Paracetamol + Tramadol Organic (Tablets) Instructions for Use

Marketing Authorization Holder

Organika, JSC (Russia)

ATC Code

N02AJ13 (Tramadol and Paracetamol)

Active Substances

Paracetamol (Rec.INN registered by WHO)

Tramadol (Rec.INN registered by WHO)

Dosage Form

Paracetamol + Tramadol Organic

Film-coated tablets, 325 mg+37.5 mg: 10, 20, 30, or 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets brownish-yellow in color, round, biconvex; the core on the cross-section is almost white.

Excipients: microcrystalline cellulose (type 101) – 26 mg, pregelatinized corn starch – 6.5 mg, sodium carboxymethyl starch (type A) – 6.5 mg, corn starch – 21.7 mg, povidone K90 (high molecular weight polyvinylpyrrolidone, plasdone K90) – 4.3 mg, magnesium stearate – 2.5 mg.

Shell composition opadry II yellow (series 85F220118) (polyvinyl alcohol – 4.4 mg, titanium dioxide – 2.7104 mg, macrogol (polyethylene glycol) – 2.222 mg, talc – 1.628 mg, iron oxide yellow dye – 0.0396 mg) – 11 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.

Clinical-Pharmacological Group

Combined drug with analgesic action

Pharmacotherapeutic Group

Combined analgesic agent (analgesic agent with mixed mechanism of action + non-narcotic analgesic agent)

Pharmacological Action

Combined analgesic agent containing tramadol and Paracetamol.

Tramadol – has a central action and an action on the spinal cord (promotes the opening of potassium and calcium channels, causes membrane hyperpolarization and inhibits the conduction of pain impulses), enhances the effect of sedative drugs. It activates opioid receptors (mu-, delta-, kappa-) on pre- and postsynaptic membranes of afferent fibers of the nociceptive system in the brain and gastrointestinal tract, inhibits the reverse neuronal uptake of catecholamines in the central nervous system.

Paracetamol – a non-narcotic analgesic, blocks COX, mainly in the central nervous system, acting on pain and thermoregulation centers. It does not cause irritation of the gastrointestinal mucosa, does not affect water-salt metabolism, as it does not affect the synthesis of prostaglandins in peripheral tissues. Due to paracetamol, rapid pain relief occurs, while tramadol provides a prolonged effect.

The synergism of the analgesic action of the two active substances reduces the risk of side effects.

Pharmacokinetics

When taken orally, the drug is rapidly and almost completely absorbed from the gastrointestinal tract.

The absorption of tramadol occurs more slowly than that of paracetamol. The bioavailability of tramadol is 75%, with repeated use it increases to 90%. The time to reach C_max of paracetamol is 1 hour and does not change when used together with tramadol.

Binding to plasma proteins of tramadol and paracetamol is about 20%. V_d – 0.9 l/kg.

Tramadol is metabolized in the liver by N- and O-demethylation followed by conjugation with glucuronic acid. Eleven metabolites have been identified, of which mono-O-desmethyltramadol has pharmacological activity. Paracetamol is metabolized mainly in the liver.

T_1/2 of tramadol is 4.7-5.1 hours, of paracetamol is 2-3 hours. Tramadol (about 30%) and its metabolites (about 60%) are excreted mainly by the kidneys. Paracetamol and its conjugates are excreted by the kidneys.

Indications

Pain syndrome of moderate and severe intensity of various etiologies, including inflammatory, traumatic, vascular origin; pain relief during painful diagnostic or therapeutic procedures.

ICD codes

Dosage Regimen

Administer orally with a sufficient amount of liquid.

Adhere strictly to the prescribed dosage and duration of treatment to minimize risks of hepatotoxicity and dependence.

The standard adult and adolescent (14 years and older) dose is one to two tablets every 4 to 6 hours as needed for pain relief.

Do not exceed eight tablets (equivalent to 3000 mg paracetamol and 300 mg tramadol) within a 24-hour period.

Initiate therapy with the lowest effective dose for the shortest duration necessary to control symptoms.

For acute pain, use only until the painful episode resolves; re-evaluate if pain persists.

For chronic pain, administer only under continuous medical supervision.

In elderly patients (over 75 years), use with caution; consider a longer dosing interval of 6 hours due to potential for reduced clearance.

In patients with moderate hepatic impairment (Child-Pugh class B) or moderate renal impairment (creatinine clearance 10-30 ml/min), increase the dosing interval to no more than every 8 hours.

Do not use in patients with severe hepatic impairment or severe renal impairment (creatinine clearance less than 10 ml/min).

Swallow tablets whole; do not crush, chew, or split.

Avoid concomitant use of other medications containing paracetamol or tramadol.

Discontinue treatment gradually if used for a prolonged period to prevent withdrawal symptoms.

Adverse Reactions

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

From the central nervous system and peripheral nervous system dizziness, headache, lethargy, paradoxical stimulation of the central nervous system (nervousness, agitation, anxiety, tremor, muscle spasms, euphoria, emotional lability, hallucinations), drowsiness, sleep disturbance, confusion, impaired coordination of movement, central genesis convulsions (with simultaneous administration of antipsychotic drugs), depression, amnesia, impaired cognitive function, paresthesia, unsteady gait.

From the digestive system dry mouth, nausea, vomiting, flatulence, abdominal pain, constipation, diarrhea, difficulty swallowing; increased activity of liver enzymes, usually without the development of jaundice.

From the cardiovascular system tachycardia, orthostatic hypotension, syncope, collapse.

From the endocrine system hypoglycemia, up to hypoglycemic coma.

From the urinary system difficulty urinating, dysuria, urinary retention. With long-term use in doses significantly exceeding the recommended ones – nephrotoxicity (interstitial nephritis, papillary necrosis).

From the senses visual impairment, taste disturbance.

From the respiratory system dyspnea.

From the skin multiform exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

From the hematopoietic organs sulfhemoglobinemia. With long-term use in doses significantly exceeding the recommended ones – aplastic anemia, pancytopenia, agranulocytosis.

Other sweating, weakness, increased fatigue, menstrual cycle disorder.

With long-term use – development of drug dependence (irritability, phobias, nervousness, sleep disorders, psychomotor activity, tremor, discomfort in the stomach or intestines).

With abrupt discontinuation of use, withdrawal syndrome may develop.

Contraindications

Hypersensitivity; acute alcohol intoxication; intoxication with drugs that depress the central nervous system (hypnotics, narcotic analgesics and psychotropic drugs); simultaneous use of MAO inhibitors (and within 2 weeks after their withdrawal); severe hepatic and/or renal failure (creatinine clearance less than 10 ml/min); epilepsy uncontrolled by therapy; withdrawal syndrome of narcotic drugs; children’s age (under 14 years); pregnancy; lactation period.

With caution shock, traumatic brain injury, intracranial hypertension, tendency to convulsive syndrome (with controlled epilepsy, the drug can be used only for vital indications), confusion of unknown etiology, respiratory failure, simultaneous use of psychotropic and central-acting analgesic drugs, local anesthetics, diseases of the biliary tract, benign hyperbilirubinemia, viral hepatitis, glucose-6-phosphate dehydrogenase deficiency, alcoholic liver disease, alcoholism, drug addiction, symptoms of “acute” abdomen of unclear genesis, elderly age (over 75 years).

Use in Pregnancy and Lactation

Contraindicated during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindication — severe hepatic failure.

With caution diseases of the biliary tract, benign hyperbilirubinemia, viral hepatitis, alcoholic liver disease.

Use in Renal Impairment

Contraindication — severe renal failure (creatinine clearance less than 10 ml/min).

Pediatric Use

Contraindication — children’s age (under 14 years).

Geriatric Use

With caution elderly age (over 75 years).

Special Precautions

Patients should be informed about the need to strictly adhere to the dosage regimen. During the period of use, other drugs containing tramadol or Paracetamol should not be used without a doctor’s prescription.

With long-term uncontrolled use, symptoms of drug dependence may appear (irritability, phobias, nervousness, sleep disorders, psychomotor activity, tremor, discomfort from the gastrointestinal tract). With abrupt withdrawal of the drug, signs of withdrawal syndrome may appear.

In patients prone to abuse or dependence, treatment should be carried out under careful medical supervision for a short period of time.

During treatment, alcohol consumption is prohibited. The risk of developing liver dysfunction increases in patients with alcoholic hepatosis.

During long-term use, monitoring of the peripheral blood picture and the functional state of the liver is necessary.

Effect on ability to drive vehicles and mechanisms

During treatment, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Concomitant use with opioid agonist-antagonists (buprenorphine, nalbuphine, pentazocine) reduces the analgesic effect as a result of competing action on receptors, and there is also a risk of withdrawal syndrome.

Drugs that depress the central nervous system (including hypnotics, tranquilizers), ethanol – enhance the side effects characteristic of tramadol.

Inducers of microsomal oxidation (including carbamazepine, phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) reduce the analgesic effect and its duration.

Naloxone activates respiration, eliminating analgesia caused by tramadol.

Long-term use of barbiturates reduces the effectiveness of paracetamol.

Ethanol contributes to the development of acute pancreatitis.

Long-term concomitant use of paracetamol and other NSAIDs increases the risk of developing nephropathy and renal papillary necrosis, and the onset of end-stage renal failure.

Simultaneous long-term administration of paracetamol in high doses and salicylates increases the risk of developing kidney or bladder cancer. Diflunisal increases the plasma concentration of paracetamol by 50% – risk of hepatotoxicity.

Concomitant use with drugs that lower the epileptic threshold (including selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics) – risk of seizures.

Drugs that inhibit CYP3A4 (ketoconazole and erythromycin) may slow down the metabolism of tramadol (N-demethylation) and the active O-demethylated metabolite.

Quinidine increases the plasma concentration of tramadol and reduces the concentration of the O-demethylated metabolite due to competitive inhibition of the CYP2D6 isoenzyme.

Inhibitors of microsomal oxidation (cimetidine) reduce the risk of hepatotoxicity.

The rate of absorption of paracetamol increases when taking metoclopramide or domperidone and decreases when taking cholestyramine.

The drug, when taken for a long time, enhances the effect of indirect anticoagulants (warfarin and other coumarins) , which increases the risk of bleeding.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.