Tradorec XL 200 mg prolonged-release tablets - Summary of Product Characteristics (SPC) (2023)

Tradorec XL200 mg delayed pills

RMS drug name: Monotramal L.P. Once a day

One extended-release tablet contains 200 mg of tramadol hydrochloride.

For the complete list of excipients, see section 6.1.

retard pill.

White to off-white, flat, round, biconvex tablet with beveled edges

Dose

The dose must be adjusted to the intensity of pain and sensitivity of each patient. In general, the lowest effective dose for analgesia should be chosen.

Adults and teenagers (from 12 years old):

The starting dose is one 100 mg prolonged-release tablet once daily. The usual dose is one 200 mg prolonged-release tablet once a day, preferably in the evening. If this does not provide adequate pain relief, the dose can be increased in 100 mg increments up to 300 mg or up to a maximum of 400 mg once daily.

Except in special clinical cases, the daily dose of 400 mg of tramadol should not be exceeded.

Tradorec XLmust not be used for longer than absolutely necessary. If the nature and severity of the disease requires continued pain control, careful periodic monitoring (including periods of inactivity, if applicable) should be performed to determine the need for continued treatment.

Children (under 12 years old):

Tradorec XLIt is not recommended for the treatment of children (under 12 years old).

Geriatric patients:

In patients up to 75 years of age without clinically apparent renal or hepatic impairment, no dose adjustment is generally required. Elimination may be prolonged in elderly patients over 75 years of age. Therefore, it may be necessary to extend the administration interval according to the patient's needs.

Kidney failure, dialysis and liver failure:

Tramadol elimination is delayed in patients with renal and/or hepatic impairment. In these patients, extending the dosing intervals should be carefully considered according to the patient's needs.

Tradorec XLit is not recommended in patients with severe hepatic impairment or severe renal impairment (creatinine clearance < 10 ml/min, see section 4.3). Caution is advised in patients with moderate hepatic or renal impairment (creatinine clearance < 30 ml/min) (see section 4.5).

type of administration

Tablets should be swallowed whole with plenty of liquid and not broken or chewed. The tablets can be taken with or without food.

Alternative tablet strengthsTradorec XLare available. If necessary, tablets with suitable strengths should be used to reach the required dose.

Tradorec XLmust be taken once every 24 hours

Known hypersensitivity to tramadol or any of the excipients.

Acute intoxication or overdose with CNS depressants (alcohol, hypnotics, other opioid analgesics, etc.).

Patients concomitantly treated with MAO inhibitors or who have been treated with MAO inhibitors within the last 2 weeks (see section 4.5).

Severe hepatic or renal impairment (creatinine clearance < 10 ml/min).

Epilepsy not adequately controlled by treatment. (See section 4.4).

Tramadol should not be used during breast-feeding if prolonged treatment is required (see section 4.6).

Consumption of alcohol is not recommended during treatment with tramadol. Concomitant treatment with carbamazepine is not recommended (see section 4.5).

Notices:

Tolerance and psychological and physical dependence may develop, especially after prolonged use. At therapeutic doses, withdrawal symptoms were reported with a frequency of 1 in 8000, while reports of dependence and abuse were less common.

Due to the potential for dependence or withdrawal to occur, the clinical need for continued analgesia should be periodically reassessed. In patients prone to drug abuse or dependence, tramadol should only be used for short periods under close medical supervision.

When a patient no longer requires tramadol therapy, it may be advisable to gradually reduce the dose to prevent withdrawal symptoms.

Tramadol is not suitable as a substitute for opioid-dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms.

Respiratory depression or patient using CNS depressants:

Caution should be exercised when administering tramadol to patients at risk of respiratory depression or who are receiving medications that may cause respiratory depression.

Sleep-related breathing disorders

Opioids can cause sleep-related breathing disorders such as central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent manner. Reduction of total opioid dose should be considered in patients with CSA.

adrenal insufficiency

Opioid analgesics can occasionally cause reversible adrenal insufficiency, requiring monitoring and glucocorticoid replacement therapy. Symptoms of acute or chronic adrenal insufficiency can, for example, be severe abdominal pain, nausea and vomiting, low blood pressure, extreme tiredness, decreased appetite and weight loss.

serotonin syndrome

Serotonin syndrome, a life-threatening condition, has been reported in patients receiving tramadol in combination with other serotonergic agents or tramadol alone (see sections 4.5, 4.8 and 4.9).

When concomitant treatment with other serotonergic agents is clinically warranted, careful monitoring of the patient is recommended, particularly during treatment initiation and dose increases.

Symptoms of serotonin syndrome may include mental status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.

If serotonin syndrome is suspected, consideration should be given to reducing the dose or discontinuing treatment, depending on the severity of the symptoms. Discontinuation of serotonergic medication usually brings about rapid improvement.

Precautions:

Tramadol should be used with caution in patients with head trauma, increased intracranial pressure, liver or kidney failure, in patients in shock, altered state of consciousness (without obvious cause), diseases of the respiratory center or respiratory dysfunction, as well as in patients with diabetes due to the appearance of hypoglycemia under tramadol.

There is an increased risk of seizures if the dose of tramadol exceeds the maximum recommended daily dose (400 mg). Convulsions have been reported at therapeutic doses. Patients with controlled epilepsy or patients at known risk of seizures should not be treated with tramadol unless absolutely necessary. There is an increased risk of seizures in patients concomitantly taking medicinal products that lower the seizure threshold (see section 4.5).

metabolismo CYP2D6

Tramadol is metabolised by the liver enzyme CYP2D6. If a patient has a deficiency or complete absence of this enzyme, an adequate analgesic effect may not be obtained. It is estimated that up to 7% of the Caucasian population may suffer from this deficiency. However, if the patient is an ultra-rapid metabolizer, there is a risk of developing opioid toxicity side effects even at commonly prescribed doses.

Common symptoms of opioid toxicity include confusion, drowsiness, shallow breathing, small pupils, nausea, vomiting, constipation, and loss of appetite. In severe cases, this can include symptoms of circulatory and respiratory depression, which can be life-threatening and very rarely fatal. Estimates of the prevalence of ultra-extensive metabolizers in different populations are summarized below:

Postoperative use in children

Postoperative administration of tramadol in children undergoing tonsillectomy and/or adenoidectomy for obstructive sleep apnea has been reported in the published literature to result in rare but potentially fatal adverse events. Extreme caution should be exercised when tramadol is given to children for the relief of postoperative pain and close monitoring should be undertaken for symptoms of opioid toxicity, including respiratory depression.

Children with respiratory failure

Tramadol is not recommended for use in children who may have compromised respiratory function, including neuromuscular disease, severe heart or respiratory disease, lung or upper respiratory tract infections, multiple trauma, or extensive surgery. These factors can worsen the symptoms of opioid toxicity.

Concomitant medications contraindicated during treatment with tramadol

Tramadol should not be used in combination with selective or non-selective MAO inhibitors. (see Section 4.3).

Concomitant medication is not recommended during treatment with tramadol

Mixed agonist-antagonists (buprenorphine, nalbuphine and pentazocine): Concomitant treatment with tramadol is not recommended, as it could theoretically reduce the analgesic effect of the pure agonist due to competitive receptor blockade, which could lead to the risk of onset of withdrawal symptoms .

Alcohol: Alcohol enhances the sedative effects of opioid analgesics. The resulting drowsiness can be dangerous when driving or operating machinery. Alcoholic beverages and medicines containing alcohol must not be consumed during treatment with tramadol (see section 4.7).

Carbamazepine (enzyme inducer): Possibility of reducing plasma concentrations of tramadol and its pharmacologically active metabolite, leading to reduced analgesic effect.

Naltrexone: Using tramadol together with naltrexone may reduce the analgesic effect. If necessary, the analgesic dose can be increased.

Concomitant medications that should be used with caution during tramadol treatment

Other morphine derivatives (including antitussives and substitution treatments) Benzodiazepines, barbiturates: Great risk of respiratory depression, which can be fatal in case of overdose.

Other CNS depressants: opioid analgesics, barbiturates, benzodiazepines, sedative antidepressants, sedative H1 antihistamines, non-benzodiazepine anxiolytics, hypnotics, neuroleptics, centrally acting antihypertensives, thalidomide, baclofen: increased risk of central nervous system depression. The resulting deterioration in reaction time can make driving and operating machinery dangerous.

Tramadol can induce seizures and increase the potential of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics, and other medications used to lower the seizure threshold (such as bupropion, mirtazapine, tetrahydrocannabinol) to cause seizures.

Concomitant therapeutic use of tramadol and serotonergic drugs such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), MAOIs (see section 4.3), tricyclic antidepressants and mirtazapine may cause a serotonin syndrome with life-threatening (see sections 4.4 and 4.8) Venlafaxine: Risk of seizures

Caution should be exercised during concomitant treatment with tramadol and coumarin derivatives (eg warfarin) due to reports of increased INR and ecchymosis in some patients.

Fertility:

Fertility studies have not been performed.Tradorec XL.

the pregnancy:

Tramadol should not be used during pregnancy unless absolutely necessary. There are not enough human data to adequately assess the safety of tramadol use in pregnant women.

As with other opioid pain relievers:

- Tramadol crosses the placenta.

- Chronic use of tramadol, at any dose, may induce withdrawal syndrome in newborns.

- At the end of pregnancy, high doses, even with short-term treatments, can cause respiratory depression in the newborn.

Animal studies have not shown teratogenic effects, but foetotoxicity has occurred due to maternal toxicity at high doses (see section 5.3).

breast-feeding:

Approximately 0.1% of the maternal dose of tramadol is excreted in breast milk. In the immediate postpartum period, with a daily maternal oral dose of up to 400 mg, this corresponds to an average amount of tramadol ingested by the infant at 3% of the dose adjusted for maternal weight. For this reason, tramadol should not be used during lactation or, alternatively, breast-feeding should be discontinued during treatment with tramadol. It is usually not necessary to stop breastfeeding after a single dose of tramadol. If prolonged treatment is required after delivery, breastfeeding is contraindicated (see section 4.3).

Tramadol may cause dizziness and/or drowsiness and, even when used as directed, influences the ability to drive and use machines. This effect may occur early in treatment and may be exacerbated by alcohol and concomitant use of other CNS depressants or antihistamines. If patients are affected, they should be advised not to drive or use machines.

This medication may impair cognitive function and affect the patient's ability to drive. This class of drugs is included in the list of drugs contained in Section 5a Regulations of the Road Traffic Act 1988. When prescribing this drug, patients should be informed of:

- The medicine may affect your ability to drive

- Do not drive until you know how the medicine affects you

- It is an offense to drive while under the influence of this medication.

- However, you do not commit a crime (the so-called "legal defense") if:

The most frequently reported side effects, nausea and dizziness, were seen in more than 10% of patients.

The frequencies are defined as follows:

immune system disorders

Rare: allergic reactions (eg dyspnoea, bronchospasm, wheezing, angioedema) and anaphylactic reaction

Metabolic and nutritional disorders

Rare: loss of appetite

Frequency not known: hypoglycaemia.

Mental problems

Rare: hallucinations, confused state, sleep disturbances, nightmares, anxiety, delirium.

After administration of tramadol, in rare cases, various psychiatric disorders Side effects may occur, the nature and severity of which vary from patient to patient (depending on individual reactivity and duration of treatment). Disturbances in well-being (generally euphoria, occasionally dysphoria), changes in activity (generally reduced, occasionally increased), and altered cognitive and sensory abilities (eg, decision-making ability, perceptual disturbances) may be observed. Addiction may occur.

Drug withdrawal symptoms similar to those seen with opioid withdrawal may occur, including agitation, anxiety, nervousness, insomnia, hyperkinesia, tremors, and gastrointestinal symptoms. Other withdrawal symptoms have also been reported, including: panic attacks, severe anxiety, hallucinations, paraesthesia, tinnitus and other CNS problems.

nervous system diseases

Very common: dizziness.

Common: headache, drowsiness

Rare: paraesthesia, tremors, convulsions.

Frequency not known: serotonin syndrome

Seizures occurred mainly after administration of high doses of tramadol or concomitant treatment with drugs that lower the seizure threshold or induce seizures. (See sections 4.4 and 4.5).

eye diseases

Rare: blurred vision, miosis.

heart diseases

Uncommon: effects on cardiovascular regulation (palpitations, tachycardia). These side effects occur mainly after intravenous administration and during physical exertion.

Rare: bradycardia

vascular diseases

Uncommon: effects on cardiovascular regulation (orthostatic hypotension or circulatory collapse). These side effects occur mainly after intravenous administration and during physical exertion.

Respiratory, thoracic and mediastinal disorders

Rare: respiratory depression

Respiratory depression may occur when administered amounts significantly exceed recommended doses and in case of concomitant administration of other CNS depressant medicinal products. (See section 4.5).

Unknown: hiccup

Worsening of asthma has been reported, although a causal relationship has not been established.

gastrointestinal problems

Very common: nausea.

Common: vomiting, constipation, dry mouth.

Uncommon: Irritation of the gastrointestinal tract (abdominal discomfort, flatulence).

Liver and biliary diseases

In some isolated cases, increased liver enzymes have been reported during therapeutic use of tramadol.

Diseases of the skin and subcutaneous tissue

Common: hyperhidrosis.

Uncommon: Skin reaction (eg pruritus, rash, hives).

Diseases of the musculoskeletal system and connective tissue

Rare: muscle weakness.

Kidney and urinary tract diseases

Rare: micturition disorders (dysuria and urinary retention).

General disturbances and administrative conditions of the website

Common: tiredness

to look for

Rare: increased blood pressure

Report suspected side effects

It is important to report suspected side effects after drug approval. Allows continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard

symptoms

In principle, the same symptoms occur with tramadol intoxication as with all other centrally acting analgesics (opioids). These include in particular miosis, vomiting, cardiovascular collapse, unconsciousness to coma, convulsions, respiratory depression to respiratory failure.

Serotonin syndrome has also been reported.

Treatment

General emergency procedures apply: including maintenance of respiratory and cardiovascular function.

Stomach emptying by vomiting (conscious patient) or by pumping the stomach. Gastric lavage may be considered if an overdose has been ingested recently. This should not delay (repeat) the administration of activated charcoal to prevent absorption of tramadol. The antidote for respiratory depression is naloxone. There is a risk of increased cramping when using naloxone. In animal studies, naloxone has been shown to be ineffective against seizures. In this case, diazepam must be administered intravenously.

Tramadol is minimally removed from plasma by hemodialysis or hemofiltration. Therefore, treatment of an acute tramadol overdose with hemodialysis or hemofiltration alone is not an adequate route to detoxification.

Pharmacotherapeutic group: analgesics, other opioids

ATC code: N02A X02

Tramadol is a centrally acting analgesic. It is a pure, non-selective µ, delta and k-morphine receptor agonist with the highest affinity for µ receptors. Other mechanisms responsible for the product's analgesic effects include inhibition of neuronal norepinephrine reuptake and increased serotonin release.

Tramadol has an antitussive effect. Unlike morphine, the analgesic tramadol does not have a respiratory depressant effect in many areas. It also has no effect on gastrointestinal motility. The effects on the cardiovascular system are quite small. Tramadol is 1/10 to 1/6 as potent as morphine.

pediatric population

The effects of enteral and parenteral administration of tramadol have been studied in clinical trials involving over 2000 pediatric patients from newborns to 17 years of age. Indications for pain management examined in these studies included pain after surgery (mainly abdominal pain), after surgical tooth extraction, due to fractures, burns and trauma, and other painful conditions likely to require analgesic treatment for at least 7 days.

In single doses of up to 2 mg/kg or multiple doses of up to 8 mg/kg per day (up to a maximum of 400 mg per day), the efficacy of tramadol has been shown to be superior to placebo and greater than or equal to that of paracetamol. . low-dose nalbuphine, pethidine, or morphine. The studies carried out confirmed the effectiveness of tramadol. The safety profile of tramadol was similar in adult and pediatric patients over 1 year (see section 4.2).

After single dose oral administrationTradorec XLit is almost completely resorbed (>90%).

Absolute bioavailability is approximately 70% regardless of food intake. The difference between absorbed and unmetabolized available tramadol is likely due to a poor first-pass effect. The first-pass effect after oral administration is a maximum of 30%.

Tramadol has a high tissue affinity (volume of distribution = 203 ± 40 liters). About 20% is bound to plasma proteins.

After administration of a single dose of 200 mgTradorec XLextended-release tablet, a mean maximum plasma concentration (Cmax) of 241 ± 62 ng/mL is reached after a mean fasting time (tmax) of 6.0 hours.

Tramadol crosses the blood-brain barrier and the placenta. Very small amounts of the active substance and its O-demethylated derivative have been found in breast milk (0.1% and 0.02% of the administered dose, respectively).

The elimination half-life is approximately 6 hours, regardless of the route of administration. In patients older than 75 years, the half-life can be increased by a factor of approximately 1.4.

In humans, tramadol is extensively metabolized by N- and O-demethylation and by conjugation of O-demethylation products with glucuronic acid. Only the metabolite O-desmethyltramadol is pharmacologically active. Significant inter-individual quantitative differences were observed between the other metabolites: to date, 11 different metabolites have been identified in urine. Animal experiments have shown that O-desmethyltramadol is 2 to 4 times more effective than the parent molecule. Its half-life (6 healthy subjects) is 7.9 hours (range 5.4 to 9.6 hours), similar to that of tramadol.

Inhibition of cytochrome CYP3A4 and/or CYP2D6, the isoenzymes responsible for biotransformation of tramadol, may alter plasma concentrations of tramadol or its active metabolite. Tramadol and its metabolites are almost completely excreted in the urine. Cumulative urinary excretion represents 90% of the total radioactivity of the administered dose. If liver or kidney function is impaired, the half-life may be slightly longer. In patients with liver cirrhosis, an elimination half-life of 13.3 ± 4.9 hours (tramadol) and 18.5 ± 9.4 hours (O-desmethyltramadol) was observed, with an extreme case of half-lives of elimination of 22.3 and 36 hours, respectively. In renal insufficiency (creatinine clearance < 5 mL/min), elimination half-lives of 11 ± 3.2 and 16.9 ± 3 hours, respectively, with an extreme case of 19.5 and 43.2 hours , respectively.Tradorec XLexhibits a linear pharmacokinetic profile within the recommended therapeutic dosage regimen.

The relationship between serum concentration and analgesic effect is dose-dependent but varies considerably between individuals. A serum concentration of 100 ng/ml to 300 ng/ml is usually effective.

pediatric population

The pharmacokinetics of tramadol and O-desmethyltramadol following single and multiple oral doses in subjects 1 to 16 years of age when dose adjusted for body weight were generally similar to those in adults, but with greater between-subject variability in children. . And below.

In children less than 1 year of age, the pharmacokinetics of tramadol and O-desmethyltramadol have been studied but not fully characterized. Information from studies involving this age group indicates that the rate of formation of O-desmethyltramadol via CYP2D6 increases continuously in neonates and it is assumed that CYP2D6 activity is reached in adults at around 1 year of age. Furthermore, immature glucuronidation systems and immature renal function may lead to slow elimination and accumulation of O-desmethyltramadol in children younger than 1 year of age.

Non-clinical data reveal no special hazard for clinical use based on studies of acute toxicity, repeated dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity. Animal studies have not shown teratogenic effects, but foetotoxicity has occurred due to maternal toxicity at high doses.

In rats, tramadol doses of at least 50 mg/kg/day caused toxic effects in pregnant animals and increased neonatal mortality. Growth retardation in the form of abnormal ossification and delay in vaginal and eye opening have been observed in puppies. There were no changes in male fertility. After higher doses (≥ 50 mg/kg/day), females had a lower degree of pregnancy.

In rabbits, maternal toxicity and skeletal abnormalities in offspring have been observed above doses of 125 mg/kg. Indications of a mutagenic effect have been found in certain in vitro tests, but none of these effects have been found in in vivo studies. Based on current knowledge, tramadol can be considered non-mutagenic.

Studies on the carcinogenic potential of tramadol hydrochloride were performed in rats and mice. The study in rats showed no evidence of an increased incidence of tumors associated with the active substance. In the mouse study, there was an increased frequency of hepatocellular adenomas in males (non-significant dose-dependent increase above 15 mg/kg) and an increase in lung tumors in females for all dose groups (significant increase, but not dose dependent).

polyvinyl acetate,Povidone, Sodium Lauryl Sulfate and Silicic Acid (Kollidon SR),

xantangummi,

hydrogenated vegetable oil (cottonseed oil),

magnesium stearate,

colloidal silica,

Hydroxypropyldistarkefosfat – (E1442) (Contramid)

Blister: Do not store more than 30⁰C.

HDPE bottles: This medicine does not require special storage conditions.

PVC/PVDC foil blisters (containing 5, 10, 15, 20, 30, 50, 60 or 100 prolonged-release tablets) or

PVC/PE/PCTFE foil blisters (5, 10, 15, 30, 60 or 100 extended-release tablets) or

HDPE bottles of 100 extended-release tablets

Not all pack sizes can be marketed.

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