PROMEDOL-ZN

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROMEDOL-ZN (PROMEDOL-ZN)

Composition:

Active substance: trimeperidine;

1 ml of solution contains promedol (trimethperidine hydrochloride) – 20 mg;

Excipient: water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear colorless liquid.

Pharmacotherapeutic group.
Analgesics. Opioids. ATC code N02A X.

Pharmacological properties.

Pharmacodynamics.

A synthetic opioid receptor agonist. Exerts pronounced analgesic effect, has moderate anti-shock, sedative and spasmolytic properties, increases uterine contractile activity.

The mechanism of action is due to stimulation of mu-, delta- and kappa-subtypes of opioid receptors. Effects on mu-receptors cause supraspinal analgesia, euphoria, physical dependence, respiratory depression, and excitation of vagus nerve centers. Stimulation of kappa-receptors leads to spinal analgesia, sedative effect, miosis.

Inhibits interneuronal transmission of pain impulses in the central part of the afferent pathway, reduces perception of pain impulses by the central nervous system (CNS), decreases emotional assessment of pain. May cause development of physical dependence and habituation.

Compared to morphine, it has weaker and shorter analgesic action. At the same time, it less suppresses the respiratory center, less stimulates the vagus nerve center and vomiting center, and does not cause spasm of smooth musculature (except myometrium). It is better tolerated than morphine.

After subcutaneous or intramuscular administration, the effect begins within 10–20 minutes and lasts for 3–4 hours or longer.

Pharmacokinetics.

Rapidly absorbed into the blood after any route of administration. Plasma protein binding reaches 40%. Metabolized via hydrolysis to meperidinic acid and normeperidinic acid, followed by their conjugation. A small amount is excreted unchanged by the kidneys.

Clinical characteristics.

Indications.

Severe pain syndrome in malignant tumors, burns, severe injuries, during preoperative preparation and in the postoperative period, in spasms of smooth musculature of internal organs and blood vessels, including peptic ulcer of the stomach and duodenum, intestinal, hepatic and renal colic, dyskinetic constipation, myocardial infarction, cardiogenic shock, angina pectoris, acute neuritis, foreign body in urinary bladder, rectum, urethra, paraphimosis, acute prostatitis. As part of premedication and during anesthesia, as an anti-shock agent, for neuroleptanalgesia (in combination with neuroleptics).

Contraindications.

• Hypersensitivity to trimethylperidine hydrochloride.
• Respiratory depression due to respiratory center suppression.
• Obstructive respiratory tract diseases, including bronchial asthma attacks.
• General exhaustion.
• Paralytic ileus or risk of its development.
• Abdominal pain of unknown etiology (prior to diagnosis establishment).
• Increased intracranial pressure or head trauma.
• Acute alcohol intoxication.
• Convulsions.
• Comatose state.
• Pheochromocytoma.
• Concomitant treatment with monoamine oxidase inhibitors (MAOIs), as well as within 2 weeks after discontinuation of MAOI therapy.
• Age under 2 years.
• Age over 65 years.
• Last 3 hours before expected delivery time.

Interaction with other medicinal products and other forms of interactions.

Trimethylperidine hydrochloride must not be used concurrently with monoamine oxidase inhibitors (MAOIs) (including moclobemide) and within 2 weeks after discontinuation of MAOI therapy (see section "Contraindications").

When used concomitantly with antidepressants (including tricyclic antidepressants), CNS excitatory or depressive effects may occur.

The CNS depressant effect is also enhanced when used concurrently with anesthetic agents.

When used concomitantly with antipsychotic agents, the sedative and hypotensive effects of trimethylperidine hydrochloride are enhanced.

Prolonged use of barbiturates (especially phenobarbital) or narcotic analgesics leads to development of cross-tolerance.

Promedol-ZN is compatible with neuroleptics (haloperidol, droperidol), anticholinergics, myotropic spasmolytics, and antihistamines.

Opioids delay absorption of the antiarrhythmic agent mexiletine.

In patients receiving the antibiotic ciprofloxacin, opioid premedication may reduce its plasma concentration.

When trimethylperidine hydrochloride is used concomitantly with cisapride, metoclopramide, or domperidone, antagonism regarding gastrointestinal tract effects is observed.

The H2-histamine receptor blocker cimetidine inhibits opioid metabolism.

Alcohol enhances the sedative and hypotensive effects of opioids.

The interaction between opioid analgesics and HIV protease inhibitors or reverse transcriptase inhibitors has not been fully established; limited studies and in vivo results do not always confirm predictions regarding the nature of possible interactions.

Special precautions.

In cases of high-dose administration and signs of intoxication, activated charcoal may be administered orally.

Administration of high doses, especially in elderly patients, may lead to respiratory depression and hypotension, resulting in circulatory insufficiency and coma. The development of adverse reactions depends on individual sensitivity to opioid receptors. In children aged 2 years and older, seizures may occur; when used in high doses, progression of renal insufficiency is possible. Seizures are more commonly observed in children.

The development of toxic effects depends on individual sensitivity to opioid receptors.

Comatose state is characterized by pinpoint pupils and respiratory depression, which may indicate overdose. Pupillary dilation indicates the development of hypoxia. Pulmonary edema following overdose is the main cause of fatal outcomes.

Repeated use may lead to tolerance development and drug dependence. Euphoria is possible.

Use with caution in patients with hepatic or renal impairment, hyperthyroidism, hypotension, adrenal insufficiency, prostate hyperplasia, impotence, shock, myasthenia gravis, inflammatory gastrointestinal disorders, and also in patients aged 60 years and older.

Alcohol consumption must be avoided.

In patients with hepatic dysfunction, it is preferable to administer immediate-release formulations orally or to administer short-acting opioids parenterally, rather than prescribing long-acting opioids such as transdermal formulations or extended-release dosage forms.

When administering the drug to patients with hepatobiliary system disorders (including biliary pancreatitis), caution is required; in such cases, trimethylperidine hydrochloride should be administered concomitantly with spasmolytic agents.

Risk of withdrawal syndrome. Abrupt discontinuation of trimethylperidine hydrochloride may result in the development of withdrawal syndrome (see section "Adverse reactions").

Respiratory depression requires respiratory support and administration of a stimulatory antagonist—naloxone. However, administration of the opioid antagonist naloxone to opioid-dependent individuals may precipitate withdrawal syndrome. Supportive therapy is aimed at respiratory support and reversing shock by administering naloxone. The dosage of naloxone administered depends on the severity of respiratory depression and the degree of coma.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

During treatment with promedol, patients should not drive or engage in other potentially hazardous activities requiring rapid psychomotor reactions.

Dosage and Administration

The need for opioid use should be carefully evaluated both before initiating therapy and during treatment. The possibility of dose reduction, discontinuation, or switching from opioids should be periodically reviewed. To minimize the occurrence of opioid-related adverse effects, concomitant use of other medicinal products should be avoided.

Adults: Administer subcutaneously or intramuscularly 0.5–1.5 mL of the 20 mg/mL solution (10–30 mg of tramadol hydrochloride). The dose may be repeated every 4 hours.

Maximum doses for adults: single dose – 2 mL of the 20 mg/mL solution (40 mg), daily dose – 8 mL of the 20 mg/mL solution (160 mg).

Dosage should be reduced in elderly patients, debilitated patients, patients with psychiatric disorders, and those with hepatic or renal impairment. Therapy should be initiated with lower doses, and longer intervals between doses should be maintained.

Children aged 2 years and older, according to age:

• 2–3 years: single dose – 0.15 mL of the 20 mg/mL solution (3 mg of tramadol hydrochloride), maximum daily dose – 0.6 mL (12 mg);
• 4–6 years: single dose – 0.2 mL (4 mg), maximum daily dose – 0.8 mL (16 mg);
• 7–9 years: single dose – 0.3 mL (6 mg), maximum daily dose – 1.2 mL (24 mg);
• 10–12 years: single dose – 0.4 mL (8 mg), maximum daily dose – 1.6 mL (32 mg);
• 13–16 years: single dose – 0.5 mL (10 mg), maximum daily dose – 2 mL (40 mg).

Children: The drug is not recommended for use in children under 2 years of age.

Overdose.

Symptoms: symptoms similar to those observed in morphine overdose: severe respiratory depression, hypotension, miosis (in case of pronounced hypoxia – mydriasis), increased intracranial pressure, and coma. Central nervous system (CNS) excitation and seizures may occur. Cases of rhabdomyolysis and associated renal failure have been reported. Early and potentially life-threatening manifestation is respiratory center depression.

Treatment: general resuscitation measures, administration of antagonists (naloxone) and opioid receptor agonist-antagonists (nalorphine), symptomatic therapy.

Naloxone reverses respiratory depression and analgesia caused by narcotic analgesics. Nalorphine reverses respiratory depression caused by narcotic analgesics while preserving their analgesic effect.

Adverse Reactions.

Immune system disorders: allergic reactions, including rashes, pruritus, urticaria; contact dermatitis.

Psychiatric disorders: hallucinations, mood changes; euphoria (with high-dose use); dysphoria.

Nervous system disorders: impaired consciousness, dizziness, headache, vertigo, somnolence; coma (with high-dose use).

Eye disorders: diplopia, miosis; pupil dilation indicating hypoxia development.

Cardiovascular system disorders: bradycardia, tachycardia, cardiac arrhythmia, orthostatic hypotension, increased intracranial pressure.

Respiratory system disorders: respiratory insufficiency, respiratory depression (with high-dose use).

Gastrointestinal disorders: nausea, vomiting, constipation, dry mouth.

Hepatobiliary disorders: spasm of the biliary tract.

Musculoskeletal system disorders: muscle rigidity (with high-dose use), seizures (especially in children).

Renal and urinary disorders: renal failure (with high-dose use), difficulty in urination, urinary tract spasms.

Reproductive system disorders: decreased libido.

General disorders and administration site reactions: general weakness, increased sweating, facial flushing, hypothermia, pain and inflammation at injection site.

Laboratory findings: changes in liver enzyme levels, hyperglycemia.

Dependence. Repeated use of trimethopidine hydrochloride may lead to dependence.

In case of physical dependence, abrupt discontinuation of trimethopidine hydrochloride may result in withdrawal syndrome (see section "Special Instructions"), characterized by symptoms such as nausea, vomiting, diarrhea, excessive sweating, mydriasis, lacrimation, chills, yawning, abdominal, muscular or joint pain, muscle tremor, anxiety, restlessness, irritability, insomnia, as well as increased heart rate, respiration, and elevated blood pressure. To prevent withdrawal syndrome, the drug should be gradually discontinued in patients at risk of dependence.

The euphoric effect of trimethopidine hydrochloride may lead to drug abuse.

If nausea, vomiting, constipation, somnolence, dizziness, disorientation, or general weakness occur upon repeated administration of the drug, the dose should be reduced.

Shelf life. 3 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25°C.

Keep out of reach of children.

Packaging.

1 ml in an ampoule; 5 ampoules in a blister. 1, 2, or 20 blisters per carton.

1 ml in an ampoule; 10 ampoules in a blister. 1 or 10 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Kharkiv Pharmaceutical Enterprise "Zdorovya Narodu".

Manufacturer's address and place of business.

41 Kulikivska Street, Kharkiv, Kharkiv Oblast, 61002, Ukraine.