Limbitryl: detailed information

Package leaflet: Information for the patient

Limbitryl 12.5 mg / 5 mg hard capsules

amitriptyline and chlordiazepoxide
Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Limbitryl is and what it is used for
What you need to know before taking Limbitryl
How to take Limbitryl
Possible side effects
How to store Limbitryl
Contents of the pack and other information

1. What Limbitryl is and what it is used for

Limbitryl contains the active substances amitriptyline, belonging to a class of medicines known as “tricyclic antidepressants”, which has antidepressant activity, and chlordiazepoxide, belonging to a class of medicines called “benzodiazepines”, substances with anxiolytic properties.
Limbitryl is used in adults for the treatment of depression associated with anxiety, including the physical and mental disorders arising from it.
Consult your doctor if you do not feel better or if you feel worse during treatment.

2. What you need to know before taking Limbitryl

Do not take Limbitryl

if you are allergic to amitriptyline and/or chlordiazepoxide or to any of the other components of this medicine (listed in section 6);
if you are allergic to benzodiazepines or tricyclic antidepressants;
if you have glaucoma, an eye disease caused by increased pressure of the fluid inside the eye;
if you have severe hepatic insufficiency (severe reduction in liver function);
if you have severe kidney damage (severe reduction in kidney function);
if you suffer from severe myasthenia gravis (a serious disease affecting muscles, characterized by weakness and fatigue);
if you have severe respiratory insufficiency (severe reduction in respiratory system activity);
if you suffer from sleep apnea syndrome (temporary cessation of breathing during sleep);
if you have heart failure (impaired heart function);
if you have recently had a heart attack;
if you have conduction disorders of the electrical impulse in the heart (cardiac rhythm disturbances);
if you have prostate hypertrophy (enlarged prostate) or other conditions causing narrowing (stenosis) of the gastrointestinal or genitourinary tract;
if you are in the first or third trimester of pregnancy (see section “Pregnancy and breastfeeding”);
if you are breastfeeding (see section “Pregnancy and breastfeeding”);
if you have experienced intoxication or have a history of dependence on substances or medicines that reduce the activity of the central nervous system (alcohol, pain-relieving medicines, or other medicines used to treat certain nervous system disorders);
if you feel confused and have difficulty orienting yourself in space and time (delirium);
if you are unable to coordinate your movements and gait (ataxia);
if you are currently taking medicines called monoamine oxidase inhibitors (MAOIs) (see sections “Warnings and precautions” and “Other medicines and Limbitryl”).

Do not give Limbitryl to children and adolescents (0–18 years of age).
Warnings and precautions
Talk to your doctor or pharmacist before taking Limbitryl.
In particular, consult your doctor or pharmacist before taking Limbitryl if you think any of the following
conditions apply to you:

you are taking other medicines similar to Limbitryl, as side effects may increase (see “Serotonin syndrome” and section “Other medicines and Limbitly”);
you are predisposed to changes in electroencephalogram (EEG) patterns;
you suffer from chronic respiratory insufficiency (chronic reduction in respiratory function), as Limbitryl may worsen respiratory function;
you suffer from hepatic insufficiency (liver disease);
you suffer from renal insufficiency (kidney disease);
you suffer from cardiac insufficiency (a condition where oxygen supply is insufficient for the heart’s demands);
you have heart rhythm problems;
you suffer from epilepsy (a disease characterized by uncontrolled body movements and loss of consciousness);
you have symptoms of urinary retention (inability of the bladder to empty completely);
you have paralytic ileus (a bowel obstruction) or other diseases causing stomach or intestinal blockage;
you suffer from hyperthyroidism (a disorder of thyroid gland function, a gland in the neck);
you suffer from mental disorders (psychotic illness);
you have previously had problems with drug or alcohol abuse;
you suffer from ataxia (reduced coordination of movements and gait);
you have damage to the heart and blood vessels;
you have brain damage;
you are debilitated (in poor general health);
you suffer from personality disorders (fixed thoughts, sensations of seeing or hearing things that do not exist, confusion, or disorientation);
you suffer from diabetes (high blood sugar levels);
you are scheduled for surgery, as treatment with Limbitryl should be discontinued several days beforehand;
you suffer from prostate hypertrophy (a condition causing increased prostate volume);
you are taking medicines containing buprenorphine or fentanyl (strong analgesics known as opioids) (see “Serotonin syndrome” and section “Other medicines and Limbitryl”);
you are taking medicines containing a substance called levodopa, used in the treatment of Parkinson’s disease (see section “Other medicines and Limbitryl”).

Pay special attention to Limbitryl:
Severe skin reactions have been reported with Limbitryl treatment, including drug reaction with eosinophilia and systemic symptoms (Drug Reaction with Eosinophilia and Systemic Symptoms, DRESS). Stop using Limbitryl and contact a doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.
Serotonin syndrome
Using this medicine together with other similar medicines or analgesics such as buprenorphine and fentanyl may lead to serotonin syndrome, a potentially life-threatening condition characterized by symptoms such as involuntary and rhythmic muscle contractions, including those controlling eye movements, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle rigidity, and fever above 38°C. Contact your doctor if you experience these symptoms.
Tendency towards suicide
Like other antidepressant medicines, Limbitryl may increase the risk of suicidal thoughts or behavior. This risk is higher if you currently suffer or have previously suffered from suicidal behavior or thoughts.
You (or the person caring for you) should monitor and immediately report to your doctor any worsening of your condition, emergence of suicidal attempts or thoughts, or changes in behavior.
If you need to take Limbitryl for a long time, your doctor may prescribe blood tests to monitor possible changes in blood cells and to check liver function.
Development of tolerance
After repeated use of this medicine for several weeks, a decrease in its effectiveness (tolerance) may occur.
Development of dependence
Using high doses and/or prolonged treatment with chlordiazepoxide may lead to physical and psychological dependence, as occurs with other medicines similar to chlordiazepoxide.
This risk is higher if you have previously abused drugs or alcohol, as you are more likely to develop habituation and dependence on this medicine.
Memory disorders (amnesia)
The use of chlordiazepoxide may cause memory disturbances. This effect is more likely to occur several hours after taking the medicine. Therefore, to reduce the risk, ensure you can have an uninterrupted sleep period of 7–8 hours after taking the medicine (see section “How to take Limbitryl”).
If you are elderly (over 65 years of age)
If you are elderly, your doctor may decide to reduce your dose.
Children and adolescents
Do not give Limbitryl to children and adolescents (0–18 years of age).
Other medicines and Limbitryl
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Concomitant use of Limbitryl and opioids (strong analgesics, medicines for addiction therapy, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are available. However, if your doctor prescribes Limbitryl together with opioids, the dose and duration of concomitant treatment must be limited by your doctor. Inform your doctor about all opioid medicines you are taking and follow the doctor’s dosage recommendations carefully. It may be helpful to inform friends or family members to watch for the signs and symptoms listed above. Contact your doctor if you experience such symptoms.
Avoid taking other medicines with sedative properties while taking Limbitryl, as they may interfere with your ability to drive or operate machinery (see section “Driving and use of machines”).
Inform your doctor if you are taking any of the following medicines, as Limbitryl may enhance their effects:

medicines that reduce central nervous system activity, such as:
- neuroleptics (medicines used for certain mental illnesses). In addition, taking these medicines together with Limbitryl may increase the risk of electrocardiogram (ECG) abnormalities (QT interval prolongation) and uncontrolled body movements (seizures);
- antiepileptics (medicines used to treat epilepsy), particularly barbiturates;
- tranquilizers, anxiolytics/sedatives (medicines causing mental and physical dullness), which may increase relaxing effects and increase the risk of falls, especially if you are elderly;
- antidepressants (medicines used to treat depression, e.g., SSRIs (fluoxetine, paroxetine, fluvoxamine), duloxetine, and bupropion). In addition, antidepressants belonging to the classes of non-selective MAO inhibitors, selective MAO-A inhibitors (such as moclobemide), and MAO-B inhibitors (such as selegiline), when taken together with Limbitryl, may increase the risk of excessive serotonin levels in the blood ("Serotonin syndrome", see section “Warnings and precautions”), hypertensive crisis, and significant increase in body temperature. If you need to start treatment with Limbitryl while taking one of these medicines, your doctor will advise you when to start Limbitryl therapy;
- hypnotics (calming medicines and sleep inducers);
- narcotic analgesics (medicines for treating severe acute or chronic pain). In addition, these medicines taken together with Limbitryl may increase euphoria and physical and psychological dependence;
- anesthetics (medicines for pain relief);
antihistamines (medicines used to counteract allergic symptoms) with sedative activity;
anticoagulants (medicines used to thin the blood);
adrenergic agents, such as noradrenaline (used to treat severe hypotension) and adrenaline (a medicine used to treat anaphylactic shock);
buprenorphine and fentanyl (strong opioid analgesics). Taking Limbitryl together with these medicines may increase the risk of excessive serotonin levels in the blood ("Serotonin syndrome", see section “Warnings and precautions”).

Inform your doctor or pharmacist if you are taking any of the following medicines, as Limbitryl may reduce
their effectiveness:

muscle relaxants (medicines used to relax muscles);
ephedrine (a medicine used to counteract certain forms of arterial hypotension).

Inform your doctor or pharmacist if you are taking any of the following medicines, as the risk of side effects with concomitant use of Limbitryl is higher:

thyroid hormones or thyroid preparations (risk of arrhythmia);
adrenergic agents, such as isoprenaline and adrenaline (risk of arrhythmia);
products containing levodopa (a medicine used to treat Parkinson’s disease);
valproic acid.

Inform your doctor or pharmacist if you are taking any of the following medicines, as they may reduce the
effects of Limbitryl:

methylphenidate (a medicine used to treat Attention Deficit Hyperactivity Disorder in children);
barbiturates, carbamazepine, phenytoin (medicines used to treat seizures);
nicotine.

Inform your doctor or pharmacist if you are taking any of the following medicines, as they may influence the
effects of Limbitryl:

cimetidine (a medicine used for stomach ulcers);
macrolide antibiotics (medicines used to treat certain bacterial infections);
azole-type antifungals (antifungal medicines);
calcium antagonists (medicines used for high blood pressure and other heart and circulatory disorders);
protease inhibitors (medicines used to treat viral infections, including HIV);
ergot alkaloids (medicines used to treat severe headaches);
antidepressant agents (medicines used to treat depression);
herbal preparations;
oral contraceptives (“the pill”);
disulfiram (a medicine used to treat alcoholism).

Inform your doctor or pharmacist if you are taking the following medicines:

cisapride (a medicine used to treat stomach reflux);
antiarrhythmic agents (medicines used to treat irregular heartbeat, e.g., quinidine);
antihistamines (medicines used to counteract allergic symptoms);
antimalarial agents (medicines used to treat malaria), because Limbitryl may enhance their effects and increase the risk of cardiac interactions;
anticholinergic agents (medicines that reduce the effects of acetylcholine), because Limbitryl may enhance their effects and may intensify side effects of other medicines (such as phenothiazines, anticholinergics used in Parkinson’s disease treatment, antihistamines, and haloperidol).

Limbitryl with food, drinks, and alcohol
Do not drink alcohol while taking Limbitryl. If you have previously abused alcohol, your doctor will monitor you during treatment with Limbitryl, as you are more likely to develop dependence on this medicine.
Consuming alcohol with Limbitryl may also severely impair your ability to drive vehicles and operate machinery (see section “Driving and use of machines”).
Fertility, pregnancy, breastfeeding
Limbitryl may cause congenital malformations (abnormalities, physical defects in babies born to mothers taking this medicine). If you are of childbearing age, you should use effective contraceptive measures.
If you are pregnant, suspect you are pregnant, plan to become pregnant, or are breastfeeding, consult your doctor before taking this medicine; your doctor will assess whether treatment with this medicine should be discontinued.
Do not take Limbitryl during pregnancy, especially during the first and last three months.
Your doctor may prescribe this medicine only if strictly necessary.
If, for serious health reasons, your doctor decides to prescribe this medicine at high doses during the late stages of pregnancy or during labor, the newborn may experience adverse effects such as low body temperature, reduced muscle tone, and breathing difficulties. In addition, newborns born to mothers who have chronically taken benzodiazepines during the later stages of pregnancy may develop physical dependence and may be at risk of developing postnatal withdrawal symptoms after birth.
Do not take Limbitryl if you are breastfeeding, as this medicine passes into breast milk. Limbitryl is contraindicated during breastfeeding. If your doctor prescribes this medicine, you will be advised to stop breastfeeding.
Driving and use of machines
Do not drive or operate machinery if, during treatment with Limbitryl, you experience side effects such as drowsiness, sedation (mental and physical relaxation), amnesia (memory disturbances), difficulty concentrating, or impaired muscle function. Your alertness may be impaired, especially if you have not slept long enough (7–8 hours) or have consumed alcoholic beverages after taking Limbitryl.
Exercise particular caution when driving or operating machinery if you are taking Limbitryl together with other sedative medicines.
Limbitryl contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Limbitryl

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Your doctor will determine the most suitable dose and frequency for you in order to avoid the possible
intake of an excessive dose of this medicine.
How much you should take
The recommended dosage is 2–6 capsules per day, according to your doctor's instructions.
Begin treatment with 1 capsule in the morning and 1 in the evening.
Always take the main dose in the evening.
How to take it
Swallow the capsule with a glass of water.
Do not chew.
If you are elderly or debilitated, or if you have kidney or liver problems
If you are elderly or debilitated, or if you have kidney or liver problems, your doctor will assess whether to prescribe lower doses than those indicated above.
Duration of treatment
Your doctor will prescribe the shortest possible duration of treatment.
Generally, the treatment duration should not exceed 8–12 weeks, including a gradual dose reduction period until treatment is discontinued.
At the beginning of treatment with Limbitryl, your doctor will explain how to gradually reduce the dose of this medicine in order to reduce the risk of withdrawal and rebound symptoms (see sections “If you stop taking Limbitryl” and “Possible side effects”).
In certain cases, your doctor may decide to extend the duration of treatment mentioned above after re-evaluating your health status.
If you take more Limbitryl than you should
If you accidentally ingest or take an excessive dose of Limbitryl, contact your doctor immediately or go to the nearest hospital.
Symptoms
If you accidentally take a dose higher than prescribed, you may be at risk of life-threatening complications, especially if you also consume alcohol or other medicines at the same time.
In cases of accidental ingestion or overdose of Limbitryl, symptoms may be numerous and include:

drowsiness,
confusion,
excitement,
restlessness,
agitation,
perception of non-existent things in reality (hallucinations),
dilation of the pupils of the eyes (mydriasis),
inability of the urinary bladder to empty completely (urinary retention),
dryness of the mouth, nose, and other mucous membranes,
reduced intestinal movements,
uncontrolled body movements (seizures),
fever,
irregular heart rhythm (arrhythmia),
increased heart rate (tachycardia),
heart failure, a condition in which oxygen supply is insufficient for the heart's needs,
decreased blood pressure,
severe heart disorder occurring when blood is inadequately oxygenated (cardiogenic shock),
higher-than-normal levels of acid in the blood (metabolic acidosis),
decreased potassium levels in the blood (hypokalaemia),
low sodium levels in the blood (hyponatraemia).

In more severe cases, symptoms may include:

movement disorder with loss of coordination of muscles and joints (ataxia),
absence (atonia) or reduction (hypotonia) of muscle tone,
low blood pressure (hypotension),
reduced breathing (respiratory depression),
prolonged loss of consciousness (coma),
death.

Overdose with amitriptyline in children may have serious consequences. Children are particularly susceptible to coma, cardiac symptoms, breathing difficulties, epileptic seizures, low sodium levels in the blood, lethargy, drowsiness, nausea, vomiting, and high blood sugar levels.
Treatment
After evaluating the symptoms, your doctor will provide appropriate supportive therapy (e.g. gastric lavage, administration of activated charcoal and other medicines, or use of devices to support heart function or breathing).
If you forget to take Limbitryl
Do not take a double dose to make up for the missed dose. Take the next dose as prescribed by your doctor.
If you stop taking Limbitryl

Do not stop treatment with Limbitryl without first consulting your doctor.
Your doctor will gradually reduce your dose during the discontinuation phase.
Abruptly stopping this medicine may cause:
- withdrawal symptoms, such as headache, muscle pain, extreme anxiety, tension, restlessness, confusion, and irritability. In severe cases, you may experience a feeling of detachment or estrangement from yourself or the external world, increased sensitivity to sounds, numbness and tingling in the legs or arms, hypersensitivity to light, noise, and physical contact, perception of non-existent things in reality, seizures;
- rebound symptoms (when the symptoms that led to treatment reappear in a more severe form after stopping treatment), such as mood changes, anxiety, restlessness, or sleep disturbances.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you experience any of the following serious side effects while taking Limbitryl; your doctor will explain how to discontinue use of the medicine:

you experience symptoms such as marked increase in body temperature, muscle rigidity, changes in mental status, which may be signs of a condition similar to neuroleptic malignant syndrome
restlessness, agitation, irritability, aggressiveness, anger
disappointment
nightmares
perception of things not present in reality (hallucinations)
manic episodes (psychosis)
abnormal behaviour
other behavioural side effects. These reactions are more frequent if you are elderly.

Frequency not known:
Stop using Limbitryl and contact a doctor immediately if you notice any of the following symptoms: widespread skin rash, high body temperature, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).
The following side effects have been observed and reported during treatment with Limbitryl, with the following frequencies:

Very common (may affect more than 1 in 10 people)

weight gain
headache
dizziness
tremor
drowsiness
visual impairment (e.g. difficulty focusing images)
sensation of increased heartbeat (palpitations)
increased heart rate (tachycardia)
dry mouth
constipation
nausea
increased sweating (hyperhidrosis).

Common (may affect less than 1 in 10 people)

reduced level of consciousness
sedation, fatigue
movement disorder with loss of coordination of muscles and joints (ataxia)
balance disorders
confusional state
altered sensation in limbs or other body parts (paraesthesia)
dilation of the pupil of the eye (mydriasis)
abnormal electrocardiogram (ECG) pattern
problems with electrical impulses controlling heart rhythm (atrioventricular block, conduction disorders)
changes in taste sensation (dysgeusia)
skin reactions (e.g. skin rash, urticaria)
erectile dysfunction.

Uncommon (may affect less than 1 in 100 people)

mood changes (hypomania)
obsessive thoughts (mania)
anxiety
insomnia
uncontrolled body movements (seizures)
increased pressure inside the eye
ringing or buzzing in the ears (tinnitus)
high blood pressure (hypertension)
diarrhoea, vomiting
inability of the urinary bladder to empty completely (urinary retention)
breast enlargement (gynaecomastia).

Rare (may affect less than 1 in 1,000 people)

reduction in the number of blood cells (e.g. thrombocytopenia, leucopenia, agranulocytosis, pancytopenia, eosinophilia)
weight loss
loss of appetite (anorexia)
delirium
hallucinations
dizziness
double vision (diplopia)
irregular heartbeat (arrhythmia)
worsening of pre-existing heart failure (a condition in which the oxygen supply is insufficient for the heart's demands)
low blood pressure (hypotension)
swelling of the salivary gland
intestinal obstruction (paralytic ileus)
yellowish discoloration of the skin and whites of the eyes (jaundice)
increased liver enzymes in the blood (blood bilirubin, transaminases, and blood alkaline phosphatase)
hair loss (alopecia)
skin reactions following exposure to light (photosensitivity reactions)
muscle weakness
altered sexual desire (libido disorders)
menstrual problems
increased body temperature (pyrexia)

Very rare (may affect less than 1 in 10,000 people)

allergy
swelling affecting the tongue and/or throat, which may cause airway obstruction and could be fatal (angioedema).

Not known (frequency cannot be estimated from available data)

abnormal secretion of antidiuretic hormone
suicide attempt
suicidal ideation
memory disorders, including memory loss (amnesia)
physical and psychological dependence
depression
psychotic disorders
behavioural changes
emotional disorders
sleep disorders
difficulty articulating words (dysarthria)
gait disorders
extrapyramidal disorders (e.g. movement difficulties)
altered body movements (dystonia)
respiratory depression
milk secretion outside the breastfeeding period (galactorrhoea)
dry eyes
low sodium concentration in the blood (hyponatraemia).

This medicine may increase the risk of falls and bone fractures, especially if you are elderly.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Limbitryl

This medicine does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Limbitryl contains

The active substances are:
- amitriptyline hydrochloride 14.15 mg equivalent to amitriptyline 12.5 mg
- chlordiazepoxide 5 mg.
The other components are: ethylcellulose, corn starch, magnesium stearate, talc, lactose (see section “Limbitryl contains lactose”). Capsule components: gelatin, titanium dioxide, natural colour E172.

Description of the appearance of Limbitryl and contents of the pack
It is presented as hard capsules for oral use, packaged in a box containing 20 capsules.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Viatris Italia S.r.l., Via Vittor Pisani, 20 - 20124 Milan – Italy
Manufacturer
Labiana Pharmaceuticals, S.L.U. – Corbera de Llobregat site – Barcelona (Spain)

Package leaflet: information for the patient

Limbitryl 25 mg / 10 mg hard capsules

amitriptyline and chlordiazepoxide

Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Limbitryl is and what it is used for
What you need to know before taking Limbitryl
How to take Limbitryl
Possible side effects
How to store Limbitryl
Contents of the pack and other information

1. What Limbitryl is and what it is used for

Limbitryl contains the active substances amitriptyline, belonging to a class of medicines known as "tricyclic antidepressants", which has antidepressant activity, and chlordiazepoxide, belonging to a class of medicines known as "benzodiazepines", substances with anxiolytic activity.
Limbitryl is used in adults for the treatment of depression associated with anxiety, including the physical and mental disorders arising from it.
If you do not feel better or feel worse during treatment, consult your doctor.

2. What you need to know before taking Limbitryl

Do not take Limbitryl

if you are allergic to amitriptyline and/or chlordiazepoxide or to any of the other ingredients of this medicine (listed in section 6);
if you are allergic to benzodiazepines or tricyclic antidepressants;
if you have glaucoma, a disease of the eye caused by increased pressure of the fluid inside the eye;
if you have severe hepatic insufficiency (severe reduction in liver function);
if you have severe kidney damage (severe reduction in kidney function);
if you suffer from severe myasthenia gravis (a serious disease affecting muscles, characterized by weakness and fatigue);
if you have severe respiratory insufficiency (severe reduction in respiratory system activity);
if you suffer from sleep apnea syndrome (temporary cessation of breathing during sleep);
if you have heart failure (impaired heart function);
if you have recently had a heart attack;
if you have conduction disorders of the electrical impulse in the heart (cardiac rhythm disturbances);
if you have benign prostatic hyperplasia (enlarged prostate) or other conditions causing narrowing (stenosis) of the gastrointestinal or genitourinary tract;
if you are in the first or third trimester of pregnancy (see section “Pregnancy and breastfeeding”);
if you are breastfeeding (see section “Pregnancy and breastfeeding”);
if you have experienced intoxication or have a history of dependence on substances or medicines that reduce the activity of the central nervous system (alcohol, pain-relieving medicines, or other medicines used to treat certain nervous system disorders);
if you feel confused and have difficulty orienting yourself in space and time (delirium);
if you are unable to coordinate your movements and gait (ataxia);
if you are currently taking medicines called monoamine oxidase inhibitors (MAOIs) (see sections “Warnings and precautions” and “Other medicines and Limbitryl”).

you are taking other medicines similar to Limbitryl, as side effects may increase (see “Serotonin syndrome” and section “Other medicines and Limbitryl”);
you are predisposed to changes in electroencephalogram (EEG) patterns;
you suffer from chronic respiratory insufficiency (chronic reduction in respiratory function), as Limbitryl may worsen respiratory function;
you suffer from hepatic insufficiency (liver disease);
you suffer from renal insufficiency (kidney disease);
you suffer from heart failure (a condition where oxygen supply is insufficient for the heart’s demands);
you have heart rhythm problems;
you suffer from epilepsy (a disease characterized by uncontrollable body movements and loss of consciousness);
you experience symptoms of urinary retention (inability of the bladder to empty completely);
you have paralytic ileus (a bowel obstruction) or other diseases causing stomach or intestinal blockage;
you suffer from hyperthyroidism (abnormal thyroid function, a gland in the neck);
you suffer from mental disorders (psychotic illness);
you have previously had problems with drug or alcohol abuse;
you suffer from ataxia (reduced coordination of movements and gait);
you have damage to the heart or blood vessels;
you have brain damage;
you are debilitated (in poor general health);
you suffer from personality disorders (fixed thoughts, hallucinations, or confusion and disorientation);
you suffer from diabetes (high blood sugar levels);
you are scheduled for surgery, as treatment with Limbitryl should be discontinued several days beforehand;
you suffer from benign prostatic hyperplasia (a condition causing increased prostate volume);
you are taking medicines containing buprenorphine or fentanyl (strong analgesics known as opioids) (see “Serotonin syndrome” and section “Other medicines and Limbitryl”);
you are taking medicines containing a substance called levodopa, used in the treatment of Parkinson’s disease (see section “Other medicines and Limbitryl”).

Pay special attention to Limbitryl:
Severe skin reactions have been reported with Limbitryl treatment, including drug reaction with eosinophilia and systemic symptoms (Drug Reaction with Eosinophilia and Systemic Symptoms, DRESS). Discontinue use of Limbitryl and contact a doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.
Serotonin syndrome
Using this medicine together with other similar medicines or analgesics such as buprenorphine and fentanyl may lead to serotonin syndrome, a potentially life-threatening condition characterized by symptoms such as involuntary rhythmic muscle contractions, including eye movement muscles, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle rigidity, and fever above 38°C. Contact your doctor if you experience these symptoms.
Tendency toward suicide
Like other antidepressant medicines, Limbitryl may increase the risk of suicidal thoughts or behavior. This risk is higher if you currently suffer from or have previously experienced suicidal thoughts or behavior.
You (or the person caring for you) should monitor and immediately report to your doctor any worsening of your condition, or the emergence of suicidal thoughts, attempts, or behavioral changes.
If you need to take Limbitryl for a long time, your doctor may prescribe blood tests to monitor possible changes in blood cells and liver function.
Development of tolerance
After repeated use of this medicine for several weeks, a decrease in its effectiveness (tolerance) may occur.
Development of dependence
Using high doses and/or prolonged use of chlordiazepoxide may lead to physical and psychological dependence, as occurs with other medicines similar to chlordiazepoxide.
This risk is higher if you have previously abused drugs or alcohol, as you may be more prone to developing dependence on this medicine.
Memory disturbances (amnesia)
Chlordiazepoxide use may cause memory disturbances. This effect is more likely several hours after taking the medicine. To reduce this risk, ensure you can have an uninterrupted sleep period of 7–8 hours before taking this medicine (see section “How to take Limbitryl”).
If you are elderly (over 65 years of age)
If you are elderly, your doctor may decide to reduce your dose.
Children and adolescents
Do not give Limbitryl to children and adolescents (0–18 years of age).
Other medicines and Limbitryl
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Concomitant use of Limbitryl and opioids (strong analgesics, medicines for addiction treatment, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes Limbitryl together with opioids, the dose and duration of concomitant treatment must be limited by your doctor. Inform your doctor about all opioid medicines you are taking and follow the doctor’s dosage recommendations carefully. It may be helpful to inform family or friends to watch for the signs and symptoms listed above. Contact your doctor if you experience such symptoms.
Avoid taking other medicines with sedative properties while taking Limbitryl, as they may interfere with your ability to drive or operate machinery (see section “Driving and using machines”).
Inform your doctor if you are taking any of the following medicines, as Limbitryl may enhance their effects:

medicines that reduce central nervous system activity, such as:
- neuroleptics (medicines used for certain mental illnesses). Additionally, taking these medicines with Limbitryl may increase the risk of electrocardiogram (ECG) abnormalities (QT interval prolongation) and uncontrolled body movements (seizures);
- antiepileptics (medicines used to treat epilepsy), especially barbiturates;
- tranquilizers, anxiolytics/sedatives (medicines causing mental and physical dullness), which may increase relaxation effects and increase the risk of falls, especially in the elderly;
- antidepressants (medicines used to treat depression, e.g., SSRIs (fluoxetine, paroxetine, fluvoxamine), duloxetine, and bupropion). Additionally, antidepressants belonging to the classes of non-selective MAO inhibitors and selective MAO-A inhibitors (such as moclobemide) and MAO-B inhibitors (such as selegiline), when taken with Limbitryl, may increase the risk of excessive serotonin levels in the blood ("Serotonin syndrome", see section “Warnings and precautions”), hypertensive crisis, and significant increase in body temperature. If you are starting Limbitryl therapy while taking any of these medicines, your doctor will advise you when to begin Limbitryl;
- hypnotics (calming medicines that promote sleep);
- narcotic analgesics (medicines for treating severe acute or chronic pain). Additionally, taking these medicines with Limbitryl may increase euphoria and physical and psychological dependence;
- anesthetics (medicines for pain relief);
antihistamines with sedative properties (medicines used to treat allergic symptoms);
anticoagulants (medicines used to thin the blood);
adrenergic agents, such as noradrenaline (used to treat severe hypotension) and adrenaline (used to treat anaphylactic shock);
buprenorphine and fentanyl (strong opioid analgesics). Taking Limbitryl with these medicines may increase the risk of excessive serotonin levels in the blood ("Serotonin syndrome", see section “Warnings and precautions”).

Inform your doctor or pharmacist if you are taking any of the following medicines, as Limbitryl may reduce
their effects:

muscle relaxants (medicines used to relax muscles);
ephedrine (a medicine used to counteract certain forms of arterial hypotension).

Inform your doctor or pharmacist if you are taking any of the following medicines, as the risk of adverse effects with concomitant use of Limbitryl is higher:

thyroid hormones or thyroid preparations (risk of arrhythmia);
adrenergic agents, such as isoprenaline and adrenaline (risk of arrhythmia);
products containing levodopa (a medicine used to treat Parkinson’s disease);
valproic acid.

Inform your doctor or pharmacist if you are taking any of the following medicines, as they may reduce the
effects of Limbitryl:

methylphenidate (a medicine used to treat attention deficit hyperactivity disorder in children);
barbiturates, carbamazepine, phenytoin (medicines used to treat seizures);
nicotine.

Inform your doctor or pharmacist if you are taking any of the following medicines, as they may influence the
effects of Limbitryl:

cimetidine (a medicine used for stomach ulcers);
macrolide antibiotics (medicines used to treat certain bacterial infections);
azole antifungals (antifungal medicines);
calcium channel blockers (medicines used for high blood pressure and other heart and circulatory disorders);
protease inhibitors (medicines used to treat viral infections, including HIV);
ergot alkaloids (medicines used to treat severe headaches);
antidepressants (medicines used to treat depression);
herbal preparations;
oral contraceptives (“the pill”);
disulfiram (a medicine used to treat alcoholism).

Inform your doctor or pharmacist if you are taking the following medicines:

cisapride (a medicine used to treat stomach reflux);
antiarrhythmic agents (medicines used to treat irregular heartbeat, e.g., quinidine);
antihistamines (medicines used to treat allergic symptoms);
antimalarial agents (medicines used to treat malaria), because Limbitryl may enhance their effects and increase the risk of cardiac interactions;
anticholinergic agents (medicines that reduce the effects of acetylcholine),

because Limbitryl may enhance their effects and may intensify the side effects of other medicines (such as phenothiazines, anticholinergics used to treat Parkinson’s disease, antihistamines, and haloperidol).
Limbitryl with food, drinks, and alcohol
Do not drink alcohol while taking Limbitryl. If you have previously abused alcohol, your doctor will monitor you during treatment with Limbitryl, as you may be more prone to developing dependence on this medicine.
Drinking alcohol with Limbitryl may severely impair your ability to drive vehicles and operate machinery (see section “Driving and using machines”).
Fertility, pregnancy, breastfeeding
Limbitryl may cause congenital malformations (abnormalities, physical defects in babies born to mothers taking this medicine). If you are of childbearing age, you should use effective contraception.
If you are pregnant, suspect you are pregnant, plan to become pregnant, or are breastfeeding, consult your doctor before taking this medicine; your doctor will assess whether treatment should be discontinued.
Do not take Limbitryl during pregnancy, especially during the first and last three months. Your doctor may prescribe this medicine only if strictly necessary.
If, for serious health reasons, your doctor prescribes this medicine at high doses during the late stages of pregnancy or during labor, the newborn may experience adverse effects such as low body temperature, reduced muscle tone, and breathing difficulties. Additionally, newborns of mothers who have chronically taken benzodiazepines during advanced pregnancy may develop physical dependence and may be at risk of postnatal withdrawal symptoms after birth.
Do not take Limbitryl if you are breastfeeding, as this medicine passes into breast milk. Limbitryl is contraindicated during breastfeeding. If your doctor prescribes this medicine, you will be advised to stop breastfeeding.
Driving and using machines
Do not drive or operate machinery if, during treatment with Limbitryl, you experience side effects such as drowsiness, sedation (mental and physical relaxation), amnesia (memory disturbances), difficulty concentrating, or impaired muscle function. Your alertness may be impaired, especially if you have not slept long enough (7–8 hours) or have consumed alcohol after taking Limbitryl.
Exercise particular caution when driving or operating machinery if you are taking Limbitryl together with other sedative medicines.
Limbitryl contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Limbitryl

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
please consult your doctor or pharmacist.
Your doctor will determine the most appropriate dose and frequency for you in order to avoid
the possible intake of an excessive dose of this medicine.

How much should you take?
The recommended dosage is 3 capsules per day, according to your doctor's instructions.

How to take it
Swallow the capsule with a glass of water.
Do not chew.

If you are elderly or debilitated, or if you have kidney or liver problems
If you are elderly or debilitated, or if you suffer from kidney or liver disorders, your doctor will evaluate whether
lower doses than those indicated above should be prescribed.

Duration of treatment
Your doctor will prescribe the shortest possible duration of treatment.
Generally, the treatment duration should not exceed 8–12 weeks, including a period of gradual dose reduction until discontinuation.
At the beginning of treatment with Limbitryl, your doctor will explain how to gradually reduce the dose of this
medicine in order to minimize the risk of withdrawal and rebound symptoms (see sections “If you stop taking Limbitryl” and “Possible side effects”).
In certain cases, your doctor may decide to extend the duration of treatment mentioned above after re-evaluating your health status.

If you take more Limbitryl than you should
In case of accidental ingestion/overdose of Limbitryl, contact your doctor immediately or go to the nearest hospital.

Symptoms
If you accidentally take a higher dose of medicine than prescribed, you may be at risk of life-threatening complications, especially if you also consume alcohol or other medicines at the same time.
In cases of accidental ingestion/overdose of Limbitryl, symptoms may be numerous and include:

drowsiness,
confusion,
excitement,
restlessness,
agitation,
perception of non-existent things (hallucinations),
dilation of the pupils of the eyes (mydriasis),
inability of the urinary bladder to empty completely (urinary retention),
dryness of the mouth, nose and other mucous membranes,
reduced intestinal movements,
uncontrolled body movements (seizures),
fever,
irregular heart rhythm (arrhythmia),
increased heart rate (tachycardia),
heart failure, a condition in which oxygen supply is insufficient for the heart's needs,
decreased blood pressure,
severe heart disorder occurring when blood is inadequately oxygenated (cardiogenic shock),
higher than normal levels of acid in the blood (metabolic acidosis),
decreased potassium levels in the blood (hypokalaemia),
low sodium levels in the blood (hyponatraemia).

In more severe cases, symptoms may include:

movement disorder with loss of coordination of muscles and joints (ataxia),
absence (atonia) or reduction (hypotonia) of muscle tone,
low blood pressure (hypotension),
reduced breathing (respiratory depression),
prolonged loss of consciousness (coma),
death.

Treatment
After evaluating the symptoms, your doctor will provide appropriate supportive therapy (e.g. gastric lavage, administration of activated charcoal and other medicines, or use of devices to support heart function or assist breathing).

If you forget to take Limbitryl
Do not take a double dose to make up for the missed dose. Take the next dose as prescribed by your doctor.

If you stop taking Limbitryl

Do not stop treatment with Limbitryl without first consulting your doctor.
Your doctor will gradually reduce your dose during the discontinuation phase.
Abruptly stopping this medicine may cause:
- withdrawal symptoms, such as headache, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, you may experience a feeling of detachment or estrangement from yourself or the external world, increased sensitivity to sound, numbness and tingling in the legs or arms, hypersensitivity to light, noise and physical contact, perception of non-existent things in reality, seizures;
- rebound symptoms (when the symptoms that led to treatment with this medicine reappear in a more severe form after stopping treatment), such as mood changes, anxiety, restlessness or sleep disturbances.