Active ingredients: Propiverine (Propiverine hydrochloride)
Mictonorm 45 mg modified release capsules
Why is Mictonorm used? What is it for?
Mictonorm is used to treat people who have difficulty controlling their bladder due to excessive bladder activity or who have problems with their spinal cord. Mictonorm contains the active substance propiverine hydrochloride. This substance prevents the bladder from contracting and increases. the volume it can hold. Mictonorm is used to treat symptoms of overactive bladder. It is a modified-release capsule that is taken once a day.
Contraindications When Mictonorm should not be used
Do not take Mictonorm
Do not take Mictonorm if you are allergic (hypersensitive) to propiverine hydrochloride or any of the other ingredients of Mictonorm.
Do not take Mictonorm if you have any of the following conditions:
- bowel obstruction
- obstruction of the outflow pathways of the bladder (difficulty urinating)
- myasthenia gravis (a disease causing muscle weakness)
- failure of the muscles that control bowel movements (intestinal atony)
- severe inflammation of the intestines (ulcerative colitis) which can cause diarrhea containing blood and mucus and pain in the abdomen
- toxic megacolon (a disease with enlarged intestine)
- increased pressure inside the eye (uncontrolled angle-closure glaucoma)
- moderate or severe liver disease
- rapid and irregular heartbeat
Precautions for use What you need to know before taking Mictonorm
Before treatment with Mictonorm tell your doctor if you suffer from:
- damage to the nerves that control blood pressure, heart rate, bowel and bladder movements and other bodily functions (autonomic neuropathy)
- kidney diseases
- liver disease
- severe heart failure
- enlargement of the prostate
- heartburn and indigestion due to the reflux of gastric juice into the throat (hiatal hernia with reflux esophagitis)
- irregular heartbeat
- rapid heartbeat
If you have any of these conditions, contact your doctor who will tell you what to do.
Interactions Which drugs or foods may change the effect of Mictonorm
Tell your doctor if you are taking or have recently taken any of the following medicines that may interact with Mictonorm:
- antidepressants (e.g. imipramine, clomipramine and amitriptyline),
- sleeping pills (e.g. benzodiazepines),
- anticholinergics taken by mouth or given by injection (used routinely to treat asthma, stomach cramps, eye problems or urinary incontinence),
- amantadine (used to treat influenza and Parkinson's disease)
- neuroleptics such as promazine, olanzapine, quetiapine (medicines used to treat psychotic disorders such as schizophrenia or anxiety)
- beta-stimulants (used in the treatment of asthma)
- cholinergics (e.g. carbachol, pilocarpine)
- isoniazid (tuberculosis medicine)
- metoclopramide (used to treat nausea and vomiting)
However, it is possible that you can still take Mictonorm. Your doctor will decide what is best for you.
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Do not take Mictonorm if you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breast-feeding.
Driving and using machines
Sometimes, Mictonorm can cause drowsiness and blurred vision. Do not drive vehicles or use machines if you are drowsy and have blurred vision.
Important information about some of the ingredients of Mictonorm
Mictonorm contains lactose (a sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Mictonorm: Posology
Always take Mictonorm exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Take the capsule at the same time every day. Swallow the capsule whole with a glass of water. Do not crush or chew the capsules. You can take them with or without food.
Adults and the elderly: The usual dose of Mictonorm is one capsule a day.
The use of Mictonorm is not recommended in children.
If you forget to take Mictonorm
Do not worry. Eliminate that dose completely. Then take your next dose at the correct time. Do not take a double dose to make up for a forgotten dose.
Overdose What to do if you have taken too much Mictonorm
If you have accidentally taken more than the prescribed dose, contact your nearest emergency room or tell your doctor or pharmacist immediately. Remember to take the pack and any remaining capsules with you.
Side Effects What are the side effects of Mictonorm
Like all medicines, Mictonorm can cause side effects, although not everybody gets them.
All medicines can cause allergic reactions, but severe allergic reactions are very rare. The following symptoms are the first signs of such reactions:
- sudden wheezing, difficulty breathing or dizziness, swelling of the eyelids, face, lips or throat
- peeling and blistering of the skin, mouth, eyes and genitals
- whole body rash Do not take the capsules anymore and contact your doctor immediately if you notice any of these symptoms during treatment.
An acute attack of glaucoma is possible. In this case, the patient will see colored rings around the lights or will feel intense pain in and around one or the other eye. If this happens, consult a doctor urgently. .
The following side effects have also been observed:
Very common (may affect more than 1 in 10 people)
- dry mouth
Common (may affect up to 1 in 10 subjects)
- vision abnormalities and difficulty focusing
- fatigue
- headache
- pain in the abdomen
- digestive disorders
- constipation
Uncommon (may affect up to 1 in 100 people)
- nausea and vomit
- dizziness
- tremor - inability to empty the bladder (urinary retention) - flushing - changes in taste - low blood pressure with sleepiness
Rare (may affect up to 1 in 1,000 people)
- rash
Very rare (may affect up to 1 in 10,000 people)
- perception of heartbeat - restlessness and confusion
Not known (frequency cannot be estimated from the available data)
- unreal feelings (hallucinations)
- speech disorders
- faster heart rate
- itch
- difficulty urinating
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.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep out of the sight and reach of children.
Do not use Mictonorm after the expiry date which is stated on the blister or bottle and on the carton after EXP. The expiry date refers to the last day of the month.
Blisters: Do not store above 25 ° C. Store in the original package to protect the capsules from moisture.
Bottle: keep the bottle tightly closed.
Stability of the bottle after first opening: 100 days.
Other information
What Mictonorm contains
The active ingredient is propiverine hydrochloride. Each capsule contains 45 mg of modified release propiverine hydrochloride.
The other ingredients are citric acid, povidone, lactose monohydrate, talc, triethyl citrate, magnesium stearate, methacrylic acid-methyl methacrylate copolymer (1: 1), methacrylic acid-methyl methacrylate copolymer (1: 2), ammonium methacrylate copolymer type A, ammonium methacrylate copolymer type B, gelatin, titanium dioxide E171, red iron oxide E172, yellow iron oxide E172.
What Mictonorme looks like. Contents of the pack
Mictonorm capsules are orange in color and contain white to off-white pellets.
They're available in
- cartons containing 14, 20, 28, 30, 49, 50, 56, 60, 84, 98, 100, 112, 168 or 280 capsules
- bottles containing 10, 14, 20, 28, 30, 49, 50, 56, 60, 84, 98 or 100 capsules The polyethylene bottle with a polypropylene screw cap contains hygroscopic silica gel.
Not all pack sizes may be marketed.
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
MICTONORM 45 MG MODIFIED RELEASE CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 45 mg of propiverine hydrochloride, equivalent to 40.92 mg of propiverine.
Excipients: lactose monohydrate (8.5 mg), for the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Modified-release capsule, hard.
Size 2 orange capsules containing white to off-white pellets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic treatment of urinary incontinence and / or increased urinary frequency and urgency in patients with overactive bladder syndrome or detrusor overactivity of neurological origin (detrusor hyperreflexia) due to spinal cord injury.
04.2 Posology and method of administration
Capsules for oral use.
The capsules must not be crushed or chewed.
The recommended daily doses are:
Adults: one capsule (= 45 mg of propiverine hydrochloride) once daily. The standard recommended dose is one propiverine 30 mg modified-release capsule once a day or one propiverine 15 mg tablet twice a day, which can be increased to one 15 mg tablet three times a day. Some patients may already respond to a dosage of 15 mg per day.
In patients where therapy with propiverine 15 mg tablets three times daily is indicated, the 15 mg tablet three times daily regimen can be replaced by Mictonorm 45 mg modified-release capsules once daily. .
The maximum daily dose is one modified-release capsule of Mictonorm 45 mg per day.
Elderly: There is generally no specific dosing regimen for the elderly (see section 5.2).
Pediatric population: Due to lack of data this product should not be used in children.
Caution should be exercised and the physician should closely monitor patients for any undesirable effects under the following conditions (see sections 4.4, 4.5, 5.2).
Use in patients with renal impairment
Caution should be exercised in the treatment of this patient group. In patients with severe renal impairment (creatinine clearance severe renal insufficiency.
Use in patients with hepatic impairment
No dose adjustment is required in patients with mild hepatic impairment; however, treatment should be proceeded with caution. No studies have been performed on the use of propiverine hydrochloride in patients with moderate or severe hepatic impairment. Its use is therefore not recommended in these patients (see section 5.2).
Patients receiving concomitant treatment with drugs that are potent inhibitors of CYP3A4 in combination with methimazole
In patients undergoing treatment with potent flavin-containing monooxygenase (FMO) inhibitors, such as methimazole, in combination with potent CYP 3A4 / 5 inhibitors, treatment should begin with a dose of 15 mg / day. The dose can be titrated to a higher. However, caution should be exercised and the physician should closely monitor these patients for any undesirable effects (see sections 4.5, 5.2).
There are no clinically relevant effects of food on propiverine pharmacokinetics (see section 5.2). Therefore there are no particular recommendations regarding the intake of propiverine in relation to food.
04.3 Contraindications
The drug is contraindicated in patients who have demonstrated hypersensitivity to the active substance or to any of the excipients, and in patients suffering from any of the following disorders:
- intestinal obstruction
- significant obstruction to the outflow of the bladder with the risk of urinary retention
- myasthenia gravis
- intestinal atony
- severe ulcerative colitis
- toxic megacolon
- uncontrolled angle-closure glaucoma
- moderate or severe hepatic impairment
- tachyarrhythmias
04.4 Special warnings and appropriate precautions for use
The drug should be used with caution in patients suffering from:
- autonomic neuropathy
- renal impairment (see section 4.2)
- hepatic impairment (see section 4.2)
Following the administration of this drug, the symptoms of the following diseases may be exacerbated:
- severe congestive heart failure (NYHA IV)
- enlarged prostate
- hiatal hernia with reflux esophagitis
- cardiac arrhythmia
- tachycardia
Propiverine, like other anticholinergics, induces mydriasis. Therefore, in predisposed individuals with narrow anterior chamber angles, the risk of inducing acute angle-closure glaucoma may be increased. Medicines belonging to this class, including propiverine, have been reported to induce or trigger acute narrow-angle glaucoma.
Before starting treatment, pollakiuria and nocturia due to kidney disease or congestive heart failure, as well as organic bladder diseases (e.g. urinary tract infections, malignant tumors) should be excluded.
This product contains lactose monohydrate. Patients with rare hereditary disorders 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
- An increase in the effects of propiverine has been observed following co-administration with tricyclic antidepressants (e.g. imipramine), tranquilizers (e.g. benzodiazepines), anticholinergics (when administered systemically), amantadine, neuroleptics (e.g. phenothiazines) ) and beta-adrenergic agonists (beta-sympathomimetics).
- A decrease in effects was found following concomitant use of cholinergic drugs.
- In patients treated with isoniazid propiverine reduces blood pressure.
- The activity of prokinetics such as metoclopramide, on the other hand, can be decreased.
- Pharmacokinetic interactions with other drugs metabolised by cytochrome P450 3A4 (CYP 3A4) are possible. However, a very pronounced increase in the concentration of these drugs is not expected, as the effects of propiverine are modest in comparison with classic enzyme inhibitors (e.g. ketoconazole or grapefruit juice). Propiverine can be considered a weak inhibitor of cytochrome P450 3A4. Pharmacokinetic studies have not yet been conducted with patients receiving potent CYP 3A4 inhibitors, such as azole antifungals (e.g. ketoconazole, itraconazole) or macrolide antibiotics (e.g.erythromycin, clarithromycin).
Patients receiving concomitant treatment with drugs that are potent inhibitors of CYP3A4 in combination with methimazole
In patients undergoing treatment with potent flavin-containing monooxygenase (FMO) inhibitors, such as methimazole, in combination with potent CYP 3A4 / 5 inhibitors, treatment should begin with a dose of 15 mg / day. The dose can be increased. However, caution should be exercised and the physician should closely monitor these patients for any undesirable effects (see section 4.2).
04.6 Pregnancy and breastfeeding
In toxicological studies in rats, no effects on male and female fertility or reproductive behavior were observed.
No clinical data are available on the use of propiverine hydrochloride in pregnant or lactating women. Animal studies have shown reproductive toxicity (see section 5.3). The potential risks for humans are unknown.
The drug is excreted in the milk of mammals. A risk to newborns cannot be excluded. The medicinal product should therefore not be given to pregnant or breastfeeding women.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed.
Propiverine hydrochloride can cause drowsiness and blurred vision. This may impair the patient's ability to perform activities that require attention, such as driving vehicles or using machines, or to perform hazardous work while being treated with this drug.
Sedatives can increase sleepiness caused by propiverine hydrochloride.
04.8 Undesirable effects
Within the system organ class, undesirable effects are listed in order of frequency according to the following convention:
Very common (≥1 / 10)
Common (≥1 / 100,
Uncommon (≥1 / 1,000 to
Rare (≥1 / 10,000,
Very rare (
Not known (frequency cannot be estimated from the available data)
All undesirable effects are transient and subside after dose reduction or termination of therapy within a maximum of 1 - 4 days.
Disorders of the immune system
Rare: hypersensitivity
Psychiatric disorders
Very rare: restlessness, confusion
Not known: hallucinations
Nervous system disorders
Common: headache
Uncommon: tremor, dizziness, dysgeusia
Eye disorders
Common: accommodation abnormalities, accommodation disorders, impaired vision
Cardiac pathologies
Very rare: palpitations
Vascular pathologies
Uncommon: decreased blood pressure with somnolence, flushing
Gastrointestinal disorders
Very common: dry mouth
Common: constipation, abdominal pain, dyspepsia
Uncommon: nausea / vomiting
Skin and subcutaneous tissue disorders
Rare: skin rash
Renal and urinary disorders
Uncommon: urinary retention
General disorders and administration site conditions
Common: fatigue
Liver enzymes should be monitored during long-term therapy, as a reversible alteration of these enzymes is rarely possible. Monitoring of intraocular pressure is recommended in patients at risk of developing glaucoma.
Particular attention should be paid to the residual urinary volume in the presence of urinary tract infections.
Post-authorization experience
The following spontaneously reported events originate from post-authorization experience, frequency is unknown (cannot be estimated from the available data): speech disturbances, tachycardia, pruritus and bladder and urethral symptoms.
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
Symptoms:
An overdose with the muscarinic receptor antagonist propiverine has the potential to cause severe anticholinergic effects characterized by peripheral symptoms and central nervous system disorders, such as:
- severe dry mouth
- bradycardia which can lead to tachycardia
- mydriasis and accommodation disorders
- urinary retention, inhibition of intestinal motility
- restlessness, confusion, hallucinations, confabulation
- dizziness, nausea, speech disturbances, muscle weakness
A 5-year-old boy who ingested 330 mg (12.69 mg / kg body weight) of propiverine hydrochloride experienced agitation, hallucinations, impaired vision, mydriasis and unsteady gait. The patient had been treated with activated charcoal and a benzodiazepine. The child had made a full recovery.
Treatment:
- In case of overdose with propiverine hydrochloride the patient should be treated with a suspension of activated charcoal with plenty of water.
- Gastric lavage should only be considered with "precautionary intubation," the use of a well-lubricated tube (dry mucous membranes) and if performed within one "hour" of ingestion of propiverine. Vomiting should not be induced.
- Forced diuresis or hemodialysis are not effective in increasing renal elimination.
- In case of severe central anticholinergic effects such as hallucinations or pronounced arousal, administration of physostigmine as an antidote may be attempted.
- Convulsions or pronounced excitation: treatment with benzodiazepines.
- Respiratory failure: treatment with artificial respiration.
- Urinary retention: treatment with catheterization.
- Mydriasis: treatment with pilocarpine eye drops and / or darkening of the patient's room.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
ATC code: G04B D06.
Pharmacotherapeutic group: urinary antispasmodics.
Mechanism of action
Inhibition of calcium influx and modulation of intracellular calcium in the smooth muscle cells of the urinary bladder, resulting in a spasmolytic effect on muscle fibers.
Inhibition of the efferent connections of the pelvic nerve due to the anticholinergic action.
Pharmacodynamic effects
In animal models, propiverine hydrochloride causes a dose-dependent decrease in intravesical pressure and an increase in bladder capacity.
The effect is due to the sum of the pharmacological properties of propiverine and three active urinary metabolites, as demonstrated in experiments conducted with isolated detrusor fibers of human and animal origin.
05.2 Pharmacokinetic properties
Absorption
Following oral administration of Mictonorm 45 mg capsules, propiverine is absorbed from the gastrointestinal tract and reaches its maximum plasma concentration after 9-10 hours. The mean absolute bioavailability of Mictonorm 45 mg capsules is 59.5 ± 23.3% (arithmetic mean ± SD of AUC0- ¥ (per os) / AUC0- ¥ (i.v.)).
Food intake does not affect propiverine pharmacokinetics.
The bioavailability of propiverine after the meal was found to be 99% compared to administration in the fasted state.
Administration of the modified-release capsule results in mean Cmax concentrations of propiverine of approximately 70 ng / ml, achieved within 9.5 hours after administration.
Distribution
Following administration of Mictonorm 45 mg capsules, steady state is reached after four to five days, at a higher concentration than after single dose administration (C average = 71 ng / ml). It was reported that after intravenous administration of propiverine hydrochloride to 21 healthy volunteers, the volume of distribution ranged from 125 to 473 l (mean 279 l), meaning that a large proportion of the available propiverine is distributed to peripheral compartments. Plasma protein binding amounts to 90 - 95% for the parent substance and approximately 60% for the major metabolite.
Pharmacokinetic characteristics (geometric mean, ± SD, range) of propiverine in 10 healthy volunteers following single administration of Mictonorm 30 mg modified-release capsules and Mictonorm 45 mg modified-release capsules
Steady state characteristics of propiverine following multiple dose administration of Mictonorm 45 mg modified-release capsules once daily for 7 days to 24 healthy volunteers
PTF = minimum-maximum fluctuation
Biotransformation
Propiverine is extensively metabolised by intestinal and hepatic enzymes. The main metabolic pathway involves the oxidation of piperidyl-N, and is mediated by CYP 3A4 and by the flavin-containing monooxygenase (FMO) 1 and 3 and leads to the formation of the much less active N-oxide compound, whose plasma concentration greatly exceeds that of the precursor substance. Four metabolites have been identified in the urine, three of which are pharmacologically active and may contribute to therapeutic efficacy.
In vitro, a slight inhibition of CYP 3A4 and CYP 2D6 can be detected, occurring at concentrations above therapeutic plasma concentrations by 10 - 100 fold (see section 4.5).
Elimination
Following the administration of an oral dose of 30 mg of 14C-propiverine hydrochloride to healthy volunteers, 60% of the radioactivity is detected in the urine and 21% in the faeces, within 12 days. Less than 1% of an orally administered dose is excreted unchanged in the urine. The mean total clearance after administration of a single 30 mg dose is 371 ml / min (191 - 870 ml / min).
Linearity / non-linearity
After oral administration of 10-45 mg propiverine hydrochloride, Cmax and AUC0-? Increased in linear relationship with dose.
Characteristics in patients
Renal impairment:
Severe renal impairment does not significantly alter the kinetics of propiverine and its major metabolite, propiverine-N-oxide, as shown in a single-dose study in 12 patients with creatinine clearance.
Liver failure:
Similar steady state pharmacokinetic values were found in 12 patients with mild to moderate hepatic impairment due to fatty liver disease, compared to those found in 12 healthy controls. No data are available for severe hepatic impairment.
Age:
When comparing trough plasma concentrations during steady state, no differences were found between elderly patients (60 - 85 years; mean 68 years) and healthy young subjects. The relationship between the parent compound and the metabolite remains unchanged in elderly patients indicating that, with regard to overall elimination, the metabolic conversion of propiverine to its main metabolite, propiverine-N-oxide, is not a limiting or related factor. "age.
05.3 Preclinical safety data
In studies conducted with long-term oral administration in two mammalian species, the main treatment-related effect was liver changes (including an increase in liver enzymes). These were characterized by hepatic hypertrophy and fatty liver degeneration. fatty liver degeneration was reversible at the end of treatment.
In animal studies, skeletal growth delays were found in offspring following oral administration of high doses of the drug to pregnant females. During lactation, propiverine hydrochloride was excreted in breast milk.
No mutagenic effects were found. Carcinogenicity studies conducted in mice demonstrated an increased incidence of hepatocellular adenomas and carcinomas in high-dose male animals. Hepatocellular adenomas, renal adenomas and urinary bladder papillomas were found in male rats in carcinogenicity studies in rats. treated with high doses, while in females the polyps of the endometrial stroma were increased with high doses.Both tumors found in rats and those found in mice were considered species-specific and therefore not clinically relevant.
In toxicological studies in rats, no effects on male and female fertility or reproductive behavior were observed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Pellets
Citric acid;
povidone;
lactose monohydrate;
talc;
triethyl citrate;
magnesium stearate;
methacrylic acid-methyl methacrylate copolymer (1: 1);
methacrylic acid-methyl methacrylate copolymer (1: 2);
ammonium methacrylate copolymer type A;
ammonium methacrylate copolymer type B.
Capsule
Jelly;
titanium dioxide E171;
red iron oxide E172;
yellow iron oxide E172.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
Bottle:
Stability after first opening: 100 days.
06.4 Special precautions for storage
Blister:
Store in the original package to protect from moisture.
Do not store above 25 ° C.
Bottle:
Keep the bottle tightly closed.
06.5 Nature of the immediate packaging and contents of the package
PVC / PVDC and aluminum blisters in packs containing 14, 20, 28, 30, 49, 50, 56, 60, 84, 98, 100, 112, 168 or 280 capsules.
Polyethylene bottles with a polypropylene screw cap containing a hygroscopic silica gel of 10, 14, 20, 28, 30, 49, 50, 56, 60, 84, 98 or 100 capsules.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
APOGEPHA Arzneimittel GmbH
Kyffhäuserstra? And 27
01309 Dresden
Germany
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 037768367 - "45 mg modified release capsules" 14 capsules in PVC / PVDC / AL blister
AIC n. 037768379- "45 mg modified release capsules" 20 capsules in PVC / PVDC / AL blister
AIC n. 037768381 - "45 mg modified release capsules" 28 capsules in PVC / PVDC / AL blister
AIC n. 037768393 - "45 mg modified release capsules" 30 capsules in PVC / PVDC / AL blister
AIC n. 037768405 - "45 mg modified release capsules" 49 capsules in PVC / PVDC / AL blister
AIC n. 037768417 - "45 mg modified release capsules" 50 capsules in PVC / PVDC / AL blister
AIC n. 037768429 - "45 mg modified release capsules" 56 capsules in PVC / PVDC / AL blister
AIC n. 037768431 - "45 mg modified release capsules" 60 capsules in PVC / PVDC / AL blister
AIC n. 037768443 - "45 mg modified release capsules" 84 capsules in PVC / PVDC / AL blister
AIC n. 037768456 - "45 mg modified release capsules" 98 capsules in PVC / PVDC / AL blister
AIC n. 037768468 - "45 mg modified release capsules" 100 capsules in PVC / PVDC / AL blister
AIC n. 037768470 - "45 mg modified release capsules" 112 capsules in PVC / PVDC / AL blister
AIC n. 037768482 - "45 mg modified release capsules" 168 capsules in PVC / PVDC / AL blister
AIC n. 037768494 - "45 mg modified release capsules" 280 capsules in PVC / PVDC / AL blister
AIC n. 037768506 - "45 mg modified release capsules" 10 capsules in PE bottle
AIC n. 037768518 - "45 mg modified release capsules" 14 capsules in PE bottle
AIC n. 037768520 - "45 mg modified release capsules" 20 capsules in PE bottle
AIC n. 037768532 - "45 mg modified release capsules" 28 capsules in PE bottle
AIC n. 037768544 - "45 mg modified release capsules" 30 capsules in PE bottle
AIC n. 037768557 - "45 mg modified release capsules" 49 capsules in PE bottle
AIC n. 037768569 - "45 mg modified release capsules" 50 capsules in PE bottle
AIC n. 037768571 - "45 mg modified release capsules" 56 capsules in PE bottle
AIC n. 037768583 - "45 mg modified release capsules" 60 capsules in PE bottle
AIC n. 037768595 - "45 mg modified release capsules" 84 capsules in PE bottle
AIC n. 037768607 - "45 mg modified release capsules" 98 capsules in PE bottle
AIC n. 037768619 - "45 mg modified release capsules" 100 capsules in PE bottle
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 15 May 2015
Date of most recent renewal: 11 May 2016
10.0 DATE OF REVISION OF THE TEXT
05/2016
