Active ingredients: Tamsulosin (Tamsulosin hydrochloride)
Pradif 0.4 mg modified-release hard capsules
Why is Pradif used? What is it for?
The active substance in Pradif is tamsulosin, a selective α1A / α1D antagonist drug that reduces muscle tension in the prostate and urethra. This allows urine to pass faster through the urethra making it easier to urinate. it decreases the feeling of urgency to urinate.
Pradif is used in men to treat symptoms of the lower urinary tract associated with an enlarged prostate (benign prostatic hyperplasia). These disorders may include difficulty passing urine (narrowing of the jet), dripping, urgency, and increasing the frequency of urination. both day and night.
Contraindications When Pradif should not be used
Do not use Pradif
- if you are allergic (hypersensitive) to tamsulosin or any of the other ingredients of Pradif. Hypersensitivity may present as sudden local swelling of soft tissues in the body (eg throat or tongue), difficulty breathing and / or itching and rash (angioedema),
- if you have severe liver problems,
- if you faint from a drop in blood pressure when changing positions (sitting down or standing up).
Precautions for use What you need to know before taking Pradif
Take special care with Pradif
- Periodic medical check-ups are needed to monitor the development of the condition for which you are being treated.
- Rarely, fainting may occur with the use of Pradif as with other medicines of this type. At the first signs of dizziness or weakness you should sit or lie down until they disappear.
- If you have severe kidney problems please tell your doctor.
- If you are undergoing or scheduled for eye surgery for clouding of the lens (cataract) or increased pressure in the eye (glaucoma). Tell your ophthalmologist if you have previously taken, are taking or are planning to take Pradif . The specialist can consequently take the most appropriate precautions regarding the medicine and the surgical technique to be used. Ask your doctor if you should postpone or temporarily stop treatment with Pradif before undergoing eye surgery for clouding of the lens (cataract) or increased pressure in the eye (glaucoma).
Children
Do not give this medicine to children or adolescents under 18 years as it is not effective in this population.
Interactions Which drugs or foods can modify the effect of Pradif
Taking Pradif with other medicines
Taking Pradif with other medicines belonging to the same class (α1-adrenoceptor antagonists) may cause an unwanted drop in blood pressure. Pradif from the body (eg ketoconazole, erythromycin).
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Taking Pradif with food and drink
Pradif should be taken after breakfast or the first meal of the day
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Pradif is not indicated for use in women.
Abnormal ejaculation (ejaculation disorders) has been reported in the man. This means that seminal fluid does not leave the body via the urethra but enters the bladder (retrograde ejaculation) or that the ejaculation volume is reduced or absent (ejaculation failure). This event is harmless.
Driving and using machines
Pradif has not been shown to affect the ability to drive or use machines or equipment. However, you must bear in mind the possibility that dizziness may arise, in which case you must not undertake those activities that require attention.
Dose, Method and Time of Administration How to use Pradif: Posology
Always take Pradif exactly as your doctor has told you. If you are unsure, you should consult your doctor or pharmacist. The usual dose is 1 capsule per day, to be taken after breakfast or after the first meal of the day each day.
The capsule should be swallowed whole, without crushing or chewing it.
Pradif is usually prescribed for long periods of time. Effects on bladder and urination are maintained following long-term treatment with Pradif.
Overdose What to do if you have taken too much Pradif
If you take more Pradif than you should
Taking too much Pradif may lead to an unwanted drop in blood pressure and an increase in heart rate, associated with a feeling of weakness. If you have taken too many doses of Pradif, consult your doctor immediately.
If you forget to take Pradif
If you have forgotten to take a dose of Pradif, you can take it later in the day. If you have missed a day, continue taking the capsule of the day at the usual time. Never take a double dose to make up for a forgotten one.
If you stop taking Pradif
When Pradif treatment is stopped prematurely, the initial symptoms may reappear. Therefore, continue to take Pradif for as long as your doctor prescribes, even if your symptoms have already disappeared. Always consult your doctor if you believe this therapy should be discontinued.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Pradif
Like all medicines, Pradif can have side effects, although not everybody gets them.
Common effects (less than 1 in 10 cases, more than 1 in 100 cases (1-10%)):
dizziness, especially when sitting or standing up.
Abnormal ejaculation (ejaculation disorder). This symptom means that seminal fluid does not go outside the body through the urethra but enters the urinary bladder (retrograde ejaculation) or that the volume of seminal fluid is reduced or absent (ejaculation failure. ) This event is harmless.
Uncommon effects (more than 1 case in 1000, less than 1 case in 100 (0.1-1%)):
headache, palpitations (the heart beats more often than normal and is also noticeable), decrease in blood pressure such as standing up quickly from sitting or lying down often associated with dizziness, stuffy or runny nose (rhinitis), diarrhea, nausea and vomiting, constipation, weakness (asthenia), skin redness (rash), itching and hives.
Rare effects (more than 1 case in 10,000, less than 1 case in 1000 (0.01-0.1%)):
fainting and cases of sudden localized swelling of the soft tissues of the body (e.g. throat and tongue), difficulty breathing with or without itching and redness of the skin (rash), as frequently in an allergic reaction (angioedema).
Very rare effects (less than 1 case in 10,000 (<0.01%)):
priapism (painful and prolonged involuntary erection requiring immediate medical treatment). Rash, inflammation, blistering of the skin and / or mucous membranes of the lips, eyes, mouth, nostrils or genitals (Stevens-Johnson syndrome).
Effects with frequency not known (frequency cannot be estimated from the available data):
- blurred vision
- visual impairment
- nosebleed (epistaxis)
- severe skin rashes (erythema multiforme, exfoliative dermatitis)
- abnormal irregular heart rhythm (atrial fibrillation, arrhythmia, tachycardia), difficulty in breathing (dyspnoea).
- if you are about to have eye surgery due to clouding of the lens (cataract) or increased pressure in the eye (glaucoma) and you are already taking or have recently taken Pradif, the pupil may dilate poorly and the iris (the colored circular part eye) may become flabby during surgery.
- dry mouth.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
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 in the original packaging.
Keep Pradif out of the reach and sight of children.
Do not use Pradif after the expiry date which is stated on the blister and carton after "EXP" (month and year). The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Pradif contains
The active ingredient is tamsulosin hydrochloride.
The other ingredients are: capsule contents: microcrystalline cellulose (E460); methacrylic acid-ethyl acrylate copolymer (1: 1); polysorbate 80 (E433); sodium lauryl sulfate; triacetin (E1518); calcium stearate (E470a); talc (E553b). Capsule shell: hard gelatin; indigo carmine (E132); titanium dioxide (E171); yellow iron oxide (E172); red iron oxide (E172). Printing ink: shellac (E904), propylene glycol (E1520), black iron oxide (E172).
Description of what Pradif looks like and contents of the pack
Pradif capsules are orange / olive green, marked with the T0.4 codes and logo.
Pradif capsules are packaged in polypropylene-aluminum blisters contained in a cardboard box.
The pack contains 10, 20, 30, 50, 60, 90, 100 or 200 capsules. 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
PRADIF HARD CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each modified-release capsule contains 0.4 mg of tamsulosin hydrochloride as the active ingredient.
Excipients: for the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Orange / olive green modified-release capsule, hard, marked with T0.4 code and logo.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Lower Urinary Tract Symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
04.2 Posology and method of administration
Oral use.
One capsule per day to be taken after breakfast or after the first meal of the day.
The capsule must be swallowed whole and must not be crushed or chewed as this can interfere with the modified release of the active ingredient.
In case of renal impairment no dosage adjustment is required.
In case of mild to moderate hepatic insufficiency, no dosage adjustment is required (see also section 4.3 Contraindications).
Pediatric population
There is no indication for specific use of Pradif in children.
The safety and efficacy of tamsulosin in children
04.3 Contraindications
Hypersensitivity to tamsulosin hydrochloride, including drug-induced angioedema or to any of the excipients; a history of orthostatic hypotension; severe hepatic insufficiency.
04.4 Special warnings and appropriate precautions for use
As with other a1-adrenoceptor antagonists, during treatment with Pradif, a reduction in blood pressure may occur in particular cases, which rarely can lead to syncope. At the first signs of orthostatic hypotension (dizziness, weakness) the patient should sit or lie down until the symptoms disappear.
Before starting Pradif therapy, the patient should be evaluated for other conditions that may cause the same symptoms as benign prostatic hyperplasia. Rectal examination and, if necessary, determination of prostate specific antigen (PSA) should be performed before starting treatment and at regular intervals thereafter.
The treatment of patients with severe renal impairment (creatinine clearance less than 10 ml / min) should be considered with caution as the medicinal product has not been studied in these subjects.
Intraoperative Floppy Iris Syndrome (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma surgery in some patients on or previously treated with tamsulosin hydrochloride.
IFIS may increase the risk of ocular complications during and after surgery.
Discontinuation of tamsulosin hydrochloride 1-2 weeks prior to cataract or glaucoma surgery is considered empirically useful, however the benefit of discontinuing treatment has not yet been established.
IFIS has also been found in patients who had stopped tamsulosin for a longer period prior to surgery.
It is not recommended to initiate therapy with tamsulosin hydrochloride in patients for whom cataract or glaucoma surgery is planned.
During the pre-operative evaluation, the ophthalmologist and the surgical team should consider whether the patient awaiting cataract or glaucoma surgery is being treated or has been treated with tamsulosin to ensure that appropriate measures can be taken to manage IFIS during the intervention.
Tamsulosin hydrochloride should not be administered in combination with strong inhibitors of CYP3A4 in patients with a poor metabolising CYP2D6 phenotype.
Tamsulosin hydrochloride should be used with caution in combination with strong and moderate inhibitors of CYP3A4 (see section 4.5).
04.5 Interactions with other medicinal products and other forms of interaction
Interaction studies have only been performed in adults.
No interactions were noted when tamsulosin hydrochloride was taken concomitantly with atenolol, enalapril or theophylline.
The concomitant use of cimetidine causes an increase in plasma tamsulosin levels while furosemide lowers them; however, the plasma concentration levels of tamsulosin are within the therapeutic range and therefore no dosage adjustment is necessary.
In vitro diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin do not change the free fraction of tamsulosin in human plasma. Tamsulosin does not modify the free fraction of diazepam, propranolol, trichlormethiazide and chlormadinone.
However, diclofenac and warfarin can increase the rate of elimination of tamsulosin.
Concomitant administration of tamsulosin hydrochloride and strong CYP3A4 inhibitors may lead to increased exposure to tamsulosin hydrochloride. Concomitant administration with ketoconazole (a known strong inhibitor of CYP3A4) resulted in an increase in the AUC and Cmax of tamsulosin hydrochloride by a factor of 2.8 and 2.2, respectively.
Tamsulosin hydrochloride should not be administered in combination with strong inhibitors of CYP3A4 in patients with a poor metabolising CYP2D6 phenotype.
Tamsulosin hydrochloride should be used with caution in combination with strong and moderate inhibitors of CYP3A4.
Concomitant administration of tamsulosin hydrochloride and paroxetine, a strong inhibitor of CYP2D6, resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively, but these increases are not considered clinically relevant. .
Concomitant use of other a1-adrenoceptor antagonists may lead to hypotensive effects.
04.6 Pregnancy and lactation
Pradif is not indicated for use in women.
Ejaculation disorders have been observed in short- and long-term clinical trials with tamsulosin hydrochloride. Cases of ejaculation disorders, retrograde ejaculation and inability to ejaculate have been reported in post-authorization studies.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed. However, the patient should be aware of the possibility of dizziness.
04.8 Undesirable effects
* Observed in post marketing
A variant of the small pupil syndrome known as the "Intraoperative Floppy Iris Syndrome" (IFIS) associated with tamsulosin therapy has been observed during cataract and glaucoma surgery during the post-marketing surveillance period. (see also section 4.4).
Post-marketing experience: In addition to the adverse events listed above, atrial fibrillation, arrhythmia, tachycardia and dyspnoea have been reported in association with the use of tamsulosin. Since these spontaneously reported events come from post-marketing experience in all the world, their frequency and the role of tamsulosin in causing them cannot be determined with certainty.
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
Overdose with tamsulosin hydrochloride can potentially result in severe hypotensive effects.
Severe hypotensive effects were observed at different levels of overdose.
Treatment
In case of acute hypotension following overdose, prompt action should be taken to support the cardiovascular system.
Blood pressure and heart rate can be restored to normal by having the patient lie down.
If this is not enough, volume expanders and, if necessary, vasoconstrictive drugs can be used. Renal function should be monitored and general supportive measures applied.
Dialysis is of little use as tamsulosin binds strongly to plasma proteins. Some measures such as emesis can be taken to prevent absorption.
In case of ingestion of large doses, gastric lavage can be useful and activated charcoal and an osmotic laxative, such as sodium sulfate, can be administered.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: a1 adrenoceptor antagonist.
ATC code: G04C A02.
Preparations for the exclusive treatment of prostate pathologies.
Mechanism of action:
tamsulosin binds selectively and competitively to postsynaptic a1 adrenoceptors, particularly the a1A and a1D subtypes. It causes smooth muscle relaxation of the prostate and urethra.
Pharmacodynamic effects:
pradif increases the maximum urinary flow. Relieves obstruction by relaxing the smooth muscles of the prostate and urethra thereby improving voiding symptoms.
It also improves filling symptoms in which bladder instability plays an important role.
These effects on filling and emptying symptoms are maintained during long-term therapy. The need for surgery or catheterization is significantly delayed.
A1-adrenoceptor antagonists can reduce blood pressure by reducing peripheral resistance. No clinically significant reduction in blood pressure was observed during clinical trials with Pradif.
Pediatric population
A double-blind, randomized, placebo-controlled, dose ranging study was conducted in children with neuropathic bladder. A total of 161 children (2-16 years of age) were randomized and treated at 1 of 3 tamsulosin dose levels (low [0.001 to 0.002 mg / kg], medium [0.002 to 0.004 mg / kg ], and high [0.004 to 0.008 mg / kg]), or with placebo. The primary endpoint was the number of patients whose vanishing point detrusor pressure (detrusor leak point pressure, LPP) decreased until stabilization of hydronephrosis and hydroureter and change in urine volumes obtained from catheterization and number of urine leaks during catheterization, as recorded in catheterization diaries. There was no significant difference between the placebo group and any of the 3 tamsulosin groups for either the primary or secondary endpoints. No dose response was observed for any dose level.
05.2 Pharmacokinetic properties
Absorption
Tamsulosin hydrochloride is absorbed from the intestine and is almost completely bioavailable.
The absorption of tamsulosin hydrochloride is reduced by taking it close to meals.
Uniform absorption can be achieved if the patient always takes Pradif after the same meal.
Tamsulosin exhibits linear kinetics.
After a single dose of Pradif in fed state, plasma levels of tamsulosin peak in approximately 6 hours and, under steady state conditions, which are reached after 5 days of treatment, Cmax is approximately 2/3 higher than that achieved. after single dose.
This has been noted in elderly patients and it is reasonable to expect the same in younger patients.
There is considerable individual variation in plasma levels after both single and repeat dosing.
Distribution
In humans, tamsulosin is approximately 99% bound to plasma proteins. The volume of distribution is low (approximately 0.2 l / kg).
Biotransformation
Tamsulosin has a poor first pass effect as it is metabolized slowly.
Tamsulosin is present in plasma mainly in the form of unchanged active ingredient.
It is metabolized in the liver.
Virtually no induction of the microsomal liver enzyme system caused by tamsulosin was observed in the rat.
In vitro results suggest that CYP3A4 and also CYP2D6 are involved in metabolism, with possible minor contributions to the metabolism of tamsulosin hydrochloride by other CYP isoenzymes. Inhibition of drug metabolising enzymes CYP3A4 and CYP2D6 may lead to increased exposure to tamsulosin hydrochloride (see sections 4.4 and 4.5).
None of the metabolites are more active than the original product.
Elimination
Tamsulosin and its metabolites are eliminated primarily in the urine and approximately 9% of a dose in the form of unchanged active substance.
After a single dose of Pradif in fed and steady state conditions, the elimination half-life was evaluated at 10 and 13 hours, respectively.
05.3 Preclinical safety data
Single and repeat dose toxicity studies were performed in mice, rats and dogs. Reproduction studies in rats, carcinogenicity studies in mice and rats, genotoxicity studies were also considered. in vivo and in vitro.
The general toxicological profile as ascertained with the higher doses of tamsulosin is consistent with the known pharmacological activity of the a1 adrenoceptor antagonist drugs.
In dogs, at very high doses, the electrocardiogram is changed. This response is considered not clinically relevant.
Tamsulosin did not show relevant genotoxic properties.
An "increased incidence of proliferative changes in the udder of rats and female mice has been reported. These findings, which are likely mediated by hyperprolactinaemia and only occur at high doses, are considered irrelevant."
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsule contents:
microcrystalline cellulose E460, methacrylic acid - ethyl acrylate copolymer (1: 1), polysorbate 80 E433, sodium lauryl sulfate, triacetin E1518, calcium stearate E470a, talc E553b.
Capsule:
hard gelatin, indigo carmine E132, titanium dioxide E171, yellow iron oxide E172, red iron oxide E172.
Printing ink:
shellac E904, propylene glycol E1520, black iron oxide E172.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
4 years.
06.4 Special precautions for storage
Store in the original packaging.
06.5 Nature of the immediate packaging and contents of the package
Polypropylene - aluminum blisters of 10 capsules, in cartons of 10, 20, 30, 50, 60, 90, 100 and 200 capsules.
PVC / PVDC - aluminum blister of 5 capsules, in box of 50 capsules.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Boehringer Ingelheim International GmbH - Binger Strasse 173 - D 55216 Ingelheim am Rhein - Germany
Representative for Italy
Boehringer Ingelheim Italia S.p.A. - Via Lorenzini, 8 - 20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Box of 20 capsules: A.I.C. N ° 030106013
Pack of 30 capsules: A.I.C. N ° 030106025
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
27 September 1996/12 July 2006.
10.0 DATE OF REVISION OF THE TEXT
10.06.2014.
