Poltram combo

Patient Information Leaflet

Poltram Combo
37.5 mg + 325 mg, film-coated tablets
Tramadoli hydrochloridum + Paracetamolum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

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

Table of Contents

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

1. What Poltram Combo is and what it is used for

Poltram Combo is a combination of two analgesic medicines, tramadol and paracetamol, which work together to relieve pain.
Poltram Combo is used to treat moderate to severe pain, when in the opinion of the doctor it is necessary to use a combination of tramadol and paracetamol.
Poltram Combo may be used in adults and adolescents aged 12 years and older.

2. Important information before taking Poltram Combo

When not to take Poltram Combo

• if the patient is allergic to paracetamol, tramadol, or any of the other ingredients of this medicine (listed in section 6)
• if the patient abuses alcohol
• in case of acute alcohol intoxication
• if the patient is taking any medicines that may cause drowsiness or reduced attention; including opioids (painkillers), such as morphine and codeine, or other psychotropic medicines (medicines affecting mood and emotions)
• if the patient is currently taking or has taken monoamine oxidase inhibitors (MAOIs) (medicines used to treat depression or Parkinson's disease) within the last 14 days before starting treatment with Poltram Combo
• in case of severe liver disease
• if epilepsy is present and is not properly controlled with prescribed antiepileptic medicines.

Warnings and precautions
Before taking Poltram Combo, discuss with a doctor if:

• the patient is taking other medicines containing paracetamol or tramadol
• there are liver disorders or liver disease, or if the patient notices yellowing of the eyes or skin. This may indicate jaundice or biliary tract disorders.
• there are kidney disorders
• there are respiratory disorders, such as asthma or severe lung diseases
• there is epilepsy or a history of seizures
• the patient has recently suffered a head injury, concussion, or severe headaches, with or without vomiting
• the patient has depression and is taking antidepressants, as some of them may interact with tramadol (see "Poltram Combo and other medicines")
• the patient is dependent on any medicines, including painkillers (used to treat moderate or severe pain), such as morphine
• the patient is taking painkillers containing buprenorphine, nalbuphine, or pentazocine
• the patient is due to undergo anaesthesia. Inform the doctor or dentist about taking Poltram Combo.

If the patient suffers from severe conditions, including severe kidney dysfunction, sepsis
(when bacteria and their toxins circulate in the blood, leading to organ damage), malnutrition,
chronic alcoholism, or if the patient is also taking flucloxacillin (an antibiotic),
serious adverse effects may occur. Cases of a severe condition called metabolic acidosis
(a disturbance in blood and body fluid balance) have been reported in patients taking paracetamol regularly
for a prolonged period or when paracetamol is taken together with flucloxacillin. Symptoms of metabolic
acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea, and vomiting.

When tramadol is taken together with certain antidepressants or tramadol alone, there is a small risk of a condition called serotonin syndrome. If the patient experiences any symptoms of this serious syndrome, immediate medical advice should be sought (see section 4 "Possible side effects").

Tolerance, dependence, and addiction
This medicine contains tramadol, which is an opioid medicine. Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient becomes accustomed to the medicine, known as tolerance). Repeated use of Poltram Combo may also lead to dependence, misuse, and addiction, which may result in life-threatening overdose.
The risk of these adverse effects may increase with higher doses and prolonged use.
Dependence may cause the patient to lose control over the dose or frequency of medicine intake.
The risk of dependence varies among individuals. The risk of dependence on Poltram Combo may be higher if:

• the patient or a family member has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs ("addiction");
• the patient smokes tobacco or uses nicotine-containing products;
• the patient has ever had mood disorders (depression, anxiety, or personality disorders) or has been treated by a psychiatrist for other mental illnesses.

If any of the following symptoms occur during treatment with Poltram Combo, this may indicate dependence:

• the patient needs to take the medicine longer than prescribed by the doctor
• the patient needs to take a higher dose than recommended
• the patient takes the medicine for reasons other than prescribed, e.g., "to calm down" or "to help sleep"
• the patient has made repeated unsuccessful attempts to stop or control medicine use
• after stopping the medicine, the patient feels unwell and feels better after taking the medicine again ("withdrawal effects")

If any of these symptoms occur, consult a doctor to discuss the best treatment approach, including when and how to discontinue the medicine safely (see section 3 "Discontinuing Poltram Combo").

Sleep-related breathing disorders
Poltram Combo may cause sleep-related breathing disorders, such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels). Symptoms may include breathing pauses during sleep, nocturnal awakenings due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If the patient or caregiver observes these symptoms, contact a doctor. The doctor may recommend reducing the dose.

If any of the following symptoms occur during treatment with Poltram Combo, inform the doctor or pharmacist:

• excessive fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These may indicate adrenal insufficiency (low cortisol levels). If such symptoms occur, contact a doctor, who will decide whether hormone replacement is necessary.

Tramadol is metabolized in the liver by an enzyme. Some individuals have a genetic variation of this enzyme, which may lead to different effects. In some people, pain relief may be insufficient, while in others, severe adverse effects are more likely.
Discontinue the medicine and contact a doctor immediately if any of the following adverse effects occur: slow or shallow breathing, confusion, drowsiness, pinpoint pupils, nausea or vomiting, constipation, or loss of appetite.

If any of the above conditions have occurred in the patient's past or occur during treatment with Poltram Combo, ensure the doctor is informed. The doctor will decide whether the patient can continue taking this medicine.

Children and adolescents
Use in children with respiratory disorders
Tramadol is not recommended in children with respiratory disorders, as tramadol toxicity symptoms may be more pronounced in this group.

Poltram Combo and other medicines
Inform the doctor or pharmacist about all medicines currently taken, recently taken, or planned for use.

Important: Poltram Combo contains paracetamol and tramadol. Inform the doctor about taking any other medicines containing paracetamol or tramadol (including over-the-counter medicines), as the maximum daily doses must not be exceeded.

Poltram Combo must not be taken together with the following medicines:

• monoamine oxidase inhibitors (MAOIs) or within 2 weeks after stopping them (see section "When not to take Poltram Combo")
• opioids (painkillers), such as morphine and codeine.

Concomitant use of Poltram Combo with the following medicines is not recommended:

• carbamazepine (usually used to treat epilepsy or severe facial pain known as trigeminal neuralgia)
• buprenorphine, nalbuphine, pentazocine (opioid painkillers). The analgesic effect may be reduced.

The risk of adverse effects increases when Poltram Combo is taken together with:

• certain antidepressants – Poltram Combo may interact with them and cause serotonin syndrome (see section 4 "Possible side effects")
• gabapentin or pregabalin used in the treatment of epilepsy or nerve-related pain (neuropathic pain)
• sedatives, hypnotics, other painkillers such as morphine or codeine (also used as cough suppressants), baclofen (a muscle relaxant), antihypertensives, antidepressants, or antihistamines used for allergies. Drowsiness or faintness may occur. Inform the doctor if such symptoms occur.
• other medicines that may cause seizures (fits), such as certain antidepressants or antipsychotics. The risk of seizures may increase if Poltram Combo is taken together with these medicines. The doctor should inform the patient whether Poltram Combo is suitable.
• derivatives of warfarin or phenprocoumon (used to thin the blood). The effect of these medicines may be altered, leading to bleeding. Any prolonged or unexpected bleeding should be reported to the doctor immediately.
• flucloxacillin (an antibiotic) due to a serious risk of blood and body fluid disturbances (called metabolic acidosis), which require urgent treatment (see section 2).

The effectiveness of Poltram Combo may be reduced when taken together with:

• metoclopramide, domperidone, or ondansetron (medicines used to treat nausea and vomiting)
• cholestyramine (used to lower blood cholesterol)
• ketoconazole or erythromycin (medicines used to treat infections).

The doctor will advise which medicines can be safely used with Poltram Combo.

Concomitant use of Poltram Combo and sedative medicines, such as benzodiazepines or similar drugs, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and potentially life-threatening outcomes. Therefore, such combination should only be considered if no other treatment options are available.

If the doctor prescribes Poltram Combo together with sedative medicines, the dose and duration of concomitant use should be minimized.

Inform the doctor about all sedative medicines being taken and strictly follow the doctor's dosing instructions. It may be helpful to inform family members or friends about the above-mentioned symptoms. Contact the doctor immediately if such symptoms occur.

Poltram Combo with food, drink, and alcohol
Poltram Combo may cause drowsiness. Since alcohol may also cause drowsiness, alcohol must not be consumed and medicines containing alcohol should not be taken during treatment with Poltram Combo.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor before using this medicine.

Because Poltram Combo contains tramadol, it must not be used during pregnancy. If the patient becomes pregnant while taking the medicine, she should contact her doctor before taking further tablets.

Tramadol is excreted in breast milk. Therefore, Poltram Combo should not be taken more than once during breastfeeding. Alternatively, if the patient needs to take Poltram Combo more than once, breastfeeding should be discontinued.

Driving and operating machinery
Poltram Combo may cause drowsiness, dizziness, or visual disturbances.
Do not drive, operate machinery, or perform any activities requiring alertness until the patient knows how Poltram Combo affects them.

Poltram Combo contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., it is considered "sodium-free".

3. How to take Poltram Combo

This medicine should always be taken as directed by the 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 taking Poltram Combo, when and for how long it should be taken, when
you should contact your doctor, and when the medicine should be discontinued (see also section 2).
The dose should be adjusted according to the intensity of pain and the individual patient's response to treatment.
The lowest effective dose for pain relief should be used.
Poltram Combo should be taken for as short a duration as possible.
Use in children under 12 years of age is not recommended.
Unless otherwise directed by the doctor, the usual dose for adults and adolescents aged 12 years and older
is 2 tablets. If necessary, further doses may be taken as directed by the doctor. The minimum
interval between doses must be 6 hours.
Do not take more than 8 tablets per day.
Do not take the medicine more frequently than directed by your doctor.

Elderly patients
In patients over 75 years of age, tramadol elimination from the body may be delayed. In such
patients, the doctor may recommend extending the time interval between doses.

Patients with renal impairment, undergoing dialysis, or with hepatic impairment
Poltram Combo should not be taken in cases of severe hepatic and/or renal impairment. In cases of mild or moderate impairment, the doctor may recommend extending the intervals between doses.

Method of administration
The tablets are for oral use.
The tablets should be swallowed whole with sufficient liquid. Do not crush or chew the tablets.
If you feel the medicine's effect is too strong (e.g. excessive drowsiness or breathing disturbances) or too weak (e.g. incomplete pain relief), contact your doctor.

Overdose of Poltram Combo
If you take more than the recommended dose, contact your doctor immediately, even if you feel well.
There is a risk of serious liver damage, the symptoms of which may appear later.
In case of tramadol overdose, symptoms may include pinpoint pupils, vomiting,
low blood pressure, rapid heartbeat, fainting, disturbances of consciousness up to coma (a state of deep unconsciousness), seizures, breathing difficulties up to respiratory arrest.
Paracetamol overdose is dangerous and may cause severe liver and kidney damage.

Missed dose of Poltram Combo
If you miss a dose, pain will likely return.
Do not take a double dose to make up for a missed dose. Simply resume taking the medicine as before.

Stopping Poltram Combo
Do not suddenly stop taking this medicine without medical advice. If you wish to discontinue
treatment, discuss this with your doctor, especially if the medicine has been taken for a long time.
Your doctor will advise when and how to stop taking the medicine; this may involve gradually reducing the dose
to reduce the likelihood of withdrawal symptoms. If Poltram Combo is stopped abruptly,
you may feel unwell. Symptoms may include anxiety, agitation, nervousness, insomnia,
hyperactivity, tremor, and/or gastrointestinal disturbances.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
Adverse effects are classified according to the following frequency of occurrence:
Very common (occur in more than 1 in 10 patients)
Common (occur in less than 1 in 10 patients)
Uncommon (occur in less than 1 in 100 patients)
Rare (occur in less than 1 in 1,000 patients)
Very rare (occur in less than 1 in 10,000 patients)
Frequency not known (cannot be estimated from available data)

Very common

• nausea
• dizziness, drowsiness – usually mild in severity.

Common

• vomiting, gastrointestinal disturbances (constipation, bloating, diarrhoea), abdominal pain, dry mouth
• itching, excessive sweating
• headache, tremor
• disorientation, sleep disturbances, mood disturbances (anxiety, nervousness, feeling of restlessness).

Uncommon

• increased blood pressure, rapid or irregular heartbeat
• difficulty or pain during urination, presence of protein in urine
• skin reactions (e.g. rash, urticaria)
• tingling, numbness or prickling sensation in limbs
• ringing in the ears
• involuntary muscle tremor
• depression, nightmares, hallucinations (seeing, hearing or feeling things that are not there)
• memory loss
• difficulty swallowing
• presence of blood in stool
• tremor
• hot flushes
• chest pain
• breathing difficulties
• increased liver enzyme levels.

Rare

• seizures, coordination difficulties, fainting
• dependence
• blurred vision.

Frequency not known

• decreased blood sugar levels
• hiccups.

The following adverse effects have been reported in patients taking only paracetamol or only tramadol. However, you should inform your doctor if they occur during treatment with Poltram Combo:

• feeling faint when standing up from a lying or sitting position, slow heartbeat, fainting, changes in appetite, muscle weakness, slower or shallower breathing, mood changes, changes in activity, sensory disturbances, worsening of asthma symptoms.
• in rare cases, rash indicating an allergic reaction, with sudden swelling of the face and neck, breathing difficulties or drop in blood pressure and fainting. If these occur, treatment must be discontinued and you should seek immediate medical advice. The medicine must not be taken again.
• frequency not known: serotonin syndrome, which may present with changes in mental state (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 taking Poltram Combo"); a serious condition that may cause acidification of the blood (so-called metabolic acidosis) in patients with severe disease taking paracetamol (see section 2).

In rare cases, use of medicines such as tramadol may lead to dependence, which may make it difficult to stop taking the medicine.
In patients who have been taking the medicine for some time, withdrawal symptoms may rarely occur after abrupt discontinuation of treatment. These may include: restlessness, anxiety, nervousness and tremor. Patients may become hyperactive, experience sleep disturbances, or have stomach or intestinal complaints. Very rarely, panic attacks, hallucinations, or unusual sensations such as skin itching, tingling and numbness, or ringing in the ears may occur. If such adverse effects occur after stopping the medicine, contact your doctor.
In exceptional cases, patients treated with tramadol have developed changes in blood composition, for example low platelet count, which may cause nosebleeds and bruising, or absence of certain types of white blood cells (agranulocytosis), leading to infection, sore throat or fever.
Concurrent use of Poltram Combo with anticoagulant medicines (e.g. phenprocoumon, warfarin) may increase the risk of bleeding. Any unexpected or prolonged bleeding should be reported to your doctor immediately.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department for Monitoring Adverse Drug Reactions, 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 effects can also be reported to the marketing authorisation holder.
By reporting adverse effects, additional information on the safety of the medicine can be collected.

5. How to store Poltram Combo

Keep this medicine out of sight and reach of children.
Keep this medicine in a safe place where others cannot access it. It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
There are no special storage requirements for this medicine.
Do not use this medicine after the expiry date stated on the carton and blister pack following EXP.
The expiry date refers to the last day of the stated month.
The label on the packaging indicates the expiry date after the abbreviation EXP, and the batch number after the abbreviation Lot/LOT.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the package and other information

What Poltram Combo contains

• The active substances are tramadol hydrochloride and paracetamol. Each tablet contains 37.5 mg of tramadol hydrochloride and 325 mg of paracetamol.
• Other components are:
  Tablet core: pregelatinized starch, corn starch, microcrystalline cellulose, sodium carboxymethyl starch (Type A), colloidal anhydrous silica, magnesium stearate.
  Tablet coating: hypromellose (6 mPa·s), polyethylene glycol 400, titanium dioxide (E171), yellow iron oxide (E172).

What Poltram Combo looks like and contents of the pack
The tablets are light yellow, oblong, biconvex (16.5 mm in length).
The tablets are packed in blisters. One package contains 10, 20, 30, 60 or 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01

Information intended exclusively for healthcare professionals:

Poltram Combo is a combination medicinal product. Symptoms of overdose may result from the toxic effects of its active substances: tramadol, paracetamol, or both components simultaneously.

Symptoms of tramadol overdose
Symptoms of tramadol poisoning are generally similar to those of other centrally-acting analgesics. These include: miosis (pupillary constriction), vomiting, circulatory collapse, disturbances of consciousness up to coma, seizures, and respiratory depression progressing to respiratory arrest.

Symptoms of paracetamol overdose
Overdose is particularly dangerous in young children. Symptoms occurring within the first 24 hours include pallor, nausea, vomiting, anorexia, and abdominal pain. Hepatic damage may occur between 12 and 48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may also develop. In severe poisoning, liver failure may progress to encephalopathy, coma, and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.

Hepatic injury is possible in adults who have ingested 7.5–10 g or more of paracetamol. It is believed that excessive amounts of a toxic metabolite (normally safely detoxified by glutathione following therapeutic doses of paracetamol) bind irreversibly to liver tissue.

Emergency treatment

• Immediately transfer the patient to a specialized medical facility.
• Maintain respiratory and circulatory functions.
• As soon as possible after overdose and before initiating treatment, collect blood samples to determine serum concentrations of paracetamol and tramadol, as well as to perform liver function tests.
• Perform liver function tests initially (at baseline) and repeat every 24 hours. Typically, increased liver enzyme activity (AlAT, AspAT) is observed, normalizing within 1 or 2 weeks.
• Empty the stomach by inducing vomiting (in conscious patients) or by performing gastric lavage.
• Provide supportive treatment: maintain airway patency and support cardiovascular function; administer naloxone to reverse respiratory depression; prevent seizures with diazepam.
• Tramadol is only minimally eliminated from the blood by hemodialysis or hemofiltration. Therefore, hemodialysis or hemofiltration cannot be used as the sole treatment method for acute tramadol poisoning.

Immediate initiation of treatment is particularly important in cases of paracetamol overdose. Despite the lack of significant early symptoms, patients should be immediately transferred to hospital for observation. Gastric lavage should be performed in all adults and adolescents who have ingested approximately 7.5 g or more of paracetamol within the last 4 hours, as well as in children who have ingested ≥150 mg/kg of paracetamol within the last 4 hours. Serum paracetamol concentration should be measured no later than 4 hours after ingestion to assess the risk of hepatotoxicity (using the paracetamol overdose nomogram). Oral methionine or intravenous N-acetylcysteine may be administered and may be beneficial up to 48 hours after overdose. The greatest benefit is achieved when intravenous N-acetylcysteine is initiated within 8 hours of overdose.

However, N-acetylcysteine should be administered even when more than 8 hours have elapsed since overdose and should be continued throughout the treatment period. N-acetylcysteine should be administered immediately whenever acute paracetamol overdose is suspected. General supportive treatment measures must be readily available.

Regardless of the reported amount of ingested paracetamol, the antidote for paracetamol—N-acetylcysteine—should be administered orally or intravenously as soon as possible, preferably within 8 hours of overdose.