Composition, form of production and packaging
Tablets coated with a coat of white or almost white, capsular-shaped, with a risk on one side; slight roughness is allowed.
diclofenac sodium 50 mg
paracetamol 500 mg
Auxiliary substances: corn starch - 290 mg, cellacephate 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 (methylparahydroxybenzoate) 17.5 mg, propylparaben 4 mg propylparahydroxybenzoate, tablet coating TC 1005 (white) 28.5 mg (hypromellose (hydroxypropylmethylcellulose) 5.5 mg, propylene glycol 4.3 mg, talc 10.8 mg, titanium dioxide - 7.98 mg).
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
Combined analgesic drug, the effect of which is due to the effects of its constituent components.
Diclofenac is a derivative of phenylacetic acid, has anti-inflammatory, analgesic, antipyretic, antiplatelet effect. Inhibiting COX-1 and COX-2, disrupts the metabolism of arachidonic acid, reduces the number of prostaglandins both in the inflammation focus and in healthy tissues, suppresses the exudative and proliferative phases of inflammation.
Paracetamol is an aniline derivative, inhibits COX mainly in the central nervous system, has little effect on water-salt metabolism and gastrointestinal mucosa. In inflamed tissues, peroxidases neutralize the effect of paracetamol on COX-1 and COX-2, which explains the almost complete absence of anti-inflammatory effect.
Absorption is fast and complete, food slows down the absorption rate. After ingestion, 50 mg C max in plasma is 1.5 Ојg / ml, T max in plasma is 2-3 hours. The concentration in the plasma is in linear dependence on the dose. Bioavailability is 50%. AUC is 2 times less after ingestion than after parenteral administration at the same dose.
Binding to plasma proteins is more than 99% (most of it is associated with albumins).
Penetrates into breast milk, synovial fluid; C max in synovial fluid is achieved 2-4 hours later than in plasma. T 1/2 of the synovial fluid is 3-6 h (the concentration of diclofenac in the synovial fluid 4-6 h after its intake is higher than in the plasma, and remain higher for another 12 h).
Changes in the pharmacokinetics of diclofenac against a background of repeated use are not noted. Do not cumulate while observing the recommended interval between meals.
About 50% of diclofenac undergoes metabolism on "first pass" through the liver. Metabolism occurs as a result of repeated or one-time hydroxylation and subsequent conjugation with glucuronic acid. The isoenzyme CYP2C9 also participates in the metabolism of diclofenac. The pharmacological activity of metabolites is less than the pharmacological activity of diclofenac.
Systemic clearance is 260 ml / min. T 1/2 from the plasma - 1-2 hours. 60% of the accepted dose is excreted as metabolites by the kidneys; less than 1% is unchanged, the rest of the dose is excreted as metabolites with bile.
Pharmacokinetics in special clinical cases
In patients with severe renal insufficiency (CC <10 ml / min), the excretion of metabolites with bile is increased, while there is no increase in their concentration in the blood.
In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetic parameters do not change.
Suction and distribution
Absorption is high. C max in the blood plasma is 5-20 Ојg / ml, T max - 0.5-2 h.
Binding to plasma proteins - 15%.
Penetrates through the BBB.
Less than 1% of the dose of paracetamol taken by the lactating mother penetrates into breast milk.
Metabolised in the liver in three main ways: conjugation with glucuronides, conjugation with sulfates, oxidation with microsomal enzymes of the liver. In the latter case, toxic intermediate metabolites are formed, which are subsequently conjugated to glutathione, and then to cysteine вЂ‹вЂ‹and mercapturic acid. The main isoenzymes of cytochrome P450 for this pathway of metabolism are the isoenzyme CYP2E1 (predominantly), CYP1A2 and CYP3A4 (a secondary role). With a deficiency of glutathione, these metabolites can cause damage and necrosis of hepatocytes.
Additional metabolic pathways include hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxyparacetamol, which are subsequently conjugated to glucuronides or sulfates. In adults, glucuronin prevails, in newborns (including premature) and young children - sulfation. Conjugated metabolites of paracetamol (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity.
T 1/2 is 1-4 hours. It is excreted by the kidneys in the form of metabolites, mainly conjugates, only 3% in unchanged form.
Pharmacokinetics in special clinical cases
In elderly patients, clearance of paracetamol decreases and T 1/2 increases.
- to reduce pain and inflammation at the time of application in 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;
Panoxen is taken orally, without chewing, during or after a meal, with a small amount of water.
Assign 1 tab. 2-3 times / day. The maximum daily dose is 3 tablets. (150 mg in terms of diclofenac).
The duration of the drug Panoxen depends on the indication for use. In acute conditions, rapidly docked conditions, the drug is used for several days. In chronic inflammatory or degenerative diseases of connective tissue, long-term use of Panoxen is possible.
With long-term use of the drug, it is necessary to carry out regular monitoring for possible erosion of the gastrointestinal mucosa with subsequent development of gastrointestinal bleeding, and also to perform functional tests of the liver with the purpose of early detection of possible hepatotoxicity of the drug.
On the part of the digestive system: epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased activity of hepatic aminotransferases, gastritis, proctitis, bleeding from the digestive tract (vomiting with blood, melena, diarrhea with blood impurities), ulceration of the gastrointestinal mucosa with or without bleeding or perforation), hepatitis, jaundice, dysfunction of the liver, stomatitis, glossitis, esophagitis, hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease, constipation, pancreatitis, fulminant hepatitis.
From the side of the nervous system: headache, dizziness, drowsiness, violation of sensitivity (including paresthesia), memory disorders, tremor, 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, a violation of taste sensations.
From the urinary system: acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis of the kidneys.
From the hemopoietic 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 cardiovascular system: a feeling of heartbeat, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.
On the part of the respiratory system: bronchial asthma (including dyspnea), pneumonitis.
From the skin: skin rash (including bullous), erythema, incl. multiform and Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura.
- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in anamnesis);
- erosive and ulcerative lesions of the gastrointestinal tract (including duodenum);
- active gastrointestinal hemorrhage;
- Inflammatory bowel disease;
severe hepatic impairment;
- severe heart failure;
- period after aortocoronary shunting;
- renal failure of severe degree (CK <30 ml / min);
progressive kidney disease;
active liver disease;
- the period of lactation (breastfeeding);
- hypersensitivity to the components of the drug;
- Hypersensitivity to other derivatives of phenylacetic acid or aniline.
With caution: gastric and duodenal ulcer (in remission or history), ulcerative colitis, Crohn's disease, liver disease in history, hepatic porphyria, benign hyperbilirubinemia (including Gilbert's syndrome), viral hepatitis, alcoholic liver damage , chronic heart failure of mild or moderate severity, hypertension, a significant decrease in BCC (including after extensive surgery), bronchial asthma, IHD, cerebrovascular disease, hyperlum diabetes mellitus, peripheral arterial disease, smoking, chronic renal failure (CK 30-60 ml / min), the presence of Helicobacter pylori infection, prolonged use of NSAIDs, alcoholism, severe physical illnesses, deficiency of glucose-6-phosphate dehydrogenase, simultaneous reception of GCS, anticoagulants, antiaggregants, selective serotonin reuptake inhibitors, in elderly patients.
PREGNANCY AND LACTATION
Safety of use of the drug during pregnancy and during breastfeeding is not established, therefore Panoxen's appointment of this category of patients is contraindicated.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated use of the drug for renal failure of severe degree (QC less than 30 ml / min), progressive kidney disease.
With caution should prescribe the drug for chronic kidney failure (KK 30-60 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated use of the drug in severe hepatic insufficiency, active liver disease.
With caution should prescribe the drug for liver diseases in history, hepatic porphyria, viral hepatitis, alcoholic liver damage.
APPLICATION FOR CHILDREN
The use of the drug is contraindicated in childhood.
APPLICATION IN ELDERLY PATIENTS
With caution should be used in elderly patients.
To reduce the risk of developing adverse events from the gastrointestinal tract, the drug should be applied at the lowest effective dose with the minimum possible short course.
Because of the important role of prostaglandins in maintaining renal blood flow, caution should be exercised in appointing 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 surgical intervention). When appointing Panoxen in such cases, it is recommended as a precaution to monitor kidney function.
In order to quickly achieve the desired therapeutic effect, the drug is taken 30 minutes before meals. In other cases, take before, during or after a meal in undiluted form, with plenty of water.
In patients with hepatic insufficiency (chronic hepatitis, compensated cirrhosis), 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 are distorted in the quantitative determination of glucose and uric acid in the plasma.
Impact on the ability to drive vehicles and manage mechanisms
Care must be taken when driving vehicles and other activities that require a high concentration of attention and speed of psychomotor reactions.
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 blood pressure increase, renal dysfunction, seizures, gastrointestinal irritation, respiratory depression. Forced diuresis, hemodialysis are ineffective (due to the high degree of binding to plasma proteins and intensive metabolism).
Symptoms: during the first 24 hours after administration - pallor of the skin, nausea, vomiting, anorexia, abdominal pain; disturbance 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. Hepatotoxic effect in adults is manifested when taking 4 g or more.
Treatment: the introduction of donors of SH-groups and a precursor of the synthesis of glutathione-methionine for 8-9 hours after an overdose and acetylcysteine вЂ‹вЂ‹- for 8 hours. The need for additional therapeutic measures (further introduction of methionine, IV injection of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as the time elapsed after its administration.
Increases the concentration in the plasma digoxin, lithium preparations.
Reduces the effect of diuretics, against the background of potassium-sparing diuretics increases the risk of hyperkalemia; against the background of anticoagulants, antiaggregants and thrombolytics (alteplase, streptokinase, urokinase) increases the risk of bleeding (more often from the gastrointestinal tract).
Reduces the effects of antihypertensive and hypnotic drugs.
Increases the likelihood of side effects of other NSAIDs and SCS (bleeding from the gastrointestinal tract), toxicity of methotrexate and nephrotoxicity of cyclosporine (due to an increase in their concentration in the plasma).
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 plikamycin 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 increased nephrotoxicity.
Selective serotonin reuptake inhibitors increase the risk of bleeding from the digestive tract.
Simultaneous use with ethanol, colchicine, corticotropin and preparations of St. John's wort increases the risk of bleeding from the gastrointestinal tract.
Means that cause photosensitivity, increase the sensitizing effect of diclofenac to UV irradiation.
The drugs that block tubular secretion increase the concentration in the plasma of diclofenac, thereby increasing its effectiveness and toxicity.
Antibacterial drugs from the quinolone group increase the risk of seizures.
Reduces the effectiveness of uricosuric drugs.
Simultaneous use of paracetamol in high doses increases the effect of anticoagulants (a decrease in the synthesis of 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 allows the development of severe intoxications even with a slight overdose.
Long-term use of barbiturates reduces the effectiveness of paracetamol.
With simultaneous intake of ethanol promotes the development of acute pancreatitis.
Inhibitors of microsomal liver enzymes (including cimetidine) reduce the risk of hepatotoxic effects.
Long-term simultaneous use of paracetamol and NSAIDs increases the risk of developing "analgesic" nephropathy and papillary necrosis of the kidneys, the onset of terminal renal failure.
The prolonged simultaneous use of paracetamol in high doses 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 manifestation of hematotoxicity of paracetamol.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C. Shelf life - 3 years.