jointly as needed to achieve the optimal dosage; in this way, a specific modulation of the doses is obtained.
The dose and frequency of administration will be determined by your doctor based on your state of health.
If you experience involuntary movements, your doctor may reduce your dose of SIRIO. If you experience involuntary movement of the eyelids (blepharospasm), please tell your doctor, who will reduce your dose of SIRIO.
If you are going to have a surgery under general anesthesia, take SIRIO as long as you can take medication.
INSTRUCTIONS FOR USE
Completely dissolve the effervescent tablet in about 150 ml of water.
If you forget to take SIRIO
Do not take a double dose to make up for a forgotten tablet.
If you stop taking SIRIO
Abrupt discontinuation of SIRIO can lead to a condition similar to neuroleptic malignant syndrome, characterized by muscle stiffness, high body temperature, mental changes and alteration of some laboratory parameters. Therefore your doctor will keep you under close observation when the dosage of SIRIO is abruptly reduced or stopped, especially if you are receiving drugs with powerful sedative action (neuroleptics).
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Sirio
If you take more SIRIO than you should
In case of accidental ingestion / intake of an excessive dose of SIRIO, notify your doctor immediately or go to the nearest hospital.
Gastric lavage and appropriate supportive care may be required.
Side Effects What are the side effects of Sirio
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects that can occur most frequently in people being treated with SIRIO are rapid and involuntary movements.
Rare (may affect up to 1 in 1,000 people)
- decrease in the number of certain cells (leukopenia, agranulocytosis, thrombocytopenia) and in the amount of hemoglobin, a protein that carries oxygen (anemia), present in the blood,
- sleepiness, numbness (paraesthesia),
- high blood pressure (hypertension), inflammation of the veins (phlebitis),
- shortness of breath (dyspnoea),
- bleeding of the stomach and intestines (gastrointestinal haemorrhage), lesion of the intestine (duodenal ulcer),
- chest pain.
Very rare (may affect up to 1 in 10,000 people)
- decrease in the amount of hemoglobin in the blood due to breakdown of red blood cells (haemolytic anemia).
Not known (frequency cannot be estimated from the available data)
- skin cancer (melanoma),
- reduced appetite,
- sleep disturbance, confusional state, paranoia, mental disorders (psychosis), depression (with or without suicidal tendencies), euphoric mood, insomnia, delirium, nightmare, hallucination, mania, agitation, anxiety, grinding of teeth (bruxism),
- inability to resist the urge to perform actions that could be harmful, which may include:
- strong impulse to gamble excessively, despite serious personal and / or family consequences (pathological gambling);
- altered or increased sexual interest (hypersexuality or increased libido);
- binge eating;
- eating more food than normal and more than is necessary to satisfy hunger (bulimia nervosa, an eating problem in which a person swallows too much food and then uses methods to avoid assimilating it;
- uncontrollable shopping or overspending.
Tell your doctor if any of these behaviors occur so he can decide what to do to manage or reduce these symptoms.
- dizziness, movement disturbances (dyskinesia), headache, loss of consciousness (syncope), dementia, slow movement (bradykinesia), loss of movement coordination (ataxia), aggravated tremor, decreased sensitivity to stimuli (hypoesthesia), syndrome Horner's syndrome (activation of latent syndrome characterized by paralysis of the nerves of the eye), decreased sense of taste (dysgeusia), neuroleptic malignant syndrome (see section 3, "If you stop taking SIRIO"),
- uncontrolled movement of the eyelid (blepharospasm), blurred vision, double vision (diplopia), dilation of the pupil of the eye (mydriasis), fixed eyes (oculogyric crisis),
- vertigo,
- irregular heartbeat (arrhythmia), perception of your own heartbeat (palpitations),
- changes in blood pressure (blood pressure fluctuation), drop in blood pressure following a sudden transition from sitting to standing (orthostatic hypotension), hot flush,
- hiccups, loss of voice (dysphonia), breathing irregularity,
- nausea, vomiting, constipation, diarrhea, abdominal pain, flatulence, increased saliva production (salivary hypersecretion), dry mouth, burning sensation in the mouth (glossodynia), difficulty swallowing (dysphagia),
- increased sweating (hyperhidrosis), hair loss and hair loss (alopecia), rash, discolouration of sweat,
- muscle stiffness, muscle spasms, contracture of the jaw which makes it impossible to open the mouth (trismus),
- retention of urine, incontinence,
- painful and persistent erection (priapism),
- fatigue, swelling (edema), weakness (asthenia), malaise,
- abnormal urine color, weight increased, weight decreased, laboratory test changes (liver enzyme increased, blood lactic dehydrogenase increased, blood bilirubin increased, blood alkaline phosphatase increased, blood urea increased, blood creatinine increased, blood uric acid increased, blood uric acid test Positive Coombs).
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Store at a temperature not exceeding 30 ° C.
If the product is contained in a glass bottle, use it within 2 months of first opening.
Keep the medicine in the original container, always keeping it tightly closed and protected from light and humidity.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package after EXP.
The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other_information "> Other information
What SIRIO contains
- The active ingredients are Melevodopa and Carbidopa.
One effervescent tablet of SIRIO 25 mg + 250 mg contains: 314 mg of melevodopa hydrochloride equivalent to 250 mg of levodopa, and 27 mg of hydrated carbidopa equivalent to 25 mg of anhydrous carbidopa.
One effervescent tablet of SIRIO 12.5 mg + 125 mg contains: 157 mg of melevodopa hydrochloride equivalent to 125 mg of levodopa, and 13.5 mg of hydrated carbidopa equivalent to 12.5 mg of anhydrous carbidopa.
One effervescent tablet of SIRIO 25 mg + 100 mg contains: 125.6 mg of melevodopa hydrochloride equivalent to 100 mg of levodopa, and 27 mg of hydrated carbidopa equivalent to 25 mg of anhydrous carbidopa.
- The other ingredients are Lactose monohydrate, Glycine sodium carbonate, Fumaric acid, Macrogol 6000, Magnesium stearate
Description of the appearance of SIRIO and contents of the pack
SIRIO comes in the form of white effervescent tablets.
For all three dosages it is available in cartons of 30 tablets contained in a yellow glass bottle, closed with a capsule containing silica gel as a desiccant.
For dosages of 12.5 mg + 125 mg and 25 mg + 100 mg it is also available in cartons of 30 and 60 tablets in aluminum blisters.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
SIRIO EFFERVESCENT TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
SIRIO 25 mg + 250 mg effervescent tablets
One effervescent tablet contains: Active ingredients: melevodopa hydrochloride 314 mg equivalent to 250 mg of levodopa, carbidopa hydrates 27 mg equivalent to 25 mg of anhydrous carbidopa.
SIRIO 12.5 mg + 125 mg effervescent tablets
One effervescent tablet contains: Active ingredients: melevodopa hydrochloride 157 mg equivalent to 125 mg of levodopa, carbidopa hydrates 13.5 mg equivalent to 12.5 mg of anhydrous carbidopa.
SIRIO 25 mg + 100 mg effervescent tablets
One effervescent tablet contains: Active ingredients: melevodopa hydrochloride 125.6 mg equivalent to 100 mg of levodopa, carbidopa hydrates 27 mg equivalent to 25 mg of anhydrous carbidopa.
Excipients with known effect:
Lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Effervescent tablets
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Parkinson's disease therapy. Treatment with SIRIO is particularly indicated in patients with motor fluctuations (akinesias on awakening, in the afternoon, at the end of the dose).
04.2 Posology and method of administration -
SIRIO, a combination of melevodopa and carbidopa, is presented in the form of effervescent tablets. Each effervescent tablet of SIRIO contains 314 mg of melevodopa hydrochloride equal to 250 mg of levodopa and 25 mg of carbidopa anhydrous (SIRIO 25 mg + 250 mg) or 157 mg of melevodopa hydrochloride equal to 125 mg of levodopa and 12.5 mg of carbidopa anhydrous ( SIRIO 12.5 mg + 125 mg) or 125.6 mg of melevodopa hydrochloride equal to 100 mg of levodopa and 25 mg of anhydrous carbidopa (SIRIO 25 mg + 100 mg).
Melevodopa-levodopa conversion table for equimolarity
The effervescent tablets are dissolved in about 150 ml of water.
The effervescent tablets, at the 3 available dosages, can be administered separately or jointly as needed to achieve the optimal dosage; in this way, a specific modulation of the doses is obtained.
Dosage should be titrated to individual patient needs and this may require adjustment of both the individual dose and the frequency of administration. Some studies show that peripheral dopa-decarboxylase is saturated by carbidopa at a dose of approximately 70-100 mg / day. Patients receiving lower doses of carbidopa are more likely to experience nausea and vomiting. Patients should be followed closely during the dose adjustment period. The onset of involuntary movements may require a reduction in the dosage of SIRIO in some patients; blepharospasm may be a useful early sign of overdosing. In the case of general anesthesia, SIRIO can be continued as long as the patient is allowed to take fluids and medicines. by mouth If therapy is temporarily interrupted, the usual daily dosage can be given as soon as the patient is able to take medication by mouth.
In patients not being treated with levodopa plus carbidopa, the optimal starting dose of SIRIO 25 mg + 100 mg is one effervescent tablet three times a day.The dosage can be increased by one effervescent tablet per day, or every other day, as needed.
The usual starting dose of SIRIO 12.5 mg + 125 mg and 25 mg + 250 mg is one effervescent tablet once or twice a day, increasing if necessary by one effervescent tablet a day or every other day until a response is achieved. optimal.
In patients already being treated with solid oral formulations (capsules or tablets) of levodopa plus carbidopa and in which the previous therapy with SIRIO effervescent tablets is replaced, the unit / daily dosage of SIRIO will be exactly equivalent in molar terms (see table) to that previously administered.
As with other available levodopa + carbidopa formulations, a maximum maintenance dose of 3 to 6 effervescent tablets per day can be administered in most patients.
04.3 Contraindications -
SIRIO must not be administered in cases where the administration of sympathomimetic amines is contraindicated. SIRIO is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients, in narrow-angle glaucoma and in the acute phase of myocardial infarction. Since levodopa can activate a malignant melanoma, it should not be used in patients with skin lesions. suspected undiagnosed or with a "history of melanoma." Non-selective monoamine oxidase inhibitors (excluding low-dose selective MAO-B inhibitors) and SIRIO should not be administered concurrently and therapy with these inhibitors should be discontinued at least two weeks prior to initiation of SIRIO therapy. It should be used in patients under the age of 18, pregnant and breastfeeding.
04.4 Special warnings and appropriate precautions for use -
SIRIO can be administered as a substitute for other levodopa formulations; in these cases the dosage of melevodopa will be exactly equivalent in molar terms to the unit / daily dosage of levodopa previously taken. Patients being treated with SIRIO should avoid taking additional doses of levodopa, unless prescribed by the treating physician, while other antiparkinsonian drugs may be continued, although dosage adjustment may be necessary.
SIRIO is not recommended for the treatment of drug-induced extrapyramidal reactions. Patients with current or history of psychosis should be treated with caution. Like levodopa, SIRIO can cause involuntary movement and mental disturbance. Patients with a history of severe involuntary movement or psychotic episodes when treated with other levodopa formulations should be observed. carefully when replacing them SIRIO. All patients should be carefully monitored for the development of mental changes, suicidal depression or other severe antisocial behaviors. SIRIO should be administered with caution to patients with severe cardiovascular or pulmonary disease, bronchial asthma , renal, hepatic or endocrine disorders. Caution should be exercised in administering SIRIO to patients with a history of myocardial infarction who have residual atrial, nodal or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the adjustment period initial of the dosages or. As with levodopa, there is a potential for more pronounced GI tract bleeding in patients with a history of peptic ulcer. Strict checks must also be carried out in the case of patients with a positive history of osteomalacia. Complex neuroleptic malignant syndrome-like symptoms with muscle stiffness, elevated body temperature, mental changes and increased serum creatine kinase have been reported when antiparkinsonian drugs were stopped abruptly. Therefore patients should be closely observed when the dose of SIRIO is abruptly reduced or discontinued, especially if the patient is receiving neuroleptics. Patients with a history of seizures should be treated with caution.
Patients should be monitored regularly for the development of impulse control disorders. Patients and caregivers should be aware that the behavioral symptoms of impulse control disorder including pathological gambling, increased libido, hypersexuality, compulsive shopping or overspending, bulimia, and the urge to eat may occur in patients treated with dopamine agonists and / or other dopaminergic treatments containing levodopa including SIRIO If such symptoms develop, re-evaluation of treatment is recommended.
Levodopa, levodopa + carbidopa, levodopa + benserazide, has been associated with somnolence and episodes of sudden sleep onset.
Sudden sleep attacks have been reported very rarely during daily activity, in some cases without awareness and no warning signs. Patients receiving levodopa, levodopa + carbidopa, levodopa + benserazide should be informed of these events and advised to use caution. while driving or using machines. Patients who have experienced episodes of somnolence and / or a sudden episode of sleep should refrain from driving and operating machinery. In addition, dose reduction or discontinuation of therapy may be considered.
In case of prolonged treatments it is advisable to carry out periodic tests of the blood formula and of the hepatic, renal and cardiovascular function. Patients with chronic open-angle glaucoma can be treated with SIRIO, provided that intraocular pressure is well compensated and the patient is carefully monitored during therapy.
The medicine contains lactose therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Laboratory tests
Laboratory test abnormalities were observed with the administration of levodopa plus carbidopa including: increases in SGOT, SGPT, LDH, bilirubin, alkaline phosphatase, as well as increases in BUN, creatinine, uric acid and positivity Coombs test. Haemolytic anemia is extremely rare. Decreased hemoglobin and hematocrit, increased serum glucose and white blood cells, and blood and bacteria in the urine have been reported.
Patients with rare hereditary problems of galactose intolerance, the Lapp Lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
Caution should be exercised when the following drugs are administered concomitantly with SIRIO.
Antihypertensives : Systemic postural hypotension may occur when SIRIO is administered to a patient already being treated with antihypertensive drugs. Therefore, when initiating therapy with SIRIO, dosage adjustment of the antihypertensive drug may be required.
Antidepressants : Monoamine oxidase-A inhibitors and SIRIO should not be administered concurrently and therapy with these inhibitors should be discontinued at least two weeks prior to initiation of SIRIO therapy. Rarely, adverse reactions, including hypertension and dyskinesia, resulting from "concomitant use of tricyclic antidepressants and levodopa.
Other drugs : phenothiazines and butyrophenones may reduce the therapeutic effects of levodopa. Furthermore, the therapeutic effects of levodopa in Parkinson's disease have been reported to be reduced by phenytoin and papaverine. Patients taking these drugs with SIRIO should be carefully monitored for a possible decrease in therapeutic response. Since levodopa competes with certain amino acids, its absorption may be impaired in some patients on a high protein diet. Vitamin B6 a medium or high doses should not be administered together with SIRIO as it antagonizes the effects of levodopa: this antagonistic activity has no clinical relevance in the case of vitamin B6 in low doses, such as those contained in polyvitamin preparations.
04.6 Pregnancy and breastfeeding -
SIRIO must not be administered during pregnancy, suspected pregnancy or breastfeeding.
04.7 Effects on ability to drive and use machines -
Patients being treated with levodopa; levodopa + carbidopa; levodopa + benserazide who have episodes of drowsiness and / or sudden sleep attacks should be advised to refrain from driving or from engaging in any activity in which impaired attention could expose themselves or others to the risk of serious harm or death (p eg the use of machinery) until these recurrent episodes and sleepiness have resolved (see section 4.4).
04.8 Undesirable effects -
a) General description
The onset of unexpected serious adverse reactions related to drug administration was not observed with SIRIO at the normally used posology in clinical studies.
The undesirable effects that may occur in patients treated with SIRIO are due to the central neuropharmacological activity of dopamine, similar to those described for the available levodopa + carbidopa formulations. These effects can usually be decreased by reducing the dosage. most common are: choreiform, dystonic and other involuntary movements.
b) Table of undesirable effects
(*) see section "c".
c) Information on serious and / or frequent individual undesirable effects
Sleep disturbance, confusional state, dizziness, dyskinesia, headache, syncope, arrhythmia, blood pressure fluctuation, nausea, vomiting, muscle stiffness, fatigue, chest pain were reactions that were generally of short duration and resolved spontaneously in most cases.
Somnolence has very rarely been associated with excessive daytime sleepiness and episodes of sudden sleep onset.
Malignant melanoma (see section 4.3 Contraindications).
Pathological gambling, increased libido, hypersexuality, compulsive shopping or overspending, bulimia and binge eating may occur in patients treated with dopamine agonists and / or other dopaminergic treatments containing levodopa including SIRIO (see section 4.4. warnings and precautions for use).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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. "address" www.agenziafarmaco.gov.it/it/responsabili ".
04.9 Overdose -
In the event of overdose, appropriate supportive therapy should be given along with immediate gastric lavage. Intravenous fluid should be administered with caution and a patent airway maintained. An electrocardiographic examination should be performed and the patient should be carefully monitored for possible development of arrhythmias; if necessary, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs together with SIRIO should be taken into consideration. To date, no experience has been reported with the use of dialysis; therefore its value in overdose is not known. Pyridoxine has no effect in "canceling" the action of SIRIO.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Melevodopa and decarboxylase inhibitor
ATC code: N04BA05
SIRIO is a "combination of melevodopa, methyl ester of levodopa and of carbidopa, an inhibitor of aromatic amino acid decarboxylase. Levodopa is a metabolic precursor of dopamine, used for years for the treatment of Parkinson's disease and parkinsonian syndrome. Levodopa relieves the symptoms of Parkinson's disease presumably as it is decarboxylated in the central gray nuclei to dopamine, a chemical mediator that is found in reduced concentrations in the Parkinsonian patient.
The product is presented in the form of effervescent tablets to be dissolved in water at the time of use.
Intraperitoneral and subcutaneous administration of the combination melevodopa and carbidopa in rats is able to antagonize reserpine-induced akinesia in a similar way to that of levodopa and carbidopa. The higher activity, after oral administration, of the combination melevodopa and carbidopa shown in this model indicates that the higher solubility of melevodopa allows for faster absorption.
The effervescent tablets are completely soluble in water, giving rise to a clear solution, unlike the suspensions which are opalescent.
Administration of SIRIO effervescent tablets:
§ is characterized by rapid absorption and rapid onset of the pharmacodynamic effect, particularly at the highest dosage;
§ it allows to reduce the interindividual variations of dopemia, more easily observable with solid formulations and probably co-responsible for the ineffectiveness of the administered dose and motor fluctuations in patients with Parkinson's disease;
§ it is particularly advantageous in Parkinsonian patients with gastric dyskinesias attributable to the disease and in patients with swallowing problems;
§ allows, by virtue of the dosages available, a precise individualization of the posology of levodopa both in the patient in the initial phase of the disease and in the patient with motor fluctuations, in which the motor release time (latency all "on) is reduced, usually without onset of dyskinesias.
05.2 "Pharmacokinetic properties -
Melevodopa is a higher solubility pro-drug of levodopa. From a kinetic point of view, melevodopa differs from levodopa for its faster absorption, responsible for the prompt onset of pharmacological action and for the lower variability of interindividual response to the drug. The liquid formulation allows the active ingredients to reach the site of absorption quickly, contributing the rapid achievement of effective plasma levels of levodopa.
After oral administration, melevodopa is rapidly and completely hydrolyzed to levodopa by intestinal esterases, consequently there is no systemic presence of unchanged melevodopa.
In pharmacokinetic studies conducted with SIRIO effervescent tablets in healthy volunteers, the maximum plasma concentration of levodopa and carbidopa is reached rapidly (approximately 0.5 hours after administration for levodopa and 2 hours after administration for carbidopa).The rate of absorption of the active substances has been shown to be independent of the dose and plasma levels vary proportionally to the administered dose.
Levodopa is extensively metabolised and mainly converted to dopamine and 3-O-methyldopa, the latter having an elimination half-life of 10 to 20 hours. Approximately 80% of levodopa is excreted in the urine within 24 hours of administration. , mainly in the form of metabolites. There is no evidence of accumulation of levodopa after repeated administration of melevodopa.
Carbidopa is rapidly absorbed after oral administration; the plasma peak is followed by a monoexponential decline in plasma levels. Carbidopa has a plasma half-life of less than 2 hours; most carbidopa is excreted in the urine within 4 hours of administration. Repeated administration of carbidopa does not result in accumulation.
05.3 Preclinical safety data -
In acute oral and intraperitoneal toxicity studies in rats and mice the LD50 values were higher than 3000 mg / kg orally and 2000 mg / kg i.p; overlapping results were observed with the levodopa plus carbidopa combination. No differences in toxicity were observed between the different weight ratios used in the toxicological studies.
Subacute toxicity studies (13 weeks) were conducted in monkeys and rats in which melevodopa plus carbidopa and levodopa plus carbidopa were compared in different dose ratios. In monkeys, the maximum tolerated doses were 76 mg / kg of melevodopa and 16 mg / kg of carbidopa in combination, while in the rat the maximum tolerated doses were 126 mg / kg of melevodopa and 27 mg / kg of carbidopa in combination. . At higher doses, signs of dopaminergic activation such as hyperexcitability, salivation, piloerection, hyperkinesis, muscle rigidity, hallucinations and self-trauma were observed with the various dose ratios for the two formulations. Melevodopa showed no mutagenic potential, clastogenic or DNA damage activity. No specific reproduction and carcinogenicity studies have been conducted with melevodopa due to the absolute toxicological overlap with levodopa. Studies in rodents did not reveal any carcinogenic potential for levodopa.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Lactose monohydrate, sodium carbonate glycine, fumaric acid, macrogol 6000, magnesium stearate.
06.2 Incompatibility "-
Incompatibilities with other medicines are unknown.
06.3 Period of validity "-
2 years. The period of validity indicated refers to the product in intact packaging, correctly stored.
If the product is contained in a glass bottle, it must be used within 2 months of first opening.
06.4 Special precautions for storage -
Store at a temperature not exceeding 30 ° C.
keep the medicine in the original container, always keeping it tightly closed and away from light and humidity.
06.5 Nature of the immediate packaging and contents of the package -
Effervescent tablets
Primary container: Bottle
Primary container: yellow glass bottle, closed with a hard-to-open cap. Silica gel is included in the capsule as a desiccant.
Final packaging: printed cardboard box.
SIRIO 25 mg + 250 mg: Box of 30 effervescent tablets
SIRIO 12.5 mg + 125 mg: Box of 30 effervescent tablets
SIRIO 25 mg + 100 mg: Box of 30 effervescent tablets
Effervescent tablets
Primary container: Blister
Primary container: Alu-Alu blister consisting of aluminum strips with desiccant closed by aluminum strips.
External packaging: printed cardboard box.
SIRIO 12.5 mg + 125 mg: Box of 30 effervescent tablets
SIRIO 25 mg + 100 mg: Box of 30 effervescent tablets
SIRIO 12.5 mg + 125 mg: Box of 60 effervescent tablets
SIRIO 25 mg + 100 mg: Box of 60 effervescent tablets
06.6 Instructions for use and handling -
Completely dissolve the effervescent tablet in about 150 ml of water.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
CHIESI FARMACEUTICI S.p.A., Via Palermo, 26 / A - Parma
08.0 MARKETING AUTHORIZATION NUMBER -
SIRIO 25 mg + 250 mg effervescent tablets, 30 tablets in glass bottle
AIC: 035625033
SIRIO 12.5 mg + 125 mg effervescent tablets, 30 tablets in glass bottle
AIC: 035625019
SIRIO 25 mg + 100 mg effervescent tablets, 30 tablets in glass bottle
AIC: 035625021
SIRIO 12.5 mg + 125 mg effervescent tablets, 30 tablets in AL / AL / desiccant / HDPE / PE blister
AIC: 035625045
SIRIO 25 mg + 100 mg effervescent tablets, 30 tablets in AL / AL / desiccant / HDPE / PE blister
AIC: 035625058
SIRIO 12.5 mg + 125 mg effervescent tablets, 60 tablets in AL / AL / desiccant / HDPE / PE blister
AIC: 035625060
SIRIO 25 mg + 100 mg effervescent tablets, 60 tablets in AL / AL / desiccant / HDPE / PE blister
AIC: 035625072
Not all pack sizes may be marketed.
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
January 16, 2004
10.0 DATE OF REVISION OF THE TEXT -
May 2015
