Morphine - instructions for use, dose, side effects, contraindications

Active substanceMorphineMorphine

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Morphine

solution PC

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Morphine

solution for injections

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Morphine sulfate

capsules inwards

MOSCOW ENDOCRINE FACTORY, FSUE Russia

MST Continus

pills inwards

Mundifarma GmbH, Germany Germany

Dosage form: & nbspinjection

Composition:

1 ml of the solution contains:

Active substance:

morphine hydrochloride trihydrate - 10.00 mg, equivalent to 8.56 mg of morphine hydrochloride

Excipients:

disodium edetate (disodium ethylenediaminetetraacetic acid) - 200 μg,

solution of hydrochloric acid 0.1 M - to a pH of 3.0 to 4.0,

water for injection - up to 1 ml.

Description:Transparent colorless or slightly colored liquid.

Pharmacotherapeutic group:Analgesic narcotic. It refers to List II of the List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation

ATX: & nbsp

N.02.A.A.01 Morphine

Pharmacodynamics:

Morphine is a phenanthrenic opium poppy alkaloid (Papaver somniferum), an agonist of opioid receptors. Has a high affinity for μ-opioid receptors.

Central action

Morphine has analgesic, antitussive,sedative, tranquilizing, depressing breathing, miotic, antidiuretic, emetic and antiemetic (later action), as well as hypotensive and heart rate-slowing actions.

Peripheral action

Constipation, reduction of biliary tract sphincters, increased muscle tone of the bladder and sphincter of the bladder, slowing the emptying of the stomach by reducing the pylorus, erythema; urticaria, pruritus and asthmatic bronchospasm due to the release of histamine, as well as the effect on the hypothalamic-pituitary axis, leading to a disruption of the effect or production of hormones such as corticosteroids, sex hormones, prolactin and antidiuretic hormone. In connection with these hormonal disorders, the appearance of the corresponding symptoms.

The onset of action after oral administration begins 30 to 90 minutes later. The duration of action is 4-6 hours and significantly increases in the case of sustained release forms. After intramuscular and subcutaneous injection, the onset of action is manifested after 15-30 minutes, with intravenous administration, after a few minutes.The duration of action does not depend on the route of administration and is 4-6 hours. After epidural and intrathecal administration, the focal analgesic effect is detected after a few minutes. The duration of action after epidural administration is 12 hours, and when intrathecal administration exceeds this value.

With epidural and intrathecal administration, the analgesic effect is achieved with a plasma concentration not exceeding 10 ng / ml.

In in vitro studies and in laboratory animals, natural opioids, such as morphine, show a different effect on the links of the immune system. The clinical significance of these phenomena is not known.

Pharmacokinetics:

Suction

After intramuscular injection, the absorption of morphine proceeds rapidly and completely, after 20 minutes the concentration (Cmax) of the drug reaches its peak.

Distribution

Morphine binds to approximately 20-35% of blood plasma proteins, mainly with albumin fraction. The volume of distribution is 1 to 4.7 l / kg after a single intravenous injection of 4 to 10 mg of the drug. High concentrations of morphine are found in the tissues of the liver, kidneys, gastrointestinal tract and muscles. Penetrates through the blood-brain barrier.

Metabolism

Morphine is metabolized predominantly in the liver, as well as in the intestinal epithelium. An important step is the glucuronation of the phenol hydroxyl group through hepatic uridine phosphate-glucuronyl transferase and N-demethylation. The main metabolites are morphine-3-glucuronide (predominantly) and morphine-6-glucuronide (to a lesser extent). In addition, sulfate conjugates and oxidized metabolites such as normorphine, morphine-N-oxide and morphine, hydroxylated in position 2. The half-life of glucuronides is much longer than free morphine. Morphine-6-glucuronide is biologically active. The likelihood of prolonged action in patients with renal insufficiency may be due to this metabolite.

Excretion

After parenteral administration of morphine in urine, 80% of the administered dose is detected: 10% unchanged, 4% as normorphine and 65% as glucuronides: morphine-3-glucuronide and morphine-6-glucuronide (10: 1 ratio). The final half-life of morphine is subject to large intra-individual variations. After parenteral administration, the mean values of the half-life are 1.7 to 4.5 hours, sometimes reaching 9 hours. Approximately 10% of the morphine glucuronides are excreted with bile, falling into the feces.

Indications:Coping with severe pain.

Contraindications:

Hypersensitivity to the active substance and excipients;

Paralytic intestinal obstruction;

Inhibition of breathing;

Severe obstructive pulmonary disease;

Acute stomach syndrome;

Blood clotting disorders and infectious lesions at the injection site with epidural administration.

Pregnancy and lactation:

Pregnancy

Data on medical use are not sufficient to assess potential teratogenic risk. A potential association with an increased incidence of herniation has been reported. Morphine penetrates the placental barrier. Studies in animals indicate potential abnormalities in offspring during pregnancy: anomalies in the development of the central nervous system, growth retardation, testicular atrophy, and disorders in the neurotransmitter systems. In addition, in some species of animals morphine influenced the sexual behavior of males and the fertility of females. Concerning, morphine It is allowed to apply during pregnancy, if the benefits for the mother clearly exceed the risk to the fetus. Unambiguous data on the mutagenicity of morphine are obtained: morphine is clastogen, this effect is also manifested in generative cell lines. Due to the mutagenic properties of morphine, it should be administered to both men and women with a childbearing potential using effective contraceptive methods.

With prolonged use during pregnancy, the development of the syndrome of "withdrawal" in newborns was reported.

Childbirth

Morphine is able to both extend and shorten the duration of labor. Newborns, whose mothers were injected with narcotic analgesics during childbirth, should be monitored for respiratory depression and withdrawal syndrome, and injected opioid receptor antagonists if necessary.

Lactation

Morphine penetrates into breast milk, its concentration in it exceeds the plasma concentration in the mother. Since a clinically significant concentration can be achieved in newborns, breastfeeding is not recommended.

Dosing and Administration:

Dose of the drug Morphine should be selected individually, depending on the severity of the pain syndrome and the individual sensitivity of the patient.

The recommended single dose range for adults and children should be considered as a guideline when selecting an individual dose.

Intramuscularly or subcutaneously

Adults

10-30 mg.

Children

0,05 - 0,2 mg / kg of body weight; a single dose should not exceed 15 mg.

Intravenously

Only if you need to quickly achieve an analgesic effect.

Adults

5 - 10 mg slowly (10 mg per minute, if necessary, dilute in isotonic sodium chloride solution).

Children

0,05 - 0,1 mg / kg of body weight (it is recommended to dilute in isotonic sodium chloride solution).

Epidurally

Adults

1 - 4 mg (diluted in 10-15 ml isotonic sodium chloride solution).

Children

0,05 - 0,1 mg / kg of body weight (it is recommended to dilute in isotonic sodium chloride solution).

With intramuscular, subcutaneous and intravenous routes, single doses may be administered every 4 to 6 hours, with a gradual decrease in the frequency of administration. Due to a longer duration of action with epidural administration, the drug is usually administered once a day.

Patients with hepatic and renal insufficiency, as well as patients with delayed peristalsis of the gastrointestinal tract, should receive morphine dose with caution.

Elderly

Patients older than 75 years and physically impaired patients are generally more sensitive to morphine. In this regard, it is necessary to select more carefully the dose and (or) less often to administer the drug. If necessary, switch to smaller dosages.

Special instructions for dose adjustment

The dose should be high enough, but at the same time, one should strive to introduce the minimum effective dose. In the treatment of chronic pain, the drug is preferably administered on a regular basis in a fixed schedule.

If analgesia is adjuvant (for example, during surgery, blockade of the plexus), after the procedure the dose needs to be adjusted.

Method and method of administration

The drug is administered intramuscularly or subcutaneously, intravenously and epidurally.

The drug should not be used for longer than required. In the treatment of chronic pain, it is necessary to regularly check the need for its prolongation (if necessary, due to short-term interruptions in the introduction), and also to review the dose. If necessary, go to other dosage forms. Since the risk of symptoms of "cancellation" with abrupt withdrawal of treatment is higher, with the withdrawal of therapy should gradually reduce the dose.

Side effects:

The frequency of undesirable reactions was estimated in the following gradation: very often (≥ 1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10 000, <1/1000), very rarely (<1/10 000), the frequency is not known (it is impossible to estimate based on the data presented).

Heart Disease

Infrequent: clinically significant decrease and increased heart rate.

The frequency is unknown: a feeling of heartbeat, heart failure.

Disturbances from the nervous system

Morphine dose-depress respiratory depression and causes a different degree of sedation from slight weakness to severe stunning.

Often: headache, dizziness, perversion of taste.

Very rarely: tremor, convulsions - especially with epidural injection. The frequency is unknown: hyperalgesia and allodynia (especially when high doses are introduced), resistant to further increase in dose (a dose reduction or an opioid analgesic change may be required). General weakness until loss of consciousness.

When epidurally administered, the following undesirable reactions are also possible:

Very rarely: serious neurological disorders, such as paralysis (for example, due to the formation of a granuloma at the tip of the catheter (see also section "Special instructions").Prolonged respiratory depression (up to 24 hours).

Disturbances on the part of the organ of sight

Very rarely: blurred vision, diplopia and nystagmus.

A typical undesirable reaction is the constriction of the pupil.

Disturbance of the respiratory system, chest and mediastinum

Rarely: bronchospasm.

Very rarely: dyspnea.

Patients in intensive care wards experienced noncardiogenic pulmonary edema.

Disorders from the gastrointestinal tract

Often: vomiting (especially at the beginning of therapy), indigestion.

Rarely: increased activity of pancreatic enzymes, pancreatitis. There was a loss of teeth, but the causal relationship with the use of morphine is not established.

The frequency is unknown: depending on the dose, it can cause nausea and dry mouth. With prolonged use, constipation is often noted.

Violation of the kidneys and urinary tract

Often: violation of urination.

Rarely: renal colic.

Disturbances from the skin and subcutaneous tissues

Often: sweating, hypersensitivity reactions, such as hives, itching.

Very rarely: other types of rashes, for example, exanthema.

Frequency unknown: redness of face.

Musculo-skeletal and connective tissue disorders

Very rarely: violent muscle twitching, muscle spasm, muscle stiffness.

Endocrine disorders

Very rarely: the syndrome of inappropriate production of antidiuretic hormone (SNAPADH, manifested by hyponatremia).

Metabolic and alimentary disorders

Often: decreased appetite.

Infections and invasions

With epidural administration of morphine, the following undesirable reactions are possible:

Infrequent: relapse of herpetic lesions of the lips.

Vascular disorders

Infrequently: clinically significant decrease and increase in blood pressure.

General violations and violations at the site of introduction

Very rarely: peripheral edema, asthenia, weakness, chills.

The frequency is unknown: addiction and dependence.

Immune system disorders

The frequency is unknown: anaphylactic and anaphylactoid reactions.

Disturbances from the liver and bile ducts

Rarely: biliary colic.

Very rarely: increased activity of liver enzymes.

Violations of the genitals and mammary gland Very rarely: erectile dysfunction, amenorrhea.

Mental disorders

Morphine leads to a variety of mental undesirable reactions, the intensity and nature of the manifestations of which are individual (depending on the personality and duration of therapy).

Very often: a change in mood, usually euphoria, sometimes dysphoria. Often: change of attention (usually oppression, sometimes enhancement or agitation), insomnia and changes in cognitive and sensory abilities (for example, disturbance of thinking, confusion of thoughts, cognitive impairment / hallucinations, confusion).

Rarely: withdrawal symptoms.

Very rarely: dependence (see also section "Special instructions"), a decrease in libido and potency.

Overdose:

Symptoms

Since the indices of individual sensitivity to morphine very much fluctuate, in adults, even with a single subcutaneous or intravenous injection of 30 mg of morphine, overdose symptoms may occur.

The triad of symptoms of opioid overdose: miosis, respiratory depression, coma. At first, the size of the pupils becomes the size of the pinhead. However, against the background of pronounced hypoxia, the pupils greatly expand. The frequency of breathing is sharply reduced (up to 2-4 breaths per minute).The patient becomes cyanotic.

An overdose of morphine leads to confusion and stupor up to the coma. Initially, blood pressure remains normal, but as the intoxication increases, they gradually decrease, which in the future can lead to shock. Possible tachycardia, bradycardia and rhabdomyolysis. Muscle relaxation, sometimes (especially in children), generalized seizures may occur. Death occurs mainly due to respiratory failure or complications such as pulmonary edema.

Treatment

In patients with unconscious apnea, artificial lung ventilation, intubation, and intravenous administration of opioid receptor antagonists (eg, 0.4 mg naloxone intravenously) are performed. Against the background of persistent respiratory failure, it is necessary to repeat the administration of a single dose of naloxone 1 to 3 times every 3 minutes to normalize the respiration rate and the patient's reaction to painful stimuli.

It is necessary to have constant medical supervision (at least 24 hours). Since the action of opioid receptor antagonists is shorter than that of morphine, the possibility of repeated occurrence of respiratory failure should be considered.A single dose of naloxone for children is 0.01 mg per 1 kg of body weight.

Additional measures of protection against supercooling and replenishment of lost liquid may be required.

Interaction:

The following drug interactions should be considered:

The simultaneous use of morphine with other central drugs such as tranquilizers, anesthetics, hypnotics and sedatives, antipsychotics, barbiturates, antidepressants, antihistamines, antiemetics, and other opioids and alcohol may lead to an increase in unwanted morphine reactions in its standard dose . Particular concern is the possibility of developing respiratory depression, sedation, hypotension and coma.

Drugs with m-cholinoblocking activity (for example, psychotropic drugs, antihistamines, antiemetics, anti-Parkinsonian drugs) can enhance m-cholinoblocking unwanted reactions of opioids (eg constipation, dry mouth, micturition).

Cimetidine and other inhibitors of microsomal liver enzymes can increase the plasma concentration of morphine byaccount of the slowing of its metabolism. Morphine can enhance the muscle relaxant effect of muscle relaxants.

Against the backdrop of concomitant use of pethidine and certain antidepressants (monoamine oxidase inhibitors), life-threatening drug interactions have occurred during the previous 14 days, leading to impairment from the central nervous, respiratory and cardiovascular systems. Such interactions are not excluded for morphine.

Simultaneous use with rifampicin can lead to a weakening effect of morphine. When epidural use of morphine should be avoided systemic administration of opioids (except for cases of emergency relief of pain).

Morphine should not be mixed with other solutions before administration.

Special instructions:

In the following conditions, it is necessary to carefully monitor and, if necessary, reduce the dose: opioid dependence, impaired consciousness, diseases in which the respiratory center and respiratory function should be avoided, cor pulmonale, increased intracranial pressure (in the absence of ventilation), hypotension due to hypovolemia,hyperplasia of the prostate with urinary retention (risk of rupture of the bladder due to urinary retention), renal colic, gallbladder disease, obstructive and inflammatory bowel disease, pheochromocytoma, pancreatitis, hypothyroidism, epileptic seizures and increased seizure tendencies, epidural administration with concomitant diseases of the nervous system , as well as with the simultaneous administration of systemic glucocorticoids. The main danger of opioid overdose is respiratory depression.

The use of morphine can lead to the development of mental dependence. The abolition after repeated administration or use of opioid receptor antagonists can lead to a typical picture of the "withdrawal" syndrome. When used correctly in patients with chronic pain, the risk of mental dependence is significantly reduced and requires a differentiated assessment.

Children under 1 year of age morphine Use with caution in connection with an increased risk of adverse events from the respiratory system.

Morphine is used in pre-, intra- and postoperative periods. In comparison with unoperated patients morphine should be used with caution in patients who underwent surgery, due to the increased risk of intestinal obstruction and respiratory depression.

The analgesic effect of morphine can lead to serious complications, for example, due to masking the symptoms of intestinal perforation.

In order to minimize the risk of potentially irreversible neurological complications, patients undergoing continuous epidural administration of morphine should be monitored for early signs of granuloma formation at the tip of the catheter (eg, analgesic effect reduction, unforeseen exacerbation of pain, neurological symptoms).

With adrenal insufficiency (for example, Addison's disease) it is necessary to monitor the plasma concentration of cortisol and, if necessary, to correct the doses of substitution therapy.

In connection with mutagenic properties morphine should be administered to men and women with childbearing potential only when using effective contraceptive measures (see section "Application during pregnancy and during breastfeeding").

The use of morphine can give positive results in the analysis for doping. The health consequences of the use of morphine should not be ignored, since the serious consequences of its use can not be ruled out.

Effect on the ability to drive transp. cf. and fur:

Morphine is able to disrupt attention and speed of reactions, leading to the inability to drive vehicles and work with mechanisms.

This effect is typical at the beginning of therapy, with increasing doses and changing drugs, as well as with simultaneous use with alcohol and sedatives.

The attending physician should evaluate the situation on an individual basis. Against the backdrop of stable therapy, a ban on engaging in these activities is not necessary.

Form release / dosage:Solution for injection 10 mg / ml in ampoules of 1 ml.

Packaging:

5 ampoules in a contour cell box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1 or 2 contour packs with instruction on the use of the drug, a knife or scarifier ampullum in a pack of cardboard.

For 20, 50 or 100 contour cell packs with 20, 50 or 100 instructions for use of the drug, respectively,knives or scarifiers ampoules in boxes of cardboard or in boxes of corrugated cardboard (for inpatient).

When packing ampoules with notches, rings or break points, knives or scarifier ampoules do not.

Storage conditions:

List II of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation" in specially equipped premises, subject to a license for the specified type of activity.

In the dark place at a temperature of no higher than 20 ° C.

Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N001645 / 01

Date of registration:08.08.2008 / 06.12.2016

Expiration Date:Unlimited

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp17.05.2018

Illustrated instructions

Instructions

Morphine (Morphine)