NOBRITOL FORTE 25 mg/10 mg HARD CAPSULES

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 all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What Nobritol and Nobritol Forte are and what they are used for
2. What you need to know before you take Nobritol and Nobritol Forte
3. How to take Nobritol and Nobritol Forte
4. Possible side effects

1. Storage of Nobritol and Nobritol Forte

1. Contents of the pack and other information

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

The active substances of 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 states.

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

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

Do not take Nobritol or Nobritol Forte:

• If you are allergic to the active substances or any of the other ingredients of these medicines (listed in section 6).
• If you have breathing difficulties related or not to sleep for a long time or suffer from severe muscular or hepatic problems.
• If you suffer from glaucoma (vision loss due to abnormally high pressure in the eye).
• If you suffer from drug or alcohol dependence, unless your doctor formally indicates it.
• If you have recently had a heart attack (myocardial infarction).
• If you have had heart problems such as cardiac rhythm disturbances detected in the electrocardiogram (ECG), cardiac block, or coronary disease.
• If you are taking medicines known as monoamine oxidase inhibitors (MAOIs).
• If you have taken MAOIs in the last 14 days.
• If you have taken moclobemide the day before.
• If you have severe liver disease.
• If you are pregnant or breastfeeding.

If you are taking Nobritol or Nobritol Forte, you must interrupt 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 to take Nobritol or Nobritol Forte if:

• you have any liver or kidney disorder,
• you suffer from muscle weakness,
• you have other diseases,
• you have allergies.

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

Be especially careful with this medicine, as the use of benzodiazepines can lead to dependence. This occurs mainly after uninterrupted use of the medicine for a long time. To minimize the risk of dependence, the following precautions should be taken:

• the use of benzodiazepines will only be done under medical prescription (never because they have worked for other patients) and will never be recommended to other people.
• do not increase the prescribed doses by the doctor, nor prolong the treatment for a longer time than recommended.
• consult your doctor regularly so that he decides whether to continue treatment.

When stopping the administration, restlessness, anxiety, insomnia, lack of concentration, headache, and hot flashes may appear. It is not recommended to interrupt the medication abruptly, but rather to gradually reduce the dose, according to the doctor's instructions.

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

Tolerance

After continued use for some weeks, a certain degree of loss of efficacy with respect to the hypnotic effects may be detected.

Duration of Treatment

The duration of treatment should be as short as possible, depending on the indication, but should not exceed 8-12 weeks, including the time necessary for gradual withdrawal of the medication.

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

Prolonged QT Interval

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

• you notice a slow heartbeat;
• you have or have had a problem in which the heart could not pump blood through the body properly (i.e., a disorder called "heart failure");
• you are taking any other medication that may cause you heart problems; or
• you have suffered a problem that has decreased your potassium or magnesium level, or have presented a high potassium level in the blood;
• you are scheduled to have surgery, as it may be necessary to interrupt treatment with amitriptyline before you are given anesthetics. In case of emergency surgery, the anesthesiologist should be informed about treatment with amitriptyline;
• you have an overactive thyroid gland or are taking medication for your thyroid.

Suicidal Thoughts and Worsening of Depression

If you are depressed, you may sometimes think about harming yourself or taking your own life. This type of thought can increase when you first start taking antidepressants, as all these medicines take time to work, usually a couple of weeks, but sometimes longer.

You are more likely to have these thoughts:

• If you have had thoughts of taking your own life or harming yourself before.
• If you are a young adult. Clinical trial data have shown an increased risk of suicidal behavior in young adults (less than 25 years) with psychiatric disorders who were treated with an antidepressant.

If you have thoughts of harming yourself or taking your own life, contact your doctor or go to a hospital immediately.

It may be helpful to tell a relative or close friend that you are depressed and ask them to read this leaflet. You can ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behavior.

Manic Episodes

Some patients with manic-depressive illness may enter a manic phase, characterized by profuse ideas that change rapidly, exaggerated joy, and excessive physical activity. In these cases, it is essential that you contact your doctor, who will probably change your medication.

Rebound Insomnia and Anxiety

A transient syndrome has been described after withdrawal of treatment, characterized by the reappearance of symptoms - although more accentuated - that led to the initiation of treatment. This episode can be accompanied by other reactions such as mood changes, anxiety, or sleep disorders and restlessness. The probability of the appearance of a withdrawal/rebound syndrome is greater after abruptly stopping treatment, so it is recommended to gradually reduce the dose until its final suppression. Follow your doctor's recommendations for use and administration instructions exactly to avoid these symptoms.

Amnesia

Nobritol and Nobritol Forte may induce anterograde amnesia. This occurs more frequently several hours after administration of the medicine, so to minimize the associated risk, you should ensure that you can sleep uninterrupted for 7-8 hours.

Psychiatric and Paradoxical Reactions

Nobritol and Nobritol Forte can produce reactions such as restlessness, agitation, irritability, aggressiveness, delirium, fits of rage, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse effects on behavior. Your doctor will suspend treatment if this occurs.

Tell your doctor if you have or have had any medical problem, especially if you have:

• glaucoma of narrow angle (vision loss due to abnormally high pressure in the eye)
• epilepsy, history of convulsions or epileptic seizures
• 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 it may be necessary to adjust your antidiabetic medication

If you use antidepressants like selective serotonin reuptake inhibitors (SSRIs), your doctor may consider changing the dose of the medicine (see also section 2 "Taking Nobritol or Nobritol Forte with other medicines" and section 3).

Elderly people have a higher probability of suffering from certain adverse effects, such as dizziness when standing up 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 for these treatments, as safety and efficacy have not been established for this age group.

Special Populations

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

If you have any liver or kidney disorder, or suffer from muscle weakness, your doctor will decide whether it is convenient for you to take a lower dose of these medicines or not to take them at all.

Other Medicines and Nobritol or Nobritol Forte

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

This is extremely important because the simultaneous use of more than one medicine can increase or decrease its effect.

Some medicines can affect the functioning of other medicines, and this can sometimes cause serious adverse effects.

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

• monoamine oxidase inhibitors (MAOIs) such as, e.g., phenelzine, iproniazid, isocarboxazid, nialamide, or tranylcypromine (used to treat depression) or selegiline (used to treat Parkinson's disease). These medicines should 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 and cold medicines and in some anesthetics)
• medicines for treating high blood pressure, such as, for example, calcium channel blockers (e.g., diltiazem and verapamil), guanethidine, betanidine, clonidine, reserpine, and methyldopa
• anticholinergic drugs such as certain medicines for the treatment of Parkinson's disease and gastrointestinal disorders (e.g., atropine, hyoscine)
• thioridazine (used to treat schizophrenia)
• tramadol (for pain relief)
• medicines for treating 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 diseases (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 tell your doctor if you are taking or have recently taken medicines that may affect heart rhythm, such as:

• medicines for treating irregular heartbeats (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, e.g., furosemide)

The concomitant use of this medicine and opioids (strong pain relievers, substitution therapy, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be fatal. Therefore, concomitant use should only be considered when other treatment options are not possible.

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

Please inform your doctor about all opioid medicines you are taking, and follow your doctor's dosage recommendations closely. It may be useful to inform friends or family to be aware of the signs and symptoms mentioned above. Contact your doctor when you experience such symptoms.

If you are going to have surgery and receive general or local anesthetics, you must inform your doctor that you are taking this medicine.

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

Taking Nobritol or Nobritol Forte with Alcohol

Avoid alcoholic beverages during treatment. The effect of alcohol can potentiate sedation, and this can affect your ability to drive or use machinery. If you need additional information on this point, consult your doctor.

Pregnancy and Breastfeeding

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

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

Your doctor will advise you whether to start/continue/stop breastfeeding or interrupt the use of this medicine, taking into account the benefit of breastfeeding for the child and the benefit 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 use tools or machines until you know how the treatment with this medicine affects you.

Nobritol and Nobritol Forte containlactose and orange yellow S (E-110)

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

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

3. How to take Nobritol and Nobritol Forte

Follow the administration instructions of this medication exactly as indicated by your doctor or pharmacist. In case of 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 in the evening. This dose can be increased up to a maximum of 100 mg per day of amitriptyline and 40 mg of medazepam, divided into two doses, depending on the individual patient's response and tolerability. When increasing the dose, administer the main dose at night.

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

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

Remember to take this medication

Your doctor will indicate the duration of your treatment with Nobritol or Nobritol Forte. Do not suspend treatment beforehand, as withdrawal effects may occur.

Elderly patients over 65 years old

The recommended dose of Nobritol and Nobritol Forte ranges from 12.5mg/5mg per day to 50mg/20mg per day, divided into two doses, depending on the specific case. It is recommended to start with 12.5-25 mg/5-10 mg per day, divided into two doses (1 capsule at night and 1 in the morning).

Use in children and adolescents

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

Patients with renal insufficiency

It is recommended to reduce the dose to half of the normal dose in adults.

Patients with hepatic insufficiency

It is recommended to reduce the dose to half of the normal dose in adults.

If you take more Nobritol or Nobritol Forte than you should

Consult your doctor or pharmacist immediately, go to the nearest hospital, or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested. Bring the packaging of this medication with you if you go to the doctor or hospital.

Among the symptoms of overdose are:

• dilated pupils
• rapid or irregular heartbeats
• difficulty urinating
• dry mouth and tongue
• intestinal blockage
• 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, cardiac insufficiency, hypotension, cardiogenic shock, metabolic acidosis, hypokalemia

Overdose of amitriptyline in children can have serious consequences. Children are especially prone to coma, cardiac symptoms, difficulty breathing, convulsions, low sodium levels in the blood, lethargy, drowsiness, nausea, vomiting, and high blood sugar levels.

If you forget to take Nobritol or Nobritol Forte

Do not take a double dose to make up for forgotten doses, but instead, continue with the normal dose.

If you interrupt treatment with Nobritol or Nobritol Forte

When stopping the administration of the preparation, restlessness, anxiety, insomnia, lack of concentration, headache, irritability, confusion, and hot flashes may appear.

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

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medications, this medication can produce adverse effects, although not all people suffer from them.

Most patients tolerate this medication 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 should go to your doctor immediately:

Amitriptilina

• Intermittent blurred vision attacks, rainbow vision, and eye pain.

You should have an eye examination immediately before being able to continue treatment with this medication. These symptoms can be a sign of acute glaucoma. Very rare adverse effects, can affect up to 1 in 10,000 people.

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

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

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

• Any degree of yellowish discoloration of the skin and the white part of the eyes (jaundice).

It is possible that your liver is affected. Rare adverse effect, can affect up to 1 in 1,000 people.

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

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

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

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

Very frequent: can affect more than 1 in 10 people

• numbness/drowsiness
• tremors of the hands or other parts of the body
• dizziness
• headache
• irregular, strong, or rapid heartbeat
• dizziness when standing up due to low blood pressure (orthostatic hypotension)
• accommodation changes
• dry mouth
• constipation
• nausea
• excessive sweating
• weight gain
• stuttering or slow speech
• aggression
• nasal congestion

Frequent: can affect up to 1 in 10 people

• confusion
• sexual changes (decreased sexual appetite, erection problems)
• attention changes
• changes in taste
• numbness or tingling in the arms or legs
• coordination changes
• dilated pupils
• heart block
• fatigue
• low sodium levels in the blood
• agitation
• urinary disorders
• urinary retention
• feeling of thirst

Infrequent: can affect up to 1 in 100 people

• excitement, anxiety, difficulty sleeping, nightmares
• seizures
• tinnitus
• increased blood pressure
• diarrhea, vomiting
• skin rash, urticaria, swelling of the face and tongue
• difficulty urinating
• increased milk production during lactation or milk secretion without lactation
• collapse situations
• worsening of heart failure
• worsening of liver function (e.g., cholestatic liver disease)
• increased pressure in the eyeball, intermittent blurred vision attacks, rainbow vision, and eye pain

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

• decreased appetite
• delirium (especially in elderly patients), hallucinations
• abnormal heart rhythm or pattern
• swelling of the salivary glands, paralytic ileus
• hair loss
• increased sensitivity to sunlight
• increased breast size in men
• fever
• weight loss
• abnormal liver function test results

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

• heart muscle disease
• feeling of restlessness and need to be in constant motion
• peripheral nerve disorder
• sudden increase in eye pressure
• particular forms of abnormal heart rhythm (also called torsades de pointes)
• allergic inflammation of the lung alveoli and lung tissue

Frequency not known (cannot be estimated from available data)

• lack of appetite
• increased or decreased blood sugar levels
• paranoia
• movement changes (involuntary or decreased movements)
• allergic inflammation of the heart muscle
• hepatitis
• hot flashes
• dry eyes
• Stop using this medication and seek immediate medical attention if you notice any of the following symptoms: Widespread rash, elevated body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).

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

Benzodiazepines

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

Amnesia

Anterograde amnesia (difficulty remembering recent events) may develop when using therapeutic doses, with a higher risk when increasing the dose. Amnestic effects may be associated with inappropriate behavior.

Depression

The use of benzodiazepines may unmask pre-existing depression.

Psychiatric and paradoxical reactions

When using benzodiazepines or similar compounds, adverse effects on behavior such as restlessness, agitation, irritability, aggression, delirium (incoherence of ideas), outbursts of anger, nightmares, hallucinations, psychosis (loss of contact with reality), inappropriate behavior, and other changes in behavior may appear. These reactions can be severe and occur more frequently in children and the elderly.

Dependence

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

• Frequently: heart problem called "prolonged QT interval" (observed on the electrocardiogram, ECG).
• Very rarely: sudden anxiety, hallucinations, excitement, and sleep disorders. If this happens, consult your doctor immediately.
• Frequency not known (cannot be estimated from available data): Dry eyes.

If you observe any other reaction not described in this prospectus, consult your doctor or pharmacist.

Reporting adverse effects

If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects that do not appear in this prospectus. You can also report them directly through the

Spanish Pharmacovigilance System for Human Use Medications: www.notificaram.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Nobritol and Nobritol Forte

Keep this medication out of sight and reach of children.

Do not store at a temperature above 30°C.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE Point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

Do not use this medication after the expiration date shown on the packaging. The expiration date is the last day of the month indicated.

6. Package contents and additional information

Composition of Nobritol and Nobritol Forte

The active ingredients are Amitriptyline hydrochloride and Medazepam.

The other components are:

• Capsule content: Lactose monohydrate, 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 iron oxide yellow (E-172).

Appearance of the product and package contents

PVC/Al blister pack containing 60 hard capsules.

Nobritol 12.5 mg/5 mg hard capsules

• Capsules with orange opaque head and light green opaque body.

Nobritol Forte 25 mg/10 mg hard capsules

• Capsules with dark green opaque head and orange opaque body.

Marketing authorization holder and manufacturer

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Date of the last revision of this prospectus: December 2024

"Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/"