Ubretid

Package leaflet: Information for the patient

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.
Ubretid, 5 mg, tablets
Distigmini bromidum
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

1. What Ubretid is and what it is 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 Ubretid is and what it is used for

Ubretid is an acetylcholinesterase inhibitor (an enzyme found at nerve endings) and is used in the treatment of:

• impaired bladder emptying due to detrusor muscle weakness in neurological diseases (neurogenic bladder emptying disorders with hypotonia of the detrusor muscle, as part of comprehensive treatment);
• constipation due to intestinal atony (atonic constipation);
• supportive treatment of pathological muscle weakness or increased muscle fatigue (myasthenia) (Myasthenia gravis).

2. Important information before using Ubretid

When not to use 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 experienced severe postoperative shock;
• if the patient has severe circulatory failure;
• if the patient has dyspnoea caused by bronchial constriction (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, please discuss this with your doctor, pharmacist, or
nurse.
Particular caution is required when administering Ubretid to patients with:

• cardiac disorders (cardiac arrhythmias, bradycardia, myocardial ischaemia);
• low blood pressure;
• peptic ulcer disease;
• epilepsy;
• hyperthyroidism;
• parkinsonism;
• recent surgery of the intestines or urinary bladder.

Children and adolescents
The safety of Ubretid in children and adolescents has not been established.
Ubretid with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
Detailed information is provided at the end of the leaflet in the section for healthcare professionals.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she might be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
There are no data on the safety of Ubretid in pregnant women. Ubretid is not recommended during pregnancy.
It is not certain whether Ubretid passes into breast milk. Therefore, Ubretid should not be used during breastfeeding.
Driving and operating machinery

Warning: this medicine may impair psychomotor performance and the ability to drive vehicles.
Ubretid may in some cases reduce the ability to drive and operate machinery due to visual disturbances caused by pupillary constriction and reduced visual acuity when changing the distance of observed objects.
Ubretid contains monohydrate lactose.
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

3. How to use Ubretid

This medicine should always be taken as directed by the physician. In case of doubt, consult your doctor or pharmacist.
When using Ubretid, consider the delayed onset and prolonged duration of action of this medicine, as well as the individual patient's response to treatment. Dosage should be determined individually and depends on the patient's general condition, particularly on the initial state of the autonomic nervous system.

Unless otherwise directed by the physician, the usual dosage is as follows:
Initially, one tablet should be taken in the morning on an empty stomach, half an hour before breakfast, until therapeutic effect occurs. Usually, after the first week of treatment, the dosage is changed to administration every two or three days (1 to 2 tablets), if maintenance treatment is anticipated.
The dose must not exceed 2 tablets per day.

Dosage according to indications:
Bladder emptying disorders due to detrusor muscle weakness in the course of nervous system diseases
It is recommended that during the first days of treatment, until improvement occurs, one tablet of Ubretid be taken daily in the morning on an empty stomach, half an hour before breakfast. For maintenance of therapeutic effect, administration of 1 to 2 tablets every two or three days is usually sufficient.

Constipation due to intestinal smooth muscle atony
Initially, half a tablet should be administered once daily, half an hour before breakfast, increasing the dose by half a tablet every third day up to a maximum of 2 tablets per day. Treatment should continue until normal bowel function returns, which should occur within a maximum of 14 days.
This medicine should be administered only when absolutely indicated and under close observation due to the significant risk of overdose or drug accumulation.

Pathological muscle weakness or increased muscle fatigue
During the first week, one tablet per day should be taken in the morning on an empty stomach, half an hour before breakfast. During the second week, the daily dose may be increased to 1½ tablets, and during the third week up to 2 tablets per day.

Dosage in special patient groups:
Patients with impaired liver function
Dosage adjustment is not necessary in patients with hepatic impairment.

Patients with impaired kidney function
Due to lack of adequate studies, dosage recommendations cannot be provided for patients with renal impairment.

Elderly patients
In elderly patients (over 65 years of age), dosage 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, as a single dose, on an empty stomach, half an hour before breakfast, with a small amount of liquid.

If a significant portion of the administered Ubretid is not absorbed into the body and does not produce its effect due to prior or concomitant food intake, it is absolutely forbidden to compensate by taking additional doses within the next few hours, as this may lead to uncontrolled accumulation of the drug in the body.

The duration of treatment depends on the course of the disease and is determined by the physician.
Ubretid is generally suitable for long-term use.

Use of a higher than recommended dose of Ubretid
Overdose of Ubretid may lead to a "cholinergic crisis," characterized primarily by marked muscle weakness (or worsening of muscle weakness in patients with myasthenia gravis). If this condition is not recognized, it may lead to life-threatening paralysis of the respiratory muscles. Other possible symptoms of overdose include: decreased arterial blood pressure, chest tightness, wheezing and increased bronchial secretion associated with bronchospasm, slowed heart rate and paradoxically increased heart rate, excessive sweating, lacrimation, miosis, nystagmus, increased peristalsis, involuntary defecation and urination or increased urge to urinate, muscle cramps, ataxia, seizures, coma, slurred speech, restlessness, agitation, and anxiety.

In case of mild overdose (exceeding recommended doses), observation alone may be sufficient. In cases of more severe poisoning, contact your local poison control center.

Missed dose of Ubretid
Do not take a double dose to make up for a missed dose.

If you have any further doubts concerning the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everybody gets them.
The following frequency categories were used in assessing adverse reactions:

Adverse reactions to Ubretid are dose-dependent and are primarily due to the drug's effect on the autonomic nervous system (muscarinic effects), and less frequently on smooth muscle (nicotinic effects). Adverse reactions are often the first sign of overdose.

The most commonly observed adverse reactions are nausea, vomiting, diarrhea, sweating, and bradycardia, similar to those observed with other acetylcholinesterase inhibitors.

Muscarinic adverse effects (can be prevented by concomitant administration of atropine or substances with similar action):

Gastrointestinal disorders
Very common: diarrhea, nausea, vomiting
Common: increased salivary secretion
Uncommon: excessive peristalsis, abdominal pain
Rare: difficulty swallowing

Vascular disorders
Uncommon: decreased arterial blood pressure

Cardiac disorders
Very common: slowing of heart rate
Rare: ventricular tachycardia
Very rare: atrial fibrillation, angina pectoris, cardiac arrest

Particular attention should be paid to the drug's effect on the circulatory system in the postoperative period. Slowing of heart rate frequently occurs, and in isolated cases, circulatory arrest may even occur.

Paradoxical reactions (increased heart rate, elevated blood pressure) are possible.

Respiratory, thoracic and mediastinal disorders
Uncommon: excessive mucus production in the bronchi
Rare: dyspnea 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: miosis (pupil constriction), excessive lacrimation
Uncommon: accommodation disorders, blurred vision

Renal and urinary disorders
Uncommon: urinary incontinence

Nicotinic adverse effects (cannot be prevented by concomitant administration of atropine or substances with similar action):

Musculoskeletal and connective tissue disorders
Rare: muscle tremors, muscle cramps, muscle weakness, and in extreme cases, neuromuscular blockade leading to muscle paralysis, which should be differentiated diagnostically from symptoms of pathological muscle weakness or increased muscle fatigability (myasthenia).

Other adverse reactions:

Immune system disorders
Very rare: anaphylactic reactions (severe and sudden allergic reactions, symptoms of which include facial, throat, or tongue swelling, breathing difficulties, skin rash, sudden weakness and pulse loss, loss of consciousness, feeling of panic). In case of anaphylactic reactions, seek immediate medical attention.

Psychiatric disorders
Very rare: anxiety, depression, irritability, hallucinations, motor restlessness

Nervous system disorders
Rare: dizziness, somnolence, 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 of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.

Reporting adverse reactions helps to gather additional information on the safety of the medicinal product.

5. How to store Ubretid

Store below 25°C. Keep in the original packaging to protect from light.
Keep the medicine out of the 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 stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Ubretid contains

• The active substance in Ubretid is distigmine bromide. Each tablet contains 5 mg of distigmine bromide.
• Other ingredients: magnesium stearate, talc, maize starch, pregelatinised maize starch, lactose monohydrate.

What Ubretid looks like and contents of the pack
White, round, biconvex tablets with bevelled edges, scored 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 and 50 tablets.
For more detailed information, please contact the responsible party or the parallel importer.
Responsible party in the Czech Republic, 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, Poland
Repackaged by:
InPharm Sp. z o.o. Services sp. k., ul. Chełmżyńska 249, 04-458 Warsaw, Poland
Marketing authorisation number in the Czech Republic, country of export: 67/004/70-C
Parallel import authorisation number: 308/23

Information intended exclusively for healthcare professionals:

Special warnings and precautions for use
Refer to section 2 of the Patient Leaflet.
Ubretid must not be combined with depolarizing muscle relaxants, as this may lead to mutual potentiation of the effects of the drugs used (synergistic interactions). Ubretid is suitable only for reversing the effects of non-depolarizing muscle relaxants; in cases of overdose with curare derivatives, the recommended dosage should not be significantly exceeded.
When administering Ubretid together with atropine sulfate (to reduce muscarinic adverse effects), caution is advised, as atropine may mask the early symptoms of overdose.

Interactions with other medicines
Anticholinergic drugs such as atropine and drugs with atropine-like effects, as well as certain psychotropic agents—including tricyclic and tetracyclic antidepressants, neuroleptics, lithium, and antihistamines—antagonize the muscarinic effects of Ubretid, while generally not affecting its nicotinic actions.
Ubretid may prolong the effect, particularly in the initial phase, of depolarizing muscle relaxants (e.g. suxamethonium or decamethonium); therefore, it should not be used concomitantly with these agents.
Ubretid antagonizes the action of curare-derivative muscle relaxants (it should be discontinued prior to surgical procedures).
Distigmine and cholinergic-acting substances mutually enhance each other’s effects when administered simultaneously. Concurrent use of Ubretid with dipyridamole results in reduced therapeutic efficacy of Ubretid. Caution is required during concomitant use, and dosage adjustment may be necessary.
Antiarrhythmic drugs such as quinidine, procainamide, propafenone, and beta-adrenergic receptor blockers, due to their anticholinergic properties, reduce the effectiveness of Ubretid.
Local anesthetics such as procaine, as well as quinine, quinidine, chloroquine, and lithium, stabilize the motor endplate and thereby antagonize the effect of distigmine and may worsen the condition in myasthenia.
Glucocorticoids may reduce the effect of Ubretid. In patients with myasthenia, this may necessitate an increase in the dose of Ubretid, which however concurrently increases the risk of cholinergic crisis.
Since cholinergic agents enhance the effects of esterase inhibitors—including those found in many insecticides—potential interactions should be considered in patients exposed to such substances.
Concomitant use of Ubretid and other direct or indirect parasympathomimetics may lead to cholinergic crisis in patients with myasthenia.
In patients previously treated with beta-adrenergic blocking agents, prolonged bradycardia and significant hypotension may occur.
The bradycardic effect of beta-blockers and the acetylcholine-like effect of anticholinesterase drugs may be additive.
A number of aminoglycoside antibiotics (particularly streptomycin, neomycin, kanamycin) may impair neuromuscular transmission in patients with myasthenia and reduce the effect of acetylcholine on muscles and nerves. Depending on the patient's response, adjustment of distigmine dosage may be required.

Management of overdose
Management of overdose consists of immediate discontinuation of Ubretid and slow intravenous administration of atropine (1 mg to 2 mg of atropine sulfate intravenously or intramuscularly). Depending on heart rate, this dose may be repeated every 2–4 hours until signs of mild atropinization appear (dry mouth, pupil dilation).
Differential diagnosis between cholinergic crisis and myasthenic crisis—which presents with very similar symptoms—is essential. The latter requires immediate administration or increase in the dose of Ubretid.
Muscarinic symptoms (nausea, increased salivation, vomiting, diarrhea, gastrointestinal cramps, increased urinary urgency, lacrimation, miosis, excessive bronchial secretion, bronchospasm, excessive sweating, marked bradycardia, and hypotension) can be prevented by concomitant use of atropine or agents with similar effects.
Nicotinic symptoms (muscular effects such as muscle fasciculations, muscle cramps, or sensation of weakness, and in extreme cases, muscle paralysis) cannot be prevented by concomitant use of atropine or agents with similar effects.