Nobritol 12.5 mg/5 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Nobritol 12.5 mg/5 mg hard capsules

Nobritol Forte 25 mg/10 mg hard capsules

Amitriptyline hydrochloride / Medazepam

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Nobritol and Nobritol Forte are and what they are used for

2. What you need to know before taking Nobritol and Nobritol Forte

3. How to take Nobritol and Nobritol Forte

4. Possible side effects

5. How to store Nobritol and Nobritol Forte

6. Contents of the pack and other information

1. What Nobritol and Nobritol Forte are and what they are used for

The active substances in Nobritol and Nobritol Forte are Amitriptyline hydrochloride, which belongs to a group of medicines called tricyclic antidepressants, and Medazepam, which belongs to the family of benzodiazepines.

Nobritol and Nobritol Forte are indicated for the treatment of depressive states accompanied by anxiety.

In most cases, only short-term treatment with Nobritol or Nobritol Forte is required.

2. What you need to know before taking Nobritol and Nobritol Forte

Do not take Nobritol or Nobritol Forte:

• If you are allergic to the active substances or any of the other components of these medicines (listed in section 6).
• If you suffer from long-standing respiratory difficulties, whether related to sleep or not, or have serious muscle or liver problems.
• If you have glaucoma (loss of vision due to abnormally high pressure in the eye).
• If you have drug or alcohol dependence, unless formally instructed otherwise by your doctor.
• If you have recently had a heart attack (myocardial infarction).
• If you have heart problems such as cardiac rhythm disturbances detected on electrocardiogram (ECG), heart block, or coronary artery disease.
• If you are taking medicines known as monoamine oxidase inhibitors (MAOIs).
• If you have taken MAOIs within the last 14 days.
• If you took moclobemide the previous day.
• If you have severe liver disease.
• If you are pregnant or breastfeeding.

If you are taking Nobritol or Nobritol Forte, you must stop treatment with this medicine and wait 14 days before starting treatment with an MAOI.

This medicine should not be used in children.

Warnings and precautions

Consult your doctor or pharmacist before starting Nobritol or Nobritol Forte if:

• you have any liver or kidney disorders,
• you suffer from muscle weakness,
• you have other illnesses,
• you have allergies.

Cardiac rhythm disturbances and hypotension may occur if you receive a high dose of amitriptyline. This may also happen with usual doses if you have pre-existing heart disease.

Exercise special caution with this medicine, as the use of benzodiazepines may lead to dependence. This mainly occurs when the medicine is taken continuously over a long period. To minimize the risk of dependence, consider the following precautions:

• Benzodiazepines should only be taken under medical prescription (never because they worked for other patients), and should never be recommended to others.
• Do not increase the doses prescribed by your doctor, nor extend treatment beyond the recommended duration.
• Consult your doctor regularly so they can decide whether treatment should continue.

When stopping treatment, symptoms such as restlessness, anxiety, insomnia, difficulty concentrating, headache, and hot flashes may occur. Generally, abrupt discontinuation of the medication is not recommended; instead, the dose should be gradually reduced according to your doctor's instructions.

Serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with treatment with this medicine. Stop using Nobritol or Nobritol Forte and seek immediate medical attention if you notice any symptoms related to these serious skin reactions described in section 4.

Tolerance

After continuous use for several weeks, a certain degree of reduced effectiveness regarding hypnotic effects may be observed.

Duration of treatment

Treatment duration should be as short as possible, depending on the indication, but should not exceed 8–12 weeks, including the time required for gradual withdrawal of the medication.

Treatment should never be prolonged without re-evaluation by your doctor.

Prolonged QT interval

Cases of a heart condition called "QT interval prolongation" (observed on electrocardiogram, ECG) and cardiac rhythm disturbances (fast or irregular heartbeat) have been reported in connection with the administration of Nobritol and Nobritol Forte. Inform your doctor if:

• you notice a slow heartbeat;
• you have or have had a condition where the heart cannot pump blood adequately around the body (i.e., a disorder called "heart failure");
• you are taking any other medication that may cause heart problems; or
• you have experienced a condition that lowered your potassium or magnesium levels, or had high potassium levels in the blood;
• you are scheduled for surgery, as it may be necessary to stop amitriptyline treatment before receiving anesthetics. In case of emergency surgery, the anesthetist must be informed about your amitriptyline treatment;
• you have an overactive thyroid gland or are receiving thyroid medication.

Suicidal thoughts and worsening depression

If you are depressed, you may sometimes think about harming yourself or ending your life. These thoughts may increase when starting antidepressants for the first time, as all these medicines take time to work—usually about two weeks, but sometimes longer.

You may be more likely to have these thoughts:

• If you have previously had thoughts of suicide or self-harm.
• If you are a young adult. Clinical trial data have shown an increased risk of suicidal behavior in young adults (under 25 years) with psychiatric disorders who were treated with an antidepressant.

If you have thoughts about harming yourself or ending your life, contact your doctor or go to a hospital immediately.

It may be helpful to tell a close family member or friend that you are depressed and ask them to read this leaflet. You may ask them to inform you if they believe your depression or anxiety is worsening or if they are concerned about changes in your behavior.

Manic episodes

Some patients with bipolar disorder may enter a manic phase, characterized by rapidly changing, excessive thoughts, exaggerated happiness, and excessive physical activity. In such cases, it is important to contact your doctor, who will likely change your medication.

Rebound insomnia and anxiety

A transient syndrome has been described after discontinuation of treatment, characterized by the return of symptoms—though more pronounced—that led to initiating treatment. This episode may be accompanied by other reactions such as mood changes, anxiety, sleep disturbances, and restlessness. The likelihood of developing a withdrawal/rebound syndrome is higher after abruptly stopping treatment; therefore, it is recommended to gradually reduce the dose until complete discontinuation. Follow exactly the usage recommendations and administration instructions given by your doctor to avoid these symptoms.

Amnesia

Nobritol and Nobritol Forte may cause anterograde amnesia. This is more likely to occur several hours after taking the medicine. To reduce the associated risk, ensure you can sleep uninterrupted for 7–8 hours after taking the medicine.

Psychiatric and paradoxical reactions

Nobritol and Nobritol Forte may cause reactions such as restlessness, agitation, irritability, aggressiveness, delusions, rage attacks, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse effects on behavior. Your doctor will discontinue treatment if this occurs.

Inform your doctor if you have or have previously had any medical problems, especially if you have:

• narrow-angle glaucoma (loss of vision due to abnormally high pressure in the eye)
• epilepsy, history of seizures or epileptic fits
• difficulty urinating
• enlarged prostate
• thyroid disease
• bipolar disorder
• schizophrenia
• severe liver disease
• severe heart disease
• pyloric stenosis (narrowing of the stomach outlet) and paralytic ileus (intestinal blockage)
• diabetes, as your antidiabetic medication may need adjustment

If you are taking antidepressants such as selective serotonin reuptake inhibitors (SSRIs), your doctor may consider adjusting your dose (see also section 2 “Taking Nobritol or Nobritol Forte with other medicines” and section 3).

Elderly people are more likely to experience certain adverse effects, such as dizziness upon standing due to low blood pressure (see also section 4 “Possible side effects”).

Children and adolescents

Do not give this medicine to children and adolescents under 18 years of age for these treatments, as safety and efficacy studies have not been conducted in this age group.

Special populations

Elderly patients may be more affected by Nobritol and Nobritol Forte than younger patients. If you are elderly, your doctor may prescribe a lower dose and monitor your response to treatment. Please follow your doctor’s instructions carefully.

If you have liver or kidney disorders or suffer from muscle weakness, your doctor will decide whether you should take a lower dose of these medicines or not take them at all.

Other medicines and Nobritol or Nobritol Forte

Inform your doctor if you are taking, have recently taken, or might need to take any other medicine.

This is extremely important because taking more than one medicine at the same time may increase or decrease their effects.

Some medicines may affect how others work, and this can sometimes cause serious adverse effects.

Inform your doctor or pharmacist if you are taking or have recently taken any other medicine, such as:

• monoamine oxidase inhibitors (MAOIs) such as phenelzine, iproniazid, isocarboxazid, nialamide, or tranylcypromine (used to treat depression) or selegiline (used to treat Parkinson’s disease). These medicines must not be taken at the same time as Nobritol and Nobritol Forte (see section 2 “Do not take Nobritol or Nobritol Forte”)
• adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine, and phenylpropanolamine (which may be present in cough or cold medicines and some anesthetics)
• medicines for high blood pressure such as calcium channel blockers (e.g., diltiazem and verapamil), guanethidine, betanidine, clonidine, reserpine, and methyldopa
• anticholinergic drugs such as certain medicines for Parkinson’s disease and gastrointestinal disorders (e.g., atropine, hyoscine)
• thioridazine (used to treat schizophrenia)
• tramadol (for pain relief)
• medicines for fungal infections (e.g., fluconazole, terbinafine, ketoconazole, and itraconazole)
• sedatives (e.g., barbiturates)
• antidepressants (e.g., SSRIs [fluoxetine, paroxetine, fluvoxamine], duloxetine, and bupropion)
• medicines for certain heart conditions (e.g., beta-blockers and antiarrhythmics)
• cimetidine (used to treat stomach ulcers)
• methylphenidate (used to treat ADHD)
• ritonavir (used to treat HIV)
• oral contraceptives
• rifampicin (for treating infections)
• phenytoin and carbamazepine (used to treat epilepsy)
• St. John’s wort (Hypericum perforatum), a herbal remedy used for depression
• thyroid medicines
• valproic acid

You should also inform your doctor if you are taking or have recently taken medicines that may affect heart rhythm, such as:

• medicines for irregular heartbeat (e.g., quinidine and sotalol)
• astemizole and terfenadine (used to treat allergies and seasonal rhinitis)
• medicines used to treat certain mental illnesses (e.g., pimozide and sertindole)
• cisapride (used to treat certain types of indigestion)
• halofantrine (used to treat malaria)
• methadone (used to treat pain and for detoxification)
• diuretics (“water pills” such as furosemide)

Concomitant use of this medicine with opioids (strong painkillers, substitution therapy medicines, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may even be fatal. Therefore, concomitant use should only be considered when no other treatment options are possible.

However, if your doctor prescribes this medicine together with opioids, the dose and duration of concomitant treatment must be limited by your doctor.

Please inform your doctor about all opioid medicines you are taking, and closely follow your doctor’s dosing recommendations. It may be helpful to inform friends or family members to watch for the aforementioned signs and symptoms. Contact your doctor if you experience such symptoms.

If you are undergoing surgery and receiving general or local anesthetics, you must inform your doctor that you are taking this medicine.

Likewise, inform your dentist that you are taking this medicine if you are to receive a local anesthetic.

Taking Nobritol or Nobritol Forte with alcohol

During treatment, avoid alcoholic beverages. Alcohol may enhance sedation, which could affect your ability to drive or operate machinery. If you need further information on this, consult your doctor.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Amitriptyline is not recommended during pregnancy unless your doctor considers it clearly necessary, and only after careful consideration of benefit versus risk. If you have taken this medicine during the last part of pregnancy, the newborn may experience withdrawal symptoms such as irritability, increased muscle tone, tremors, irregular breathing, poor sucking, loud crying, urinary retention, and constipation.

Your doctor will advise you whether to start/continue/breastfeed or discontinue use of this medicine, taking into account the benefits of breastfeeding for the child and the benefits of treatment for you.

Breastfeeding

Benzodiazepines are excreted in breast milk, so their use is contraindicated in breastfeeding mothers.

Driving and using machines

During treatment with Nobritol or Nobritol Forte, you may feel drowsy or dizzy. Do not drive or operate tools or machinery until you know how this medicine affects you.

Nobritol and Nobritol Forte contain lactose and orange yellow (E-110)

This medicine contains lactose. If your doctor has informed you that you have an intolerance to certain sugars, consult with them before taking this medicine.

This medicine may cause allergic-type reactions because it contains orange yellow S (E-110).

3. How to take Nobritol and Nobritol Forte

Follow exactly the instructions for use of this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The dose should be started at a low level and gradually increased, carefully monitoring the clinical response and any signs of intolerance.

It is recommended to start treatment with one capsule in the morning and another at night. This dose may be gradually increased up to a maximum of 100 mg daily of amitriptyline and 40 mg of medazepam, divided into two doses, depending on the patient's individual response and tolerability. When increasing the dose, the larger dose should be administered at night.

The maintenance dose is the same as the lowest effective dose.

Never change the prescribed dose by yourself. If you think that the effect of the medicine is too strong or too weak, consult your doctor.

Remember to take this medicine

Your doctor will inform you about the duration of your treatment with Nobritol or Nobritol Forte. Do not stop treatment prematurely, as withdrawal effects may occur.

Elderly patients over 65 years of age

The recommended dose of Nobritol and Nobritol Forte ranges between 12.5 mg/5 mg per day and 50 mg/20 mg per day, divided into two doses, depending on individual circumstances. It is recommended to start with 12.5–25 mg/5–10 mg daily, divided into two doses (one capsule in the morning and one at night).

Use in children and adolescents

This medicine should not be administered to children or adolescents for the treatment of depression. For further information, see section 2.

Patients with renal impairment

It is recommended to reduce the dose to half the normal adult dose.

Patients with hepatic impairment

It is recommended to reduce the dose to half the normal adult dose.

If you take more Nobritol or Nobritol Forte than you should

Contact your doctor or pharmacist immediately, go to the nearest hospital, or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medicine and the amount ingested. Take the medicine's packaging with you if you go to the doctor or hospital.

Symptoms of overdose may include:

• dilated pupils
• rapid or irregular heartbeat
• difficulty urinating
• dry mouth and tongue
• intestinal obstruction
• epileptic seizures
• fever
• agitation
• confusion
• hallucinations
• uncontrolled movements
• low blood pressure, weak pulse, paleness
• difficulty breathing
• bluish discoloration of the skin
• decreased heart rate
• drowsiness
• loss of consciousness
• coma
• various cardiac symptoms, such as cardiac block, heart failure, hypotension, cardiogenic shock, metabolic acidosis, hypokalemia

Overdose of amitriptyline in children may have serious consequences. Children are particularly prone to coma, cardiac symptoms, breathing difficulties, seizures, low blood sodium levels, lethargy, drowsiness, nausea, vomiting, and elevated blood sugar levels.

If you forget to take Nobritol or Nobritol Forte

Do not take a double dose to make up for missed doses. Instead, continue with your normal dose.

If you stop taking Nobritol or Nobritol Forte

When stopping treatment, symptoms such as restlessness, anxiety, insomnia, difficulty concentrating, headache, irritability, confusion, and hot flushes may occur.

To avoid withdrawal symptoms, do not stop taking this medicine abruptly, especially if you have been taking it for a long time.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Most patients tolerate this medicine well, but some, especially at the beginning of treatment, may feel somewhat tired or drowsy during the day.

If you notice any of the following symptoms, you must see your doctor immediately:

Amitriptyline

• Intermittent attacks of blurred vision, rainbow-colored vision (halos around lights), and eye pain.

An immediate eye examination must be performed before continuing treatment with this medicine. These symptoms may be signs of acute glaucoma. Very rare adverse effects, affecting up to 1 in 10,000 people.

• A heart problem known as "prolonged QT interval" (which can be seen on your electrocardiogram). Frequent adverse effect, may affect up to 1 in 10 people.

• Severe constipation, stomach swelling, fever, and vomiting.

These symptoms may be due to paralysis of parts of the intestine (paralytic ileus). Rare adverse effect, may affect up to 1 in 1,000 people.

• Any degree of yellowing of the skin or the whites of the eyes (jaundice).

Your liver may be affected. Rare adverse effect, may affect up to 1 in 1,000 people.

• Bruising, bleeding, paleness, or persistent sore throat and fever.

These symptoms may be early signs of possible blood or bone marrow problems. Blood-related effects may include a decrease in the number of red blood cells (which carry oxygen throughout the body), white blood cells (which help fight infections), and platelets (which help with blood clotting). Rare adverse effect, may affect up to 1 in 1,000 people.

• Suicidal thoughts or behaviors. Rare adverse effects, may affect up to 1 in 1,000 people.

The following adverse effects have been reported with the following frequencies:

Very common: may affect more than 1 in 10 people

• Numbness/drowsiness
• Tremor of the hands or other parts of the body
• Dizziness
• Headache
• Irregular, strong, or rapid heartbeat
• Dizziness upon standing due to low blood pressure (orthostatic hypotension)
• Accommodation disturbances
• Dry mouth
• Constipation
• Nausea
• Excessive sweating
• Weight gain
• Stuttering or slow speech
• Aggression
• Nasal congestion

Common: may affect up to 1 in 10 people

• Confusion
• Sexual disturbances (decreased sexual desire, erectile problems)
• Attention disturbances
• Changes in taste sensation
• Numbness or tingling in the arms or legs
• Coordination disturbances
• Dilated pupils
• Heart block
• Fatigue
• Low blood sodium concentration
• Restlessness
• Urinary disorders
• Urinary retention
• Feeling of thirst

Uncommon: may affect up to 1 in 100 people

• Excitement, anxiety, difficulty sleeping, nightmares
• Seizures
• Tinnitus
• Increased blood pressure
• Diarrhea, vomiting
• Skin rash, rash with hives (urticaria), swelling of the face and tongue
• Difficulty urinating
• Increased milk production during breastfeeding or milk secretion without breastfeeding
• Collapse episodes
• Worsening of heart failure
• Worsening of liver function (e.g., cholestatic liver disease)
• Increased pressure in the eyeball, intermittent attacks of blurred vision, rainbow-colored vision, and eye pain

Rare: may affect up to 1 in 1,000 people

• Decreased appetite
• Delirium (especially in elderly patients), hallucinations
• Abnormal heart rate or heart rhythm
• Swelling of the salivary glands, paralytic ileus
• Hair loss
• Increased sensitivity to sunlight
• Breast enlargement in men
• Fever
• Weight loss
• Abnormal liver function test results

Very rare: may affect up to 1 in 10,000 people

• Diseases of the heart muscle
• Feeling of restlessness and need to keep moving constantly
• Peripheral nerve disorders
• Acute increase in eye pressure
• Specific types of abnormal heart rhythm (also known as torsades de pointes)
• Allergic inflammation of the lung alveoli and lung tissue

Frequency not known (cannot be estimated from available data)

• Absence of appetite sensation
• Increase or decrease in blood sugar levels
• Paranoia
• Movement disorders (involuntary movements or reduced movements)
• Hypersensitivity inflammation of the heart muscle
• Hepatitis
• Hot flushes
• Dry eyes
• Stop using this medicine and seek immediate medical attention if you experience any of the following symptoms: Widespread rash, high body temperature, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).

An increased risk of bone fractures has been observed in patients treated with this type of medicine.

Benzodiazepines

Other adverse effects such as drowsiness, emotional blunting, reduced level of alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia (inability to coordinate voluntary muscle movements), or diplopia (double vision) have been reported. These phenomena occur predominantly at the beginning of treatment and usually disappear with continued administration. Other adverse reactions such as gastrointestinal disturbances, changes in libido (sexual desire), or skin reactions may occur occasionally.

Amnesia

Anterograde amnesia (difficulty remembering recent events) may occur with therapeutic doses, and the risk increases with higher doses. Amnesic effects may be associated with inappropriate behaviors.

Depression

The use of benzodiazepines may unmask pre-existing depression.

Psychiatric and paradoxical reactions

When using benzodiazepines or similar compounds, adverse behavioral effects such as restlessness, agitation, irritability, aggressiveness, delirium (incoherent thinking), rage attacks, nightmares, hallucinations, psychosis (loss of contact with reality), inappropriate behavior, and other behavioral disturbances may occur. These reactions can be severe and occur more frequently in children and elderly patients.

Dependence

Administration of the product (even at therapeutic doses) may lead to physical dependence: discontinuation of treatment may lead to withdrawal or rebound phenomena. Psychological dependence may also occur. Cases of abuse have been reported.

• Frequent: heart problem known as "QT interval prolongation" (seen on electrocardiogram, ECG).
• Very rare: sudden anxiety, hallucinations, excitement, and sleep disturbances. If this occurs, consult your doctor immediately.
• Frequency not known (cannot be estimated from available data): Dry eyes.

If any other reaction not described in this leaflet occurs, consult your doctor or pharmacist.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. You may also report them directly via the

Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Nobritol and Nobritol Forte

Keep this medicine out of sight and reach of children.

Do not store above 30°C.

Medicines must not be disposed of via wastewater drains or household waste. Unused medicines and waste materials, including packaging, should be returned to the SIGRE collection point at your pharmacy. If you are unsure about how to dispose of unused medicines or their packaging, please consult your pharmacist. This helps protect the environment.

Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.

6. Contents of the pack and other information

Composition of Nobritol and Nobritol Forte

The active substances are Amitriptyline hydrochloride and Medazepam.

The other components are:

• Capsule contents: Monohydrate lactose, magnesium stearate, talc.
• Capsule coating:
• Nobritol 12.5 mg/5 mg hard capsules: Orange-yellow S (E-110), indigotine (E-132), titanium dioxide (E-171), gelatin, erythrosine (E-172), and quinoline yellow (E-104).
• Nobritol Forte 25 mg/10 mg hard capsules: Orange-yellow S (E-110), indigotine (E-132), titanium dioxide (E-171), gelatin, erythrosine (E-172), and yellow iron oxide (E-172).

Appearance of the product and pack contents

PVC/Al blister containing 60 hard capsules.

Nobritol 12.5 mg/5 mg hard capsules:

• Capsules with an opaque orange cap and an opaque light green body.

Nobritol Forte 25 mg/10 mg hard capsules:

• Capsules with an opaque dark green cap and an opaque orange body.

Marketing Authorization Holder and Manufacturer

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Date of the most recent revision of this leaflet: December 2024

“Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/”