Release form and composition
Available in the form of tablets: flat-cylindrical in shape, from white with cream to white with a yellow tint (10 pieces in blister packs, 1 or 2 packs in a cardboard pack).
Active ingredients in 1 tablet:
- Metamizole sodium (analgin) – 300 mg;
- Naproxen – 100 mg;
- Caffeine – 50 mg;
- Phenobarbital – 10 mg;
- Codeine – 8 mg.
Additional components: magnesium stearate, talc and potato starch.
Piralgin tablets No. 10x2
Name
Piralgin tablets in container pack No. 10x2
Description
Tablets of white or almost white, white with yellow or white with a yellowish tint, flat-cylindrical with a chamfer and a score on one side.
Main active ingredient
Codeine+caffeine+metamizole sodium+naproxen+phenobarbital
Release form
Pills
pharmachologic effect
Pharmacodynamics
The drug has analgesic, antipyretic, anti-inflammatory, antispasmodic and sedative effects. The pharmacological effects of the combination drug are due to the properties of its active ingredients. Metamizole sodium and naproxen are nonsteroidal anti-inflammatory drugs that have antipyretic effects and analgesic activity. In addition, naproxen is characterized by a pronounced anti-inflammatory effect. Codeine and caffeine enhance the analgesic effect of the analgesics included in the drug Piralgin. Phenobarbital has a sedative, hypnotic, antispasmodic effect, and reduces the tone of skeletal muscles.
Indications for use
Short-term treatment of acute pain syndrome of moderate intensity of various origins, which is not relieved by taking monocomponent drugs. Can be used to relieve joint pain, menstrual pain, neuralgia, headaches and toothaches.
Directions for use and doses
The drug is taken orally, usually 1 tablet 1-3 times a day. The maximum daily dose is 3 tablets; taking 4 tablets per day is permissible only on the recommendation of a doctor. Children over 12 years of age – half the dose for adults. The maximum duration of continuous use of the drug is no more than 3 days. Side effects can be minimized by using the lowest effective dose for the shortest period of time necessary to relieve symptoms. Special categories of patients Patients with impaired liver and kidney function, elderly patients: dosage reduction is recommended. Children: Do not use in children under 12 years of age. Directions for use The tablet is taken orally with a sufficient amount of water. If you missed another dose of the drug, you should take the missed tablet of the drug and then continue taking the tablets as usual. With caution: patients with increased excitability, sleep disorders, risk of developing intestinal obstruction.
Use during pregnancy and lactation
The use of the drug is contraindicated.
Impact on the ability to drive a car and potentially dangerous mechanisms
The drug may affect the speed of psychomotor reactions and the ability of patients to safely drive a vehicle. During the treatment period, the patient should not drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Precautionary measures
It is unacceptable to use the drug to relieve acute abdominal pain (until the cause is determined). You should only take this medication for a maximum of three days. Long-term continuous (more than 3 days) use of painkillers for headaches may worsen symptoms. Piralgin contains codeine, which can be addictive if taken continuously for more than three days. Associated with the presence of metamizole sodium Regular long-term use of the drug is not recommended due to the myelotoxicity of metamizole; with long-term use (more than 7 days), it is necessary to monitor the qualitative and quantitative composition of peripheral blood, especially the leukocyte formula. Agranulocytosis When using the drug, the development of agranulocytosis is possible, and therefore, if an unmotivated increase in temperature, chills, sore throat, difficulty swallowing, stomatitis, as well as inflammation of the external genitalia and anus is detected, immediate discontinuation of the drug is necessary. If signs of agranulocytosis or thrombocytopenia occur, a complete blood count (including leukocyte count) should be performed. Discontinuation of treatment should not be delayed until laboratory results are available. Pancytopenia If pancytopenia occurs, treatment should be stopped immediately and the results of a complete blood count should be monitored until they return to normal. All patients should be instructed to immediately consult a doctor if signs of illness or symptoms indicating pathological changes in the blood system appear during treatment (for example, poor general health or malaise, fever, hemorrhages, bleeding, pallor). Anaphylactic/anaphylactoid reactions The risk of potential severe anaphylactoid reactions to metamizole sodium increases significantly in patients with: allergic diseases (including hay fever) or a history of such; analgesic-induced asthmatic syndrome or intolerance to analgesics in the form of urticaria and combined angioedema; bronchial asthma, especially in combination with rhinosinusitis and nasal polyps; chronic urticaria; intolerance to dyes (for example, tartrazine) or preservatives (for example, benzoates); alcohol intolerance. Anaphylactic shock may occur primarily in susceptible patients. Therefore, special caution is required when used in patients with bronchial asthma or atopy. Severe Skin Reactions Life-threatening skin reactions have been reported: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of metamizole sodium. If signs of SJS or TEN develop (such as progressive skin rash, often with blistering and/or mucosal lesions), treatment with metamizole sodium should be stopped immediately and never restarted. Isolated hypotensive reactions Metamizole sodium may cause hypotensive reactions. These reactions may be dose dependent and are more likely to be expected with parenteral administration. The risk of such reactions is also increased: in patients with previous hypotension, blood volume deficit or dehydration, unstable circulation or with incipient circulatory failure (for example, in patients with myocardial infarction, multiple injuries); when treated with cytostatics; for chronic alcoholism; in patients with high fever. Therefore, careful review of indications and regular follow-up are required in such patients. Preventative measures (eg, stabilization of circulation) may be necessary. When taking the drug, urine may turn red due to the excretion of metamizole sodium metabolite, which has no clinical significance. Related to the presence of naproxen Patients with gastrointestinal diseases, especially ulcerative colitis or Crohn's disease (including a history), should take naproxen sodium under close medical supervision, as these diseases may recur or worsen. Serious gastrointestinal adverse events may occur suddenly. As with other nonsteroidal anti-inflammatory drugs, the cumulative incidence of serious adverse events, gastrointestinal bleeding, or perforation increases linearly with the duration of treatment. Taking high doses of naproxen sodium may also increase the risk of unwanted effects. It is necessary to pay attention to the anti-inflammatory and antipyretic effect of naproxen sodium in infectious diseases, since the symptoms of these diseases may be masked. The risk of gastrointestinal bleeding, ulceration and perforation increases in patients taking NSAIDs in high doses, in patients with a history of peptic ulcers complicated by bleeding and perforation, as well as in elderly patients. To minimize the risk of adverse gastrointestinal events, attention should be paid to concomitant use with protective agents (for example, misoprostol or proton pump inhibitors). Cardiovascular and Cerebrovascular Effects Patients with hypertension and/or mild to moderate heart failure should be under medical supervision as reports of fluid retention or edema have been reported when taking NSAIDs. Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and during long-term treatment) may cause a slight increase in the risk of arterial thrombosis (for example, the risk of myocardial infarction or stroke). Although evidence suggests that the use of naproxen (1000 mg daily) may be associated with a minor risk, this risk cannot be excluded. Data regarding the effects of low doses of naproxen sodium, such as 100 mg, are insufficient to judge the possible risk of thrombosis. Associated with the presence of caffeine When using the drug, you should avoid excessive consumption of coffee, strong tea, other tonic drinks, alcohol and medications containing caffeine. Caffeine can cause a false increase in uric acid in the blood, determined by the Bittner method. Caffeine may increase urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic acid (VMA), and catecholamines, which may lead to false-positive diagnoses of pheochromocytoma and neuroblastoma. Associated with the presence of phenobarbital In patients treated with antiepileptic drugs, mood changes and suicidal thoughts are observed. The mechanism of these changes is unknown, and the available information does not exclude the possibility of an increased risk of suicide when taking phenobarbital. Patients taking phenobarbital should be closely monitored for signs of depression, suicidal thoughts or behavior. If signs of suicidal thoughts or behavior occur, patients should be advised to seek immediate medical attention from a physician. Associated with the presence of codeine Caution should be exercised when prescribing the drug to patients whose condition may be aggravated by the use of opioids, especially elderly patients who are characterized by increased sensitivity of the central nervous system and gastrointestinal tract. Use with caution in patients concomitantly taking other CNS depressants, those suffering from prostatic hypertrophy, inflammatory or obstructive bowel disease. When prescribing the drug to patients with dementia, as well as arterial hypotension and hypothyroidism, the individual benefit/risk ratio must be taken into account. Patients should be advised not to exceed the dosage indicated in the instructions, since frequent or too long use of painkillers to relieve headaches can lead to their worsening. Long-term regular use of the drug can lead to the development of physical and psychological dependence (drug addiction) and the “rebound” phenomenon, i.e. the appearance of symptoms such as anxiety and irritability when you stop taking it. Patients should be advised that they should not take the drug for more than 3 days continuously without consulting a doctor. CYP2D6-dependent metabolism activity Codeine is metabolized by the liver enzyme CYP2D6 to morphine, its active metabolite. If there is a deficiency or complete absence of this enzyme, the patient cannot achieve an adequate therapeutic effect. Estimates indicate that up to 7% of Caucasians may be deficient in this enzyme. On the other hand, if the patient is a so-called "ultra-rapid metabolizer" of CYP2D6, there is an increased risk of side effects of opioid toxicity even at therapeutic doses. In these patients, the rapid conversion of codeine to morphine results in higher than expected serum morphine levels. Common symptoms of opioid toxicity include confusion, drowsiness, shallow breathing, constricted pupils, nausea, vomiting, constipation and lack of appetite. In severe cases, symptoms of cardiovascular and respiratory depression may develop, which can be life-threatening and very rarely fatal. Postoperative use in children There are reports that the administration of codeine at moderate therapeutic doses to children following tonsillectomy and/or adenoidectomy for the treatment of obstructive sleep apnea may result in rare but life-threatening side effects, including death. It cannot be excluded that these patients could belong to the so-called. "ultra-rapid" or extensive metabolizers of CYP2D6 with an increased ability to convert codeine to morphine. Serotonin syndrome Serotonin syndrome may occur during concurrent use of opioids and serotonergic drugs, even when the drugs are used at recommended doses. If concomitant use of opioids and serotonergic drugs is indicated, patients should be closely monitored, particularly during treatment initiation and dose increases. Symptoms of serotonin syndrome may include changes in mental status (agitation, hallucinations, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neurological disorders (hyperreflexia, incoordination, rigidity). The development of symptoms usually occurs within a few hours to a few days from the start of concomitant therapy, but may occur later, especially after increasing the dose. If serotonin syndrome is suspected, discontinue the opioid and/or the concomitantly used serotonergic drug. If manifestations of serotonin syndrome develop, the patient should be advised to immediately seek medical help. The patient is advised of the need to inform the specialist about the concomitant use of serotonergic drugs. Adrenal Insufficiency Cases of adrenal insufficiency have been reported with the use of opioids. Adrenal insufficiency can manifest itself with nonspecific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, a laboratory test of adrenal function should be performed as soon as possible. The patient should be placed on corticosteroid replacement therapy and discontinue opioid use. If opioids are discontinued, adrenal function should be reassessed to determine the need to discontinue corticosteroid therapy. In some cases, a change to another opioid drug is recommended, as there have been cases where adrenal insufficiency did not occur when the opioid was changed. Available data do not allow us to identify any specific opioid drug that is most likely associated with the development of adrenal insufficiency. Androgen deficiency (androgen deficiency) Chronic use of opioids can affect the hypothalamic-pituitary-gonadal axis, which can lead to androgen deficiency, which manifests as low libido, impotence, erectile dysfunction, amenorrhea and infertility. At present, the role of opioids in the development of the clinical syndrome of hypogonadism has not been established, since other medical and physical indicators, lifestyle, and psychological stress factors could affect hormone levels, which were not properly controlled during the studies. If a patient develops symptoms or signs of androgen deficiency, laboratory testing should be performed. What are the possible conditions and signs of addiction development? If you take the drug exactly as directed, it is unlikely that you will become dependent. However, in a number of situations listed below, it is recommended to consult your doctor for additional advice: if your doctor has prescribed you to take this medicine for a longer period of time; if you are prescribed by your doctor to take a higher dose than recommended; if you feel very unwell when you stop taking the medicine, but feel better when you start taking it again.
Interaction with other tools
When treating with Piralgin, simultaneous intake of alcoholic beverages is prohibited! Associated with the presence of metamizole sodium Metamizole may cause a decrease in serum levels of cyclosporine. Therefore, it should be monitored in case of simultaneous use with metamizole sodium. With simultaneous use of metamizole sodium and chlorpromazine, severe hypothermia may occur. Adding metamizole to methotrexate may increase the hematological toxicity of methotrexate, especially in elderly patients. Therefore, this combination should be avoided. Metamizole may, when used simultaneously, reduce the antiplatelet effect of low doses of acetylsalicylic acid. Therefore, metamizole should be used with caution in patients taking acetylsalicylic acid in low doses for cardioprotection. Bupropion blood levels may be reduced by metamizole. Therefore, caution is necessary when using metamizole and Bupropion simultaneously. For substances from the pyrazolone group, it is known that they can interact with oral anticoagulants, captopril, lithium preparations and triamterene, as well as alter the effectiveness of antihypertensive drugs and diuretics. The extent to which metamizole leads to such interactions is unknown. Related to the presence of naproxen Concomitant use of acetylsalicylic acid and other NSAIDs is not recommended due to the increased risk of gastrointestinal ulcers and bleeding due to the synergistic effect. Concomitant use should be avoided. Naproxen sodium may decrease platelet aggregation and prolong bleeding time. The effect should be taken into account when determining bleeding time and during concomitant anticoagulant treatment. Concomitant use of Naprosyn is not recommended since it contains the same active substance, i.e. naproxen. Since naproxen sodium is almost completely bound to plasma proteins, caution should be exercised during concomitant use of hydanthione derivatives or sulfonylureas. Naproxen sodium may reduce the natriuretic effect of furosemide. Naproxen sodium may reduce the antihypertensive effect of other antihypertensive drugs (diuretics, ACE inhibitors and angiotensin II antagonists). Plasma concentrations of digoxin, phenytoin and lithium increase with simultaneous use. Monitoring plasma levels of lithium, digoxin and phenytoin is usually not required when used correctly (no more than 4 days). Concomitant use of ACE inhibitors or angiotensin II receptor antagonists with drugs that inhibit cyclooxygenase may lead to a further deterioration of renal function in patients with impaired renal function or in elderly patients, including the possible development of acute renal failure, which is usually reversible. Therefore, especially in elderly patients, these combinations should be used with caution. After initiation of combination therapy, patients should be adequately hydrated and renal function should be regularly monitored in these patients. Concomitant use of naproxen and potassium-sparing diuretics may lead to hyperkalemia. Naproxen sodium reduces the tubular secretion of methotrexate, so the toxicity of methotrexate may be increased with concomitant use (within 24 hours). With simultaneous use of probenecid, the biological half-life of naproxen sodium is prolonged and its plasma concentration increases. Concomitant use of cyclosporine may increase the risk of renal dysfunction. Naproxen sodium, like other NSAIDs, may increase the risk of renal dysfunction in patients taking ACE inhibitors concomitantly. In vitro studies have shown that concomitant use of naproxen sodium and zidovudine increases plasma concentrations of zidovudine. Corticosteroids: Increase the risk of gastrointestinal ulcers and bleeding. Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin. Antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding. Related to the presence of caffeine Caffeine may enhance the effects of ergotamine. Other drugs whose effects may be altered by interaction with caffeine: hydrocylamide, mexiletine, ciprofloxacin, enoxacin, pipemidic acid, fluvoxamine, phenylpropanolamine, phenytoin, clozapine, lithium, theophylline, pentobarbital, diazepam, methoxalene. Concomitant use of caffeine with MAO inhibitors (MAOIs) can cause a dangerous rise in blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesics-antipyretics, potentiates the effects of xanthine derivatives, β- and β-adrenergic agonists, and psychostimulants. Cimetidine, hormonal contraceptives, isoniazid enhance the effect of caffeine. Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics and sedatives, is an antagonist of anesthetics and other drugs that depress the central nervous system, and is a competitive antagonist of adenosine drugs. The simultaneous use of caffeine with thyroid-stimulating drugs increases the thyroid effect. Associated with the presence of phenobarbital Phenobarbital induces liver enzymes and, accordingly, may accelerate the metabolism of certain drugs that are metabolized by these enzymes (including paracetamol, salicylates, anticoagulants, cardiac glycosides (digitoxin), antimicrobials (chloramphenicol, doxycycline, metronidazole, rifampicin), antivirals, antifungal (griseofulvin, itraconazole), antiepileptic (anticonvulsants), psychotropic (tricyclic antidepressants, clonazepam), hormonal (estrogens, progestogens, corticosteroids, thyroid hormones), immunosuppressive (glucocorticosteroids, cyclosporine, cytostatics), antiarrhythmic, antihypertensive (?-blockers, blockers calcium channels), oral hypoglycemic drugs, etc.). Phenobarbital may accelerate the metabolism of oral contraceptives, resulting in loss of their effect. Phenobarbital enhances the effect of analgesics, local anesthetics and drugs that depress the central nervous system. The simultaneous use of phenobarbital with drugs that have a sedative effect leads to an increase in the sedative-hypnotic effect and may be accompanied by respiratory depression. Possible effect on the concentration of phenytoin in the blood, as well as carbamazepine and clonazepam. Medicines with acidic properties (ascorbic acid, ammonium chloride) enhance the effect of barbiturates. MAO inhibitors prolong the effect of phenobarbital. Rifampicin may reduce the effect of phenobarbital. When used with gold preparations, the risk of kidney damage increases. With long-term simultaneous use with non-steroidal anti-inflammatory drugs, there is a risk of gastric ulcers and bleeding. The simultaneous use of phenobarbital with zidovudine increases the toxicity of these drugs. Associated with the presence of codeine Codeine should not be used in combination with MAO inhibitors due to the possible risk of central nervous system agitation or depression; codeine should not be used earlier than 2 weeks after discontinuation of MAO inhibitors. Anticholinergics (atropine, etc.) and antidiarrheals (loperamide, kaolin) should be used with caution along with codeine - the risk of acute constipation increases; metoclopramide and domperidone - due to possible antagonism; antihypertensive drugs – enhance the hypotensive effect; non-narcotic analgesics – enhanced analgesic effect; quinidine – reducing the analgesic effect of codeine. With the simultaneous use of drugs that exhibit an inhibitory effect on the central nervous system (anaesthetics, neuroleptics, tricyclic antidepressants, anxiolytics, sedatives, hypnotics, antihistamines with a sedative effect), as well as alcohol, it is possible to increase the sedative effect of codeine and the inhibitory effect on the respiratory center . The use of codeine in combination with opioid antagonists (buprenorphine, naloxone, naltrexone) may cause withdrawal symptoms. Chloramphenicol inhibits the biotransformation of codeine in the liver and thereby enhances its effect. Concomitant use of ciprofloxacin should be avoided since opioids reduce plasma concentrations of the drug. Taking ritonavir and cimetidine leads to an increase in codeine plasma concentrations. When used concomitantly, codeine slows down the absorption of mexiletine. When using codeine in large doses, the effect of cardiac glycosides (digoxin and others) may be enhanced.
Contraindications
Hypersensitivity to active and auxiliary substances, severe hepatic and/or renal failure, severe heart failure, hepatic porphyria, bronchial asthma, complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, glucose deficiency -6-phosphate dehydrogenase, hematopoietic disorders, anemia, leukopenia, agranulocytosis, cerebrovascular or gastrointestinal bleeding, acute or recurrent erosive and ulcerative lesions of the gastrointestinal tract, conditions accompanied by respiratory depression, increased intracranial pressure, acute myocardial infarction, perioperative period with coronary artery bypass surgery, arrhythmias, alcohol intoxication, history of abuse of opioids, tranquilizers, sedatives, glaucoma, pregnancy, lactation, children under 12 years of age. The drug is contraindicated in adolescents from 12 to 18 years of age with respiratory pathologies. The drug is contraindicated in patients with established CYP2D6 status as an ultra-rapid metabolizer.
Compound
Each tablet contains: active substances - metamizole sodium (analgin) - 300 mg, naproxen - 100 mg, caffeine - 50 mg, phenobarbital - 10 mg, codeine - 8 mg; excipients: magnesium stearate (E-470), sodium lauryl sulfate (E-487), talc (E-553), potato starch.
Overdose
Associated with the presence of metamizole sodium Symptoms: hypothermia, marked decrease in blood pressure, palpitations, shortness of breath, tinnitus, nausea, vomiting, stomach pain, oliguria, anuria, tachycardia, weakness, drowsiness, delirium, impaired consciousness, convulsive syndrome; the development of acute agranulocytosis, hemorrhagic syndrome, acute renal and liver failure, paralysis of the respiratory muscles is possible. Naproxen-associated symptoms of overdose may include central nervous system disturbances, headache, dizziness, drowsiness and loss of consciousness, as well as abdominal pain, nausea and vomiting. In addition, gastrointestinal bleeding and impaired liver and kidney function. Hypotension, respiratory depression, and cyanotic coma may also occur. Associated with the presence of caffeine Symptoms of caffeine overdose: nervousness, restlessness, insomnia, agitation, irritability, state of passion, anxiety, tremors, muscle twitching, convulsions, ringing in the ears, facial flushing, pyrexia, increased frequency of urination, gastrointestinal disorders, epigastric pain, arrhythmias (including tachycardia, extrasystole), psychomotor agitation. Associated with the presence of phenobarbital Symptoms of phenobarbital overdose: nausea, headache, ataxia, nystagmus, weakness, respiratory depression with the risk of stopping it, depression of cardiovascular activity, including rhythm disturbances, decreased blood pressure, up to a collapsed state, slow pulse, hypothermia, decreased diuresis, depression of the central nervous system, up to coma. Associated with the presence of codeine Symptoms of codeine overdose: acute depression of the respiratory center can cause cyanosis, slow breathing, drowsiness, and rarely - pulmonary edema; possible occurrence of shortness of breath, apnea, arterial hypotension, tachycardia, convulsions, collapse, urinary retention; Signs of histamine release may occur. Treatment of overdose: gastric lavage, symptomatic therapy.
Side effect
According to the World Health Organization, adverse reactions are classified according to their frequency of development as follows: very often (? 1/10); often (? 1/100,
Indications for use
Piralgin is a drug used to relieve pain of various origins, and is especially effective in the following cases:
- Headache;
- Migraine;
- Toothache;
- Menstrual pain;
- Radiculitis;
- Pain in muscles and joints;
- Neuralgia.
Piralgin is also prescribed for diseases with fever, colds and other diseases accompanied by inflammation and pain.
Contraindications
- Children under 12 years of age;
- Pregnancy;
- Lactation (or feeding should be interrupted);
- Traumatic brain injury;
- Increased intracranial pressure;
- Conditions accompanied by respiratory depression;
- Bronchospasm;
- Heart rhythm disturbances;
- Acute myocardial infarction;
- High blood pressure;
- Blood diseases;
- Glaucoma;
- Peptic ulcer of the stomach and duodenum in the acute stage;
- Severe liver or kidney dysfunction;
- Alcohol intoxication;
- Glucose-6-phosphate dehydrogenase deficiency;
- Hypersensitivity to the components of the drug.
Carefully:
- Impaired liver and/or kidney function;
- Peptic ulcer of the stomach and duodenum in remission;
- History of alcoholism;
- Elderly age.
I.B. Muravyova, JSC "Research and Production, pharmacist"
PIRALGIN is the drug of choice for moderate pain. As defined by the International Association for the Study of Pain (IASP), pain is an unpleasant sensory and emotional sensation associated with actual or potential tissue damage, or described in terms of such damage. On the one hand, the ability to feel pain helped a person survive in the process of evolution, since, being a mechanism of adaptation to existence in the surrounding aggressive environment, it gave a signal about existing damage, the need to stop contact with the aggressive factor and mobilize the body’s strength for recovery . However, pain can be not only a signal of danger. Under conditions of strong and prolonged irritation, it itself can acquire the features of an irritating factor, causing severe stress and depletion of the reserves of the nervous, endocrine and cardiovascular systems of the body, causing painful shock. Pain is the most common symptom, for which almost half of all patients seek medical help. Each specific manifestation of a pain reaction requires the prescription of a drug from a specific pharmacological group. The most pronounced analgesic effect among drugs that reduce the concentration of endogenous algogens is possessed by drugs from the pharmacological group “Non-narcotic analgesics, including non-steroidal and other anti-inflammatory drugs”. The mechanism of anti-inflammatory, analgesic and antipyretic action of non-steroidal anti-inflammatory drugs is associated with inhibition of the activity of a special enzyme - cyclooxygenase (COX), which occurs both in peripheral tissues and in the structures of the central nervous system. Non-narcotic analgesics and most NSAIDs block the activity of both isoforms of cyclooxygenase. The effectiveness and toxicity of “standard” drugs from the group “Non-narcotic analgesics, including NSAIDs and other anti-inflammatory drugs” is usually associated with their low selectivity, i.e. ability to suppress the activity of both to the same extent • NSAIDs that significantly suppress the activity of COX-1 (acetylsalicylic acid, indomethacin, piroxicam) more often cause damage to the digestive tract than
• NSAIDs that exhibit equivalent inhibitory activity against both isoforms of COX (diclofenac sodium, ibuprofen, pyralgin, etc.), and even more so
• NSAIDs-selective COX-2 inhibitors, which are considered the least toxic, however, can increase the risk of heart attacks (Celecoxib, Rofecoxib, etc.).
When prescribing drugs in this group, one should take into account the safety of use for the patient, the cause and intensity of pain, as well as the severity of the concomitant inflammatory process. The chosen remedy should eliminate pain as much as possible and not cause serious side effects. The traditional tactics recommended by WHO (1986) for the treatment of chronic and acute pain are to prescribe non-opioid analgesics from the pharmacological group “NSAIDs, including non-narcotic analgesics”. For moderate to severe pain that is not relieved by non-opioid analgesics, your doctor will prescribe an opioid analgesic on a special prescription form. The drug Piralgin tablets, produced by the Belarusian enterprise RUE Belmedpreparaty, is a drug prescribed for moderate pain syndrome and is sold in pharmacies without a doctor’s prescription. One tablet of the drug Piralgin contains 300 mg of analgin (metamizole sodium), 100 mg of naproxen, 50 mg of caffeine, 10 mg of phenobarbital, 8 mg of codeine. The drug has analgesic, antipyretic, anti-inflammatory, antispasmodic, and sedative effects. Piralgin is a combination drug that combines the properties of active ingredients. Metamizole sodium and naproxen are drugs from the group of non-narcotic analgesics that have a pronounced anti-inflammatory, antipyretic effect, and analgesic activity, which is enhanced by codeine (blocks opiate receptors, stimulates the antinociceptive system and changes the emotional perception of pain). Iieeeeeeeea .5 2008 tel./fax editorial office: (495) 6727029\92, 3684703
Iaa.ieiaey Naproxen also has a pronounced anti-inflammatory effect. Phenobarbital has a sedative effect. Caffeine causes dilation of blood vessels in skeletal muscles, brain, heart, kidneys; increases mental and physical performance, helps eliminate fatigue and drowsiness; increases blood pressure during hypotension; increases the permeability of histohematic barriers and increases the bioavailability of non-narcotic analgesics, thereby enhancing the therapeutic effect. The components of the drug are well absorbed in the gastrointestinal tract. Metamizole sodium: in the intestinal wall it is hydrolyzed to form an active metabolite, 4-methyl-amino-antipyrine, which in turn is metabolized to 4-formyl-amino-antipyrine and other metabolites. The level of binding of the active metabolite to proteins is 50–60%. Excretion of metabolites passes through the kidneys. In addition, metabolites are excreted in breast milk. Naproxen: bioavailability is 95%. Binds to blood proteins. The half-life is 12–15 hours. It is excreted in the urine mainly in the form of a metabolite (dimethylnaproxen), in small quantities in bile. Caffeine: well absorbed in the intestine, half-life is 5 hours (sometimes up to 10 hours). It is excreted primarily by the kidneys in the form of metabolites, about 10% unchanged. Codeine: slightly bound to plasma proteins. It undergoes biotransformation in the liver (10% is converted into morphine by demethylation). Excreted by the kidneys (5–15% unchanged). Phenobarbital: bioavailability is 80%. In plasma, it is 50% protein bound and penetrates well through the placenta. Biotran is formed in the liver. The main metabolite has no pharmacological activity. It is excreted by the kidneys, including 20–25% unchanged. Piralgin is indicated for moderately severe pain syndromes of various origins. Particularly effective
Iieeeeeeeea .5 2008 tel./fax editorial office: (495) 6727029\92, 3684703
effective for pain in joints, muscles, radiculitis, menstrual pain, neuralgia, as well as for headaches, migraines, toothaches. Piralgin can be used for fevers, colds and other diseases accompanied by pain and inflammation. The drug is usually prescribed 1 tablet 1-3 times a day. The maximum daily dose is 4 tablets. The drug should not be taken for more than 5 days as an anesthetic without a doctor's prescription. When using the drug, dyspeptic disorders, allergic skin reactions, epigastric pain, dizziness, drowsiness, and palpitations are possible. Rarely, suppression of hematopoiesis. The main contraindications include hypersensitivity to the components of the drug, severe dysfunction of the liver or kidneys, peptic ulcer of the stomach and duodenum in the acute stage, bronchospasm, blood diseases, increased intracranial pressure, cranial trauma, acute myocardial infarction, alcohol intoxication, glaucoma, pregnancy and breastfeeding, as well as children under 12 years of age. Thus, the 5-component composition of the drug, significantly expanding the range of indications for use, the unique composition of components that mutually enhance each other’s effects, a longer anti-inflammatory effect, a proven therapeutic effect in combination with its affordability for patients - there, with limited financial resources, there are advantages of Piralgin compared to other drugs of the pharmacological group “Non-narcotic analgesics, including non-steroidal and other anti-inflammatory drugs”.
Literature 1. Guidelines “Procedure and timing of prescribing narcotic analgesics,” Ministry of Health of the Russian Federation, No. 2001/129 dated July 19, 2001.
2. Kukushkin M.L. Etiopathogenetic principles of treatment of chronic pain, journal “Attending Physician”, No. 4, April 2008.
3. Ananyev L.P. “Combined analgesics in the treatment of pain syndromes”, journal “Consilium medicum”, volume 07/№08/2005.
special instructions
If long-term treatment is necessary (more than 5 days), it is necessary to monitor liver function and peripheral blood patterns.
In case of acute pain in the abdominal area, Piralgin can make it difficult to make a correct diagnosis.
In case of prolonged uncontrolled use of the drug, drug dependence may develop.
During treatment, you should refrain from drinking alcoholic beverages, and also be careful when driving a car and performing potentially dangerous types of work.
Pyralgin
Medical supervision is required while taking the drug.
When using the drug for more than 5 days, it is necessary to monitor the peripheral blood picture and the functional state of the liver.
Taking the drug may make it difficult to establish a diagnosis for acute pain in the abdominal area.
During the period of productive cough, it is able to suppress the cough reflex, which can lead to the accumulation of sputum in the lumen of the bronchi and, as a result, to a deterioration in the patient’s condition. The patient must be informed that with prolonged use of the drug without appropriate medical supervision, addiction and drug dependence may develop.
During treatment with Piralgin, it is necessary to refrain from drinking alcohol due to worsening tolerability of the drug.
Piralgin should not be taken by patients who have previously experienced hypersensitivity to medications containing metamizole sodium.
The drug should be avoided in patients with gastric and duodenal ulcers in the acute phase, as well as in patients with severe renal and liver failure.
Metamizole sodium contained in the drug Piralgin may turn the urine red, but this has no clinical significance.
The drug Piralgin should be taken with caution in elderly patients in whom signs of intoxication occur more often.
Long-term use of the drug Piralgin can lead to the development of codeine addiction.
Phenobarbital can be addictive. The formation of dependence can occur with long-term uncontrolled use of the drug. If a patient develops an addiction, the intervention of a specialist narcologist is required.
Participation of the CYP2D6 isoenzyme in metabolism
Codeine is metabolized by the CYP2D6 isoenzyme to the active metabolite, morphine. If the patient has insufficient activity of this isoenzyme, or this enzyme is absent in the body, it is not possible to achieve a sufficient analgesic effect during treatment. An estimated 7% of the Caucasian population has insufficient CYP2D6 activity. With high metabolic activity of codeine, there is an increased risk of developing adverse effects of opioid toxicity, even when taking the drug in recommended doses. In patients in this group, codeine is rapidly metabolized to morphine, which reaches higher plasma concentrations than in the rest of the population.
Common symptoms of opioid toxicity include: confusion, drowsiness, shallow breathing, constricted pupils, nausea, vomiting, constipation and lack of appetite. In severe cases, circulatory and respiratory collapse may develop, which poses a threat to the patient's life.
The expected frequency of high isoenzyme activity for different isoenzymes in different populations is shown below:
| Population | Frequency % |
| Africans/Ethiopians | 29% |
| African Americans | 3,4-6,5% |
| Mongoloid race | 1,2-2% |
| Caucasian | 3,6-6,5% |
| Greeks | 6,0% |
| Hungarians | 1,9% |
| Northern Europeans | 1-2% |
Drug interactions
Tranquilizers and sedatives enhance the analgesic effect of Piralgin.
With the simultaneous use of other non-narcotic analgesics, the toxic effect may be enhanced.
Metamizole sodium, which is part of the drug, reduces the concentration of cyclosporine in the blood.
Phenylbutazone, barbiturates and other inducers of microsomal liver enzymes weaken the effect of metamizole sodium.
Allopurinol, oral contraceptives and tricyclic antidepressants increase the toxicity of metamizole sodium.
