Omnopon neo

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OMNOPON NEO (OMNOPON NEO)

Composition:

Active substances:

1 ml of solution contains morphine hydrochloride, recalculated to 100% substance – 11.5 mg; noscapine, recalculated to 100% substance – 5.4 mg; papaverine hydrochloride, recalculated to 100% substance – 0.72 mg; codeine, recalculated to 100% substance – 1.44 mg;

Excipients: disodium edetate, glycerin, 1 M hydrochloric acid solution, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear colorless or slightly yellow liquid.

Pharmacotherapeutic group. Analgesics. Opioids. Natural opium alkaloids. Morphine, combinations.

ATC code N02A A51.

Pharmacological Properties

Pharmacodynamics

An opioid analgesic. Has a pronounced analgesic effect. The mechanism of action is due to stimulation of various subtypes of opioid receptors in the central nervous system (delta, mu, and kappa). Activation of delta-receptors causes analgesia; mu-receptors—supraspinal analgesia, euphoria, physical dependence, respiratory depression, and stimulation of vagal centers; kappa-receptors—spinal analgesia, sedative effect, and miosis.

It suppresses interneuronal transmission of pain impulses in the central part of the afferent pathway, reduces the emotional assessment of pain, and induces euphoria, which promotes the development of dependence (both physical and psychological). By reducing excitability of pain centers, it exerts an anti-shock effect. At high doses, it exhibits sedative activity and induces sleep. It inhibits conditioned reflexes, reduces summation capacity of the central nervous system, and potentiates the effects of depressant agents. It reduces excitability of the thermoregulatory center and stimulates vasopressin secretion. It has practically no effect on vascular tone. It depresses the respiratory center, reduces excitability of the cough center, stimulates vagal nuclei leading to bradycardia, and stimulates neurons of the oculomotor nerves, causing pupillary constriction (miosis). It may stimulate chemoreceptors in the trigger zone of the medulla oblongata, inducing nausea and vomiting. However, it suppresses the vomiting center; therefore, repeated administration of the drug or emetics given after it do not induce vomiting. It increases smooth muscle tone in internal organs: sphincters of Oddi, urinary bladder, gastric antrum, intestines, biliary tract, and bronchi. It reduces peristalsis, slows down movement of food masses, and promotes constipation.

Omnopon NEO is in some cases better tolerated than morphine and less frequently causes spasm of smooth muscles (due to the spasmolytic effects of papaverine and noscapine).

It has been reported that in male rats, morphine may reduce fertility and cause chromosomal damage in germ cells.

Pharmacokinetics

After subcutaneous administration, it is rapidly absorbed into systemic circulation. The majority of the dose is metabolized, forming glucuronides and sulfates. It penetrates histohematic barriers, including the blood-brain barrier and placental barrier (it may cause respiratory center depression in the fetus), and enters breast milk. The elimination half-life is 2–3 hours. It is excreted primarily via the kidneys as metabolites—about 90%; the remainder is excreted with bile. Small amounts are secreted by all exocrine glands. In patients with impaired liver or kidney function, as well as in elderly patients, the elimination half-life may be prolonged.

Clinical characteristics.

Indications.

Severe pain, including pain associated with malignant tumors, myocardial infarction, severe injuries, preoperative preparation, and the postoperative period.

Contraindications.

Respiratory impairment due to respiratory center depression, severe hepatic insufficiency, head trauma, increased intracranial pressure, stroke, cachexia, epileptic status, general severe exhaustion, abdominal pain of unknown etiology, acute alcohol intoxication, delirium, concomitant use of monoamine oxidase inhibitors (MAOIs), fever, arterial hypotension, atrioventricular conduction disturbances, coma, glaucoma, bronchoobstructive syndrome, age over 75 years, bronchospasm or predisposition to bronchospasm, individual hypersensitivity to components of the drug.

The drug is contraindicated in children (under 18 years of age) for post-tonsil-/adenoidectomy pain relief in the treatment of obstructive sleep apnea, as these patients are more susceptible to respiratory complications. The drug is contraindicated in children under 12 years of age.

Interaction with other medicinal products and other forms of interactions.

When used concomitantly: with other agents that depress the central nervous system (benzodiazepines or drugs with similar effects, gabapentin or pregabalin), enhanced central nervous system depression may occur, increasing the risk of sedation, respiratory depression, coma, and fatal outcome; therefore, doses and duration of concomitant therapy should be reduced (see section "Special precautions"). With beta-blockers – enhanced central nervous system depressant effects. With phenylbutazone – possible morphine accumulation. With dopamine – reduced analgesic effect of Omnopon NEO. With cimetidine – enhanced respiratory depression. With phenothiazine derivatives and barbiturates – enhanced hypotensive effect and respiratory depression. Long-term use of barbiturates (especially phenobarbital) or narcotic analgesics may lead to development of cross-tolerance. Chlorpromazine enhances the analgesic, miotic, and sedative effects of Omnopon NEO.

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

The spasmolytic effect of papaverine is enhanced by diphenhydramine, metamizole, and diclofenac. The hypotensive effect is enhanced when used concomitantly with antihypertensive agents, tricyclic antidepressants, procainamide, reserpine, and quinidine.

When used concomitantly with cardiac glycosides, a pronounced enhancement of myocardial contractile function is observed.

Papaverine may reduce the antiparkinsonian effect of levodopa and the antihypertensive effect of methyldopa. When used concomitantly with intracavernous alprostadil, there is a risk of priapism. Phentolamine potentiates the effect of papaverine on the corpora cavernosa of the penis when administered together.

Papaverine may potentiate the effects of alcohol when used concomitantly.

In patients who smoke, papaverine metabolism is accelerated, and its plasma concentration and pharmacokinetic effects are reduced.

A possible reduction in the tonic effect of anticholinergic drugs on smooth muscle under the influence of papaverine may occur.

A possible reduction in the spasmolytic activity of papaverine under the influence of morphine may occur. However, papaverine is used with morphine to reduce the spasmogenic effect of the latter. Cases of hepatitis development have been reported with concomitant use of papaverine and furadantin.

When used concomitantly, reserpine-containing drugs enhance the antihypertensive effect of papaverine.

When combined with antidepressants, an enhanced hypotensive effect may occur.

In patients with acute coronary syndrome who received morphine, delayed and reduced effects of oral antiplatelet therapy with P2Y12 inhibitors (e.g., prasugrel, clopidogrel, ticagrelor) have been observed. This interaction may be related to reduced gastrointestinal motility and may apply to other opioids. The clinical significance of this interaction is unknown, but data suggest a potential reduction in the efficacy of P2Y12 inhibitors in patients who received them concomitantly with morphine (see section "Special precautions"). For patients with acute coronary syndrome in whom morphine cannot be discontinued and for whom rapid P2Y12 inhibition is considered critical, parenteral administration of a P2Y12 inhibitor may be advisable.

Special precautions for use.

Do not use for labor analgesia, as morphine crosses the placental barrier and may cause respiratory depression in the newborn.

Use with caution in patients with impaired liver or kidney function, hypothyroidism, adrenal insufficiency, prostate hypertrophy, shock, myasthenia gravis, inflammatory gastrointestinal disorders, and in patients aged 60 years and older.

Morphine causes pronounced euphoria. Repeated use may lead to drug dependence.

Withdrawal syndrome may develop several hours after discontinuation of prolonged treatment and peak at 36–72 hours.

Alcohol consumption must be avoided during treatment.

In case of overdose, activated charcoal may be administered orally if the patient is conscious.

Patients must be closely monitored for signs of respiratory depression and sedation. Therefore, patients and caregivers should be informed about these symptoms (see section "Interaction with other medicinal products and other forms of interaction").

Respiratory depression requires respiratory support and administration of a stimulatory antagonist—naloxone. The use of the opioid antagonist naloxone in opioid-dependent individuals may precipitate withdrawal symptoms. Supportive therapy includes respiratory support and reversal of shock by administering naloxone, the dose of which depends on the severity of respiratory depression and the level of coma.

High doses of the drug, especially in elderly patients, may lead to respiratory depression and hypotension, resulting in circulatory failure and coma. The occurrence of adverse reactions depends on individual sensitivity to opioid receptors. Hyperthermia may occur in elderly patients. Use the drug with caution in patients with supraventricular tachycardia, severe heart failure with signs of decompensation, and in those with stenosing coronary atherosclerosis.

Seizures are more frequently observed in children. The drug's toxicity depends on individual sensitivity to morphine and the amount administered.

Comatose state is characterized by pinpoint pupils and respiratory depression, which may indicate overdose. Pupil dilation indicates the development of hypoxia.

The drug is not recommended for use in children with impaired respiratory function, including neuromuscular disorders, severe cardiac and/or respiratory insufficiency, multiple injuries, or major surgical procedures, as these factors may exacerbate codeine/morphine toxicity symptoms. The drug may be used in children aged 12 years and older only if non-opioid analgesics (such as ibuprofen, paracetamol) are ineffective, due to the risk of respiratory depression.

Morphine carries the same risks of abuse as other potent opioid agonists and should be used with special caution in patients with a history of alcohol or drug dependence.

Cases of hyperalgesia, where increasing the dose fails to provide analgesic effect, may occur very rarely, particularly with high-dose administration. In such cases, the dose should be reduced or the drug replaced with another opioid medicinal product.

Data indicate reduced fertility and increased risk of chromosomal damage in rats following morphine administration.

Rifampicin reduces plasma morphine levels when co-administered. The analgesic effect of morphine should be monitored, and the morphine dose adjusted during and after rifampicin treatment.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially sodium-free.

Acute chest syndrome (ACS) in patients with sickle cell anemia

Due to a possible association between ACS development and morphine use in patients with sickle cell anemia receiving morphine during vaso-occlusive crisis, careful monitoring for symptoms of ACS is required.

Sleep-related breathing disorders

Opioids may cause sleep-related breathing disorders, including central sleep apnea (CSA) and nocturnal hypoxemia. Opioid use increases the risk of CSA in a dose-dependent manner. For patients with CSA, consider reducing the total opioid dose.

Adrenal insufficiency

Opioid analgesics may cause reversible adrenal insufficiency, requiring patient monitoring and glucocorticoid replacement therapy. Symptoms of adrenal insufficiency may include nausea, vomiting, loss of appetite, increased fatigue, weakness, dizziness, or low blood pressure.

Reduced sex hormone levels and increased prolactin levels

Long-term use of opioid analgesics may be associated with reduced sex hormone levels and increased prolactin levels. Symptoms include decreased libido, impotence, or amenorrhea.

Severe skin reactions (SSRs)

Cases of acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported in association with morphine use. Most of these reactions occurred within the first 10 days of treatment. Patients should be informed about the signs and symptoms of AGEP and advised to seek medical attention if such symptoms occur.

If signs or symptoms suggestive of these skin reactions appear, morphine should be discontinued and alternative treatment considered.

Hepatobiliary system disorders

Morphine may cause dysfunction and spasm of the sphincter of Oddi, thereby increasing intra-abdominal pressure and raising the risk of symptoms related to the biliary tract and pancreatitis.

Risk associated with concomitant use of sedatives, such as benzodiazepines or benzodiazepine-like drugs

Concomitant use of morphine and sedative medicinal products, such as benzodiazepines or drugs with similar effects, may result in sedation, respiratory depression, coma, and death (see section "Interaction with other medicinal products and other forms of interaction"). When concomitant use of these sedatives is necessary and no alternative treatment options are available, these risks should be taken into account. If concomitant use of morphine with sedatives is decided upon, the lowest effective doses should be used, and the duration of treatment should be as short as possible.

Opioid use disorders (OUD) (abuse, dependence, and withdrawal syndrome)

Tolerance and physical and/or psychological dependence may develop after repeated opioid use; repeated use of the drug may lead to OUD. Higher doses and longer duration of opioid treatment may increase the risk of OUD development. Misuse or intentional inappropriate use of morphine may lead to overdose and/or death. The risk of OUD is increased in patients with a personal or family history (parents or siblings) of substance use disorders (including alcohol-related disorders), in current tobacco users, or in patients with existing mental disorders (e.g., severe depression, anxiety, or personality disorders).

Morphine carries the same risks of abuse as other potent opioid agonists and should be used with special caution in patients with a history of alcohol or drug dependence.

Before initiating and during morphine treatment, the treatment goals and a plan for discontinuation should be discussed with the patient (see section "Method of administration and dosage"). Patients should also be informed about the risks and signs of OUD before and during treatment. Patients should be advised to contact their physician if such signs appear.

The potential risk can be minimized by appropriate selection of morphine dose or formulation and by gradual discontinuation of morphine. Abrupt discontinuation or prolonged intervals between doses may precipitate withdrawal syndrome.

Patients should be monitored for signs of drug-seeking behavior (e.g., early requests for additional doses). This includes monitoring concomitant use of opioids and psychoactive medicinal products (e.g., benzodiazepines). Patients showing signs and symptoms of OUD should be referred for consultation with an addiction specialist.

Oral antiplatelet therapy with P2Y12 inhibitors (e.g., prasugrel, clopidogrel, ticagrelor)

Reduced efficacy of P2Y12 inhibitors was observed during the first 24 hours of concomitant treatment with morphine (see section "Interaction with other medicinal products and other forms of interaction").

Use during pregnancy or breastfeeding.

The medicinal product is contraindicated during pregnancy and breastfeeding.

Newborns of mothers who received opioid analgesics during pregnancy should be monitored for neonatal abstinence syndrome. Treatment may include opioid and supportive therapy.

Fertility. Preclinical data indicate that morphine may reduce fertility (see section "Pharmacological properties").

Ability to affect reaction speed when driving or operating machinery.

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

Method of Administration and Dosage

The medicinal product should be administered subcutaneously. The dosage regimen is individual. Generally, adults are given 1 ml.

The dose should be reduced in elderly patients, individuals with psychiatric disorders, and patients with hepatic or renal impairment.

Omnopon NE is the drug of choice in oncological diseases. The appropriate dose should be administered every 12–24 hours depending on the severity of pain.

Maximum doses for adults: single dose – 1.5 ml; daily dose – 5 ml.

Goals of treatment and its discontinuation

Before initiating treatment, the treatment strategy—including duration, treatment goals, and a plan for treatment discontinuation—should be discussed and agreed upon with the patient, in accordance with the pain management protocol. During therapy, the physician should maintain regular contact with the patient to assess the need for continued treatment, consider the possibility of treatment discontinuation, and, if necessary, adjust the dosage. When the patient no longer requires therapy, it may be advisable to gradually reduce the dose to prevent the development of withdrawal syndrome. In the absence of adequate pain control, consider the possibility of hyperalgesia, tolerance, or progression of the underlying disease (see section "Special Warnings and Precautions for Use").

Duration of treatment

The medicinal product should not be used longer than necessary.

Children.

Use in children (under 18 years of age) for postoperative pain relief following tonsil-/adenoidectomy for the treatment of obstructive sleep apnea is contraindicated, as these patients are more susceptible to respiratory complications.

The medicinal product is contraindicated in children under 12 years of age.

Overdose.

The earliest and most dangerous manifestation is respiratory center depression. Respiratory failure may lead to fatal outcome. Aspiration pneumonia is possible.

Treatment: general resuscitation measures, administration of opioid receptor antagonists and agonist-antagonists (naloxone, nalorphine). The specific antidote for morphine poisoning is naloxone (0.01 mg/kg intravenously, repeated every 20–30 minutes if necessary, then intramuscularly every 2 hours until respiration is restored). Perform transfusion therapy, oxygen therapy, and peritoneal dialysis. Central nervous system stimulants (analgetics) are contraindicated.

Adverse reactions.

Cardiovascular system: bradycardia or tachycardia, cardiac arrhythmias, orthostatic hypotension, arterial hypotension may occur during prolonged use.

Respiratory system: respiratory depression, bronchospasm, apnea, central sleep apnea syndrome.

Central and peripheral nervous system: sedative or excitatory effects (especially in elderly patients), delirium, hallucinations, increased intracranial pressure with a risk of subsequent cerebral circulation impairment, headache, hypothermia, drowsiness, weakness, dizziness, mood disturbances, anxiety, hyperhidrosis, dysphoria, allodynia, hyperalgesia (see section "Special precautions for use"). When high doses are used, euphoria and muscle rigidity may develop.

Eye organs: miosis, visual disturbances, diplopia.

Gastrointestinal system: dry mouth, nausea, vomiting, constipation, anorexia, diarrhea, pancreatitis.

Hepatobiliary system: biliary tract spasm leading to increased levels of biliary enzymes, jaundice, hepatic function disturbances, increased hepatic transaminase activity, sphincter of Oddi spasm.

Urinary system: impaired urine flow or worsening of urinary flow in patients with benign prostatic hyperplasia and urethral stenosis.

Blood and lymphatic system: eosinophilia.

Skin, subcutaneous tissue and immune system: allergic reactions including pruritus, urticaria, anaphylactic shock, skin rash, skin hyperemia, anaphylactoid reactions, acute generalized exanthematous pustulosis (AGEP).

Psychiatric disorders: development of dependence.

General disorders: decreased libido, sweating.

Other: injection site reactions, including thrombosis at the injection site, withdrawal syndrome.

Drug dependence and withdrawal syndrome

Repeated administration of opioid analgesics, even at therapeutic doses, may lead to development of physical and/or psychological dependence and tolerance. The risk of drug dependence may vary depending on individual patient risk factors, dosage, and duration of treatment. Abrupt discontinuation of treatment or administration of opioid antagonists may trigger withdrawal syndrome; sometimes withdrawal symptoms may occur between doses (see section "Special precautions for use").

Physical withdrawal symptoms: body aches, tremor, restless legs syndrome, diarrhea, abdominal cramps, flu-like symptoms, nausea, tachycardia, mydriasis.

Psychological withdrawal symptoms: anxiety, irritability, dysphoric mood.

One of the factors contributing to drug dependence is drug craving.

Reporting of adverse reactions.

Reporting of adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store in the 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 pack; 1, 2 or 20 blisters per carton.

Prescription status.

Prescription only.

Manufacturer.

Limited liability company "Kharkiv Pharmaceutical Enterprise "Zdorovya Narodu".

Manufacturer's address and location of operations.

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