Instruction for use: Codeine + Caffeine + Metamizole sodium + Paracetamol + Phenobarbital (Codeinum + Coffeinum + Methamizolum natrium + Paracetamolum + Phenobarbitalum)

Pharmacological groups

Paracetamol + Phenobarbital

Opioid narcotic analgesics in combinations

Nosological classification (ICD-10)

G43 Migraine

The pain of migraine, Migraine, hemiplegic migraine, Migraine headache, A migraine attack, Continuous headache, hemicranias

K08.8.0 * Painful toothache

Dentinal pain, Dentinal pains, Pain pulpitis, Anesthesia in dentistry, Pain syndromes in dental practice, Pain after removal of tartar, Pain when extracting a tooth, Toothache, Pain after dental interventions

M79.2 Neurology and neuritis, unspecified

Pain syndrome with neuralgia, Brachialgia, Occipital and intercostal neuralgia, Neuralgia, Neuralgic pain, Neuralgia, Neuralgia of intercostal nerves,Neuralgia of the posterior tibial nerve, Neuritis, Neuritis traumatic, Neuritis, Neurological Pain Syndromes, Neurological contractures with spasms, Acute neuritis, Peripheral neuritis,Post-traumatic neuralgia,Severe pain of a neurogenic nature, Chronic neuritis, Essential neuralgia

N94.6 Dysmenorrhea Unspecified

Pain during menstruation, Functional disorders of the menstrual cycle, Menstrual cramps, Emmeniopathy, Pain during menstruation, Painful menstrual irregularities, algomenorrhea, algomenoreya, Pain smooth muscle spasm, Pain spasm of smooth muscles (renal and biliary colic, intestinal spasms, dysmenorrhea), Pain spasm of smooth muscles of internal organs (kidney and biliary colic, intestinal spasms, dysmenorrhea), Disalgomenoreya, dysmenorrhea, Dysmenorrhea (essential) (Exfoliative), menstrual disorder, menstruation painful, metrorrhagia, Violation of the menstrual cycle, Menstrual irregularities, Prolaktinzavisimoe menstrual disorders, Prolaktinzavisimoe menstrual dysfunction, Pain spasm of smooth muscles of internal organs, Spasmodic dysmenorrhea, Primary disalgomenoreya

R51 Headache

Pain in the head, Cephalgia, Pain with sinusitis, Pain in the back of the head, Painful headache, Headache of vasomotor genesis, Headache of vasomotor origin, Headache with vasomotor disorders, Headache, Neurological headache, Serial headache

R52.0 Acute pain

Acute pain syndrome, Acute pain syndrome with osteoarthritis, Acute pain syndrome of traumatic origin, Severe pain of a neurogenic nature, Severe pain, Pain syndrome at delivery

R52.2 Other constant pain

Pain syndrome, rheumatic origin, Pain at vertebral lesions, Pain in the chamber, Pain for burns, Pain syndrome weak or moderate, Perioperative pain,Moderate to severe pain, Moderately or weakly expressed pain syndrome, Moderate to severe pain, Ear pain of otitis, Neuropathic pain, neuropathic pain

R52.9 Unspecified Pain

Pain after cholecystectomy, Pain shooting, Non-malignant pain, Obstetric and gynecological pain, Pain syndrome, Pain in the postoperative period, Pain in the postoperative period after orthopedic surgery, Pain of inflammatory genesis, Pain than cancer genesis, Pain syndrome after diagnostic procedures, Pain after surgery Diagnostic, Pain after surgery, Pain after orthopedic surgery, Pain after injuries, Pain after the removal of hemorrhoids, Pain at the non-rheumatic inflammation of nature, Pain in inflammatory lesions of the peripheral nervous system, Pain in diabetic neuropathy, Pain in acute inflammatory diseases of the musculoskeletal system, Pain when the tendon pathology, Pain smooth muscle spasm, Pain spasm of smooth muscles (renal and biliary colic, intestinal spasms, dysmenorrhea), Pain spasm of smooth muscles of internal organs, Pain spasm of smooth muscles of internal organs (kidney and biliary colic, intestinal spasms, dysmenorrhea), Pain in trauma syndrome, Pain with injuries and after surgical interventions, Pain in chronic inflammatory diseases of the musculoskeletal system, Pain with duodenal ulcer, Pain syndrome in gastric ulcer, Pain syndrome in gastric ulcer and duodenal ulcer, pain, Pain during menstruation, pain syndromes, painful condition, Painful foot fatigue, Sore gums when wearing dentures, Soreness of the cranial nerves exit points, Painful menstrual irregularities, Painful dressings, Painful muscle spasm, Painful teeth growth, Melosalgia, Pain in the area of the surgical wound, Pain in the postoperative period, Pain in the body, Pain after diagnostic procedures, Pain after orthopedic surgery, Pain after surgery, The pains of the flu, Pain in diabetic polyneuropathy, Pain for burns, Pain during sexual intercourse, Pain during diagnostic procedures, Pain during therapeutic procedures, for colds Pain, Pain in sinusitis, Pain in trauma, Pain traumatic, The pain in the postoperative period, Pain after diagnostic procedures, The pain after sclerotherapy, Pain after surgery, postoperative Pain, Pain postoperative and posttraumatic, posttraumatic pain, Pain when swallowing, Pain in infectious and inflammatory diseases of the upper respiratory tract, The pain of burns, The pain in traumatic muscle injury, Pain in trauma, The pain of tooth extraction, The pain of traumatic origin, Pain caused by spasm of smooth muscles, Expressed pain syndrome, Expressed pain syndrome, traumatic origin, Postoperative pain, Post-traumatic pain, Post-traumatic pain syndrome, Torpid pain, Traumatic pain, Traumatic pain, Mild pain, Moderately severe pain, Moderate pain, Polyarthralgia with polymyositis

T14.9 Injury unspecified

Pain syndrome after trauma, Pain syndrome with injuries, Pain syndrome with trauma and after surgery, Pain in case of injury, Pain of a traumatic nature, Joint pain with injuries, Postoperative and post-traumatic pain, Pain in case of injury, Pain of a traumatic origin, Severe pain syndrome of traumatic origin, Deep tissue damage, Deep scratches on the trunk, Closed injury, Minor Household Injuries, Minor skin damage, Violations of the integrity of soft tissues, Uncomplicated trauma, Extensive traumatic injury, Acute pain syndrome of traumatic origin, Edema with trauma, Postponed sports injuries, Post-traumatic pain, Soft tissue injuries, Joint wounds, Sports injuries, Injury, Traumatic pain, Traumatic pains, Traumatic infiltrate,Injuries to sports

T30 Thermal and chemical burns, unspecified

Pain syndrome with burns, Pain in burns, Pain with burns, Sluggishly healing post-burn wounds, Deep burns with a wet scab, Deep burns with abundant compartments, Deep burn, Laser burn, Burn, Burning of the rectum and perineum, Burn with mild exudation, Burn disease, Burn injury, Superficial burn, Superficial burn of I and II degree, Superficial skin burns, After-burn trophic ulcer and wound, Post-burn complication, Loss of fluid during burns, Sepsis burn, Thermal burns, Thermal skin lesions, Thermal burn, Trophic after-burn ulcers, Chemical burn, Surgical burn

T88.9 Complication of surgical and medical care, unspecified

Pain in the postoperative period, Pain in the postoperative period after orthopedic surgery, Pain syndrome after diagnostic procedures, Pain after surgery Diagnostic, Pain after surgery, Pain after orthopedic surgery, Pain after the removal of hemorrhoids, Pain in the application of excimer laser, Pain with injuries and after surgical interventions, Pain syndromes in the dental practice, Painful diagnostic intervention, Painful diagnostic manipulations, Painful instrumental diagnostic procedures, Painful instrumental manipulation, Painful treatments, Painful manipulations, Painful dressings, Painful therapeutic interventions, Pain in the area of the surgical wound, Pain in the postoperative period, Pain after diagnostic procedures, Pain after orthopedic surgery, Pain during diagnostic procedures, Pain during therapeutic procedures, Pain in orthopedics, The pain in the postoperative period, Pain after diagnostic procedures, The pain after sclerotherapy, The pain after dental surgery, postoperative Pain, Pain postoperative and posttraumatic, The pain of tooth extraction, Inflammation after surgery or injury, Inflammation after orthopedic surgery, Inflammation after surgery, The inflammatory syndrome after surgery, Festering postoperative fistula, Operating wound, Complications after tooth extraction

Z100 * CLASS XXII Surgical practice

Abdominal surgery, adenomectomy, Amputation, Coronary angioplasty, Angioplasty of the carotid arteries, Antiseptic skin treatment for wounds, Antiseptic Hand, Appendectomy, atherectomy, Balloon coronary angioplasty, Vaginal hysterectomy, The coronary bypass, Interventions in the vagina and cervix, Interventions on the bladder, Intervention in the mouth, Restoration and reconstructive surgery, Hand hygiene of medical personnel, Gynecologic surgery, Gynecological intervention, Gynecological surgery, Hypovolemic shock during operations, Disinfection of purulent wounds, Disinfection of wounds edges, Diagnostic intervention, Diagnostic procedures, Cervical Diathermocoagulation, Long-surgery, Replacing the fistula catheters, Infection in orthopedic surgery, Artificial heart valve, cystectomy, Short-term outpatient surgery, Short-term operation, Short surgical procedures, Krikotireotomiya, Blood loss during surgery, Bleeding during surgery and in the postoperative period, Kuldotsentez, laser photocoagulation, laser coagulation, retinal laser coagulation, Laparoscopy, Laparoscopy in Gynecology, CSF fistula, Small gynecological operations, Small surgical procedures, Mastectomy and subsequent plastic, mediastinotomy, Microsurgical operations on the ear, Mukogingivalnye operation, suturing, Minor surgery, neurosurgical operation, Immobilization of the eyeball in ophthalmic surgery, testectomy, pancreatectomy, Perikardektomiya, The period of rehabilitation after surgery, The period of, convalescence after surgery, Percutaneous transluminal coronary angioplasty, Pleural thoracentesis, Pneumonia postoperative and posttraumatic, Preparation for surgical procedures, Preparation for surgery, Preparation of the surgeon's hands before surgery, Preparation of the colon for surgical procedures, Postoperative aspiration pneumonia in neurosurgical and thoracic surgery, Postoperative nausea, Postoperative bleeding, postoperative granuloma, postoperative shock, The early postoperative period, myocardial revascularization, Radiectomy, gastric Resection, bowel resection, uterine Resection, liver Resection, enterectomy, Resection of part of the stomach, Reocclusion of the operated vessel, Bonding tissues during surgical procedures, Removal of sutures, Condition after eye surgery, Condition after surgery, Condition after surgery in the nasal cavity, Condition after gastrectomy, Status after resection of the small intestine, Condition after tonsillectomy, Condition after removal of the duodenum, Condition after phlebectomy, Vascular surgery, Splenectomy, Sterilization of surgical instruments, Sterilization of surgical instruments, sternotomy, Dental surgery, Dental intervention in periodontal tissues, strumectomy, Tonsillectomy, Thoracic surgery, total gastrectomy, Transdermal intravascular coronary angioplasty, Transurethral resection, Turbinektomiya, Removal of a tooth, cataract surgery, Removal of cysts, tonsillectomy, Removal of fibroids, Removing the mobile primary teeth, Removing polyps, Removing broken tooth, Removal of the uterus body, Removal of sutures, Urethrotomy, Fistula likvoroprovodyaschih ways, Frontoetmoidogaymorotomiya, Surgical infection, Surgical treatment of chronic limb ulcersm, Surgery, The surgery in the anal area, The surgery on the colon, Surgical practice, The surgical procedure, Surgical interventions, Surgery on the gastrointestinal tract, Surgical procedures on the urinary tract, Surgical procedures on the urinary system, Surgical intervention of the genitourinary system, Surgical procedures on the heart, Surgical manipulation, surgery, Surgery on the veins, Surgical intervention, Vascular surgery, Surgical treatment of thrombosis, cholecystectomy, Partial gastric resection, transabdominal hysterectomy, Percutaneous transluminal coronary angioplasty, Percutaneous transluminal angioplasty, Coronary artery bypass, tooth Extirpation, Extirpation of milk teeth, pulpectomy, pulsative cardiopulmonary bypass, tooth Extraction, teeth Extraction, cataract extraction, Electrocoagulation, endourological intervention, episiotomy, Etmoidotomiya, Complications after tooth extraction

Characteristics of Codeine + Caffeine + Metamizol sodium + Paracetamol + Phenobarbital

An analgesic combined agent whose action is due to its constituent components.

Pharmacology

Pharmacological action - analgesic.

Pharmacodynamics

The combined agent, has analgesic, antipyretic and antimigraine action. Caffeine stimulates the psychomotor centers of the brain, has an analeptic effect, enhances the effect of analgesics, eliminates drowsiness and fatigue, increases physical and mental performance. Codeine stimulates opiate receptors and enhances the analgesic effect of other analgesics that make up this remedy. Paracetamol, a non-narcotic analgesic, blocks COX (cyclooxygenase) mainly in the central nervous system (CNS), affecting pain centers and thermoregulation; has analgesic and antipyretic effect. Metamizole sodium - NSAIDs (non-steroidal anti-inflammatory drugs), has analgesic and anti-inflammatory effects. Phenobarbital - an antiepileptic agent, has a sedative, hypnotic, spasmolytic and miorelaksiruyuschee action.

Pharmacokinetics

Active substances combination codeine + caffeine + metamizol sodium + paracetamol + phenobarbital fairly quickly absorbed into the digestive tract (gastrointestinal tract). Their binding to plasma proteins is negligible. The active substances in the combination are relatively quickly metabolized, mainly in the liver. Caffeine, phenobarbital and metamizole sodium are inducers of cytochrome P450 isoenzymes and, in this connection, can influence the metabolism and toxicity of a number of drugs (drug). They are excreted mainly by the kidneys.

Cmax paracetamol in blood plasma is achieved 2 hours after ingestion. Metabolism occurs mainly in the liver to glucuronides and sulfate metabolites.

Metamizole sodium is rapidly absorbed from the gastrointestinal tract, and its Cmax in blood plasma is reached after 60-90 min.

Phenobarbital, caffeine and metamizol sodium penetrate the fetal system and are excreted into breast milk.

T1 / 2 codeine is 3-4 hours, caffeine 3-6 hours, paracetamol 1.5-3 hours, metamizole sodium 1-4 hours (up to 10 hours) and phenobarbital 90-100 hours.

Application of Codeine + Caffeine + Metamizol sodium + Paracetamol + Phenobarbital

Adults. Short-term symptomatic treatment of pain syndrome of various genesis in the absence of an adequate response to its arrest with monotherapy with analgesics: headache and toothache, migraine; algodismenorea; pain in case of injuries, burns and after surgical interventions; neuralgia and neuritis.

Children and teenagers from 12 years. Acute pain syndrome of average intensity, which can not be stopped by analgesics of the first choice for children with monotherapy (paracetamol or ibuprofen).

Contraindications

Hypersensitivity to any active component of the combination codeine + caffeine + metamizol sodium + paracetamol + phenobarbital; diseases of the hemopoietic system: hemorrhagic diathesis, aplastic anemia, leukopenia and agranulocytosis; bronchial asthma on the background of hypersensitivity to NSAIDs (aspirin bronchial asthma); congenital deficiency of glucose-6-phosphate dehydrogenase; hepatic porphyria; severe impairment of kidney and liver function; abuse of opiates, tranquilizers (anxiolytics) and sedatives in history; childhood and adolescence (up to 18 years) after tonsillectomy and / or adenoidectomy due to the syndrome of nocturnal apnea in view of the increased risk of serious and life-threatening adverse reactions (see "Precautions"); patients with high activity of the isoenzyme CYP2D6; peptic ulcer of the stomach and duodenum in the stage of exacerbation; children and adolescents (up to 18 years old) with impaired respiratory function, including neuromuscular disorders, severe heart or respiratory system diseases, upper respiratory tract or lung infections, multiple injuries or extensive surgical interventions (see "Precautions"); gluten enteropathy; simultaneous reception of alcohol; increased intraocular (glaucoma) and intracranial pressure; severe illness CCC (acute myocardial infarction, arrhythmia, arterial hypertension); children's age till 12 years; pregnancy; the period of breastfeeding.

Restrictions for use

Elderly age; simultaneous reception of drugs containing paracetamol.

pregnancy and lactation

When taking a combination of codeine + caffeine + metamizole sodium + paracetamol + phenobarbital during pregnancy, the active substances in its composition can have damaging effects on the fetus, and they are excreted in breast milk, so this combination is contraindicated during pregnancy and during pregnancy breastfeeding.

Codeine is contraindicated in the period of breastfeeding. When administered in therapeutic doses, codeine and its active metabolites can be excreted into breast milk in very low doses, and they are unlikely to affect the newborn. But if the patient has a high activity of the isoenzyme CYP2D6, then the body can produce higher concentrations of the metabolite codeine - morphine, which is excreted in breast milk and in very rare cases leads to symptoms of opioid toxicity in the newborn, which may be the result of a lethal outcome.

Side effects of Codeine + Caffeine + Metamizol sodium + Paracetamol + Phenobarbital

Most of the undesirable phenomena are temporary and pass after the cessation of treatment. When taking a combined remedy in some patients, the following undesirable reactions may occur.

On the part of the immune system: a high risk of developing anaphylactic reactions and agranulocytosis, which may occur at any stage of treatment, these reactions do not depend on the daily dose of the combined agent; hypersensitivity reactions - skin itching, rash, urticaria, bronchospasm (triggering an attack of bronchial asthma), dyspnea.

On the part of the gastrointestinal tract (gastrointestinal tract): dry mouth, epigastric pain, loss of appetite, nausea, vomiting, constipation and diarrhea.

From the side of the CNS (central nervous system): dizziness, headache, decreased speed of psychomotor reactions, drug dependence (codeine), drowsiness, fatigue, coordination disorder, tremor, anxiety, irritability; at long uncontrolled reception in high doses - accustoming (weakening of an anesthetizing effect).

From the CCC (cardiovascular system): a feeling of palpitations, excessive decrease in blood pressure, tachycardia, extrasystole.

From the side of the kidneys and urinary tract: with prolonged intake of high doses of the combined agent, it is possible to develop a violation of kidney function (interstitial nephritis, development of kidney failure).

On the part of the blood and lymphatic system: hemolytic anemia, in very rare cases - thrombocytopenia.

On the part of the skin: in very rare cases - severe reactions from the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis).

Laboratory and instrumental data: an increase in the activity of hepatic transaminases.

Interaction

Components of the combination codeine + caffeine + metamizole sodium + paracetamol + phenobarbital affect the metabolism of many drugs, so it should be avoided simultaneously with other drugs.

Metamizole sodium reduces the activity of indirect anticoagulants and the concentration of cyclosporine in the blood plasma. Tricyclic antidepressants, oral contraceptive drugs and allopurinol disrupt metamizole sodium metabolism in the liver and enhance its effect. The simultaneous use of metamizole sodium with chloramphenicol and other agents that suppress the function of the bone marrow increases myelotoxic effect.

Barbiturates, phenylbutazone and other inducers of microsomal liver enzymes weaken the action of metamizole sodium. Metamizole sodium, displacing from the bond with protein oral hypoglycemic drugs, indirect anticoagulants, GCS and indomethacin, increases their activity.

Paracetamol. Simultaneous use with aminophenazone can lead to an increase in the effects of both agents and increase their toxicity. Paracetamol increases the effect of anticoagulants of indirect action. Since paracetamol is an inducer of microsomal liver enzymes, it can reduce the effect of drugs by accelerating the process of their biotransformation. Oral contraceptive drugs weaken its effect by induction of conjugation with glucuronide and sulfate. Rifampicin reduces the analgesic effect due to the same mechanism. Cimetidine reduces toxicity and enhances the analgesic effect. Paracetamol extends T1 / 2 chloramphenicol due to competitive inhibition of metabolism and leads to an increased risk of damage to the bone marrow. Simultaneous reception of alcohol and hepatotoxic drugs increases the risk of impaired liver function due to the summation of hepatotoxic effects and increased formation of the hepatotoxic metabolite of paracetamol due to the induction of liver enzymes.

Codeine enhances the inhibitory effect of alcohol, barbiturates, benzodiazepines, hypnotics and sedatives on the central nervous system. The use of MAO inhibitors or tricyclic antidepressants together with codeine can lead to a mutual enhancement of effects. Simultaneous reception of drugs with anticholinergic activity increases the risk of constipation up to intestinal obstruction.

Caffeine reduces the intensity of action of hypnotic drugs. Strengthens the effects of NSAIDs.

Phenobarbital lowers the concentration of dicumarol in the blood serum and its anticoagulant activity, accelerates the decomposition of griseofulvin, quinidine, doxycycline, estrogens, sometimes phenytoin, carbamazepine due to the induction of liver enzymes. Its depressing effect on the central nervous system increases with simultaneous reception with alcohol, tricyclic antidepressants, phenothiazine, narcotic analgesics. Valproate sodium and valproic acid suppress the metabolism of phenobarbital.

Overdose

Symptoms: In case of an overdose of a combined remedy, the following symptoms may appear: CNS depression, accompanied by dizziness, drowsiness, retardation of psychomotor reactions, respiratory depression, considerable weakness, down to loss of consciousness; also bradycardia is possible, marked decrease in blood pressure.

Treatment: if symptoms of an overdose of a combination of codeine + caffeine + metamizole sodium + paracetamol + phenobarbital are observed, it should be stopped, gastric lavage should be done, activated charcoal and symptomatic therapy should be prescribed. Before excretion of active substances from the body, adequate ventilation of the lungs and stable hemodynamic parameters of the body should be maintained.

Paracetamol. A dose of paracetamol 7.5 g can cause a violation of liver function, possibly the development of liver failure with a fatal outcome. An effective antidote is N-acetylcysteine, this medication should be started immediately, even in the absence of acute overdose symptoms.

The timely initiation of therapy with paracetamol overdose is crucial.

Routes of administration

Inside.

Precautions of Codeine + Caffeine + Metamizol sodium + Paracetamol + Phenobarbital

Before the appointment of a combination of codeine + caffeine + metamizole sodium + paracetamol + phenobarbital should carefully evaluate the relationship between benefit and risk in its use, if the potential risk of use exceeds the intended benefit, then alternative treatment should be discussed.

Admission of a combined remedy should be stopped immediately if signs of anaphylaxis develop (severe allergic reactions that occur suddenly and are accompanied by a skin rash, shortness of breath, complaints from the gastrointestinal tract and SSS) and agranulocytosis (severe neutropenia, fever, sepsis and other signs of an infectious disease).

This combination should not be taken to patients who had hypersensitivity reactions after taking drugs containing methamizole sodium.

In view of the risk of overdose, it is necessary to simultaneously take drugs containing paracetamol with caution.

Excess of recommended doses can lead to very serious violations of the liver function. In this case, it is necessary to begin treatment with antidote as soon as possible (see "Overdose").

With prolonged and frequent admission of a combined remedy, it is necessary to monitor the blood picture and the parameters of renal and hepatic function.

Avoid this combination in patients with peptic ulcer and duodenal ulcer in the phase of exacerbation, as well as in patients with severe renal and hepatic insufficiency.

During treatment should be abandoned the use of alcohol in view of the poor tolerability of simultaneous reception with a combined agent.

The metamizole sodium contained in the combination can stain the urine red, but this has no clinical significance.

The combination of codeine + caffeine + metamizole sodium + paracetamol + phenobarbital should be taken with caution elderly patients in view of the fact that signs of intoxication in this group of patients occur more often.

After a long reception (more than 3 months), the analgesic with the regimen of taking a day or more may cause a headache or worsen the already existing. Headache caused by excessive intake of an analgesic should not be cured by an increase in its dose. In these cases, the use of analgesic should be discontinued after consultation with the attending physician.

Continued use of a combination of codeine + caffeine + metamizole sodium + paracetamol + phenobarbital may lead to the development of codeine dependence.

The involvement of the CYP2D6 isoenzyme in metabolism

Codeine is metabolized by the isoenzyme CYP2D6 to the active metabolite - morphine. If the patient lacks the activity of this isoenzyme or if the enzyme is absent in the body, then in this case it is impossible to achieve a sufficient analgesic effect in the treatment. Presumably, 7% of the population of the Caucasoid race may have insufficient activity of this isoenzyme. If the patient has a high activity of codeine metabolism (codeine is rapidly metabolized to morphine, and morphine in the blood plasma reaches higher concentrations than the rest of the population), then there is an increased risk of developing undesirable effects of opioid toxicity even when taking the combined drug at recommended doses.

Common symptoms of opioid toxicity include: confusion, drowsiness, shallow breathing, narrowing of the pupils, nausea, vomiting, constipation and lack of appetite. In severe cases, circulatory and respiratory collapse may occur, which can endanger the life of the patient and, in very rare cases, lead to death.

The expected frequency (in%) of the high activity of isoenzymes in different populations is reflected below: Africans, incl. Ethiopians - 29%; African Americans - 3.4-6.5%; representatives of the Mongoloid race - 1.2-2%; Caucasoid race - 3.6-6.5% (Greeks - 6%, Hungarians - 1.9%); Northern Europe - 1-2%.

Use in children with impaired respiratory function

Codeine and codeine-containing drugs are not recommended for use in children with impaired respiratory function, including neuromuscular disorders, severe heart or respiratory disease, upper respiratory tract or lung infections, multiple injuries or extensive surgical interventions. These conditions can exacerbate the symptoms of morphine toxicity.

The combination of codeine + caffeine + metamizol sodium + paracetamol + phenobarbital can change the results of doping control in athletes.

It is difficult to establish a diagnosis for acute abdominal pain syndrome.

Patients suffering from atopic bronchial asthma, pollinosis, have an increased risk of developing hypersensitivity reactions.

Impact on the ability to manage vehicles and mechanisms. Most of the components of the combination codeine + caffeine + metamizole sodium + paracetamol + phenobarbital affects the CNS, changing the speed of psychomotor reactions, so it is not recommended to take this combination during vehicle management and work with mechanisms.