Ubretid

Package Leaflet: Information for the Patient

Ubretid, 5 mg, Tablets

Distigmine bromide

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your 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 pack 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 neurological 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 of myasthenia gravis (a disease characterized by muscle weakness or increased muscle fatigue).

2. Important information before taking Ubretid

When not to take Ubretid:

• if you are allergic to distigmine bromide or any of the other ingredients of this medicine (listed in section 6);
• if you have had a severe postoperative shock;
• if you have severe circulatory failure;
• if you have breathing difficulties due to bronchial asthma;
• in cases of severe spastic conditions or mechanical intestinal obstruction;
• in cases of mechanical urinary tract obstruction.

Warnings and precautions

Before starting treatment with Ubretid, discuss it with your doctor, pharmacist, or nurse.
Particular caution should be exercised when taking Ubretid in patients with:

• heart rhythm disorders, bradycardia, coronary insufficiency;
• low blood pressure;
• peptic ulcer disease;
• epilepsy;
• hyperthyroidism;
• Parkinson's disease;
• recent intestinal or urinary bladder surgery.

Children and adolescents

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

Ubretid and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.
Detailed information is provided 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 are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
There is no data on the safety of 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 taken 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

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

3. How to take Ubretid

Always take this medicine exactly as your doctor has told you.
If you are not sure, ask your doctor or pharmacist.
When taking Ubretid, consider the delayed onset and long duration of action of this medicine, as well as the individual patient's reaction to its administration. The dosage should be determined individually. It depends on the patient's overall condition, especially the initial state of the autonomic nervous system.
Unless your doctor has told you otherwise, the usual dose of Ubretid is:

Initially, one tablet is given in the morning on an empty stomach, half an hour before breakfast, until therapeutic effects occur. 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 neurological diseases

It is recommended to take one 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 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 returns, 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), a dose reduction is necessary.
Children and adolescents
The safety of 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 case the medicine is not absorbed into the body due to previous or simultaneous food intake 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.

Overdose of Ubretid

Overdose of Ubretid may 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 combined 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 case of overdose (exceeding the recommended doses), you should contact a doctor or go to the nearest hospital.

Missed dose of Ubretid

Do not take a double dose to make up for a missed dose.
If you have any further questions about taking this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Ubretid can cause side effects, although not everybody gets them.
Side effects are often the first symptom of overdose.

If you notice any of the following symptoms, contact your doctor immediately – you may need urgent medical attention:

Facial swelling, throat swelling, tongue swelling, difficulty breathing, skin rash, sudden weakness and loss of pulse, loss of consciousness, feeling of panic. These may be symptoms of a severe and sudden allergic reaction, which occurs very rarely (may occur in less than 1 in 10,000 treated patients).

The following side effects have also been reported:

Very common (may occur in more than 1 in 10 treated patients)

• slowed heart rate
• diarrhea, nausea, vomiting
• excessive sweating

Common (may occur in less than 1 in 10 treated patients)

• constricted (reduced) pupils, excessive lacrimation
• increased salivation

Uncommon (may occur in less than 1 in 100 treated patients)

• decreased blood pressure
• excessive intestinal activity, abdominal pain
• excessive mucus production in the bronchi
• accommodation disorders (problems with visual acuity of objects at different distances), blurred vision
• urinary incontinence

Rare (may occur in less than 1 in 1,000 treated patients)

• ventricular tachycardia
• shortness of breath due to bronchial spasms with excessive mucus production, difficulty swallowing
• 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
• dizziness, drowsiness, headache, speech disorders
• rash
• menstrual disorders

Very rare (may occur in less than 1 in 10,000 treated patients)

• atrial fibrillation, angina pectoris, cardiac arrest
• breathing difficulties in patients with progressive muscular dystrophy (progressive muscle wasting)
• generalized tonic-clonic seizure and paralysis (muscle movements on both sides of the body, including seizures)
• anxiety, depression, irritability, hallucinations, restlessness

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C
PL-02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl .
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to 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 package 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 carton and on the blister after EXP. 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 dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Ubretid contains

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

What Ubretid looks like and contents of the pack

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.
Pack sizes: 20 or 50 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder

CHEPLAPHARM Arzneimittel GmbH
Ziegelhof 24
17489 Greifswald
Germany

Manufacturer

Takeda Austria GmbH
St. Peter Strasse 25
A-4020 Linz
Austria
To obtain more detailed information on this medicine, contact:
Komtur Polska Sp. z o.o.
phv@komtur.com

Date of last revision of the leaflet:

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Information intended for healthcare professionals only:

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 administered medicines (synergistic interactions). The medicine is suitable only for counteracting the effects of non-depolarizing muscle relaxants, and in the case of overdose of curare derivatives, the recommended dosage should not be significantly exceeded.
When administering Ubretid with atropine sulfate (to reduce muscarinic 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 effects to atropine, and some psychotropic medicines, such as tricyclic and tetracyclic antidepressants, neuroleptics, lithium, and antihistamines, antagonize the muscarinic effects of Ubretid, in most cases without affecting its nicotinic 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 derivative 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. Concurrent use of Ubretid with dipyridamole results in decreased therapeutic effect of Ubretid. Caution should be exercised when using these medicines together, 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 gravis.
Corticosteroids may weaken the effect of Ubretid. Especially in patients with myasthenia gravis, 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 patients exposed to these substances, the possibility of such interactions should be considered.
Concurrent use of Ubretid and other direct or indirect parasympathomimetics may cause cholinergic crisis in patients with myasthenia gravis.
In patients previously treated with beta-adrenergic blockers, cases of prolonged bradycardia and significant hypotension are possible.
The heart rate-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 disorders of neuromuscular transmission in patients with myasthenia gravis 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.

Overdose

Treatment 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 symptoms of mild atropinization appear (dryness of the mouth, pupil dilation).
Differential diagnosis of cholinergic crisis with very similar symptoms of myasthenic crisis is necessary. The latter requires immediate administration or increase of Ubretid doses.
The occurrence of muscarinic symptoms (nausea, increased salivation, vomiting, diarrhea, intestinal cramps, increased urge to urinate, lacrimation, pupil constriction, nystagmus, increased peristalsis, involuntary defecation and urination, excessive sweating, significant bradycardia, and decreased blood pressure) can be prevented by concurrent use of atropine or substances with similar effects.
The occurrence of nicotinic symptoms (muscle symptoms, such as muscle tremors, muscle cramps, or feeling of weakness, in extreme cases, muscle paralysis) cannot be prevented by concurrent use of atropine or substances with similar effects.