ANAFRANIL 25 mg Injectable Solution and Perfusion Solution

Introduction

Package Leaflet: Information for the Patient

Anafranil 25 mg Solution for Injection and Infusion

Clomipramine Hydrochloride

Read all of this leaflet carefully before you start using 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 or pharmacist.
• 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 experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Anafranil 25 mg Solution for Injection and Infusion is and what it is used for
2. What you need to know before you use Anafranil 25 mg Solution for Injection and Infusion
3. How to use Anafranil 25 mg Solution for Injection and Infusion
4. Possible side effects
5. Storage of Anafranil 25 mg Solution for Injection and Infusion
6. Contents of the pack and other information

1. What Anafranil 25 mg Solution for Injection and Infusion is and what it is used for

Anafranil belongs to a group of medicines called tricyclic antidepressants, used to treat depression and mood disorders.

In adults, Anafranil can be used to treat depression, obsessive-compulsive disorders, phobias, panic attacks, and narcolepsy syndrome.

2. What you need to know before you use Anafranil 25 mg Solution for Injection and Infusion

Do not use Anafranil:

• if you are allergic to clomipramine hydrochloride or any of the other ingredients of this medicine (listed in section 6).
• if you have had any unusual or allergic reaction to any other tricyclic antidepressant.
• if you are taking any other type of medication for depression. Tell your doctor.
• if you have recently had a heart attack or if you have any serious heart disease.

If the answer is YES to any of the above, Anafranil may not be suitable for you.

Warnings and precautions

Talk to your doctor or pharmacist before starting Anafranil:

• if you have suicidal thoughts,
• if you have epileptic seizures,
• if you have heart rhythm disorders,
• if you have schizophrenia or other mental problems,
• if you have glaucoma (high eye pressure),
• if you have liver or kidney disease,
• if you have any blood disorder,
• if you have difficulty urinating (e.g., due to prostate disease),
• if you have hyperthyroidism,
• if you have frequent constipation,
• if you have fainting spells.

Your doctor will take this into account before and during treatment with Anafranil.

Before using Anafranil, talk to your doctor if any of the above circumstances have ever occurred to you.

Information for families and caregivers

You should monitor if the depressed patient shows signs of changes in behavior such as unusual anxiety, agitation, aggression, sleep disturbances, irritability, aggression, overexcitement, or other unusual changes in behavior, worsening of depression, or suicidal thoughts. You should inform the patient's doctor immediately of any of these symptoms, especially if they are severe, appear suddenly, or were not part of the patient's previous symptoms. You should evaluate the appearance of these symptoms day by day, especially at the beginning of treatment with antidepressants and when the dose is increased or decreased, as these changes can be sudden.

Symptoms like those described may be associated with an increased risk of suicidal thoughts and behaviors and may indicate the need for strict monitoring and possible changes in medication.

Additional safety information

It is essential that your doctor monitors your treatment; performs a blood test and checks your blood pressure and heart function at the beginning of treatment and regularly throughout, to rule out the appearance of blood and liver or heart function disorders.

Anafranil may cause dry mouth, which can increase the risk of dental caries, which means that in long-term treatments, regular dental checks should be performed. Before undergoing any surgery or dental procedure, inform your doctor or dentist that you are using Anafranil.

Anafranil may cause dry eyes; patients who wear contact lenses and experience eye irritation should consult their doctor.

Anafranil may make your skin more sensitive to the sun. Do not take the sun directly and protect yourself with protective clothing and sunglasses.

If you normally suffer from anxiety disorders, at the beginning of treatment with Anafranil, you may experience an increase in anxiety symptoms that usually disappear within 2 weeks after starting treatment.

Serotonin syndrome

Get in touch with your doctor immediately if you suffer from high body temperature, involuntary rhythmic muscle contractions, agitation, convulsions, delirium, coma. These are signs and symptoms that may refer to serotonin syndrome.

Use in elderly patients (65 years or older)

Older patients usually need lower doses than other adult patients. Older patients may be more sensitive to adverse effects. Your doctor will give you special information about the precautions, doses, and follow-up necessary. In patients over 50 years old, an increase in bone fractures has been observed.

Children and adolescents

The use of Anafranil by intramuscular or intravenous route is not recommended in children or adolescents.

Use of Anafranil with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, as it may be necessary to vary the dose or interrupt some of the treatments. This warning is valid for medicines purchased with and without a prescription, especially in the case of:

• daily consumption of alcohol or if you change your tobacco consumption
• inform your doctor that you are taking Anafranil in case you need to receive anesthesia
• medicines used to treat blood pressure and heart function
• other antidepressants, lithium, sedatives, tranquilizers, anticonvulsants (e.g., barbiturates), and antiepileptics (e.g., valproate)
• medicines used as substitution treatment for opioid dependence (buprenorphine/opioids)
• medicines for treating mental illnesses
• medicines for preventing blood clots (anticoagulants)
• medicines for asthma or allergies
• medicines for Parkinson's disease
• thyroid medicines
• medicines for treating ulcers or acidity (e.g., cimetidine)
• medicines used to treat fungal infections of the skin or nails (e.g., terbinafine)
• medicines used for attention disorders (e.g., methylphenidate)
• medicines for preventing conception (oral contraceptives or other estrogens)
• medicines used to increase urine production (diuretics)
• certain antibiotics such as rifampicin

The concomitant administration of antidepressants (MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants), or medicines used as substitution treatment for opioid dependence (buprenorphine/opioids) with Anafranil may lead to serotonin syndrome, a potentially fatal disease.

Pregnancy, breastfeeding, and fertility

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

Anafranil should only be administered to pregnant women if, in the doctor's judgment, the expected benefit to the mother is greater than any possible risk to the fetus. Your doctor will inform you of the benefits and possible risks of treatment during pregnancy.

Since the active ingredient of Anafranil passes into breast milk, breastfeeding should be discontinued during treatment with Anafranil.

No effects on reproductive function have been detected.

Driving and using machines

Anafranil may cause decreased attention, blurred vision, drowsiness, disorientation, etc. If this happens to you, do not drive, operate machinery, and avoid situations that require a special state of alertness. Alcohol consumption can enhance these effects.

3. How to use Anafranil 25 mg Solution for Injection and Infusion

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again. Your doctor will decide the most suitable dose for your particular case.

The recommended initial dose is 1-2 ampoules per day, which can be gradually increased.

Once an improvement has occurred and at the doctor's discretion, the injections are replaced by tablets:

For the treatment of depression, mood disorders, obsessive-compulsive disorders, and phobias, the recommended daily dose is between 100 mg and 150 mg.

For panic attacks and agoraphobia, treatment is started with 10 mg per day, and after a few days, the dose is slowly increased to 100 mg.

For narcolepsy syndrome, the recommended daily dose is between 25 mg and 75 mg.

Treatment with Anafranil should be carried out under the direction of your doctor. Note that you should not administer higher doses, more frequently, or for longer than prescribed by your doctor.

How to use Anafranil

1. Breakable ampoule. Breaking line below the black dot
2. Place your thumb above the black dot and break the ampoule by pressing backwards.

If you use more Anafranil than you should

In case of overdose with Anafranil, inform your doctor or go immediately to the emergency department of the nearest hospital. The symptoms of overdose usually appear a few hours after ingestion and are: drowsiness, poor concentration, slow or fast or irregular pulse, restlessness and agitation, loss of muscle coordination and muscle stiffness, breathing difficulties, convulsions, vomiting, and fever.

In cases of overdose or accidental ingestion, consult the Toxicology Information Service. Telephone 91 562 04 20.

If you forget to use Anafranil

Do not take a double dose to make up for forgotten doses. If you forget a dose, try to have it administered as soon as possible, then return to your usual administration schedule. If it coincides with the next administration, skip this dose and continue with your normal administration schedule. If you have any doubts, consult your doctor.

If you stop treatment with Anafranil

The diseases treated with Anafranil, such as depression, obsessive-compulsive syndromes, and chronic anxiety states, require long-term treatment.

Do not change or stop treatment without prior notice to your doctor, who may indicate a gradual reduction of the dose before completely stopping the medication. This would be to prevent worsening of the general condition and reduce the risk of symptoms due to sudden withdrawal of the medication, such as headaches, nausea, vomiting, diarrhea, insomnia, nervousness, and anxiety. If you have any other doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. They usually do not require medical attention and may occur during treatment while the body gets used to the medicine.

Consult your doctor if any of these effects continue or are bothersome.

Some effects can be serious:

If you experience any of the following side effects, consult your doctor as soon as possible, as they may require medical attention: seeing or hearing things that do not really exist, yellowing of the skin and eyes, skin reactions (itching or redness), frequent infections with fever and sore throat (due to a decrease in white blood cells), allergic reactions with or without cough and difficulty breathing, inability to coordinate movements, increased eye pressure, severe stomach pain, severe loss of appetite, sudden muscle contraction, weakness and muscle stiffness, muscle spasms, difficulty urinating, rapid or irregular heartbeat, difficulty speaking, confusion and delirium, hallucinations, convulsive attacks.

The side effects reported are detailed below according to the following frequencies:

• Very common (occurring in at least 1 in 10 patients treated)

Restlessness, dizziness, tremors, headache, involuntary muscle movements, drowsiness, urinary disorders, nausea, dry mouth, constipation, increased appetite, increased sweating, fatigue, libido disorders, erectile dysfunction, blurred vision, weight gain.

• Common (occurring in at least 1 in 100 and less than 1 in 10 patients treated)

Confusion, disorientation, hallucinations (particularly in elderly patients and/or with Parkinson's disease), anxiety, agitation, sleep disturbances, manic symptoms, aggression, feeling of disconnection or being outside oneself, worsening of depression, insomnia, nightmares, delirium, language disorders, sensation of tingling, strong muscle tension, taste disorders, memory loss, concentration loss, muscle weakness, hot flashes, rapid or irregular heartbeat, low blood pressure when changing position, vomiting, abdominal discomfort, diarrhea, decreased appetite, allergic skin reactions, hypersensitivity to light, itching, abnormal milk secretion from the mammary glands, breast enlargement, yawning, ringing in the ears, pupil dilation, increased liver enzymes in blood.

• Uncommon (occurring in at least 1 in 1,000 and less than 1 in 100 patients treated)

Activation of psychotic symptoms, convulsions, uncoordinated movements, increased blood pressure, arrhythmias.

• Rare (occurring in less than 1 in 10,000 patients treated)

Malignant neuroleptic syndrome, urinary retention, changes in the heart conduction system, liver inflammation, small bleeding under the skin, edema, allergic reaction at the injection site, hair loss, high fever, severe allergic reactions, changes in antidiuretic hormone secretion, changes in the count of immune system cells, increased eye pressure, changes in the electroencephalogram.

• Frequency not known

Increased blood prolactin levels, muscle fiber rupture (rhabdomyolysis), ejaculatory failure or delayed ejaculation, serotonin syndrome, movement disorders (extrapyramidal symptoms), increased risk of bone fractures in patients over 50 years old.

The following symptoms have occurred usually after sudden withdrawal or dose reduction: nausea, vomiting, abdominal pain, diarrhea, insomnia, headache, nervousness, and anxiety.

If you follow a treatment with Anafranil for a long time, go to your doctor for regular check-ups to ensure that no adverse reactions occur that are not described.

Reporting of side effects

If you experience any side effect, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Anafranil 25 mg Solution for Injection and Infusion

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

Do not store above 30°C.

Keep in the original package to protect from light.

Do not use this medicine if you notice that the package is damaged or shows signs of tampering.

Do not use this medicine after the expiry date stated on the package after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Place the packages and medicines you no longer need in the SIGRE point of the pharmacy. Ask your pharmacist how to dispose of packages and medicines you no longer need. This way, you will help protect the environment.

6. Packaging Content and Additional Information

Composition of Anafranil

• The active ingredient is clomipramine hydrochloride.
• The other components (excipients) are: glycerol and water for injectables.

Appearance of the Product and Packaging Content

Anafranil 25 mg injectable and perfusion solution is presented in 2 ml glass ampoules. Each package contains 6 ampoules and the clinical package of 100 ampoules.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Holder:

Alfasigma S.p.A

Via Ragazzi del ’99, n.5

40133 Bologna, ITALY

Manufacturer:

Alfasigma S.p.A.

Vía Pontina, Km 30,400

00071 Pomezia, ITALY

Local Representative:

Alfasigma España, S.L.

C/ Aribau 195, 4º

08021 Barcelona, SPAIN

Date of the Last Revision of this Prospectus: August 2021

Other Sources of Information:

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