Tramal

Package leaflet: Information for the patient

Tramal, 50 mg/1 ml, solution for injection
Tramadoli hydrochloridum
Please read the entire leaflet carefully before use, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. The medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

1. What Tramal is and what it is used for
2. Important information before using Tramal
3. How to use Tramal
4. Possible side effects
5. How to store Tramal
6. Contents of the pack and other information

1. What Tramal is and what it is used for

Tramadol – the active substance in Tramal – is an analgesic belonging to the group of
opioid agents acting on the central nervous system. It exerts analgesic effects by acting on specialized nerve cells in the spinal cord and brain.
Tramal is used in the treatment of moderate to severe pain.

2. Important information before using Tramal

When not to use Tramal:

• if the patient is allergic to tramadol or any of the other ingredients of this medicine (listed in section 6);
• in case of acute alcohol intoxication, sedative drugs, painkillers or psychotropic medicines (drugs affecting mood and emotions);
• if the patient is taking medicines from the group of MAO inhibitors (certain antidepressants) or within 14 days after stopping them (see "Tramal and other medicines");
• in patients with uncontrolled epilepsy;
• in the treatment of opioid dependence.

Warnings and precautions
Before starting treatment with Tramal, discuss this with your doctor:

• in case of dependence on other painkillers (opioids);
• in disorders of consciousness (if the patient feels faint);
• in shock (cold sweats may be a symptom);
• in case of increased intracranial pressure (which may occur after head injury or brain diseases);
• in case of respiratory disorders;
• in patients with increased sensitivity to opioid medicines;
• in patients with epilepsy or increased risk of seizures, as this risk may be further increased;
• in patients with liver or kidney disease;
• if the patient suffers from depression and is taking antidepressants, because some of them may interact with tramadol (see "Tramal and other medicines"). There is a small risk of developing a condition called serotonin syndrome when tramadol is taken together with certain antidepressants or tramadol alone. If the patient experiences any symptoms of this serious condition, they should immediately consult a doctor (see section 4 "Possible side effects").

Tolerance, dependence and addiction
This medicine contains tramadol, which is an opioid medicine. Repeated use of opioids may
reduce the effectiveness of the medicine (the patient's body becomes accustomed to the medicine,
known as tolerance). Repeated use of Tramal may also lead to dependence, abuse and addiction,
which may result in life-threatening overdose. The risk of these adverse effects may increase with
higher doses and longer duration of treatment.
Dependence or addiction may cause the patient to lose control over the amount or frequency of
medicine intake.
The risk of dependence or addiction varies among individuals. Higher risk of dependence on
Tramal may apply to people in the following situations:

• the patient or someone in their family has ever abused or been dependent on alcohol, prescription medicines or illegal drugs ("addiction");
• the patient is a smoker;
• the patient has ever had mood problems (depression, anxiety or personality disorders) or has been treated by a psychiatrist for other mental illnesses. If the patient notices any of the symptoms listed below while taking Tramal, this may indicate dependence or addiction.
• Needing to take the medicine for longer than recommended by the doctor.
• Needing to take a higher dose than recommended.
• The patient uses the medicine for reasons other than those for which it was prescribed, e.g. "to calm down" or "to sleep better".
• The patient has made repeated, unsuccessful attempts to stop or control the use of the medicine.
• After stopping the medicine, the patient feels unwell, and feels better after taking it again ("withdrawal symptoms"). If the patient notices any of these symptoms, they should consult a doctor to discuss the best treatment approach, including when and how to safely stop taking the medicine (see section 3, "Stopping treatment with Tramal").

Tramal may cause psychological and physical dependence. Long-term use of Tramal may lead to
reduced effectiveness, leading to taking increasingly higher doses (development of tolerance).
In patients with a tendency to drug abuse or history of addiction, treatment should be short-term
and under strict medical supervision.
Excessive fatigue, loss of appetite, severe abdominal pain, nausea, vomiting or low blood pressure.
This may indicate adrenal insufficiency (low cortisol levels). If such symptoms occur, contact a doctor,
who will decide whether hormone replacement is necessary.
Sleep-related breathing disorders
Tramal may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing
during sleep) and hypoxemia (low blood oxygen levels). Symptoms may include breathing pauses
during sleep, night awakenings due to breathlessness, difficulty maintaining sleep or excessive
daytime sleepiness. If the patient or another person observes these symptoms, contact a doctor.
The doctor may recommend reducing the dose.
Caution is advised in patients with suppressed respiratory centre function, especially when taking
other medicines that depress the central nervous system (see "Tramal and other medicines") or
when taking doses higher than recommended (see "Taking more than the recommended dose of
Tramal" in section 3 and section 4), as respiratory depression cannot be ruled out in such cases.
Seizures have been observed in patients taking tramadol at recommended doses. The risk of
seizures may be higher if the tramadol dose exceeds the recommended maximum daily dose (400 mg)
or if the patient is taking other medicines that lower the seizure threshold (see section "Tramal and
other medicines").
Consult a doctor if any of the above situations occur during treatment with Tramal, even if these
warnings refer to conditions from the past.
Tramadol is metabolized in the liver by an enzyme. Some people have a variation of this enzyme,
which may lead to different effects. In some people, pain relief may be insufficient, while in others,
serious adverse effects may be more likely.
Stop taking the medicine and contact a doctor immediately if the patient experiences any of the
following adverse effects: slowed or shallow breathing, confusion, drowsiness, pinpoint pupils,
nausea or vomiting, constipation, loss of appetite.
Children and adolescents
Use in children with breathing disorders
Tramadol is not recommended in children with breathing disorders, as tramadol toxicity symptoms
may be more severe in them.
Tramal and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently
taken, as well as any medicines the patient plans to take.
Tramal should not be used together with MAO inhibitors (medicines used to treat depression) or
within 14 days after stopping them; see section "When not to use Tramal".
The pain-relieving effect of Tramal may be reduced and its duration shortened when taken together
with medicines containing:

• carbamazepine (an antiepileptic medicine),
• pentazocine, nalbuphine or buprenorphine (painkillers),
• ondansetron (an antiemetic medicine). Consult a doctor about using Tramal and its dosing.

The risk of adverse effects increases:

• when Tramal is taken together with other painkillers such as morphine and codeine (also as a cough suppressant) and alcohol. Drowsiness or faintness may occur. In such cases, consult a doctor.
• when Tramal is taken together with sedatives or sleeping pills (e.g. benzodiazepines) or gabapentin or pregabalin used to treat epilepsy or nerve-related pain (neuropathic pain), increasing the risk of drowsiness, breathing difficulties (respiratory depression), coma and potentially life-threatening effects. Therefore, concomitant use should only be considered when other treatment options are not possible. However, if a doctor prescribes Tramal together with sedatives, the doctor should limit the dose and duration of combined treatment.

Inform the doctor about all sedative medicines being taken and strictly follow the doctor's
dosing instructions. It may be helpful to inform friends or relatives so they are aware of the
above symptoms. If such symptoms occur, contact a doctor.

• if the patient is taking other medicinal products that may cause seizures, such as certain antidepressants or antipsychotics, including: selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other medicines that lower the seizure threshold (such as bupropion, mirtazapine, tetrahydrocannabinol). The risk of seizures may increase if the patient takes Tramal together with these medicines. Consult a doctor whether the patient can take Tramal while using the above medicines.
• if the patient is taking certain antidepressants, Tramal may interact with them and cause serotonin syndrome (see section 4 "Possible side effects").
• when anticoagulant medicines containing coumarin derivatives (to reduce blood clotting), e.g. warfarin, are taken together with Tramal. Bleeding may occur due to the effect of these medicines on the blood clotting system.

Ketoconazole (an antifungal medicine) and erythromycin (a bactericidal antibiotic) may inhibit
tramadol metabolism and likely that of its active metabolite.
Taking Tramal with food, drink and alcohol
Do not drink alcohol while taking Tramal, as the effect of the medicine may be intensified, potentially
leading to respiratory depression.
Food does not affect the effect of Tramal.
Pregnancy, breastfeeding and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a
child, she should consult a doctor or pharmacist before using this medicine.
The safety of using tramadol during pregnancy has not been established. Therefore, Tramal should
not be used during pregnancy.
Long-term use of tramadol during pregnancy may lead to withdrawal symptoms in the newborn.
Breastfeeding
Tramadol is excreted in breast milk. Therefore, during breastfeeding, Tramal should not be taken
more than once, or if Tramal has been taken more than once, breastfeeding should be discontinued.
Experience with the use of tramadol in humans does not indicate that tramadol affects fertility in
men and women.
Driving and operating machinery
Even at recommended doses, Tramal may cause drowsiness, dizziness and blurred vision, which
may affect reaction speed. If these symptoms occur, the patient should not drive or operate any
machinery.
Tramal contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per 2 ml, meaning the medicine is
considered "sodium-free".

3. How to use Tramal

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Before starting treatment and regularly during treatment, your doctor will discuss with you what to expect from using Tramal, when and for how long it should be taken, when to contact your doctor, and when the medicine should be discontinued (see also section 2).
Your doctor will adjust the dose according to the intensity of pain and your individual response to treatment. The dose used will be the lowest effective dose that adequately relieves pain. Usually, up to 8 ml of Tramal (equivalent to 400 mg of tramadol hydrochloride) is administered per day. Exceptionally, if clinically justified, your doctor may prescribe higher daily doses.
If your doctor has not instructed otherwise, the usual dosage is as follows:
Adults and adolescents over 12 years of age
Depending on the intensity of pain, usually 1–2 ml of Tramal injection solution (equivalent to 50–100 mg of tramadol hydrochloride) is administered every 4–6 hours.
Children over 1 year of age
The usual single dose is 1 to 2 mg of tramadol hydrochloride per kilogram of body weight. The lowest effective dose should always be used.
The total daily dose should not exceed 8 mg of tramadol hydrochloride per kilogram of body weight, and should not exceed the maximum daily dose of 400 mg of tramadol hydrochloride.
Elderly patients
In patients over 75 years of age, elimination of tramadol may be delayed. In these patients, your doctor may recommend extending the interval between doses.
Patients with renal impairment, on dialysis, or with hepatic impairment
Tramal should not be used in cases of severe hepatic and/or renal impairment.
In cases of mild or moderate impairment, your doctor may recommend longer intervals between doses.
Method of administration
Tramal is administered by slow intravenous injection, e.g. into a vein in the elbow crease, or by intramuscular or subcutaneous injection.
It may also be diluted and administered as an intravenous infusion.
Duration of treatment
Tramal should not be used longer than absolutely necessary. If long-term treatment is required due to the type and severity of the condition, your doctor will monitor your condition regularly (possibly interrupting treatment temporarily, if necessary) to determine whether and at what dose Tramal treatment should continue.
If you feel the effect of Tramal is too strong or too weak, consult your doctor or pharmacist.
Detailed information for healthcare professionals is provided at the end of this leaflet.
Use of a higher than recommended dose of Tramal
After administration of doses higher than recommended, the following may occur: pinpoint pupils, vomiting, drop in blood pressure, rapid heartbeat, collapse, disturbances of consciousness up to coma (a deep state of unconsciousness), seizures, respiratory depression up to respiratory arrest.
In such cases, seek immediate medical attention!
Missing a dose of Tramal
If you forget to take the medicine at the scheduled time, your pain symptoms may return.
Do not take a double dose to make up for a missed dose.
Resume your usual dosing schedule as prescribed.
Stopping Tramal
If Tramal is stopped suddenly or treatment is prematurely discontinued, pain symptoms are likely to return.
If you wish to discontinue treatment due to side effects, inform your doctor.
Do not stop using this medicine suddenly without your doctor’s advice. If you wish to stop taking Tramal, especially after long-term use, discuss this with your doctor.
Your doctor will advise when and how to stop Tramal treatment; this may involve gradually reducing the dose to minimize the risk of withdrawal symptoms.
Generally, no serious post-treatment symptoms are observed after discontinuation of Tramal.
However, in rare cases, after abrupt discontinuation of Tramal following prolonged use, patients may feel unwell. Symptoms may include restlessness, anxiety, nervousness, tremors, hyperactivity, difficulty sleeping, and gastrointestinal or intestinal disturbances.
Very rarely, the following may occur: panic attacks, hallucinations, abnormal sensations such as itching, tingling, numbness, and tinnitus.
Other rare central nervous system disturbances, such as confusion, delusions, altered perception of self (depersonalization), altered perception of reality (derealization), and persecutory delusions (paranoia), have been reported very rarely.
If any of the above symptoms occur after stopping this medicine, consult your doctor immediately.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should consult a doctor immediately if symptoms of allergic reactions occur, such as:
swelling of the face, tongue and (or) throat and (or) difficulty swallowing or
urticaria associated with breathing difficulties, drop in blood pressure, weakness, fainting
due to life-threatening anaphylactic shock. Allergic reactions are rare

• occurring in 1 to 10 out of 10,000 patients.

The most commonly reported adverse reactions occurring more frequently than in 1 out of 10 people during
treatment with Tramal were nausea and dizziness.
Very common dizziness,
(occurring more frequently than nausea.
in more than 1 in 10 people):
Common headache, drowsiness,
(occurring in 1 to 10 in 100 people): vomiting, constipation, dryness of the oral mucosa,
excessive sweating,
fatigue.
Uncommon cardiac and circulatory disorders (palpitations, rapid
(occurring in 1 to 10 in 1,000 people): heartbeat, feeling of weakness due to reduced blood pressure
in patients changing body position from lying to standing, and collapse). Such adverse reactions may occur
especially after intravenous administration of tramadol pharmaceutical forms, and in patients after physical exertion.
Vomiting reflex, gastrointestinal irritation (feeling of pressure
in the stomach, bloating), diarrhoea,
skin reactions (e.g. itching, rash, urticaria).
Rare bradycardia,
(occurring in 1 to 10 in 10,000 people): increased blood pressure,
changes in appetite,
slow breathing, "shortness of breath" (dyspnoea).
Exacerbation of bronchial asthma has been reported during tramadol treatment,
although a causal relationship between these events has not been established. In case of ingestion of doses significantly higher than recommended,
and concomitant use of other medicines that depress central nervous system function (e.g. sedatives,
sleep-inducing medicines, other analgesics, alcohol),
respiratory depression may occur.
Abnormal perception of stimuli (e.g. itching, tingling, numbness),
tremor, seizures, muscle spasms, uncoordinated movements,
fainting, speech disorders;
Seizures occur mainly after administration of high doses
of tramadol and when other medicines that may provoke seizures are used concomitantly;
Hallucinations, confusion, sleep disturbances, delirium, restlessness and nightmares.
Psychiatric disorders may occur after administration of Tramal. Their severity and type may vary (depending on
the patient's personality and duration of treatment). These may include, for example,
mood disturbances (usually excitement, sometimes irritability),
changes in activity (usually decreased, sometimes increased), and
reduced sensory and cognitive perception (changes in sensations
and recognition which may lead to incorrect assessment of situations).
The medicine may cause dependence.
Withdrawal symptoms may occur if treatment is stopped abruptly (see "Discontinuation of Tramal treatment");
Pupil constriction (miosis), blurred vision, excessive dilation
of pupils (mydriasis),
muscle weakness;
difficulty or pain during urination, reduced urine volume
(urinary retention);
allergic reactions (e.g. difficulty breathing, wheezing,
skin swelling) and shock (sudden circulatory failure);
Very rare increase in liver enzyme activity.
(occurring less frequently than
in 1 in 10,000 people):
Unknown (frequency cannot be estimated from the available data): low blood sugar concentration, hiccups, serotonin syndrome, whose
symptoms may include changes in mental status (e.g. agitation,
hallucinations, coma), as well as other symptoms such as fever,
increased heart rate, unstable blood pressure, involuntary muscle contractions,
muscle rigidity, lack of coordination and (or) gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section
2 "Important information before using Tramal").
Reporting of adverse reactions
If any adverse reactions occur, including any not listed
in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring Adverse Drug Reactions
of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Tramal

Keep this medicine out of sight and reach of children.
This medicine should be stored in a closed and secure place, inaccessible to others. It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
No special storage instructions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What Tramal contains

• The active substance is tramadol hydrochloride. Each 1 ml ampoule of injection solution contains 50 mg of tramadol hydrochloride. Each 2 ml ampoule of injection solution contains 100 mg of tramadol hydrochloride.
• The other ingredients are: sodium acetate trihydrate, water for injections.

What Tramal looks like and contents of the pack
A clear, colourless solution in glass ampoules of 1 or 2 ml, packed in cardboard packaging containing 5 ampoules.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer:
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany
For further information about this medicine, please contact the representative of the Marketing Authorisation Holder:
Stada Pharm Sp. z o.o.
ul. Krakowiaków 44
02-255 Warsaw
Tel. +48 22 737 79 20

Information intended exclusively for healthcare professionals:

Instructions for use of Tramal vials
Tramal medication is supplied in breakable ampoules. These ampoules have a marked break line to facilitate opening:

1. Position the ampoule with the break line facing upwards,
2. Snap off the neck of the ampoule with a downward motion.

Pharmaceutical incompatibilities
Tramal 50 mg/1 ml solution for injection must not be used simultaneously with injectable solutions of diclofenac, indomethacin, phenylbutazone, diazepam, flunitrazepam, midazolam, or glyceryl trinitrate.

Use of Tramal in the treatment of children aged 1 year and older (see section 3).

Estimation of injection volume

1. Estimate total dose of tramadol hydrochloride (mg): body weight (kg) × dose (mg/kg b.w.)
2. Estimate the volume (ml) of diluted solution to be injected: divide the total dose (mg) by the appropriate concentration of the diluted solution (mg/ml; see table below).

Table: Dilution of the medicinal product Tramal 50 mg/1 ml, solution for injection

According to the calculations, dilute the contents of the Tramal vial by adding an appropriate diluent, mix, and administer the calculated volume of the diluted solution. Any unused portion of the solution must be discarded.
Example
If the physician has prescribed a dose of 1.5 mg hydrochloride tramadol/kg body weight for a child weighing 27 kg, the total required dose is 27 kg × 1.5 mg/kg = 40.5 mg hydrochloride tramadol.
An appropriate concentration of the diluted solution is 10.0 mg/ml, corresponding to approximately 4 ml (40.5 mg / 10 mg/ml = 4.05 ml) of the diluted solution volume.
Accordingly, to obtain a solution with a concentration of 10.0 mg/ml, add 1 ml of Tramal 50 mg/1 ml injection solution (1 vial containing 1 ml solution with 50 mg) to 4 ml of 0.9% NaCl or 5% glucose solution.
Administer 4 ml of the diluted solution containing 40 mg hydrochloride tramadol.