Bupraxon (Tablets) Instructions for Use

Marketing Authorization Holder

Moscow Endocrine Plant FSUE (Russia)

ATC Code

N02AE01 (Buprenorphine)

Active Substances

Naloxone (Rec.INN registered by WHO)

Buprenorphine (Rec.INN registered by WHO)

Dosage Form

Bupraxon

Sublingual tablets 0.216 mg+0.222 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Sublingual tablets round, biconvex, white in color.

Excipients: lactose monohydrate – 27.729 mg, mannitol – 18 mg, potato starch – 9 mg, povidone – 1.233 mg, crospovidone – 1.8 mg, citric acid monohydrate – 0.6 mg, magnesium stearate – 0.6 mg, colloidal silicon dioxide – 0.6 mg.

10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (100) – cardboard boxes (for hospitals).
10 pcs. – contour cell packs (200) – cardboard boxes (for hospitals).
10 pcs. – contour cell packs (400) – cardboard boxes (for hospitals).

Clinical-Pharmacological Group

Opioid analgesic

Pharmacotherapeutic Group

Narcotic analgesic agent

Pharmacological Action

Combined medicinal product. When used sublingually, the pharmacological action is determined by the buprenorphine contained in the preparation.

Buprenorphine is an opioid analgesic, a semi-synthetic derivative of thebaine. It is a partial agonist of the μ-opioid receptor subtype and a partial antagonist of the κ-opioid receptors. In equivalent doses, the severity of the analgesic effect is similar to morphine. As a partial agonist of opioid receptors, it depresses respiration, affects smooth muscle, although to a lesser extent than morphine and other opiates, and has a lower potential for developing physical dependence compared to them. At the same time, the activation of μ-opioid receptors determines a certain addictive potential of buprenorphine.

Naloxone is an opioid receptor antagonist. It effectively eliminates or reduces the effects of opiates and opioids. It restores breathing, reduces sedative and euphoric effects. It can cause opiate withdrawal syndrome if they were previously administered for pain relief or in drug-dependent people using opioid analgesics. The pharmacological effect develops only with parenteral (IV, IM, SC) administration. When administered sublingually, it practically does not enter the systemic circulation and has no effect.

Pharmacodynamic effects are absent. Naloxone exhibits practically no pharmacological activity when taken orally; the efficacy ratio of naloxone for oral and parenteral administration is 1:50.

The onset of action of buprenorphine after sublingual administration of this combination occurs after 30 minutes. The maximum effect is observed after 3 hours. The duration of the analgesic effect is 5 hours.

Pharmacokinetics

Buprenorphine

When taken sublingually, buprenorphine is well absorbed. Systemic bioavailability is 50-55%. C_max in blood plasma after taking 400 mcg of buprenorphine is reached after 2 hours and averages 1.13 ng/ml. Buprenorphine penetrates the blood-brain barrier well. Binding to plasma proteins, primarily α- and β-globulins, is 96%. The V_d of buprenorphine is 2.5 L, indicating its active uptake by body organs. Buprenorphine is metabolized in the liver by N-dealkylation to form norbuprenorphine with the participation of the CYP3A4 isoenzyme, followed by glucuronidation, forming conjugates with glucuronic acid. The main metabolite, norbuprenorphine, does not have significant analgesic activity and is also glucuronidated.

The T_1/2 of buprenorphine from blood plasma is 24-42 hours. It is excreted as metabolites by the kidneys – 30% and with bile – 69%; unchanged – about 1%.

Naloxone

When taken sublingually, naloxone is practically not absorbed. Systemic bioavailability is less than 5%. The concentration in blood plasma is not clinically significant. Binding to plasma proteins, mainly albumin, is 45%.

The absorbed insignificant amounts of naloxone included in this combination do not create therapeutic concentrations in the blood plasma and do not affect the effects and metabolism of buprenorphine. Naloxone is rapidly metabolized in the liver, undergoing direct glucuronidation to naloxone-3-glucuronide, as well as N-dealkylation and reduction (at the 6-oxo group). The T_1/2 of naloxone is 2-12 hours. Metabolites are excreted mainly by the kidneys.

Indications

Postoperative pain syndrome (severe and moderate intensity), pain syndrome caused by injuries and burns, during diagnostic procedures.

ICD codes

Dosage Regimen

For sublingual use. 1-2 single doses are used every 6-8 hours. No more than 8 single doses per day.

The dose should be reduced in elderly patients, in hypovolemic conditions, in the risk of surgical pathology, with simultaneous use of sedatives and other narcotic analgesics.
This combination in reduced doses should be used against the background of the action of general anesthetics, hypnotics, anxiolytics, antidepressants and antipsychotics to avoid excessive depression of the CNS and suppression of the respiratory center activity.

Adverse Reactions

Definition of the frequency of adverse reactions: very common (≥1/10); common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000); very rare (<1/10,000); unknown (cannot be estimated from the available data).

The side effects of this combination are determined by the buprenorphine contained in it.

Allergic reactions rarely – rash, urticaria.

From the nervous system: very often – sedative effect; often – weakness, dizziness, headache; rarely – tinnitus, confusion, drowsiness, weakness/fatigue, lethargy, slowing of mental and motor reactions, slurred speech, paresthesia, euphoria, nervousness, depression, psychosis. With long-term use, the development of tolerance and opioid dependence is possible.

From the skin rarely – cyanosis, itching.

From the urinary system rarely – urinary retention.

From the metabolism rarely – sweating.

From the digestive system often – nausea; rarely – vomiting, dry mouth, constipation.

From the respiratory system rarely – depression of the respiratory center, shortness of breath, hypoventilation.

From the senses often – miosis, blurred vision, diplopia; very rarely – conjunctivitis.

From the cardiovascular system often – increased blood pressure, rarely – tachycardia, bradycardia, chills/feeling of cold, “hot flashes”.

In case of overdose due to the action of buprenorphine, nausea, vomiting, sedative effect, drowsiness, miosis, respiratory depression are possible.

Contraindications

Conditions that may lead to respiratory impairment or are already accompanied by depression of the respiratory center or severe depression of the CNS; simultaneous use with MAO inhibitors, both during the entire period of use of MAO inhibitors and within 14 days after their discontinuation; stomatitis and mucositis, ulcerative-necrotic and inflammatory lesions of the oral mucosa; drug dependence, incl. opioid; convulsive conditions; traumatic brain injury; acute alcohol intoxication; bronchial asthma, status asthmaticus; cardiopulmonary failure; heart rhythm disorders (supraventricular and ventricular paroxysmal tachycardia, atrial fibrillation and flutter, ventricular fibrillation and flutter, extrasystole); paralytic ileus; acute surgical diseases of the abdominal organs before diagnosis; use during pregnancy and breastfeeding; age under 18 years; hypersensitivity to buprenorphine, naloxone.

With caution

Respiratory failure; hepatic and/or renal failure; myxedema; hypothyroidism, adrenal insufficiency; CNS depression; toxic psychosis; prostatic hyperplasia; urethral strictures; alcoholism; elderly and senile age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

The drug is approved for use in impaired liver function

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age

Special Precautions

Naloxone is included in this combination to increase narcological safety when using the latter. In case of non-medical use of medicinal products containing this combination (due to the presence of a narcotic analgesic in the composition), naloxone will block the effects of buprenorphine and will not lead to the action that is pursued when abusing buprenorphine. In persons with physical dependence on opioids, this may lead to the development of withdrawal syndrome.

Buprenorphine is metabolized in the liver. In patients with impaired liver function, the intensity and duration of action of buprenorphine may change. The use of this combination in such patients should be carried out under medical supervision.

Nicotine reduces the pharmacological activity of this combination.

In case of accidental or intentional ingestion in children, respiratory depression may occur, which may lead to death.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Potentiates the effect of antipsychotics, benzodiazepines, phenothiazines, as well as other tranquilizers; anxiolytics, sedatives, hypnotics, general anesthetics, antihistamines, ethanol.

When combined with MAO inhibitors, malignant hyperthermia, convulsions, coma, arterial hypertension may develop.

When combined with full opioid agonists, opioid withdrawal syndrome may develop.

When used with valproic acid/sodium valproate, the depressant effect on the CNS increases.

When taking other analgesics, cerebrospinal fluid pressure may increase, so this combination should be used with caution in cases where cerebrospinal fluid pressure may be increased, because buprenorphine can lead to miosis and altered level of consciousness.

Drugs that inhibit the activity of the CYP3A4 isoenzyme (including ketoconazole, macrolides, erythromycin) or HIV protease inhibitors (ritonavir) may enhance the effects and duration of action of buprenorphine, which will require dose adjustment of one or both drugs.

When taken concomitantly with inducers of the CYP3A4 isoenzyme (including phenobarbital, carbamazepine, phenytoin, rifampicin), the concentration of buprenorphine in the blood plasma may decrease. Since the interaction of buprenorphine with all inducers of the CYP3A4 isoenzyme has not been studied, it is recommended to monitor the condition of patients who have received this combination for signs and symptoms of withdrawal syndrome.

St. John’s wort, as an inducer of the CYP3A4 isoenzyme, is able to reduce the concentration of buprenorphine in the blood plasma.

Ethanol enhances the CNS depression caused by buprenorphine. During the treatment period, it is necessary to refrain from drinking alcohol.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.