Prospect: information for the patient

Nobritol 12.5 mg / 5 mg hard capsules

Nobritol Forte 25 mg / 10 mg hard capsules

Amitriptyline hydrochloride / Medazepam

Read this prospect carefully before starting to use this medication, as it contains important information for you.

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

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

2.What you need to knowbefore starting to take Nobritol and Nobritol Forte

3.How to take Nobritol and Nobritol Forte

4.Adverse effects

1. Storage of Nobritol and Nobritol Forte

6.Contents of the package and additional information

The active ingredients of Nobritol and Nobritol Forte are Amitriptyline hydrochloride, which belongs to a group of medications 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 a short-term treatment with Nobritol or Nobritol Forte is needed.

Do not take Nobritol or Nobritol Forte:

• if you are allergic to the active ingredients or any of the other components of these medications (listed in section 6).
• if you have respiratory difficulties related or unrelated 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 eye pressure).
• 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 electrocardiogram (ECG) detected rhythm alterations, cardiac block, or coronary disease.
• if you are taking medications 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 the treatment with this medication and wait 14 days before starting treatment with an MAOI.

This medication 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 disorders,
• you suffer from muscle weakness,
• you have other diseases,
• you have allergies.

Abnormal heart rhythms and hypotension may occur if you receive a high dose of amitriptyline. This can also occur with regular doses if you have a pre-existing heart disease.

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

• the use of benzodiazepines should be made only under medical prescription (never because they have worked in other patients) and never recommended to others.
• do not increase the prescribed doses at all, or prolong the treatment longer than recommended.
• consult your doctor regularly to decide if you should continue treatment.

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

Severe skin reactions, including drug reactions with eosinophilia and systemic symptoms (DRESS), have been reported in association with treatment with this medication. 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 continuous use for several weeks, a certain degree of loss of efficacy with respect to hypnotic effects may be detected.

Duration of treatment

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

Never prolong treatment without a reevaluation by your doctor.

Prolonged QT interval

Cases of a heart condition called "prolonged QT interval" (observed on the electrocardiogram, ECG) and abnormal heart rhythms (rapid 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 properly throughout the body (i.e., a condition called "heart failure");
• you are taking any other medication that may cause heart problems; or
• you have recently had a problem that has decreased your potassium or magnesium levels, or have high potassium levels in your blood;
• you have a scheduled surgery, as you may need to stop taking amitriptyline before receiving anesthetics. In case of emergency surgery, inform the anesthesiologist about your treatment with amitriptyline;
• you have an overactive thyroid gland or are receiving thyroid medication.

Thoughts of suicide and worsening of depression

If you are depressed, you may sometimes think about harming yourself or taking your life. These types of thoughts may increase when you first start taking antidepressants, as all these medications take time to work, usually two weeks, but sometimes longer.

You may be more likely to have these thoughts:

• if you have had thoughts of taking your life or harming yourself before.
• if you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in young adults (under 25 years) with psychiatric disorders who received treatment with an antidepressant.

Inform your doctor or go to the hospital immediately if you have thoughts of harming yourself or taking your life.

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

Manic episodes

Some patients with manic-depressive illness may enter a manic phase, characterized by rapid, changing ideas, excessive joy, and excessive physical activity. In these cases, it is essential to contact your doctor, who will likely change your medication.

Rebound insomnia and anxiety

A transient syndrome characterized by the reappearance of symptoms - although more pronounced - that led to the initiation of treatment has been described after withdrawal of the medication. This episode may be accompanied by other reactions such as mood changes, anxiety, or sleep and restlessness disturbances. The probability of the appearance of a withdrawal/rebound syndrome is higher after abrupt termination of treatment, so it is recommended to gradually reduce the dose until its definitive suppression. Follow exactly the usage and administration instructions indicated by your doctor to avoid the appearance of these symptoms.

Amnesia

Nobritol and Nobritol Forte may induce anterograde amnesia. This occurs more frequently after several hours have passed since the administration of the medication, so it is recommended to ensure that you can sleep uninterrupted for 7-8 hours to minimize the associated risk.

Psychiatric and paradoxical reactions

Nobritol and Nobritol Forte may produce reactions such as restlessness, agitation, irritability, aggression, delusions, anger attacks, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse effects on behavior. Your doctor will suspend treatment in case of this occurrence.

Inform 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 eye pressure)
• epilepsy, history of seizures, or convulsions
• difficulty urinating
• prostate enlargement
• 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 you may need to adjust your diabetes medication

If you are taking selective serotonin reuptake inhibitors (SSRIs), your doctor may consider changing your medication dose (see section 2 "Taking Nobritol or Nobritol Forte with other medications" and section 3).

Older adults are more likely to experience certain adverse effects, such as dizziness when standing due to low blood pressure (see section 4 "Possible adverse effects").

Children and adolescents

Do not administer this medication to children and adolescents under 18 years old for these treatments, as there have been no safety and efficacy studies for this age group.

Special populations

Older adults may be affected by Nobritol and Nobritol Forte more than young patients. If you are an older adult, your doctor may prescribe a lower dose and monitor your response to treatment. Please follow your doctor's instructions carefully.

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

Other medications and Nobritol or Nobritol Forte

Inform your doctor if you are taking, have taken recently, or may need to take another medication.

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

Some medications can affect the functioning of other medications, and this can sometimes cause severe adverse effects.

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

• monoamine oxidase inhibitors (MAOIs) such as, for example, phenelzine, iproniazid, isocarboxazid, nialamide, or tranylcypromine (used to treat depression) or selegiline (used to treat Parkinson's disease). These medications 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 cold or flu medications and some anesthetics)
• medications to treat high blood pressure such as, for example, calcium channel blockers (e.g., diltiazem and verapamil), guanethidine, betanidine, clonidine, reserpine, and methyldopa
• anticholinergic medications such as certain medications for Parkinson's disease and gastrointestinal disorders (e.g., atropine, hyoscyamine)
• thioridazine (used to treat schizophrenia)
• tramadol (to relieve pain)
• medications to treat fungal infections (e.g., fluconazole, terbinafine, ketoconazole, and itraconazole)
• sedatives (e.g., barbiturates)
• antidepressants (e.g., SSRIs [fluoxetine, paroxetine, fluvoxamine], duloxetine, and bupropion)
• medications for certain heart conditions (e.g., beta-blockers and antiarrhythmics)
• cimetidine (used to treat stomach ulcers)
• methamphetamine (used to treat ADHD)
• ritonavir (used to treat HIV)
• oral contraceptives
• rifampicin (to treat infections)
• phenytoin and carbamazepine (used to treat epilepsy)
• St. John's Wort (Hypericum perforatum), a herbal remedy used to treat depression
• thyroid medications
• valproic acid

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

• medications to treat irregular heartbeats (e.g., quinidine and sotalol)
• astemizole and terfenadine (used to treat allergies and seasonal rhinitis)
• medications used to treat certain mental disorders (e.g., pimozide and sertindole)
• cisapride (used to treat certain types of indigestion)
• halofantrine (used to treat malaria)
• methadone (used to treat pain and withdrawal)
• diuretics ("urine pills" such as furosemide)

The concomitant use of this medication and opioids (strong painkillers, medication for withdrawal, and some cough medications) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be fatal. Therefore, concomitant use should only be considered when other treatment options are not possible.

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

Please inform your doctor about all the opioid medications you are taking, and follow your doctor's dose recommendation closely. It may be helpful to inform friends or family members to be aware of the signs and symptoms mentioned above. Contact your doctor when you experience these symptoms.

If you are to undergo surgery and receive general or local anesthetics, inform your doctor that you are taking this medication.

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

Taking Nobritol or Nobritol Forte with alcohol

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

Pregnancy and breastfeeding

Pregnancy

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

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 medication 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 initiate/continue/suspend breastfeeding or interrupt the use of this medication, 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 lactating mothers.

Driving and operating machinery

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

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

This medication contains lactose. If your doctor has indicated that you have a lactose intolerance, consult with them before taking this medication.

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

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

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

It is recommended to start treatment with one capsule in the morning and another at night. 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 response of the patient and tolerance. When increasing the dose, administer the main dose at night.

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

Never change the dose prescribed by yourself. 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 as withdrawal effects may occur.

Patients over 65 years old

The recommended dose of Nobritol and Nobritol Forte ranges from 12.5mg/5mg per day to 50mg/20 mg per day divided into two doses, depending on each 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 another 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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested. Bring the packaging of this medication with you to the doctor or hospital.

The symptoms of overdose include:

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

Amitriptyline overdose in children could have severe consequences. Children are especially prone to coma, cardiac symptoms, difficulty breathing, seizures, 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 compensate for the missed doses, but rather continue with the normal dose.

If you interrupt treatment with Nobritol or Nobritol Forte

Stopping the administration of the preparation may cause restlessness, anxiety, insomnia, lack of concentration, headache, irritability, confusion, and hot flashes.

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 questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

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

Amitriptilina

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

You should have an eye examination immediately before you can continue treatment with this medicine. These symptoms may be a sign of acute glaucoma.Very rare side effects, which can affect up to 1 in 10,000 people.

• A heart problem called “prolonged QT interval” (which can be seen on your electrocardiogram).Common side effect, which can affect up to 1 in 10 people.

• Important constipation, bloating of the stomach, fever, and vomiting.

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

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

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

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

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

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

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

Very common: can affect more than 1 in 10 people

• drowsiness/somnolence
• hand tremors or other body parts
• dizziness
• headache
• irregular, strong, or fast heartbeat
• dizziness when standing due to low blood pressure (orthostatic hypotension)
• accommodation disturbances
• dry mouth
• constipation
• nausea
• excessive sweating
• weight gain
• slurred speech or slow speech
• aggression
• congested nose

Common: can affect up to 1 in 10 people

• confusion
• sexual dysfunction (decreased libido, erectile dysfunction)
• attention disturbances
• changes in taste
• numbness or tingling in the arms or legs
• coordination disturbances
• dilated pupils
• cardiac arrest
• fatigue
• low sodium levels in the blood
• agitation
• urinary disturbances
• urinary retention
• thirst

Uncommon: can affect up to 1 in 100 people

• excitement, anxiety, difficulty sleeping, nightmares
• seizures
• tinnitus
• increased blood pressure
• diarrhea, vomiting
• skin rash, hives (urticaria), facial swelling, and tongue swelling
• 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, 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 heart pattern
• salivary gland swelling, paralytic ileus
• hair loss
• increased sensitivity to sunlight
• enlargement of the breasts in men
• fever
• weight loss
• abnormal liver function test results

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

• heart muscle diseases
• feeling of restlessness and need to be in constant movement
• peripheral nerve damage
• acute increase in eye pressure
• particular forms of abnormal heart rhythm (also called torsades de pointes)
• allergic inflammation of the alveolar and pulmonary tissue

Frequency not known (cannot be estimated from available data)

• lack of appetite sensation
• increase or decrease in blood sugar levels
• paranoia
• movement disturbances (involuntary movements or decreased movements)
• hypersensitivity inflammation of the heart muscle
• hepatitis
• apathy
• dry eyes
• Stop using this medicine and seek medical attention immediately if you notice any of the following symptoms: Generalized rash, elevated body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).

A higher risk of bone fractures has been observed in patients treated with this type of medication.

Benzodiacepinas

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

Amnesia

Anterograde amnesia (difficulty remembering recent events) may develop at therapeutic doses, with a higher risk at increased doses. Amnestic effects may be associated with inappropriate behavior.

Depression

The use of benzodiazepines may unmask an underlying 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), anger attacks, nightmares, hallucinations, psychosis (loss of contact with reality), inappropriate behavior, and other conduct disturbances may occur. These reactions can be severe and occur more frequently in children and the elderly.

Dependence

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

• Commonly: heart problem called “prolonged QT interval” (which can be seen on the electrocardiogram, ECG).
• Very rarely:sudden anxiety, hallucinations, excitement, and sleep disturbances. If this happens, see your doctor immediately.
• Frequency not known(cannot be estimated from available data): Dry eyes.

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

Reporting of adverse reactions

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

Spanish System for Pharmacovigilance of Medicines for human use: www.notificaram.es.

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

Keep this medication out of the sight and reach of children.

Do not store at a temperature above 30°C.

Do not dispose of medications through drains or trash. Dispose of packaging and medications you no longer need at the SIGRE point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. This 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.

Composition of Nobritol and Nobritol Forte

The active principles are Amitriptilina hydrochloride and Medazepam

The other components are:

• Content of the capsule: Lactose monohydrate, magnesium stearate, talc.
• Capsule coating:
• Nobritol 12.5 mg/5 mg hard capsules: Yellow-orange S (E-110), indigotin (E-132), titanium dioxide (E-171), gelatin, erythrosine (E-172), and yellow quinoline (E-104).
• Nobritol Forte 25 mg/10 mg hard capsules:Yellow-orange S (E-110), indigotin (E-132), titanium dioxide (E-171), gelatin, erythrosine (E-172), and yellow iron oxide (E-172).

Appearance of the product and content of the packaging

PVC/Al blister containing 60 hard capsules

Nobritol 12.5 mg/5 mg hard capsules

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

Nobritol Forte 25 mg/10 mg hard capsules

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

Holder of the marketing authorization and responsible manufacturer

Kern Pharma, S.L.

Venus, 72 - Pol. Ind.Colón II

08228 Terrassa -Barcelona

Spain

Last review date of this leaflet: December 2024

“Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/”