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 the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, 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 present at nerve endings) and is used in the treatment of:

• impaired bladder emptying with detrusor muscle weakness due to neurological disorders (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. 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 insufficiency;
• if the patient has dyspnea caused by bronchial spasm (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, discuss this with your doctor, pharmacist, or nurse.
Special caution is required when administering Ubretid to patients with:

• cardiac disorders (cardiac arrhythmias, bradycardia, myocardial ischemia);
• 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, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
There is no data on the safety of Ubretid in pregnant women.
Ubretid is not recommended during pregnancy.
It is uncertain whether Ubretid passes into human breast milk. Therefore, Ubretid should not be used during breastfeeding.

Driving and operating machinery

Warning: this medicine may reduce psychomotor performance and ability to drive.
Ubretid may in some cases impair the ability to drive and operate machinery due to visual disturbances caused by pupillary constriction and reduced visual acuity when shifting focus between objects at different distances.

Ubretid contains 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 exactly as directed by the physician. If in doubt, consult a 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 must be determined individually and depends on the patient's general condition, particularly the initial state of the autonomic nervous system.

Unless otherwise directed by the physician, the usual dosage is as follows:

Initially, take 1 tablet in the morning on an empty stomach, half an hour before breakfast, until therapeutic effect is achieved. Usually, after the first week of treatment, the dosage is reduced to administration every two or three days (1 to 2 tablets), if maintenance therapy 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 neurological diseases

It is recommended that during the first days of treatment, until improvement occurs, 1 tablet of Ubretid be taken daily in the morning on an empty stomach, half an hour before breakfast. To maintain therapeutic effect, administration of 1 to 2 tablets every two or three days is usually sufficient.

Constipation due to intestinal smooth muscle atony

Initially, administer ½ tablet daily, taken half an hour before breakfast. Increase the dose by ½ 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 used only when absolutely indicated and under close supervision due to the significant risk of overdose or drug accumulation.

Pathological muscle weakness or increased muscle fatigue

During the first week, take 1 tablet daily 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, to 2 tablets per day.

Dosage in special patient groups:

Patients with hepatic impairment

Dosage adjustment is not necessary in patients with liver dysfunction.

Patients with renal impairment

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 required.

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 does not get absorbed into the body and does not exert 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 pronounced 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 musculature. Other possible symptoms of overdose include: decreased arterial blood pressure, chest tightness, wheezing and increased bronchial secretion associated with bronchospasm, bradycardia and paradoxical tachycardia, excessive sweating, lacrimation, miosis, nystagmus, increased peristalsis, involuntary defecation and urination or increased urinary urgency, muscle cramps, ataxia, seizures, coma, slurred speech, restlessness, agitation, and anxiety.

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

Missed dose of Ubretid

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

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following frequency categories were used to assess adverse reactions:

Adverse reactions to Ubretid are dose-dependent and are primarily due to the drug's effects 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 increase in 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 significance is attributed 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 arterial 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, muscle paralysis due to neuromuscular blockade, which must be differentiated diagnostically from symptoms of pathological muscle weakness or increased muscle fatigue (myasthenia).

Other adverse reactions:

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

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

Nervous system disorders
Rare: dizziness, somnolence, headache, speech disturbances
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 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
Reporting adverse reactions helps to collect more information on the safety of the medicine.

5. How to store Ubretid

Store below 25°C.
Keep in the original packaging to protect from light.
Keep this 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 should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the packaging and other information

What Ubretid contains

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

What Ubretid looks like and contents of the packaging
White, round, biconvex tablets with bevelled edges and a score line on one side,
allowing the tablet to be divided into 4 parts, and marked "UB 5.0" on the other side.
The tablet can be divided into equal doses.
Pack sizes: 20 or 50 tablets.
For more detailed information, please contact the responsible entity or the parallel importer.
Marketing Authorisation Holder 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:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Marketing Authorisation number in the Czech Republic, country of export: 67/004/70-C
Parallel Import Authorisation number: 252/24

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 curare derivative overdose, the recommended dosage should not be significantly exceeded.
When Ubretid is administered concomitantly with atropine sulfate (to reduce muscarinic adverse effects), caution is required, as atropine may mask the early symptoms of overdose.

Interactions with other medicinal products
Anticholinergic drugs such as atropine and drugs with atropine-like activity, as well as certain psychotropic agents including tricyclic and tetracyclic antidepressants, neuroleptics, lithium, and antihistamines, antagonize the muscarinic effects of Ubretid, while generally having no influence on its nicotinic effects.
Ubretid may prolong the action, particularly in the initial phase, of depolarizing muscle relaxants (e.g. suxamethonium or decamethonium); therefore, it should not be combined with these agents.
Ubretid antagonizes the effects of curare-derivative muscle relaxants (it should be discontinued prior to surgical procedures).
The effects of distigmine and cholinergically-acting substances are mutually enhanced when administered simultaneously. Concomitant use of Ubretid with dipyridamole results in reduced therapeutic efficacy of Ubretid. Caution is advised during concomitant administration, 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 effect of Ubretid.
Local anesthetics such as procaine, quinine, quinidine, chloroquine, and lithium stabilize the motor end plate and thereby antagonize the effect of distigmine and may worsen the condition in myasthenia gravis.
Glucocorticoids may reduce the effect of Ubretid. In patients with myasthenia gravis, this may necessitate an increase in the dose of Ubretid, which in turn increases the risk of cholinergic crisis.
Since cholinergic drugs 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 gravis.
In patients previously treated with beta-adrenergic blocking agents, prolonged bradycardia and significant hypotension may occur.
The heart rate-lowering effect of beta-blockers and the acetylcholine-like effect of anticholinesterase drugs may be additive.
Several antibiotics of the aminoglycoside group (particularly 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, adjustment of distigmine dosage may be necessary.

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, dilated pupils).
Differential diagnosis between cholinergic crisis and myasthenic crisis—both presenting with similar symptoms—is essential. The latter requires immediate administration or dose increase of Ubretid.
Muscarinic symptoms (nausea, increased salivation, vomiting, diarrhea, gastrointestinal cramps, urinary urgency, lacrimation, miosis, excessive bronchial secretion, bronchospasm, increased sweating, marked bradycardia, and decreased arterial pressure) can be prevented by concomitant administration of atropine or agents with similar activity.
Nicotinic symptoms (muscular effects such as muscle twitching, muscle cramps, or sensation of weakness, and in extreme cases, states of muscular paralysis) cannot be prevented by concomitant administration of atropine or agents with similar activity.