Panoxen, pills, 20 pcs.

Composition

Active ingredients:

paracetamol 500 mg,

diclofenac sodium 50 mg;

Auxiliary substances:

corn starch – 290 mg,

cellacefate (acetylcellulose) – 15 mg,

diethyl – 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 (parahydroxybenzoate) – 4 mg.

Shell composition:

tablet coating TS 1005 (white) – 28.5 mg (hypromellose-5.5 mg, propylene glycol-4.3 mg, talc-10.8 mg, titanium dioxide-7.98 mg).

Pharmacological action

Panoxen is a combined analgesic drug, the action of which is due to the components included in its composition.

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

Paracetamol-an aniline derivative, inhibits COX mainly in the central nervous system, has a weak 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 an anti-inflammatory effect

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 mcg / ml, Tmax in plasma is 2-3 hours. The concentration in plasma is linearly dependent on the dose. Bioavailability is 50%. AUC is 2 times lower after oral administration than after parenteral administration at the same dose.

Distribution

Binding to plasma proteins is more than 99% (most of it binds to albumins).

Penetrates synovial fluid; Cmax in synovial fluid is reached 2-4 hours later than in plasma. T1 / 2 from synovial fluid is 3-6 hours (concentrations of diclofenac in synovial fluid 4-6 hours after its administration are higher than in plasma, and remain higher for another 12 hours).

There were no changes in the pharmacokinetics of diclofenac during repeated use. It does not accumulate if the recommended interval between meals is observed.

Penetrates into breast milk.

Metabolism

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

Deduction

Systemic clearance is 260 ml / min. T1 / 2 from plasma – 1-2 hours.60% of the dose is excreted as 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 cases

In patients with severe renal insufficiency (creatinine clearance less than 10 ml / min), the excretion of metabolites in the bile increases, while their concentration in the blood does not increase.

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

Paracetamol

Suction and distribution

Absorption is high. Cmax in blood plasma is 5-20 mcg / ml, Tmax-0.5-2 hours.

Binding to plasma proteins is 15%.

Penetrates through 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, and 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 cytochrome P 450 isoenzymes for this pathway of metabolism are CYP2E1 (mainly), CYP1A2 and CYP3A4 (secondary role). When glutathione is deficient, these metabolites can cause hepatocyte damage and necrosis.

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

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

Pharmacokinetics in special clinical cases

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

Indications

• for reducing pain and inflammation at the time of application in inflammatory diseases of musculoskeletal system (rheumatoid arthritis, psoriatic, juvenile 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 (tenosynovitis, bursitis);
• post-traumatic pain syndromes, accompanied by inflammation;
• toothache.

Use during pregnancy and lactation

Contraindicated in children under 12 years of age.

The safety of using the drug during pregnancy and lactation has not been established, so the appointment of this category of patients is contraindicated.

Contraindications

• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance of acetylsalicylic acid or other NSAIDs (including in the anamnesis);
• erosive-ulcerative lesions of the gastrointestinal tract (including the duodenum);
• active gastrointestinal bleeding;
• inflammatory bowel disease;
• severe hepatic impairment;
• severe heart failure;
• after the coronary artery bypass surgery;
• renal failure severe (CC less than 30 ml/min);
• progressive kidney disease;
• active liver disease;
• hyperkalemia;
• pregnancy;
• lactation (breastfeeding);
• children age,
• hypersensitivity to the components of the drug;
• hypersensitivity to other derivatives of phenylacetic acid or aniline.

With caution: peptic ulcer of the stomach and duodenum (in remission or in the anamnesis), ulcerative colitis, Crohn’s disease, liver disease in the anamnesis, hepatic porphyria, benign hyperbilirubinemia (including Gilbert’s syndrome), viral hepatitis, alcoholic liver damage, chronic heart failure of mild or moderate severity, arterial hypertension, a significant decrease in BCC (including after extensive surgery), bronchial asthma, CHD, cerebrovascular diseases, hyperlipidemia, diabetes mellitus, peripheral arterial diseases, smoking, chronic renal failure (creatinine clearance 30-60 ml/min), presence of Helicobacter pylori infection, long-term use of NSAIDs, alcoholism, severe somatic diseases, glucose-6-phosphate dehydrogenase deficiency, concomitant use of corticosteroids, anticoagulants, antiplatelet agents, selective reuptake inhibitors serotonin, elderly patients.

Side effects

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

Nervous system disorders: headache, dizziness; drowsiness, sensory disturbances (including paresthesia), memory disorders, tremor, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental disorders.

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

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

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

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

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

Respiratory system disorders: bronchial asthma (including shortness of breath), pneumonitis.

From the side of the skin: skin rash (incl.bullous), erythema multiforme and Stevens-Johnson syndrome, Lyell’s syndrome, exfoliative dermatitis, pruritus, hair loss, photosensitization, purpura.

Other services: edema.

Interaction

Diclofenac

Increases the plasma concentration of digoxin, lithium preparations reduces the effect of diuretics, against the background of potassium-sparing diuretics, the risk of 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 medications.

Increases the likelihood of side effects of other NSAIDs and corticosteroids (gastrointestinal bleeding), methotrexate toxicity and cyclosporine nephrotoxicity (due to increased plasma concentrations).

Acetylsalicylic acid reduces the concentration of diclofenac in the blood.

Reduces the effect of hypoglycemic agents.

Paracetamol increases the risk of developing 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 prostaglandin synthesis in the kidneys, which is manifested by increased nephrotoxicity.

Selective serotonin reuptake inhibitors increase the risk of gastrointestinal bleeding.

Concomitant use with ethanol, colchicine, corticotropin, and St. John’s wort increases the risk of gastrointestinal bleeding.

Agents that cause photosensitization increase the sensitizing effect of diclofenac to UV radiation.

Agents that block tubular secretion increase the plasma concentration of diclofenac, thereby increasing its effectiveness and toxicity.

Antibacterial agents from the quinolone group increase the risk of seizures.

Paracetamol

Reduces the effectiveness of uricosuric drugs.

Concomitant use of paracetamol in high doses increases the effect of anticoagulants (a decrease in the synthesis of blood clotting factors in the liver).

Inducers of microsomal liver enzymes (phenytoin, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants), ethanol and hepatotoxic agents increase the production of hydroxylated active metabolites, which causes the possibility of severe intoxication even with a small overdose.

Long-term use of barbiturates reduces the effectiveness of paracetamol.

When taken at the same time, ethanol contributes to the development of acute pancreatitis.

Inhibitors of microsomal liver enzymes (including cimetidine) reduce the risk of hepatotoxic effects.

Long-term concomitant use of paracetamol and NSAIDs increases the risk of developing” analgesic ” nephropathy and papillary necrosis of the kidneys, the onset of terminal renal failure.

Long-term concomitant use of high-dose 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 hepatotoxicity.

Myelotoxic agents increase the manifestations of paracetamol hematotoxicity.

How to take, course of administration and dosage

Panoxen is taken orally, without chewing, during or after a meal, with a small amount of water.

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

The duration of use of the drug Panoxen depends on the indication for use. In acute conditions, quickly relieved conditions, the drug is used for several days. In 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 possible erosion of the gastrointestinal mucosa with the subsequent development of gastrointestinal bleeding, as well as conduct liver function tests for the purpose of early detection of possible hepatotoxicity of the drug.

Overdose

Diclofenac

Symptoms: vomiting, gastrointestinal bleeding, 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 increased blood pressure, impaired renal function, convulsions, gastrointestinal irritation, respiratory depression. Forced diuresis and 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; impaired glucose metabolism, metabolic acidosis. Symptoms of impaired liver function 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: administration of SH-group donors and glutathione synthesis precursor methionine within 8-9 hours after 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 on the time elapsed after taking it.

Special instructions

To reduce the risk of adverse events from the gastrointestinal tract, the drug should be used at the lowest effective dose in the shortest possible course.

Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing to patients with cardiac or renal insufficiency, as well as in the treatment of 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 meals. In other cases, take it before, during or after meals in an undigested form, washed down with a sufficient amount of water.

In patients with hepatic insufficiency (chronic hepatitis, compensated cirrhosis of the liver), the kinetics and metabolism do not differ from similar processes in patients with normal liver function.

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

Influence on the ability to drive motor vehicles and manage mechanisms

Caution should be exercised when driving vehicles and other activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Pills.

Storage conditions

At a temperature not exceeding 25 °C.

Shelf life

2 years

Active ingredient

Diclofenac, Paracetamol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Rheumatoid Arthritis, Lumbago, Osteoarthritis and Arthritis, Bursitis, Gout, Tendon Inflammation, Osteochondrosis, Sciatica, Osteoarthritis

Weight

Weight: 31 g.