Panoxen, 50 mg+500 mg 20 pcs

Panoxen is a combined analgesic drug, the effect of which is due to its constituent components.

Diclofenac is a derivative of phenylacetic acid, has anti-inflammatory, analgesic, antipyretic, antiaggregant effect. By inhibiting COX-1 and COX-2 it disrupts arachidonic acid metabolism, decreases quantity of prostaglandins both in inflammation focus and healthy tissues, inhibits exudative and proliferative phases of inflammation.

Paracetamol is aniline derivative, it inhibits COX mainly in CNS, 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 lack of anti-inflammatory effect

Pharmacokinetics

Diclofenac

Absorption

Absorption is rapid and complete; food slows 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. Plasma concentrations are linearly related to the dose. Bioavailability is 50%. AUC is 2 times less after oral administration than after parenteral administration in the same dose.

Distribution

The binding to plasma proteins is more than 99% (most is bound to albumin).

It penetrates synovial fluid; Cmax in synovial fluid is reached 2-4 h later than in plasma. T1/2 from synovial fluid is 3-6 h (diclofenac concentrations in synovial fluid are higher in 4-6 h after dosing than in plasma and remain high for 12 h).

There is no change in pharmacokinetics of diclofenac on repeated use. It does not cumulate if the recommended interval between meals is observed.

It penetrates into the breast milk.

Metabolism

About 50% of diclofenac is metabolized during “first passage” through the liver. Metabolism occurs as a result of multiple 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.

The systemic clearance is 260 ml/min. T1/2 from plasma is 1-2 hours. 60% of the administered 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 failure (CKR less than 10 ml/min) excretion of metabolites in bile is increased, while there is no increase of their concentration in blood.

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

Paracetamol

Intake and distribution

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

The binding to plasma proteins is 15%.

It penetrates through the GEB.

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

Metabolism

It is metabolized in the liver by three main pathways: conjugation with glucuronides, conjugation with sulfates, and oxidation by hepatic microsomal enzymes. In the latter case toxic intermediate metabolites are formed, which subsequently conjugate with glutathione and then with cysteine and mercapturic acid. The main cytochrome P450 isoenzymes for this metabolic pathway are CYP2E1 (predominantly), CYP1A2 and CYP3A4 (secondary role). When deficient in glutathione, 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 to glucuronides or sulfates. In adults, glucuronidation predominates; in newborns (including premature infants) and young children, sulfation predominates. Conjugated metabolites of paracetamol (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity.

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

Pharmacokinetics in special clinical cases

In elderly patients, paracetamol clearance is decreased and T1/2 is increased.

Indications

Active ingredient

Composition

Active substances:

Paracetamol 500 mg,

Diclofenac sodium 50 mg;

Associates:

Corn starch – 290 mg,

Cellacephate (acetyl phthalyl 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 (propylparahydroxybenzoate) – 4 mg.

Composition of the shell:

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

How to take, the dosage

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

Panoxen is prescribed 1 tablet 2-3 times a day. Maximal daily dose is 3 tablets (150 mg converted into diclofenac).

The duration of use of the drug Panoxen depends on the indication for use. In acute conditions, the drug is used for a few days in the case of fast-absorbing conditions. In chronic inflammatory or degenerative diseases of connective tissue the long-term use of the drug Panoxen is possible.

When using the drug for a long time it is necessary to perform regular monitoring for possible gastrointestinal mucosal erosion with subsequent development of gastrointestinal bleeding, as well as to perform liver function tests to detect possible hepatotoxicity of the drug at an early stage.

Interaction

Diclofenac

Enhances plasma concentrations of digoxin, lithium drugs reduces the effect of diuretics, against potassium-saving diuretics increases the risk of hyperkalemia; against anticoagulants, antiaggregants and thrombolytics (alteplase, streptokinase, urokinase) increases the risk of bleeding (often from the GI tract).

Limits the effects of hypotensive and sleeping pills.

Increases the likelihood of side effects of other NSAIDs and GCS (gastrointestinal bleeding), methotrexate toxicity and cyclosporine nephrotoxicity (by increasing their plasma concentrations).

Acetylsalicylic acid reduces the blood concentration of diclofenac.

Decreases the effect of hypoglycemic agents.

Paracetamol increases the risk of nephrotoxic effects of diclofenac.

Cefamandole, cefoperazone, cefotetan, valproic acid and plikamycin increase the incidence of hypoprothrombinemia.

Cyclosporine and gold drugs 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 GI bleeding.

Simultaneous use with ethanol, colchicine, corticotropin and preparations of St. John’s wort increases the risk of GI bleeding.

Photosensitizing agents increase sensitizing effect of diclofenac to UV radiation.

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

The quinolone antibacterials increase the risk of seizures.

Paracetamol

Decreases the effectiveness of uricosuric agents.

The concomitant use of paracetamol in high doses increases the effect of anticoagulants (decreased synthesis of clotting factors in the liver).

The inducers of microsomal liver enzymes (phenytoin, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants), ethanol and hepatotoxic agents increase production of hydroxylated active metabolites, which leads to possible severe intoxications even with a small overdose.

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

The simultaneous use of ethanol promotes the development of acute pancreatitis.

Liver microsomal enzyme inhibitors (including cimetidine) reduce the risk of hepatotoxic effects.

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

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

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

Myelotoxic agents increase the manifestations of hematotoxicity of paracetamol.

Special Instructions

In order to reduce the risk of gastrointestinal adverse events, the drug should be used in the lowest effective dose with the shortest possible course.

Because of the important role of prostaglandins in maintaining renal blood flow, special caution should be exercised when prescribing in patients with cardiac or renal insufficiency, as well as in therapy in elderly patients receiving diuretics and in patients who for any reason have decreased BOD (e.g., after major surgery). When prescribing Panoxen in these cases it is recommended to monitor renal function as a precautionary measure.

In order to achieve the desired therapeutic effect, the drug is taken 30 minutes before meals. Otherwise, the drug is taken before, during or after meals, unchewed, with plenty of water.

In patients with hepatic insufficiency (chronic hepatitis, compensated cirrhosis) the kinetics and metabolism are not different from those of patients with normal liver function.

The results of laboratory studies of quantitative determination of glucose and uric acid in plasma are distorted against the background of using the drug.

Impact on driving and operating machinery

Cautious driving and other activities requiring increased concentration and quick psychomotor reactions are to be observed.

Contraindications

Side effects

Digestive system disorders: Epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased liver aminotransferase activity, gastritis, proctitis, GI bleeding (vomiting with blood, melena, diarrhea with blood admixture), gastrointestinal mucosal ulceration (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, fulminant hepatitis.

Nervous system disorders: headache, dizziness; somnolence, sensitivity disorders (including paraesthesia), memory disorders, tremor, seizures, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental disorders.

Sensory organs: vertigo, visual disturbances (blurred vision, diplopia), hearing disorders, tinnitus, taste disorders.

Urinary system disorders: acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary renal necrosis.

Hematopoietic system disorders: thrombocytopenia, leukopenia, anemia, including hemolytic or aplastic, agranulocytosis, methemoglobinemia.

Allergic reactions: urticaria, anaphylactic/anaphylactoid reactions (including marked BP decrease and shock), angioedema (including face).

Cardiovascular system disorders: palpitations, chest pain, increased BP, vasculitis, heart failure, myocardial infarction, allergic purpura.

Respiratory system: bronchial asthma (including dyspnea), pneumonitis.

Skin disorders: skin rash (including bullous), erythema, including erythema multiforme and Stevens-Johnson syndrome, Lyell syndrome, exfoliative dermatitis, itching, hair loss, photosensitization, purpura.

Others: edema.

Overdose

Diclofenac

Symptoms: vomiting, gastrointestinal bleeding, epigastric pain, diarrhea, dizziness, tinnitus, lethargy, seizures; rarely – increased BP, acute renal failure, hepatotoxic effect, respiratory depression, coma.

Treatment: gastric lavage, activated charcoal, symptomatic therapy aimed at elimination of BP increase, renal dysfunction, seizures, gastrointestinal irritation, respiratory depression. Forced diuresis and hemodialysis are ineffective (due to high degree of binding to plasma proteins and intense metabolism).

Paracetamol

Symptoms: during the first 24 hours after ingestion – pale skin, nausea, vomiting, anorexia, abdominal pain; impaired glucose metabolism, metabolic acidosis. Symptoms of hepatic dysfunction may appear 12-48 hours after overdose. In severe overdose – hepatic 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 occurs when taking 4 g or more.

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

Pregnancy use

It is contraindicated in children under 12 years of age.

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