ADOLONTA 100 mg/2 ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Adolonta 100 mg/ 2 ml Solution for Injection and Infusion

Tramadol, Hydrochloride

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

• Keep this package 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 symptoms 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 package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Adolonta and what is it used for
2. What you need to know before you use Adolonta
3. How to use Adolonta
4. Possible side effects
5. Storage of Adolonta
6. Contents of the pack and further information

1. What is Adolonta and what is it used for

Tramadol - the active substance of this medicine - is an analgesic belonging to the group of opioids that acts on the central nervous system. It relieves pain by acting on specific nerve cells in the spinal cord and brain.

Adolonta is used to treat moderate to severe pain in adults and children from 3 years of age.

2. What you need to know before you use Adolonta

Do not use Adolonta:

• if you are allergic to tramadol or any of the other ingredients of this medicine (listed in section 6);
• in case of acute intoxications caused by alcohol, sleeping pills, analgesics or other psychotropic medicines (medicines that act on mood and emotions);
• if you are taking MAO inhibitors (a certain type of medicine used to treat depression) or if you have taken them in the last 14 days before treatment with this medicine (see "Using Adolonta with other medicines");
• if you have epilepsy and your convulsive seizures are not adequately controlled with treatment;
• for the treatment of withdrawal syndrome;
• in children under 3 years of age.

Warnings and precautions

Consult your doctor before starting to use Adolonta:

• if you think you are dependent on other analgesics (opioids);
• if you have disorders of consciousness (if you think you are going to faint);
• if you are in a state of shock (a sign of this state may be cold sweat);
• if you have increased intracranial pressure (e.g. after a head injury or diseases that affect the brain);
• if you have difficulty breathing;
• if you are epileptic or have convulsive seizures, as the risk of seizures may increase;
• if you suffer from depression and are taking antidepressants, as some may interact with tramadol (see "Using Adolonta with other medicines");
• if you have any liver or kidney disease.

Tolerance, dependence and addiction

This medicine contains tramadol, which is an opioid medicine. Repeated use of opioids can make the medicine less effective (the body gets used to it, which is known as pharmacological tolerance). Repeated use of Adolonta can also lead to dependence, abuse and addiction, which could result in a potentially life-threatening overdose. The risk of these side effects may be greater with a higher dose and longer use.

Dependence or addiction can cause a feeling of lack of control over the amount of medicine you need to use or how often you need to use it.

The risk of dependence or addiction varies from person to person. The risk of becoming dependent on or addicted to Adolonta may be greater if:

• You or any member of your family have abused alcohol or experienced dependence on it, prescription medicines or illegal drugs ("addiction").
• You are a smoker.
• You have had problems with your mood (depression, anxiety or personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following symptoms while using Adolonta, it could be a sign of dependence or addiction:

• You need to use the medicine for longer than indicated by your doctor.
• You need to use a higher dose than recommended.
• You are using the medicine for reasons other than those prescribed, for example, "to feel calm" or "to help you sleep".
• You have made repeated unsuccessful attempts to stop using the medicine or control its use.
• You feel unwell when you stop using the medicine, and you feel better once you take it again ("withdrawal symptoms").

If you notice any of these signs, consult your doctor to determine the best treatment option for you, when it is appropriate to stop the medicine and how to do it safely (see section 3, if you stop treatment with Adolonta).

Respiratory disorders related to sleep

Adolonta contains an active substance that belongs to the group of opioids. Opioids can cause respiratory disorders related to sleep, such as central sleep apnea (shallow or paused breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood).

The risk of experiencing central sleep apnea depends on the dose of opioids. Your doctor may consider reducing the total dose of opioids if you experience central sleep apnea.

There is a weak risk that you may experience a serotonin syndrome that can occur after taking tramadol in combination with certain antidepressants or tramadol alone. Consult a doctor immediately if you experience any of the symptoms associated with this serious syndrome (see section 4 "Possible side effects").

Seizures have been reported in patients taking tramadol at the recommended dose. The risk may increase when the dose of tramadol exceeds the maximum recommended daily dose (400 mg).

Keep in mind that this medicine can cause physical and psychological dependence. When this medicine is used for a long period, its effect may decrease, and higher doses may be needed (development of tolerance). In patients with a tendency to abuse medicines or those with drug dependence, treatment with tramadol should only be carried out for short periods and under strict medical control.

Also, inform your doctor if any of these problems occur during treatment with this medicine or if you have experienced them before.

Tramadol is transformed in the liver by an enzyme. Some people have a variation of this enzyme, and this can affect each person differently. In some people, sufficient pain relief may not be achieved, while others are more likely to experience serious side effects. If you notice any of the following side effects, you must stop using this medicine and consult a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, general malaise or vomiting, constipation, loss of appetite.

Inform your doctor if you experience any of the following symptoms while taking tramadol:

Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting or low blood pressure. These may be indicators of adrenal insufficiency (low cortisol levels). If you have these symptoms, contact your doctor, who will decide if you need to take hormonal supplements.

Using Adolonta with other medicines

Inform your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Concomitant treatment with Adolonta and MAO inhibitors (a certain type of medicine used to treat depression) should be avoided.

The effect and duration of pain relief produced by Adolonta may be reduced if you take medicines that contain:

• Carbamazepine (for epileptic seizures);
• Ondansetron (to prevent nausea).

Your doctor will indicate if you should use this medicine and in what dose.

The risk of side effects increases

• if you are using this medicine simultaneously with other analgesics such as morphine and codeine (even when used to treat cough) and alcohol. In these cases, you may feel drowsy or dizzy. If this happens, consult your doctor.

Concomitant use of Adolonta with sedatives or medicines for the treatment of insomnia (such as benzodiazepines) or gabapentin or pregabalin for the treatment of epilepsy or pain due to nerve problems (neuropathic pain) increases the risk of drowsiness, respiratory difficulties (respiratory depression), coma or can be potentially life-threatening. Due to this, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes tramadol with sedative medicines, they will limit the dose and duration of concomitant treatment.

Inform your doctor about all sedative medicines you are taking and strictly follow your doctor's dosage recommendation. It may be useful to inform your friends and family about the signs and symptoms indicated above. Inform your doctor if you experience any of these symptoms;

• if you are taking medicines that can cause or may cause seizures, such as certain antidepressants or antipsychotics. The risk of seizures increases if you use Adolonta simultaneously with these medicines. Your doctor will tell you if Adolonta is suitable for you;
• if you are taking medicines for the treatment of depression. Adolonta may interact with these medicines, and you may experience a serotonin syndrome (see section 4 "Possible side effects");
• if you are taking anticoagulant medicines such as warfarin while using Adolonta. The effect of these medicines on blood coagulation may be affected, and bleeding may occur;
• if you take medicines that can increase the accumulation of tramadol and, therefore, its side effects (such as ritonavir, quinidine, paroxetine, fluoxetine, sertraline, amitriptyline, isoniazid, ketoconazole and erythromycin).

Using Adolonta with food and alcohol

Do not consume alcohol during treatment with this medicine, as its effect may be intensified. Food does not affect the effect of the medicine.

Children and adolescents

Use in children with respiratory problems:

Tramadol is not recommended in children with respiratory problems, as the symptoms of tramadol toxicity may worsen in these children.

In particular, in children, the first injection with tramadol should be administered under strict medical supervision.

Monitor the child, especially during the first administration. In case of warning signs (such as altered consciousness, constricted pupils, vomiting, seizures, very slow breathing...), call a doctor immediately or consult an emergency service (see section "If you use more Adolonta than you should").

Pregnancy, breastfeeding and fertility

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

There is very little information available on the safety of tramadol in pregnant women. Therefore, you should not use this medicine if you are pregnant.

Chronic treatment during pregnancy may cause withdrawal syndrome in newborns.

Tramadol is excreted in breast milk. For this reason, you should not use this medicine more than once during breastfeeding, or if you use Adolonta more than once, you should interrupt breastfeeding.

Based on human experience, it is not suggested that tramadol affects fertility in men and women.

Driving and using machines

Ask your doctor if you can drive or use machines during treatment with this medicine. It is important that before driving or using machines, you observe how this medicine affects you. Do not drive or use machines if you feel sleepy, dizzy, have blurred vision or double vision, or have difficulty concentrating. Be especially careful at the start of treatment, after a dose increase, after a change in formulation, and/or when administered concomitantly with other medicines.

This medicine contains less than 23 mg (1 mmol) of sodium per 2 ml ampoule; this is essentially "sodium-free".

3. How to use Adolonta

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

Before starting treatment and regularly during treatment, your doctor will also explain what you can expect from using Adolonta, when and for how long you should use it, when you should contact your doctor, and when you should stop using it (see also section 2).

The dose should be adjusted to the intensity of the pain and your individual sensitivity. Normally, the lowest possible dose that produces pain relief should be used. Do not administer more than 8 ml of Adolonta (equivalent to 400 mg of tramadol hydrochloride) per day, unless your doctor has instructed you to do so.

Unless your doctor has given you different instructions, the recommended dose is:

Adults and adolescents over 12 years

Depending on your pain, doses of 1-2 ml of Adolonta (equivalent to 50-100 mg of tramadol hydrochloride) may be administered.

Depending on the pain, the effect may last between 4-6 hours.

Additional information on administration is provided for doctors and healthcare professionals at the end of this prospectus.

Children

For children over 3 years of age, the recommended single dose is 1-2 mg of tramadol hydrochloride per kilogram of body weight.

The lowest effective dose that produces pain relief should be used. Daily doses of more than 8 mg of tramadol hydrochloride per kilogram of body weight or 400 mg of tramadol hydrochloride, whichever is less, should not be exceeded.

Additional information on administration is provided for doctors and healthcare professionals at the end of this prospectus.

Elderly patients

In elderly patients (over 75 years), the elimination of tramadol may be slow. If this is your case, your doctor may recommend prolonging the dosing intervals.

Patients with hepatic or renal insufficiency/patients on dialysis

If you have severe liver or kidney disease, treatment with this medication is not recommended. If you have moderate liver or kidney disorders, your doctor may prolong the dosing intervals.

How and when should Adolonta be used?

Administration will be by parenteral route: intramuscular, subcutaneous, intravenous (slow injection) or by perfusion.

Additional information on administration is provided for doctors and healthcare professionals at the end of this prospectus.

For how long should Adolonta be used?

This medication should not be administered for longer than strictly necessary. If you require prolonged treatment, your doctor will monitor you at short and regular intervals (if necessary with interruptions in treatment) to determine whether you should continue treatment with tramadol and at what dose.

If you think the effect of this medication is too strong or too weak, tell your doctor or pharmacist.

If you use more Adolonta than you should

If you have used an extra dose by mistake, it will generally not have negative effects. You should continue with the next dose as prescribed.

After using very high doses of the medication, pupil contraction, vomiting, decreased blood pressure, increased heart rate, collapse, decreased level of consciousness up to coma (deep unconsciousness), epileptic seizures, and breathing difficulties that can lead to respiratory arrest may occur. In this case, call a doctor immediately!

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount used. It is recommended to bring the medication prospectus to the healthcare professional.

If you forget to use Adolonta

If you forget to use the medication, it is likely that the pain will return. Do not use a double dose to make up for forgotten doses; simply continue using the medication as you have been doing until now.

If you stop treatment with Adolonta

If you stop or finish treatment with this medication too soon, it is likely that the pain will return. If you want to stop treatment due to adverse effects, consult your doctor.

You should not stop using this medication suddenly unless your doctor tells you to do so. If you want to stop using your medication, talk to your doctor first, especially if you have been using it for a long time. Your doctor will inform you when and how to stop it, which can be done by gradually reducing the dose to reduce the likelihood of unnecessary adverse effects (withdrawal symptoms).

Generally, no adverse effects are usually experienced when treatment with tramadol is stopped. However, in rare cases, people who have been using this medication for some time may feel unwell if they stop treatment abruptly. They may feel agitated, anxious, nervous, or trembly. They may be overactive, have difficulty sleeping, or have digestion and intestinal problems. Very few people may have panic attacks, hallucinations, unusual perceptions such as itching, tingling, and numbness, and ringing in the ears (tinnitus). Very rarely, more unusual symptoms of the central nervous system have been detected, such as confusion, delirium, change in perception of personality (depersonalization), and change in perception of reality (derealization) and persecution delusions (paranoia). If you experience any of these symptoms after stopping treatment with this medication, consult your doctor.

If you have any other questions about using this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

You should consult your doctor immediately if you experience symptoms of an allergic reaction such as swelling of the face, tongue, and/or throat and/or difficulty swallowing and rash along with difficulty breathing.

The most common side effects during treatment with tramadol are nausea and dizziness, which occur in more than 1 in 10 people.

Very common: may affect more than 1 in 10 people

• Dizziness.
• Nausea.

Common: may affect 1 in 10 people

• Headache, numbness.
• Fatigue.
• Vomiting, constipation, dry mouth.
• Sweating (hyperhidrosis).

Uncommon: may affect 1 in 100 people

• Effects on the heart and circulation (strong and fast heartbeats, feeling of dizziness or collapse). These side effects may occur particularly in patients who are incorporated or who make physical effort.
• Desire to vomit (retching), gastrointestinal discomfort (e.g., feeling of pressure in the stomach, bloating), diarrhea.
• Skin reactions (e.g., itching, skin rash).

Rare: may affect 1 in 1,000 people

• Allergic reactions (e.g., difficulty breathing, wheezing, skin swelling) and shock (sudden circulatory failure) have occurred in very rare cases.
• Slow heartbeat.
• Increased blood pressure.
• Abnormal sensations (e.g., itching, tingling, numbness), tremors, epileptic seizures, muscle twitches, uncoordinated movements, transient loss of consciousness (syncope), speech disorders.
• Seizures occur mainly after using high doses of tramadol or when another medication that can induce them has been taken simultaneously.
• Changes in appetite.
• Hallucinations, confusion, sleep disturbances, delirium, anxiety, and nightmares.
• Psychological changes may occur after treatment with tramadol. The intensity and nature may vary (depending on the patient's personality and the duration of treatment). These may appear in the form of mood changes (usually euphoria, occasionally irritability), changes in activity (usually decreased and occasionally increased), and decreased cognitive and sensory perception (alterations of the senses and perception that can lead to errors of judgment).
• It can cause dependence on the medication. When treatment is stopped abruptly, withdrawal syndrome may appear (see "If you stop treatment with Adolonta").
• Blurred vision, pupil contraction (miosis), excessive pupil dilation (mydriasis).
• Slow breathing, shortness of breath (dyspnea).
• Cases of worsening asthma have been reported, but it has not been established whether they were caused by tramadol. If the recommended doses are exceeded or if it is taken concomitantly with other medications that depress brain function, a decrease in respiratory frequency may occur.
• Muscle weakness.
• Difficulty or pain when urinating, less urine than normal (dysuria).

Very rare: may affect 1 in 10,000 people

• Increased liver enzymes.

Frequency not known: frequency that cannot be estimated from the available data

• Decrease in blood sugar levels.
• Hypo.
• Serotonin syndrome, which can manifest as changes in mental state (e.g., agitation, hallucinations, coma), and other effects, such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle stiffness, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "What you need to know before you start using Adolonta").

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Adolonta

Keep this medication out of sight and reach of children.

Store this medication in a safe and protected place, where others cannot access it. This medication can cause serious harm and even be fatal to people who have not been prescribed it.

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

This medication does not require special storage conditions.

Medications should not be thrown away through drains 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.

6. Package contents and additional information

Composition of Adolonta 100 mg/2 ml solution for injection and perfusion

The active ingredient is tramadol hydrochloride. Each ampoule contains 100 mg of tramadol hydrochloride in 2 ml of injectable solution.

The other components are: sodium acetate and water for injectables.

Appearance of the product and package contents

Clear and colorless solution. It is presented in transparent glass ampoules supplied in packages of 5 and 100 ampoules of 2 ml.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Grünenthal Pharma, S.A.

Doctor Zamenhof, 36 - 28027 Madrid, Spain

Manufacturer:

Grünenthal GmbH

Zieglerstrasse 6 - D-52078 Aachen, Germany

Date of the last revision of this prospectus: June 2024

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/

___________________________________________________________________________

This information is intended only for healthcare professionals:

Information on the handling of Adolonta 100 mg/2 ml solution for injection and perfusion

The medication is supplied in ampoules with a break point. The ampoule has a break line and can be easily opened:

1. Turn the ampoule with the tip upwards.
2. Open the ampoule at the break line.

Additional information on administration

For moderate pain, administer 1 ml of the solution (corresponding to 50 mg of tramadol hydrochloride). If there is no effect after 30-60 minutes, another ml can be administered.

If, in the case of intense pain, a higher dose is required, 2 ml of injectable solution (equivalent to 100 ml of tramadol hydrochloride) can be administered.

Higher doses may be required on demand (pain treatment according to needs) for the treatment of post-surgical pain in the first hours after surgery. The doses required in 24 hours after surgery are usually not higher than those of a normal administration.

This medication is administered intravenously (generally in the superficial veins of the arm), intramuscularly (generally in the buttocks), or subcutaneously under the skin.

Intravenous administration should be slow with 1 ml of injectable solution (equivalent to 50 mg of tramadol hydrochloride) per minute.

Alternatively, the medication can be diluted in a suitable solution for perfusion (e.g., 0.9% sodium chloride solution or 5% glucose solution) for intravenous perfusion or patient-controlled analgesia (PCA).

Incompatibilities of Adolonta

It has been shown that this medication is incompatible (immiscible) with injectable solutions containing diclofenac, indomethacin, phenylbutazone, diazepam, flunitrazepam, midazolam, and glyceryl trinitrate.

How to use Adolonta for the treatment of children over 3 years (see section 3 "How to use Adolonta")

Calculation of the injection volume

1. Calculate the total dose of tramadol hydrochloride (mg) required: body weight (Kg) × dose (mg/Kg).
2. Calculate the volume (ml) of the diluted solution to be injected: divide the total dose (mg) by a suitable concentration of solution (mg/ml; see table below).

Table: Dilution of Adolonta 100 mg/2 ml solution for injection and perfusion (suitable solvent see section "How and when should Adolonta be used").

According to your calculations, dilute the contents of the Adolonta ampoule by adding the appropriate amount of solvent, mix, and administer the calculated volume of diluted solution. Discard the remaining injectable solution.

Example

For a child who weighs 27 Kg and is to be administered a dose of 1.5 mg of tramadol hydrochloride per kilogram of body weight.

The total required dose is 27 kg × 1.5 mg/Kg = 40.5 mg of tramadol hydrochloride.

A suitable concentration of diluted solution is 10.0 mg/ml, so the volume to be injected would be around 4 ml (40.5 mg/10.0 mg/ml = 4.05 ml).

According to the above, 1 ml of injectable solution is diluted by adding 4 ml of solvent (e.g., 0.9% sodium chloride solution or 5% glucose solution) to obtain a diluted solution with a concentration of 10 mg of tramadol hydrochloride per ml.

4 ml of diluted solution (40 mg of tramadol hydrochloride) are administered.