Panoxen tablets, No. 20

• to reduce pain and inflammation at the time of application for inflammatory diseases of the musculoskeletal system (rheumatoid arthritis, psoriatic, juvenile and chronic arthritis, ankylosing spondylitis, acute gouty arthritis);

• degenerative diseases of the musculoskeletal system (deforming osteoarthritis, osteochondrosis);

• lumbago, sciatica, neuralgia, myalgia;

• diseases of the periarticular tissues (tendovaginitis, bursitis);

• post-traumatic pain syndromes accompanied by inflammation;

• toothache.

Panoxen is taken orally, without chewing, during or after meals, with a little water.

Assign 1 tab. 2-3 times / day The maximum daily dose is 3 tab. (150 mg in terms of diclofenac).

The duration of the use of the drug Panoxen depends on the indication for use. In acute conditions, quickly relieved conditions, the drug is used for several days. With chronic inflammatory or degenerative diseases of the connective tissue, long-term use of Panoxen is possible.

With prolonged use of the drug, it is necessary to carry out regular monitoring for the possible occurrence of erosion of the gastrointestinal mucosa with the subsequent development of gastrointestinal bleeding, as well as to carry out functional liver tests in order to early detect possible hepatotoxicity of the drug.

Coated tablets, white or off-white, capsule-shaped, with a score on one side; slight roughness is allowed.

1 tab.

diclofenac sodium 50 mg

paracetamol 500 mg

Excipients: corn starch - 290 mg, cellacephate (acetylphthalyl cellulose) - 15 mg, diethyl phthalate - 2.5 mg, talc - 10 mg, magnesium stearate - 10 mg, titanium dioxide - 13 mg, microcrystalline cellulose - 70 mg, povidone K-30 - 18 mg, methylparaben (methyl parahydroxybenzoate) - 17.5 mg, propylparaben (propyl parahydroxybenzoate) - 4 mg, TC 1005 tablet coating (white) - 28.5 mg (hypromellose (hydroxypropyl methylcellulose) - 5.5 mg, propylene glycol - 4.3 mg, talc dioxide - 10.8 mg, titanium - 7.98 mg).

• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including history);

• erosive and ulcerative lesions of the gastrointestinal tract (including the duodenum);

• active gastrointestinal bleeding;

• inflammatory bowel disease;

• severe liver failure;

• severe heart failure;

• period after coronary artery bypass grafting;

• severe renal failure (CC <30 ml / min);

• progressive kidney disease;

• active liver disease;

• hyperkalemia;

• pregnancy;

• lactation period (breastfeeding);

• childhood;

• hypersensitivity to drug components;

• hypersensitivity to other derivatives of phenylacetic acid or aniline.

With care:gastric ulcer and duodenal ulcer (in remission or history), ulcerative colitis, Crohn's disease, history of liver disease, hepatic porphyria, benign hyperbilirubinemia (including Gilbert's syndrome), viral hepatitis, alcoholic liver damage, chronic heart disease mild to moderate failure, arterial hypertension, a significant decrease in BCC (including after extensive surgery), bronchial asthma, coronary artery disease, cerebrovascular diseases, hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, chronic renal failure (CC 30 -60 ml / min), the presence of Helicobacter pylori infection, prolonged use of NSAIDs, alcoholism, severe somatic diseases, deficiency of glucose-6-phosphate dehydrogenase, simultaneous administration of corticosteroids, anticoagulants,antiplatelet agents, selective serotonin reuptake inhibitors, in elderly patients.

pharmachologic effect

Combined analgesic drug, the action of which is due to the effects of its constituent components.

Diclofenac - a derivative of phenylacetic acid, has anti-inflammatory, analgesic, antipyretic, antiplatelet effect. By oppressing COX-1 and COX-2, it disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins both in the focus of inflammation and in healthy tissues, and suppresses the exudative and proliferative phases of inflammation.

Paracetamol is an aniline derivative that inhibits COX mainly in the central nervous system, has little effect on water-salt metabolism and the gastrointestinal mucosa. In inflamed tissues, peroxidases neutralize the effect of paracetamol on COX-1 and COX-2, which explains the almost complete absence of the anti-inflammatory effect.

Pharmacokinetics

Diclofenac

Suction

Absorption is fast and complete, food slows down the rate of absorption. After oral administration of 50 mg Cmax in plasma is 1.5 ?g / ml, Tmax in plasma is 2-3 hours. Plasma concentration is linearly dependent on the dose. Bioavailability is 50%. AUC is 2 times less after oral administration than after parenteral administration at the same dose.

Distribution

Plasma protein binding is more than 99% (most of it binds to albumin).

Penetrates into breast milk, synovial fluid; Cmax in synovial fluid is reached 2-4 hours later than in plasma. T1 / 2 from the synovial fluid is 3-6 hours (the concentration of diclofenac in the synovial fluid 4-6 hours after its administration is higher than in plasma, and remains higher for another 12 hours).

There are no changes in the pharmacokinetics of diclofenac against the background of repeated use. Does not cumulate if the recommended interval between meals is observed.

Metabolism

About 50% of diclofenac is metabolized during the 'first pass' through the liver. Metabolism occurs as a result of multiple or single hydroxylation and subsequent conjugation with glucuronic acid. The isoenzyme CYP2C9 is also involved in the metabolism of diclofenac. The pharmacological activity of metabolites is less than the pharmacological activity of diclofenac.

Withdrawal

Systemic clearance is 260 ml / min. T1 / 2 from plasma - 1-2 hours. 60% of the dose taken is excreted in the form of metabolites by the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites in the bile.

Pharmacokinetics in special clinical situations

In patients with severe renal insufficiency (CC <10 ml / min), the excretion of metabolites in the bile increases, while an increase in their concentration in the blood is not observed.

In patients with chronic hepatitis or compensated liver cirrhosis, pharmacokinetic parameters do not change.

Paracetamol

Absorption and distribution

The absorption is high. Cmax in blood plasma is 5-20 ?g / ml, Tmax is 0.5-2 hours.

Plasma protein binding - 15%.

Penetrates the BBB.

Less than 1% of the dose of paracetamol taken by a nursing mother passes into breast milk.

Metabolism

It is metabolized in the liver in three main ways: conjugation with glucuronides, conjugation with sulfates, oxidation by microsomal liver enzymes. In the latter case, toxic intermediate metabolites are formed, which are subsequently conjugated with glutathione, and then with cysteine ??and mercapturic acid. The main isoenzymes of cytochrome P450 for this metabolic pathway are the isoenzyme CYP2E1 (mainly), CYP1A2 and CYP3A4 (minor role). When glutathione is deficient, these metabolites can cause damage and necrosis of hepatocytes.

Additional metabolic pathways are hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxyparacetamol, which are subsequently conjugated with glucuronides or sulfates. In adults, glucuronidation predominates, in newborns (including premature infants) and young children - sulfation. Conjugated paracetamol metabolites (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity.

Withdrawal

T1 / 2 is 1-4 hours. It is excreted by the kidneys in the form of metabolites, mainly conjugates, only 3% unchanged.

Pharmacokinetics in special clinical situations

In elderly patients, paracetamol clearance decreases and T1 / 2 increases.

Side effect

From the digestive system: epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased activity of hepatic aminotransferases, gastritis, proctitis, bleeding from the gastrointestinal tract (vomiting of blood, melena, diarrhea mixed with blood), ulceration of the gastrointestinal mucosa ( with or without bleeding or perforation), hepatitis, jaundice, abnormal liver function, stomatitis, glossitis, esophagitis, hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease, constipation, pancreatitis, fulminant hepatitis.

From the nervous system: headache, dizziness, drowsiness, impaired sensitivity (including paresthesia), memory disorders, tremors, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental violations.

From the senses: vertigo, visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, impaired taste.

From the urinary system: acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, renal papillary necrosis.

From the hematopoietic system: thrombocytopenia, leukopenia, anemia, incl. hemolytic or aplastic, agranulocytosis, methemoglobinemia.

Allergic reactions: urticaria, allergic purpura, anaphylactic / anaphylactoid reactions (including marked decrease in blood pressure and shock), angioedema (including facial).

From the side of the cardiovascular system: palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

From the respiratory system: bronchial asthma (including shortness of breath), pneumonitis.

On the part of the skin: skin rash (including bullous), erythema, incl. multiforme and Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, pruritus, hair loss, photosensitivity, purpura.

Others: edema.

Application during pregnancy and lactation

The safety of using the drug during pregnancy and during breastfeeding has not been established, therefore, the appointment of Panoxen for this category of patients is contraindicated.

Application for violations of liver function

The use of the drug is contraindicated in severe hepatic failure, active liver disease.

With caution, the drug should be prescribed for a history of liver disease, hepatic porphyria, viral hepatitis, alcoholic liver damage.

Application for impaired renal function

The use of the drug is contraindicated in severe renal failure (CC less than 30 ml / min), progressive kidney disease.

The drug should be prescribed with caution in chronic renal failure (CC 30-60 ml / min).

Application in children

The use of the drug is contraindicated in childhood.

Use in elderly patients

The drug should be used with caution in elderly patients.

special instructions

To reduce the risk of developing adverse events from the gastrointestinal tract, the drug should be used in the minimum effective dose for the minimum possible short course.

Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing to patients with heart or renal failure, as well as when treating elderly patients receiving diuretics, and patients who, for any reason, have a decrease in BCC (for example, after extensive surgery). When prescribing Panoxen in such cases, it is recommended to monitor renal function as a precautionary measure.

In order to quickly achieve the desired therapeutic effect, the drug is taken 30 minutes before a meal. In other cases, take before, during or after meals unchewed with plenty of water.

In patients with liver failure (chronic hepatitis, compensated liver cirrhosis), kinetics and metabolism do not differ from those in patients with normal liver function.

Against the background of the use of the drug, the results of laboratory studies are distorted in the quantitative determination of the content of glucose and uric acid in plasma.

Influence on the ability to drive vehicles and use mechanisms

Care must be taken when driving vehicles and other activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Diclofenac

Symptoms: vomiting, bleeding from the gastrointestinal tract, epigastric pain, diarrhea, dizziness, tinnitus, lethargy, convulsions; rarely - increased blood pressure, acute renal failure, hepatotoxic effect, respiratory depression, coma.

Treatment: gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating an increase in blood pressure, impaired renal function, seizures, irritation of the gastrointestinal tract, respiratory depression. Forced diuresis, hemodialysis are ineffective (due to the high degree of binding to plasma proteins and intensive metabolism).

Paracetamol

Symptoms: during the first 24 hours after administration - pallor of the skin, nausea, vomiting, anorexia, abdominal pain; violation of glucose metabolism, metabolic acidosis. Symptoms of liver dysfunction may appear 12-48 hours after an overdose. In severe overdose - liver failure with progressive encephalopathy, coma, death; acute renal failure with tubular necrosis (including in the absence of severe liver damage); arrhythmia, pancreatitis. The hepatotoxic effect in adults is manifested when taking 4 g or more.

Treatment: the introduction of SH-group donors and the precursor of glutathione synthesis - methionine within 8-9 hours after an overdose and acetylcysteine ??- within 8 hours.The need for additional therapeutic measures (further administration of methionine, intravenous administration of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as from the time elapsed after taking it.

Drug interactions

Diclofenac

Increases plasma concentration of digoxin, lithium preparations.

Reduces the effect of diuretics, against the background of potassium-sparing diuretics, the risk of developing hyperkalemia increases; against the background of anticoagulants, antiplatelet agents and thrombolytics (alteplase, streptokinase, urokinase), the risk of bleeding increases (more often from the gastrointestinal tract).

Reduces the effects of antihypertensive and hypnotic drugs.

Increases the likelihood of side effects of other NSAIDs and GCS (bleeding from the gastrointestinal tract), the toxicity of methotrexate and the nephrotoxicity of cyclosporine (due to an increase in their plasma concentration).

Acetylsalicylic acid reduces the concentration of diclofenac in the blood.

Reduces the effect of hypoglycemic agents.

Paracetamol increases the risk of developing the nephrotoxic effects of diclofenac.

Cefamandol, cefoperazone, cefotetan, valproic acid and plicamycin increase the incidence of hypoprothrombinemia.

Cyclosporine and gold preparations increase the effect of diclofenac on the synthesis of prostaglandins in the kidneys, which is manifested by an increase in nephrotoxicity.

Selective serotonin reuptake inhibitors increase the risk of gastrointestinal bleeding.

ќдновременное применение с этанолом, колхицином, кортикотропином и препаратами зверобо¤ продыр¤вленного повышает риск развити¤ кровотечений из ? “.

—редства, вызывающие фотосенсибилизацию, повышают сенсибилизирующее действие диклофенака к ”‘-облучению.

—редства, блокирующие канальцевую секрецию, повышают концентрацию в плазме диклофенака, тем самым увеличива¤ его эффективность и токсичность.

јнтибактериальные средства из группы хинолона повышают риск развити¤ судорог.

ѕарацетамол

—нижает эффективность урикозурических средств.

ќдновременное применение парацетамола в высоких дозах повышает эффект антикоагул¤нтов (снижение синтеза факторов свертывани¤ крови в печени).

»ндукторы микросомальных ферментов печени (фенитоин, барбитураты, рифампицин, фенилбутазон, трициклические антидепрессанты), этанол и гепатотоксичные средства увеличивают продукцию гидроксилированных активных метаболитов, что обусловливает возможность развити¤ т¤желых интоксикаций даже при небольшой передозировке.

?лительное применение барбитуратов снижает эффективность парацетамола.

ѕри одновременном приеме этанол способствует развитию острого панкреатита.

»нгибиторы микросомальных ферментов печени (в т.ч. циметидин) снижают риск гепатотоксического действи¤.

?лительное одновременное применение парацетамола и Ќѕ¬— повышает риск развити¤ 'анальгетической' нефропатии и папилл¤рного некроза почек, наступлени¤ терминальной почечной недостаточности.

Long-term concomitant use of high doses of paracetamol and salicylates increases the risk of developing kidney or bladder cancer.

Diflunisal increases the plasma concentration of paracetamol by 50%, which increases the risk of developing hepatotoxicity.

Myelotoxic drugs increase the manifestations of paracetamol hematotoxicity.