Ubretid

Leaflet attached to the packaging: patient information

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Ubretid, 5 mg, tablets

Distigmine bromide

It is necessary to carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• The leaflet should be kept so that it can be re-read if necessary.
• In case of any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for a particular person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform 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 detrusor muscle, as part of comprehensive treatment);
• constipation due to intestinal muscle weakness (atonic 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 other component 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 dyspnea caused by bronchospasm (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, the patient should discuss it with their doctor, pharmacist, or nurse.
Particular caution should be exercised when using Ubretid in patients with:

• heart rhythm disorders (arrhythmias, bradycardia, myocardial ischemia);
• low blood pressure;
• peptic ulcer disease;
• epilepsy;
• hyperthyroidism;
• Parkinson's disease;
• 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

The patient should inform their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Detailed information is provided at the end of the leaflet in the information for healthcare professionals.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.
There is no data on the safety of using Ubretid in pregnant women.
Ubretid is not recommended for use during pregnancy.
It is not known whether Ubretid passes into breast milk. Therefore, Ubretid should not be used during breastfeeding.

Driving and operating machinery

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

If the patient has previously been diagnosed with intolerance to some sugars, they should consult their doctor before taking the medicine.

3. How to take Ubretid

This medicine should always be taken according to the doctor's instructions. In case of doubts, the patient should consult their doctor or pharmacist.
When taking Ubretid, the delayed onset and long duration of action of this medicine should be taken into account, 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:

Urinary bladder emptying disorders with bladder muscle weakness in the course of nervous system diseases

It is recommended to take 1 tablet of Ubretid per day in the morning on an empty stomach, half an hour before breakfast, until improvement occurs. To maintain the therapeutic effect, it is usually sufficient to administer 1 to 2 tablets every 2 or 3 days.

Constipation due to intestinal muscle weakness

Initially, ½ tablet per day is administered half an hour before breakfast, with the dose increased every 3 days by ½ tablet to a maximum of 2 tablets per day. Treatment is continued until normal bowel function is restored, which should occur within a maximum of 14 days.
The medicine is administered 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, 1 tablet per day is taken in the morning on an empty stomach, half an hour before breakfast.
In the second week, the daily dose can be increased to 1½ tablets, and in the third week to 2 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 relevant studies, it is not possible to provide recommendations for dosing in patients with renal failure.

Patients of advanced age

In patients of advanced age (over 65 years), a dose reduction is necessary.

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 is not absorbed into the body and does not take effect, it is strictly forbidden to take a compensatory dose within a 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 than recommended dose of Ubretid

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

Missing a dose of Ubretid

A double dose should not be taken to make up for a missed dose.
In case of any further doubts related to the use of this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Ubretid can cause side effects, although they may not occur in every patient.
In the assessment of 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 a substance with similar action):

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.
Often, a slowed heart rate 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: dyspnea due to bronchospasm 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 lacrimation
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 a substance with similar action):

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 from symptoms of myasthenia gravis.
Other side effects:

Immune system disorders

Very rare: anaphylactic reactions (severe and sudden allergic reactions, the symptoms of which include, among others, facial swelling, throat swelling, tongue swelling, difficulty breathing, skin rash, sudden weakness, and loss of pulse, loss of consciousness, feeling of panic). In the event of anaphylactic reactions, medical attention should be sought immediately.

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 any side effects occur, including any side effects not listed in the leaflet, the patient should inform their 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, more information can be gathered on the safety of the medicine.

5. How to store Ubretid

Store at a temperature below 25°C.
Store in the original packaging to protect from light.
The medicine should be stored 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. The patient should ask their 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. 1 tablet contains 5 mg of distigmine bromide.
• Other ingredients are: magnesium stearate, talc, corn starch, gelatinized starch, 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 equal parts, and marked with "UB 5.0" on the other side.
The tablet can be divided into equal doses.
Packaging sizes: 20 or 50 tablets.
For more detailed information, the patient should contact the marketing authorization holder or 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:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Marketing authorization number in the Czech Republic, the country of export: 67/004/70-C

Parallel import authorization number: 252/24

Date of leaflet approval: 25.06.2024

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

Special warnings and precautions for use

See 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 medicines used (synergistic interactions). The medicine is only suitable 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.
In the case of concurrent administration of Ubretid with atropine sulfate (to reduce muskarynowe side effects), caution should be exercised, as atropine may mask the occurrence of initial symptoms of overdose.

Interactions with other medicines

Cholinolytic medicines, such as atropine and medicines with similar action to atropine, as well as 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 action is mutually enhanced if the medicines are taken simultaneously. Concurrent use of Ubretid with dipyridamole results in weakened therapeutic effect of Ubretid. Caution should be exercised when using Ubretid concurrently, 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.
Glycocorticosteroids may weaken the effect of Ubretid. Especially in patients with myasthenia, this may be associated with the need to increase the dose of Ubretid, which, however, increases the risk of 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 taken into account.
Concurrent use of Ubretid and other direct or indirect parasympathomimetics may cause 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 series 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, if necessary, until the appearance of symptoms of mild atropinization (dryness of the mouth, pupil dilation).
A differential diagnosis of cholinergic crisis with a very similar symptomatology of myasthenic crisis is necessary. 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, lacrimation, pupil constriction, excessive bronchial secretion, bronchospasm, increased sweating, significant bradycardia, and decreased blood pressure) can be prevented by concurrent administration of atropine or a substance with similar action.
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 concurrent administration of atropine or a substance with similar action.