Tramadol Stada^® (Capsules) Instructions for Use

Marketing Authorization Holder

Stada Arzneimittel, AG (Germany)

ATC Code

N02AX02 (Tramadol)

Active Substance

Tramadol (Rec.INN registered by WHO)

Dosage Form

Tramadol Stada®

Capsules 50 mg: 10, 20, 30, or 50 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 4, opaque, white; capsule contents – white powder.

Excipients : calcium hydrogen phosphate dihydrate – 97 mg, magnesium stearate – 5.5 mg, colloidal anhydrous silicon dioxide (colloidal silicon anhydrous) – 2.5 mg.

Capsule shell composition gelatin – 39.2 mg, titanium dioxide (E171) – 800 mcg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Clinical-Pharmacological Group

Opioid analgesic with a mixed mechanism of action

Pharmacotherapeutic Group

Opioid analgesic agent

Pharmacological Action

Opioid synthetic analgesic with central and spinal cord action (promotes the opening of potassium and calcium channels, causes membrane hyperpolarization and inhibits the conduction of pain impulses), enhances the effect of sedative drugs. Activates opioid receptors (mu-, delta-, kappa-) on pre- and postsynaptic membranes of afferent fibers of the nociceptive system in the brain and gastrointestinal tract. Slows down the destruction of catecholamines, stabilizes their concentration in the central nervous system.

It is a racemic mixture of 2 enantiomers – dextrorotatory (+) and levorotatory (-), each of which exhibits a different receptor affinity: (+)Tramadol is a selective agonist of mu-opioid receptors and also selectively inhibits the neuronal reuptake of serotonin;

(-)Tramadol inhibits the neuronal reuptake of norepinephrine. Mono-O-desmethyltramadol (M1 metabolite) also selectively stimulates mu-opioid receptors. The affinity of tramadol for opioid receptors is 10 times weaker than that of codeine and 6000 times weaker than that of morphine. The severity of the analgesic effect is 5-10 times weaker than morphine.

The analgesic effect is due to a decrease in the activity of the nociceptive and an increase in the antinociceptive systems of the body.

In therapeutic doses, it does not significantly affect hemodynamics and respiration, does not change pressure in the pulmonary artery, slightly slows down intestinal peristalsis without causing constipation. It has some antitussive and sedative effects. It depresses the respiratory center, excites the trigger zone of the vomiting center, and the nuclei of the oculomotor nerve.

With prolonged use, the development of tolerance is possible. The analgesic effect develops 15-30 minutes after oral administration and lasts up to 6 hours.

Pharmacokinetics

Absorption – 90%; bioavailability – 68% when taken orally (increases with repeated use). Time to reach maximum concentration -2 hours.

Penetrates the blood-brain barrier and placenta, 0.1% is excreted in breast milk.

It is metabolized in the liver by N- and O-demethylation followed by conjugation with glucuronic acid. 11 metabolites have been identified, of which mono-O-desmethyltramadol (M1) has pharmacological activity.

Elimination half-life in the second phase – 6 hours (Tramadol), 7.9 hours (mono-O-desmethyltramadol); in patients over 75 years old – 7.4 hours (Tramadol); in liver cirrhosis – 13.3 ± 4.9 hours (Tramadol), 18.5 ± 9.4 hours (mono-O-desmethyltramadol), in severe cases – 22.3 hours and 36 hours, respectively; in chronic renal failure (creatinine clearance less than 5 ml/min) – 11 ± 3.2 hours (Tramadol), 16.9 ± 3 hours (mono-O-desmethyltramadol), in severe cases – 19.5 hours and 43.2 hours respectively.

Excreted by the kidneys (25-35% unchanged), the average cumulative renal excretion rate is 94%.

Indications

• Moderate and severe pain syndrome of various etiologies (postoperative period, trauma, pain in cancer patients, during diagnostic and therapeutic procedures).

ICD codes

Dosage Regimen

Tramadol Stada^® is used as prescribed by a doctor, the dosage regimen of the drug is selected individually depending on the severity of the pain syndrome and the patient’s sensitivity. The duration of treatment is determined individually, the drug should not be prescribed for longer than is therapeutically justified.

Unless otherwise prescribed, Tramadol Stada^® should be prescribed in the following doses: For adults and children over 14 years old the usual initial dose is 1 capsule (50 mg) orally with a small amount of liquid, regardless of meal time. If there is no effect within 30-60 minutes, you can take another 1 capsule. For severe pain, a single dose can be 100 mg (2 capsules) immediately. If necessary, the drug is prescribed again, but not earlier than after 6-8 hours. The maximum daily dose is 400 mg (8 capsules).

In elderly patients (aged 65 to 75 years) due to the possibility of delayed excretion, the interval between drug administrations may be increased according to individual characteristics. For patients over 75 years of age it is recommended to reduce the daily dose to 300 mg.

Inpatients with renal and hepatic impairment a dose reduction or an increase in the interval between single doses is recommended. In patients with creatinine clearance less than 30 ml/min or 0.5 ml/s, it is recommended to double the time interval between drug doses at the beginning of treatment.

Tramadol Stada^® should not be prescribed for longer than therapeutically necessary.

Adverse Reactions

The most common side effects of Tramadol Stada^® are nausea and dizziness.

From the nervous system increased sweating, dizziness, headache, weakness, increased fatigue, lethargy, restlessness, anorexia, paradoxical stimulation of the central nervous system (nervousness, agitation, anxiety, tremor, muscle spasms, euphoria, emotional lability, hallucinations), drowsiness, sleep disorders, confusion, impaired coordination of movements, central genesis convulsions (with simultaneous administration of antipsychotic drugs (neuroleptics)), depression, amnesia, cognitive impairment, paresthesia, unsteady gait, impaired concentration, asthenia.

From the digestive system dry mouth, nausea, vomiting, flatulence, dyspepsia, abdominal pain, constipation or diarrhea, difficulty swallowing.

From the cardiovascular system manifestations of vasodilation – tachycardia, orthostatic hypotension, fainting, collapse, increased blood pressure, palpitations.

From the musculoskeletal system increased muscle tone.

Allergic reactions urticaria, itching, exanthema, rash, including bullous, angioedema.

From the urinary system difficulty urinating, dysuria, urinary retention.

From the sensory organs impaired visual acuity, sometimes mydriasis, taste disturbance. From the respiratory system: dyspnea, pulmonary edema.

Other weight loss, menstrual cycle disorder. With long-term use – drug dependence.

Upon abrupt withdrawal – withdrawal syndrome (possible symptoms: panic attacks, anxiety, hallucinations, paresthesia, tinnitus, paradoxical symptoms from the central nervous system (depersonalization, derealization, paranoia)). In case of significant excess of the recommended dose or simultaneous use of other drugs that affect the central nervous system, respiratory depression may be observed. Epileptiform seizures may mainly occur after the use of high doses of tramadol or with the simultaneous use of drugs that lower the seizure threshold.

Contraindications

• Hypersensitivity to the components of the drug and other opioids;
• Conditions accompanied by respiratory depression or severe depression of the central nervous system (alcohol intoxication, hypnotics, opioid analgesics, psychotropic drugs);
• Simultaneous use of MAO inhibitors (and for two weeks after their withdrawal);
• Severe hepatic and/or renal failure (creatinine clearance less than 10 ml/min);
• Pharmacoresistant epilepsy;
• Use of tramadol as a drug for the treatment of drug withdrawal syndrome;
• Suicidal tendencies,
• Substance abuse;
• Pregnancy;
• Breastfeeding period;
• Childhood (under 14 years).

With caution

Use the drug with caution and under medical supervision in patients with impaired renal and liver function, with traumatic brain injuries, with impaired consciousness of various origins, convulsions, intracranial hypertension, epilepsy, in persons with drug dependence (especially narcotic and alcohol), in patients against the background of abdominal pain of unclear genesis (“acute” abdomen), in renal failure (creatinine clearance from 10 to 30 ml/min). With simultaneous use with selective serotonin reuptake inhibitors (some antidepressants and appetite suppressants), tricyclic antidepressants, other tricyclic compounds (for example, promethazine), antimigraine drugs (triptans), opioid analgesics, neuroleptics and other drugs that lower the seizure threshold.

Use in Pregnancy and Lactation

The safety of tramadol use during pregnancy has not been established. Its use should be avoided due to the risk of developing addiction in the fetus and the occurrence of withdrawal syndrome in the neonatal period.

If it is necessary to use during breastfeeding, the issue of suspending breastfeeding should be considered (the drug is excreted in breast milk).

Use in Hepatic Impairment

Contraindicated in severe renal failure. Use with caution and under medical supervision in patients with impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance less than 10 ml/min). Use the drug with caution in renal failure (creatinine clearance from 10 to 30 ml/min).

Pediatric Use

Contraindicated in children under 14 years of age.

Geriatric Use

In elderly patients (aged 65 to 75 years) due to the possibility of delayed excretion, the interval between drug administrations may be increased according to individual characteristics. For patients over 75 years of age it is recommended to reduce the daily dose to 300 mg.

Special Precautions

Not used for the therapy of opioid withdrawal syndrome.

Ethanol should not be consumed simultaneously with the use of tramadol.

Tramadol Stada^® should be avoided in patients with drug dependence (including dependence on opioids, alcohol).

The use of tramadol drugs increases the risk of suicide in patients with suicidal tendencies.

Effect on the ability to drive vehicles and mechanisms

When using Tramadol Stada^® capsules, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms mydriasis, miosis, vomiting, collapse, impaired consciousness (up to coma), convulsions, depression of the respiratory center, apnea, decreased blood pressure, tachycardia.

Treatment ensuring airway patency, maintaining respiration and cardiovascular activity. Opiate-like effects can be stopped by naloxone, convulsions – by benzodiazepine. Hemodialysis or hemofiltration is not very effective.

Drug Interactions

Enhances the effect of drugs that depress the central nervous system, and ethanol. Microsomal oxidation inducers (including carbamazepine, barbiturates) reduce the severity of the analgesic effect and the duration of action. Long-term use of opioid analgesics or barbiturates stimulates the development of cross-tolerance.

Anxiolytics increase the severity of the analgesic effect; the duration of anesthesia increases when combined with barbiturates.

Naloxone activates respiration, eliminating analgesia after the use of opioid analgesics.

Quinidine increases the plasma concentration of tramadol and reduces the M1 metabolite due to competitive inhibition of the CYP2D6 isoenzyme. CYP2D6 isoenzyme inhibitors (such as fluoxetine, paroxetine and amitriptyline) reduce the metabolism of tramadol. Pre- or postoperative use of the antiemetic ondansetron (5-HT3-serotonin receptor antagonist) increased the need for tramadol in patients with postoperative pain syndrome.

With simultaneous use of tramadol and indirect anticoagulants – coumarin derivatives (for example, warfarin) – it is necessary to carefully monitor patients, since in some of them the prothrombin time indicator increases with the development of bleeding and subcutaneous hemorrhages.

Selective serotonin reuptake inhibitors (some antidepressants and appetite suppressants), tricyclic antidepressants, other tricyclic compounds (for example, promethazine), antimigraine drugs (triptans), opioid analgesics, monoamine oxidase inhibitors, neuroleptics and other drugs that lower the seizure threshold increase the risk of seizures.

Selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, antimigraine drugs (triptans) and drugs that disrupt the metabolism of tramadol (inhibitors of CYP2D6 and CYP3A4 isoenzymes), when used together with tramadol, can cause serotonin syndrome. Symptoms of serotonin syndrome: confusion, agitation, hyperthermia, sweating, ataxia, hyperreflexia, myoclonus and diarrhea. Discontinuation of serotonergic drugs causes rapid relief of symptoms.

Storage Conditions

The drug belongs to list No. 1 of potent substances of the Permanent Committee for Drug Control of the Ministry of Health and Social Development of the Russian Federation. Store in a place inaccessible to children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.