Ubretid

Leaflet attached to the packaging: patient information

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.

Ubretid, 5 mg, tablets

Distigmine bromide

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if necessary.
• In case of any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Ubretid and what is it used for
• 2. Important information before taking Ubretid
• 3. How to take Ubretid
• 4. Possible side effects
• 5. How to store Ubretid
• 6. Contents of the packaging and other information

1. What is Ubretid and what is it used for

Ubretid is an acetylcholinesterase inhibitor (an enzyme found in nerve endings) and is used to treat:

• urinary bladder emptying disorders with bladder muscle weakness in the course of nervous system diseases (neurogenic urinary bladder emptying disorders with hypotonia of the urinary sphincter muscle, as part of comprehensive treatment);
• constipation due to intestinal muscle weakness (atomic constipation);
• supporting treatment for myasthenia gravis (a disease characterized by muscle weakness or increased muscle fatigue).

2. Important information before taking Ubretid

When not to take Ubretid:

• if the patient is allergic to distigmine bromide or any of the other ingredients of this medicine (listed in section 6);
• if the patient has had a severe postoperative shock;
• if the patient has severe circulatory failure;
• if the patient has breathing difficulties caused by bronchial constriction (bronchial asthma);
• in cases of severe spastic or mechanical intestinal obstruction;
• in cases of mechanical urinary tract obstruction.

Warnings and precautions

Before starting treatment with Ubretid, you should discuss it with your doctor, pharmacist, or nurse.
You should be particularly careful when taking Ubretid if you have:

• heart rhythm disorders (arrhythmias, bradycardia, myocardial ischemia);
• low blood pressure;
• peptic ulcer disease;
• epilepsy;
• hyperthyroidism;
• parkinsonism;
• recent intestinal or urinary bladder surgery.

Children and adolescents

The safety of using Ubretid in children and adolescents has not been established.

Ubretid and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Detailed information can be found at the end of the leaflet in the information for healthcare professionals.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist before taking this medicine.
There is no data on the safety of using Ubretid in pregnant women. Ubretid is not recommended during pregnancy.
It is not known whether Ubretid passes into breast milk. Therefore, Ubretid should not be used during breastfeeding.

Driving and using machines

Warning: the medicine may impair psychomotor performance and the ability to drive vehicles.
Ubretid may, in some cases, reduce the ability to drive vehicles and operate machinery due to vision disturbances caused by pupil constriction and decreased visual acuity when changing the distance of observed objects.

Ubretid contains lactose monohydrate

If you have previously been diagnosed with intolerance to some sugars, you should consult your doctor before taking the medicine.

3. How to take Ubretid

This medicine should always be taken as directed by your doctor. If you have any doubts, you should consult your doctor or pharmacist.
When taking Ubretid, you should consider the delayed onset and long duration of action of this medicine, as well as the individual patient's response to its use. The dosage should be determined individually. It depends on the patient's overall condition, especially the initial state of the autonomic nervous system.
Unless the doctor recommends otherwise, the usual dose of the medicine is:

Initially, one tablet is given in the morning on an empty stomach, half an hour before breakfast, until therapeutic effects appear. Usually, after the first week of treatment, the medicine is taken every two or three days (one to two tablets), in cases where maintenance treatment is planned.
The dose should not exceed two tablets per day.
Dosage depending on the indications for use:
Urinary bladder emptying disorders with bladder muscle weakness in the course of nervous system diseases
It is recommended that in the first days of treatment, until improvement occurs, one tablet of Ubretid should be taken daily in the morning on an empty stomach, half an hour before breakfast. To maintain the therapeutic effect, it is usually sufficient to administer one to two tablets every two or three days.
Constipation due to intestinal muscle weakness
Initially, half a tablet is given per day, half an hour before breakfast, with the dose increased every third day by half a tablet to a maximum of two tablets per day. Treatment is continued until normal bowel function is restored, which should occur within a maximum of 14 days.
The medicine is given only in cases of absolute indications for its use, under supervision, due to the significant risk of overdose or accumulation.
Myasthenia gravis
In the first week, one tablet is taken per day in the morning on an empty stomach, half an hour before breakfast.
In the second week, the daily dose can be increased to one and a half tablets, and in the third week to two tablets per day.
Dosage in special patient groups:
Patients with liver function disorders
No dose adjustment is necessary in patients with liver failure.
Patients with kidney function disorders
Due to the lack of appropriate studies, it is not possible to provide recommendations for dosing in patients with renal failure.
Elderly patients
In elderly patients (over 65 years), it is necessary to reduce the dose.
Children and adolescents
The safety of using Ubretid in children and adolescents has not been established.
Method of administration
The daily dose should be taken orally, once, on an empty stomach, half an hour before breakfast, with a small amount of liquid.
In cases where, due to previous or simultaneous food intake, a significant portion of the administered Ubretid does not get absorbed into the body and does not take effect, it is strictly forbidden to take a compensatory dose within the next few hours, as this is associated with the risk of uncontrolled accumulation of the medicine in the body.
The treatment period depends on the course of the disease and is determined by the doctor.
Ubretid is basically suitable for long-term use.

Using a higher dose of Ubretid than recommended

Overdosing on Ubretid can lead to the occurrence of a "cholinergic crisis", which is characterized primarily by significant muscle weakness (or increased muscle weakness in patients with myasthenia). If this situation is not recognized, it can lead to life-threatening paralysis of the respiratory muscles. Other possible symptoms of overdose include: decreased blood pressure, chest tightness, wheezing, increased bronchial secretion with bronchial constriction, slowed heart rate, and paradoxically accelerated heart rate, excessive sweating, tearing, pupil constriction, nystagmus, increased peristalsis, involuntary defecation and urination or increased urge to urinate, muscle spasms, convulsions, coma, slurred speech, anxiety, agitation, and fear.
In cases of slight overdose (exceeding the recommended doses), observation may be sufficient. In cases of more severe poisoning, you should contact the local poison control center.

Missing a dose of Ubretid

You should not take a double dose to make up for a missed dose.
If you have any further doubts about taking this medicine, you should consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Ubretid can cause side effects, although not everybody gets them.
In assessing side effects, the following frequency criteria were used:
Ubretid's side effects are dose-dependent and are primarily the result of the medicine's effect on the autonomic nervous system (muskarynowe effects), and less often on the muscles (nikotynowe effects). Side effects are often the first symptom of overdose.
The most commonly observed side effects are nausea, vomiting, diarrhea, sweating, and bradycardia, similar to the side effects observed with other acetylcholinesterase inhibitors.
Muskarynowe side effects (which can be prevented by simultaneous administration of atropine or substances with similar effects):
Gastrointestinal disorders
Very common: diarrhea, nausea, vomiting
Common: increased salivation
Uncommon: excessive peristalsis, abdominal pain
Rare: difficulty swallowing
Vascular disorders
Uncommon: decreased blood pressure
Cardiac disorders
Very common: slowed heart rate
Rare: ventricular tachycardia
Very rare: atrial fibrillation, angina pectoris, cardiac arrest
The effect of the medicine on the circulatory system is particularly significant in the postoperative period.
Bradycardia often occurs, and in individual cases, cardiac arrest may even occur.
Paradoxical reactions (accelerated heart rate, increased blood pressure) are possible.
Respiratory, thoracic, and mediastinal disorders
Uncommon: excessive mucus production in the bronchi

Rare: shortness of breath due to bronchial constriction with excessive mucus production
Very rare: breathing difficulties in patients with progressive muscular dystrophy (progressive muscle atrophy)
Skin and subcutaneous tissue disorders
Very common: excessive sweating
Eye disorders
Common: pupil constriction, excessive tearing
Uncommon: accommodation disorders, blurred vision
Renal and urinary disorders
Uncommon: urinary incontinence
Nikotynowe side effects (which cannot be limited by simultaneous administration of atropine or substances with similar effects):
Musculoskeletal and connective tissue disorders
Rare: muscle tremors, muscle cramps, muscle weakness, in extreme cases, muscle paralysis due to neuromuscular blockade, which must be differentiated diagnostically from symptoms of myasthenia gravis.
Other side effects:
Immune system disorders
Very rare: anaphylactic reactions (severe and sudden allergic reactions, whose symptoms include, among others, facial swelling, throat swelling, tongue swelling, difficulty breathing, skin rash, sudden weakness, and loss of consciousness). In case of anaphylactic reactions, you should immediately consult a doctor.
Psychiatric disorders
Very rare: anxiety, depression, irritability, hallucinations, restlessness
Nervous system disorders
Rare: dizziness, drowsiness, headache, speech disorders
Very rare: generalized tonic-clonic seizure and paralysis
Skin and subcutaneous tissue disorders
Rare: rash
Reproductive system and breast disorders
Rare: menstrual disorders.

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
By reporting side effects, you can help gather more information on the safety of the medicine.

5. How to store Ubretid

Store in a temperature below 25°C. Store in the original packaging to protect from light.
The medicine should be stored in a place that is out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Ubretid contains

• The active substance of the medicine is distigmine bromide. One tablet contains 5 mg of distigmine bromide.
• The other ingredients are: magnesium stearate, talc, corn starch, corn starch paste, lactose monohydrate.

What Ubretid looks like and what the packaging contains

White, round, flat tablets with beveled edges and notches on one side, allowing the tablet to be divided into 4 parts, and marked with "UB 5.0" on the other side.
The tablet can be divided into equal doses.
Packaging sizes: 20 and 50 tablets.
For more detailed information, you should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in the Czech Republic, the country of export:

CHEPLAPHARM Arzneimittel GmbH, Ziegelhof 24, 17489 Greifswald, Germany

Manufacturer:

Takeda Austria GmbH, St. Peter Str. 25, A-4020 Linz, Austria

Parallel importer:

InPharm Sp. z o.o., ul. Strumykowa 28/11, 03-138 Warsaw

Repackaged by:

InPharm Sp. z o.o. Services sp. k., ul. Chełmżyńska 249, 04-458 Warsaw
Marketing authorization number in the Czech Republic, the country of export:67/004/70-C

Parallel import authorization number: 308/23

Date of leaflet approval: 22.12.2023

[Information about the trademark]
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Information intended only for healthcare professionals:

Special warnings and precautions for use

You should read section 2 of the Patient Leaflet.
Ubretid should not be combined with depolarizing muscle relaxants, as this is associated with mutual enhancement of the effects of the administered medicines (synergistic interactions). The medicine is suitable only for reversing the effects of non-depolarizing muscle relaxants, and in the event of an overdose of curare derivatives, the recommended dosage should not be significantly exceeded.
When administering Ubretid simultaneously with atropine sulfate (to reduce muskarynowe side effects), you should be cautious, as atropine may mask the occurrence of the initial symptoms of overdose.

Interactions with other medicines

Cholinolytic medicines, such as atropine and medicines with similar effects, and some psychotropic medicines, such as tricyclic and tetracyclic antidepressants, neuroleptics, lithium, and antihistamines, antagonize the muskarynowe effects of Ubretid, in most cases without affecting its nikotynowe effects.
Ubretid may prolong the action, especially in the initial phase, of depolarizing muscle relaxants (e.g., suxamethonium or decamethonium), and therefore should not be combined with these medicines.
Ubretid antagonizes the effect of muscle relaxants from the curare derivatives group (it should be discontinued before surgical operations).
The action of distigmine and substances with cholinergic effects is mutually enhanced if the medicines are taken simultaneously. The simultaneous use of Ubretid with dipyridamole leads to a weakening of the therapeutic effect of Ubretid. Caution should be exercised when using these medicines simultaneously, and the dosage should be adjusted if necessary.
Antiarrhythmic medicines, such as quinidine, procainamide, propafenone, or beta-adrenergic receptor blockers, due to their cholinolytic properties, weaken the effect of Ubretid.
Local anesthetics, such as procaine, quinine, quinidine, chloroquine, and lithium, stabilize the motor end plate and thus antagonize the effect of distigmine and may worsen the condition in myasthenia.
Corticosteroids may weaken the effect of Ubretid. Especially in patients with myasthenia, this may be associated with the need to increase the dosage of Ubretid, which, however, also increases the risk of a cholinergic crisis.
Since cholinergic medicines enhance the action of esterase inhibitors, which are contained in many insecticides, in the case of patients exposed to such substances, the possibility of such interactions should be considered.
The simultaneous use of Ubretid and other direct or indirect parasympathomimetics may lead to the occurrence of a cholinergic crisis in patients with myasthenia.
In patients previously treated with beta-adrenergic blockers, cases of prolonged bradycardia and significant hypotension are possible.
The heart-slowing effect of beta-blockers and the acetylcholine-like effect of anticholinesterase medicines may be additive.
A number of antibiotics from the aminoglycoside group (mainly streptomycin, neomycin, kanamycin) may cause disturbances in neuromuscular transmission in patients with myasthenia and reduce the effect of acetylcholine on muscles and nerves. Depending on the patient's response, it may be necessary to adjust the dose of distigmine.

Procedure in case of overdose

The procedure in case of overdose involves immediate discontinuation of Ubretid and slow intravenous administration of atropine (in a dose of 1 mg to 2 mg of atropine sulfate intravenously or intramuscularly). Depending on the heart rate, this dose can be repeated at intervals of 2-4 hours, until the symptoms of mild atropinism appear (dryness of the mouth, pupil dilation).
A differential diagnosis is necessary to distinguish between a cholinergic crisis and a myasthenic crisis, which has very similar symptoms. The latter requires immediate administration or increase in the dose of Ubretid.
The occurrence of muskarynowe symptoms (nausea, increased salivation, vomiting, diarrhea, intestinal cramps, increased urge to urinate, tearing, pupil constriction, excessive bronchial secretion, bronchial constriction, increased sweating, significant bradycardia, and decreased blood pressure) can be prevented by simultaneous administration of atropine or substances with similar effects.
The occurrence of nikotynowe symptoms (muscle symptoms, such as muscle tremors, muscle cramps, or a feeling of weakness, in extreme cases, muscle paralysis) cannot be prevented by simultaneous administration of atropine or substances with similar effects.