Spasmalgon Effect, 30 pcs.

Pharmacokinetics:

Paracetamol

Characterized by high and rapid absorption from the GI tract, mainly in the small intestine. The time of reaching maximum plasma concentration (TCmax) is 0.5-1.5 hours after oral administration. Maximum plasma concentration (Cmax) is 5-20 µg/ml. Binding to plasma proteins is insignificant – 15%.

Paracetamol is evenly distributed and penetrates through the blood-brain barrier, as well as into most body tissues. The estimated volume of distribution is 0.95 l/kg. It is metabolized in the liver (90-95%): 80% enters into conjugation reactions with glucuronic acid and sulfates to form inactive metabolites; 17% undergoes hydroxylation to form 8 active metabolites, which conjugate with glutathione to form already inactive metabolites.

In glutathione deficiency, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. CYP2E1 isoenzyme is also involved in metabolism of the drug. The elimination half-life (T1/2) is 1.5-2.5 hours. It is excreted by the kidneys as metabolites, mainly conjugates, only 3% unchanged. The drug clearance decreases and T1/2 increases in elderly patients.

Naproxen

The absorption from the gastrointestinal tract of naproxen is fast and complete. Bioavailability is 95%. Food intake has almost no effect on the completeness or rate of absorption. The tCmax is 1-2 hours. Binding to plasma proteins is more than 99%. Equilibrium concentration is reached by 4-5 doses of the drug (2-3 days). Metabolized in the liver to dimethylnaproxen with the participation of CYP2C9 isoenzyme. T1/2 is 12-15 hours. Clearance is 0.13 ml/min/kg. It is excreted by kidneys (98%), 10% of which are unchanged; 0.5-2.5% of the taken dose is excreted in the bile. Cumulation of metabolites is possible in renal insufficiency.

Caffeine

The caffeine contained in the drug is almost completely and quickly absorbed, the maximum concentration in plasma is reached within 1 hour. It quickly passes through the blood-brain and placental barriers, enters the breast milk, and is eliminated (including as metabolites) mainly by the kidneys about 65-80%. The main metabolites are 1-methylxanthine, 1-methylureic acid and acetylated derivatives of uracil, a small amount of caffeine is converted to theophylline and theobromine. T1/2 is 3.5 hours.

Drotaverine

In oral administration, absorption of drotaverine is high and rapid. Bioavailability is 100%. After presystemic metabolism, 65% of the administered dose of drotaverine enters the systemic bloodstream. Time to reach Cmax in blood is 45-60 minutes. Binding to plasma proteins is 95-97%, mainly to albumin, gamma- and beta-globulins, as well as as high-density lipoproteins. It is evenly distributed in tissues, penetrates into smooth muscle cells. It does not penetrate through the blood-brain barrier.

Drotaverine and/or its metabolites may slightly penetrate through the placental barrier. The T1/2 is 8-10 hours. It is almost completely metabolized in the liver by O-desethylation. Metabolites rapidly conjugate with glucuronic acid. The main metabolite is 4′-dezethyldrotaverine, the other metabolites are 6-dezethyldrotaverine and 4′-dezethyldrotaveraldine. T1/2 is 8-10 hours. In 72 hours it is almost completely eliminated from the body. Mostly (more than 50% of drotaverine) is excreted by the kidneys, mainly as metabolites, to a lesser extent (about 30%) in the bile. Unchanged drotaverine is not detected in the urine.

Pheniramine

The maximum concentration of pheniramine in blood plasma is reached after about 1-2.5 hours. T1/2 is 16-19 hours. 70-83% of the dose taken is excreted from the body through the kidneys as metabolites or unchanged.

Indications

– Pain syndrome of various genesis, including joint and muscle pain; in sciatica, algodysmenorrhea (menstrual pain), neuralgia, toothache, headache (including headache due to cerebral vasospasm);

– pain syndrome associated with smooth muscle spasm, including chronic cholecystitis, cholelithiasis, post-cholecystectomy syndrome, colic of the kidneys;

– Post-traumatic and post-operative pain syndrome, including those accompanied by inflammation;

– colds accompanied by febrile syndrome (as symptomatic therapy).

Active ingredient

Composition

1 film-coated tablet contains:

active ingredients: paracetamol 325.0 mg, naproxen 100.0 mg, caffeine 50.0 mg, drotaverine hydrochloride 40.0 mg, pheniramine maleate 10.0 mg;

excipients: Microcrystalline cellulose 118.6 mg, pregelatinized corn starch 30.0 mg, hyprolose 20.0 mg, croscarmellose sodium 60.0 mg, citric acid 10.0 mg, diatrium edetate 0.4 mg, ascorbic acid 20.0 mg, talc 12.0 mg, magnesium stearate 4.0 mg;

film coating: Opadray fx green 65 F210000 30.0 mg (polyvinyl alcohol 14.100 mg, talc 6.588 mg, macrogol 3.990 mg, pearlescent pigment* 3.000 mg, polysorbate 80 0.810 mg, titanium dioxide 0.750 mg, indigo carmine dye aluminum varnish 0.507 mg, quinoline yellow dye aluminum varnish 0.255 mg).

*Pearlescent pigment consists of mica and contains 69-75% potassium aluminosilicate (E555) and 25-31% titanium dioxide (E171).

How to take, the dosage

The drug is taken orally 1 tablet 1-3 times a day. The maximum daily dose is 4 tablets.

The treatment duration is not more than 3 days as antipyretic and not more than 5 days as analgesic. Treatment with the drug can be continued only after consultation with a doctor.

The indicated doses of the drug must not be exceeded!

Interaction

The simultaneous administration of SPASMALGON® EFFECT with barbiturates, tricyclic antidepressants, rifampicin, alcoholic beverages increases the risk of hepatotoxic effect (these combinations should be avoided).

Paracetamol increases the effect of indirect anticoagulants and reduces the effectiveness of uricosuric drugs.

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

The simultaneous use of paracetamol with ethanol (drinks and medicines containing alcohol) increases the risk of acute pancreatitis.

Microsomal oxidation inhibitors (including cimetidine) reduce the risk of hepatotoxic effects of paracetamol.

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

Naproxen may cause decreased diuretic effect of furosemide, increased effect of indirect anticoagulants, increased toxicity of sulfonamides and methotrexate, decreased excretion of lithium and increased its concentration in plasma.

Special Instructions

If it is necessary to determine 17-ketosteroids, SPASMALGON® EFFECT should be stopped 48 hours before the study.

The effect of caffeine on the CNS depends on the type of nervous system and may manifest itself as both excitation and inhibition of higher nervous activity.

The patient should avoid alcohol during treatment.

In some cases there may be decreased concentration and psychomotor reaction rate, so the patient must be careful during treatment to drive motor vehicles and engage in other potentially dangerous activities that require increased concentration and rapid psychomotor reactions.

Synopsis

Contraindications

– Hypersensitivity to the components of the drug;

– gastrointestinal erosive and ulcerative lesions (acute phase);

– gastrointestinal bleeding;

– complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid or other NSAIDs (including a history);

– severe hepatic impairment;

– severe renal impairment;

– Inhibition of bone marrow hematopoiesis;

– conditions after aortocoronary bypass surgery;

– severe organic diseases of the cardiovascular system (including acute myocardial infarction);

– paroxysmal tachycardia;

– frequent ventricular extrasystoles;

– severe arterial hypertension;

– hyperkalemia;

– pregnancy and breastfeeding;

– childhood and adolescence under 18 years of age.

. The drug should be used with caution in patients with cerebrovascular disease, diabetes mellitus, peripheral arterial disease, gastrointestinal ulcers in the anamnesis, renal and hepatic insufficiency of mild to moderate severity, viral hepatitis, alcohol-induced liver injury, benign hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes), epilepsy, susceptibility to seizures, glucose-6-phosphate dehydrogenase deficiency, elderly patients.

If any of the above diseases/conditions are present, the patient should consult a physician before using the drug.

Side effects

Allergic reactions: skin rash, pruritus, urticaria, angioedema.

Hematopoietic disorders: thrombocytopenia, leukopenia, agranulocytosis, anemia, methemoglobinemia.

CNS disorders: agitation, anxiety, increased reflexes, tremor, headache, sleep disturbances, dizziness, decreased concentration.

Cardiovascular system disorders: palpitations, arrhythmias, increased blood pressure (BP).

Gastrointestinal system disorders: gastrointestinal erosive and ulcerative lesions, nausea, vomiting, discomfort in the epigastrium, abdominal pain, constipation, liver function disorders.

Urinary system disorders: impaired renal function.

Senses: decreased hearing, tinnitus, increased intraocular pressure in patients with closed-angle glaucoma.

Others: dermatitis, tachypnea (rapid breathing).

If any of the side effects listed are worsened, or if the patient notes any other side effects not listed in the instructions, they should tell their physician.

Overdose

Symptoms: pale skin, anorexia (lack of appetite), abdominal pain, nausea, vomiting, gastrointestinal bleeding, agitation, motor restlessness, confusion, tachycardia, arrhythmia, hyperthermia (increased body temperature), rapid urination, headache, tremor or muscle twitching; epileptic seizures, increased activity of “hepatic” transaminases, hepatonecrosis, increased prothrombin time.

The symptoms of hepatic dysfunction may appear 12-48 hours after overdose. In severe overdose liver failure with progressive encephalopathy, coma, death; acute renal failure with tubular necrosis; arrhythmia, pancreatitis develop. If an overdose is suspected, seek immediate medical attention from a physician.

Treatment: gastric lavage followed by intake of activated charcoal.

The specific antidote for paracetamol poisoning is acetylcysteine. Administration of acetylcysteine is relevant within 8 h after paracetamol ingestion. In gastrointestinal bleeding it is necessary to administer antacids and gastric lavage with ice-cold 0.9% sodium chloride solution; maintenance of ventilation and oxygenation; in epileptic seizures – intravenous diazepam; maintenance of balance of fluids and salts in the body.