Safiston, tablets 20 pcs

Pharmacotherapeutic group:

An analgesic combined (NSAID+analgesic non-narcotic agent+psychostimulant).

ATC code:

N02BE51

Pharmacological properties

Pharmacodynamics

Safiston is a combined drug, the effect of which is determined by the components that make up it. The combination of the three components of the drug leads to mutual enhancement of their pharmacological action. Paracetamol and propiphenazone have analgesic and antipyretic effects.

Paracetamol is a non-narcotic analgesic. It blocks cyclooxygenase (COX) only in the central nervous system (CNS), affecting the centers of pain and thermoregulation (in inflamed tissues cellular peroxidases neutralize the effect of paracetamol on COX), which explains the almost complete lack of anti-inflammatory effect.

The lack of effect on prostaglandin (PG) synthesis in peripheral tissues determines the absence of its negative effect on water-salt metabolism (sodium and water retention) and gastrointestinal mucosa.

Propiphenazone is a pyrazolone derivative. Its mechanism of action is by inhibiting COX, involved in the formation of prostaglandins from arachidonic acid.

Caffeine increases reflex excitability of the spinal cord, stimulates respiratory and vasomotor centers, dilates blood vessels of skeletal muscles, brain, heart and kidneys, reduces platelet aggregation, reduces sleepiness, fatigue.

In this combination low-dose caffeine has almost no stimulating effect on the central nervous system, but helps to regulate the tone of the brain vessels, reduces sleepiness, increases the analgesic effect of other drug components.

Pharmacokinetics

Paracetamol

Absorption – high, binding to plasma proteins – 15%, time to reach maximum plasma concentration (Tcmax) – 20-30 minutes. It penetrates through the blood-brain barrier (BBB). Less than 1% of dose taken by a nursing mother passes into breast milk.

Therapeutic effective concentration of paracetamol in plasma is achieved when administered at a dose of 10-15 mg/kg.

Metabolized in the liver: 80% reacts in conjugation with glucuronic and sulfuric acids to form inactive metabolites, 17% reacts in hydroxylation to form inactive metabolites, which conjugate with glutathione to form inactive metabolites.

If there is a lack of glutadione these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The elimination half-life is 2-3 hours. In elderly patients, paracetamol clearance is decreased and the elimination half-life is increased. Excreted by the kidneys unchanged in 3%.

Propifenazone

Maximum concentration of propifenazone in plasma is reached after 30 minutes. It is metabolized in the liver. Half-life period is 1-1.5 hours. Combination with paracetamol increases its elimination time by 40%, which plays a significant role as it allows reducing the number of drug intakes during a day. It is eliminated by kidneys.

Caffeine

Time of maximum concentration – 1 hour; elimination half-life – 3.5 hours; 65-80% of caffeine is eliminated by kidneys mainly as 1-methyloxatin, 1-methylureic acid and acetylated derivatives of uracil, a small amount is transformed into theophylline and theobromine.

Indications

It is used for relief of pain syndrome of low and medium intensity of different genesis: headache, migraine, toothache, arthralgia, myalgia, algodysmenorrhea, and also as an antipyretic in febrile states against infection and inflammatory diseases (ARVI, including influenza, etc.).

Active ingredient

Caffeine, Paracetamol, Propiphenazone

Composition

Per 1 tablet:
active ingredient:

• caffeine – 50.0 mg,
• paracetamol – 250.0 mg,
• propifenazon – 150.0 mg.

Excipients: microcrystalline cellulose – 100.0 mg, croscarmellose sodium – 8.0 mg, sodium carboxymethyl starch -44.8 mg, povidone (polyvinylpyrrolidone) – 18.0 mg, colloidal silicon dioxide – 3.2 mg, magnesium stearate – 16.0 mg.

How to take, the dosage

Appoint adults 1 – 2 tablets, children 12 – 18 years -1 tablet 1 – 3 times a day, preferably 1 -2 hours after meals with plenty of fluids.

Maximal daily dose is two tablets. The daily dose should not exceed six tablets.

The drug should not be used for more than 5 days as an analgesic and for not more than 3 days as an antipyretic without the prescription and supervision of the physician.

The daily dose or the duration of treatment may be increased only under the supervision of a physician. Do not exceed the recommended dose.

Interaction

The effectiveness of the drug may decrease when concomitant use with cholestyramine, cholinolytics, antidepressants, alkaline substances.

Simultaneous use of Safistone with barbiturates, anticonvulsants, ethanol significantly increases hepatotoxic effects.

Metoclopramide accelerates absorption of paracetamol. Under the influence of paracetamol the elimination half-life of chloraphenicol is 5 times longer. Concomitant use of paracetamol in high doses increases the effect of anticoagulants. Myelotoxic agents increase the manifestation of hematotoxicity of paracetamol.

Caffeine accelerates absorption of ergotamine, reduces absorption of calcium preparations, reduces the effect of narcotics and hypnotics, increases excretion of lithium preparations, accelerates absorption and enhances the effect of cardiac glycosides, increases their toxicity.

Simultaneous use of caffeine with beta-adrenoblockers may lead to mutual suppression of therapeutic effects, with beta-adrenomimetics – to additional stimulation of the central nervous system and other toxic effects.

Caffeine may decrease clearance of theophylline, and possibly other xanthines, increasing the possibility of additive pharmacodynamic and other toxic effects. Monoamine oxidase inhibitors, furazolidone, procarbazine, selegiline, and large doses of caffeine can cause dangerous cardiac arrhythmias or marked increases in blood pressure. Nicotine increases the excretion rate of caffeine. Caffeine is an adenosine antagonist.

Propiphenazole may increase the effect of oral hypolipidemic agents, sulfonamide drugs, anticoagulants, the ulcerogenic effect of glucocorticosteroids, reduces the effectiveness of potassium-saving diuretics.

Special Instructions

When using the drug for a long time (more than 5 days) it is necessary to monitor the peripheral blood picture and the functional state of the liver.

During the treatment it is necessary to refrain from drinking alcohol-containing beverages (increased risk of gastrointestinal bleeding).

The excessive use of caffeine-containing products (coffee, tea) during the treatment may cause overdose symptoms. Taking the drug may make it difficult to establish a diagnosis in acute abdominal pain syndrome.

Impact on the ability to drive vehicles and operate machinery requiring high concentration

When taking the drug, caution should be exercised when driving vehicles and engaging in other activities requiring high concentration and quick psychomotor reactions.

Contraindications

• High sensitivity to the ingredients of the drug,
• severe renal and/or hepatic failure,
  
• deficiency of glucose-6-phosphate dehydrogenase enzyme.
• deficiency of glucose-6-phosphate dehydrogenase enzyme,
• depression of medullary hematopoiesis (leukopenia, anemia, incl.ч. hemolytic),
• acute hematoporphyria,
• Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis and intolerance to non-steroidal anti-inflammatory drugs (including history), conditions accompanied by respiratory depression,
• intracranial hypertension,
• acute myocardial infarction,
• ischemic heart disease, arrhythmias,
arterial hypertension,
• gastric and duodenal ulcer, <
• glaucoma,
• insomnia,
• pregnancy,
• lactation period in women,
• children under 12 years of age.

With caution
benign hyperbilirubinemia (including Gilbert, Dubin-Johnson, Rotor syndrome), advanced age, alcoholism, epilepsy and susceptibility to seizures.

Side effects

Central nervous system: dizziness, insomnia.

Gastrointestinal tract: nausea, vomiting, heaviness and discomfort in the stomach;

Blood system: Thrombocytopenia, agranulocytosis, hemolytic anemia;

Allergic reactions: skin rash, itching, urticaria, Quincke’s edema, erythema multiforme exudative (including.Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome).

Overdose

Symptoms: (caused by paracetamol, appears after taking 10-15 g) pale skin, decreased appetite, nausea, vomiting, epigastric pain, hepatotoxic and nephrotoxic effects, in severe cases – liver failure, hepatonecrosis, increased “liver” transaminases activity, increased prothrombin time, encephalopathy and coma.

Treatment: gastric lavage, administration of activated charcoal, symptomatic therapy, injection of donors of SH-groups and precursors of glutathione synthesis – methionine in 8-9 hours after overdose and N-acetylcysteine in 12 hours after it.

High doses of caffeine cause the following symptoms: headache, tremor, irritability, gastralgia, agitation, motor anxiety, confusion, tachycardia, arrhythmia, hyperthermia, rapid urination, headache, nausea, vomiting, tinnitus, convulsions (in acute overdose – tonic-clonic).

Treatment: gastric lavage, administration of activated charcoal, laxatives, maintenance of ventilation and oxygenation, in convulsions intravenous diazepam, phenobarbital, maintenance of water-electrolyte balance.

Pregnancy use

The drug is contraindicated in pregnancy and during breast-feeding.

Similarities

Novalgin, Caffetine Lite