Spazmalgon Effect of a tablet p / o, No. 10

• Pain syndrome of various origins, incl. joint pain, muscle pain, sciatica, algodismenorrhea, neuralgia, toothache, headache (including those caused by spasm of the cerebral vessels);

• pain syndrome associated with smooth muscle spasm, incl. with chronic cholecystitis, cholelithiasis, postcholecystectomy syndrome, renal colic;

• post-traumatic and postoperative pain syndrome, incl. accompanied by inflammation;

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

The drug is taken orally 1 tab. 1-3 times / day The maximum daily dose is 4 tab.

The duration of treatment is no more than 3 days as an antipyretic agent and no more than 5 days as a pain reliever. Continuation of treatment with the drug is possible only after consulting a doctor.

Do not exceed the indicated dose of the drug.

Active ingredients:

Paracetamol - 325 mg

Naproxen 100 mg

caffeine (anhydrous) 50 mg

drotaverine hydrochloride - 40 mg

pheniramine maleate - 10 mg

Excipients: microcrystalline cellulose - 118.6 mg, pregelatinized corn starch - 30 mg, hyprolose - 20 mg, croscarmellose sodium - 60 mg, citric acid - 10 mg, disodium edetate - 0.4 mg, ascorbic acid - 20 mg, talc - 12 mg, magnesium stearate - 4 mg.

The composition of the film shell: opadry fx green 65 F210000 - 30 mg (polyvinyl alcohol - 14.1 mg, talc - 6.588 mg, macrogol - 3.99 mg, pearlescent pigment * - 3 mg, polysorbate-80 - 0.81 mg, titanium dioxide - 0.75 mg, aluminum varnish based on indigo carmine dye - 0.507 mg, aluminum varnish based on quinoline yellow dye - 0.255 mg).
* Pearlescent pigment consists of mica and contains 69-75% potassium aluminosilicate (E555) and 25-31% titanium dioxide (E171).

• Erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase);

• gastrointestinal bleeding;

• complete or incomplete combination of bronchial asthma,

• recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including a history);

• severe liver failure;

• severe renal failure;

• oppression of bone marrow hematopoiesis;

• condition after coronary artery bypass grafting;

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

• paroxysmal tachycardia;

• frequent ventricular premature beats;

• severe arterial hypertension;

• hyperkalemia;

• pregnancy, lactation period;

• children and adolescents up to 18 years old;

• hypersensitivity to the components of the drug.

With caution: in patients with cerebrovascular diseases, diabetes mellitus, peripheral arterial disease, history of gastrointestinal ulcers, with mild or moderate renal and hepatic insufficiency, viral hepatitis, alcoholic liver damage, benign hyperbilirubinemia (Gilbert and Dubin-Johnson syndromes Rotor), epilepsy, tendency to seizures, deficiency of glucose-6-phosphate dehydrogenase, in elderly patients.

pharmachologic effect

The combined drug has an analgesic, anti-inflammatory, antispasmodic, antipyretic effect.

Paracetamol is a non-narcotic analgesic that has antipyretic and analgesic effects due to the blockade of COX in the central nervous system and the effect on the centers of pain and thermoregulation.

Naproxen is an NSAID that has anti-inflammatory, analgesic and antipyretic effects associated with non-selective suppression of the activity of COX, which regulates the synthesis of prostaglandins.

Caffeine causes dilation of blood vessels in skeletal muscles, heart, kidneys; increases mental and physical performance, helps to eliminate fatigue and drowsiness; increases the permeability of histohematogenous barriers and increases the bioavailability of non-narcotic analgesics, thereby enhancing the therapeutic effect. Has a tonic effect on the vessels of the brain.

Drotaverine has a myotropic antispasmodic effect due to inhibition of phosphodiesterase IV, acts on the smooth muscles of the gastrointestinal tract, biliary tract, genitourinary system, blood vessels.

Pheniramine is a histamine H1 receptor blocker. It has an antispasmodic and mild sedative effect, reduces exudation phenomena, and also enhances the analgesic effect of paracetamol and naproxen.

Pharmacokinetics

Paracetamol

It is characterized by high and rapid absorption from the gastrointestinal tract, mainly in the small intestine. Cmax in blood plasma is reached within 0.5-1.5 hours after oral administration and is 5-20 ?g / ml. The degree of binding to plasma proteins is insignificant - 15%. Paracetamol is evenly distributed and penetrates the BBB, as well as into most body tissues. The apparent Vd 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 are conjugated with glutathione to form inactive metabolites. With a lack of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The isoenzyme CYP2E1 is also involved in the metabolism of the drug. T1 / 2 - 1.5-2.5 h.It is excreted by the kidneys in the form of metabolites, mainly conjugates, only 3% - unchanged. In elderly patients, the clearance of the drug decreases and T1 / 2 increases.

Naproxen

Absorption from the gastrointestinal tract of naproxen is fast and complete. Bioavailability is 95%. Eating practically does not affect either the completeness or the rate of absorption. Time to reach Cmax is 1-2 hours. Plasma protein binding is more than 99%. Css is achieved by taking 4-5 doses of the drug (2-3 days). It is metabolized in the liver to dimethylnaproxen with the participation of the isoenzyme CYP2C9. “1 / 2 - 12-15 hours. Clearance - 0.13 ml / min / kg. It is excreted by the kidneys (98%), 10% of which is unchanged; with bile, 0.5-2.5% of the dose taken is excreted. With renal failure, the accumulation of metabolites is possible.

Caffeine

Caffeine, which is part of the drug, is almost completely and quickly absorbed, Cmax in blood plasma is reached after 1 hour. 65-80%. The main metabolites are 1-methylxanthine, 1-methyl uric acid and acetylated uracil derivatives, a small amount of caffeine is converted to theophylline and theobromine. T1 / 2 - 3.5 h.

Drotaverin

When taken orally, absorption is high and fast. Bioavailability is 100%. After presystemic metabolism, 65% of the taken dose of drotaverine enters the systemic circulation. The time to reach Cmax in the blood is 45-60 minutes. Plasma protein binding - 95-97%, mainly with albumin, gamma and beta globulins, as well as HDL. It is evenly distributed in tissues, penetrates into smooth muscle cells. Does not penetrate the BBB. Drotaverine and / or its metabolites can slightly penetrate the placental barrier. T1 / 2 - 8-10 hours. Almost completely metabolized in the liver by O-desethylation. Metabolites are rapidly conjugated with glucuronic acid. The main metabolite is 4-desethyldrotaverine, other metabolites are 6-desethyldrotaverine and 4'-desethyldrotaverine. “1 / 2 - 8-10 hours. In 72 hours it is almost completely excreted from the body.Basically (more than 50% of drotaverine) is excreted by the kidneys, mainly in the form of metabolites, to a lesser extent (about 30%) - with bile. Unchanged drotaverine is not detected in urine.

Pheniramine

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

Side effect

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

From the hematopoietic system: thrombocytopenia, leukopenia, agranulocytosis, anemia, methemoglobinemia.

From the nervous system: agitation, anxiety, increased reflexes, tremors, headache, sleep disturbances, dizziness, decreased concentration.

On the part of the organ of hearing: hearing loss, tinnitus.

From the side of the organ of vision: increased intraocular pressure in patients with angle-closure glaucoma.

From the side of the cardiovascular system: a feeling of palpitations, arrhythmias, increased blood pressure.

From the digestive system: erosive and ulcerative lesions of the gastrointestinal tract, nausea, vomiting, epigastric discomfort, abdominal pain, constipation, liver dysfunction.

From the urinary system: impaired renal function.

Others: dermatitis, tachypnea.

Application during pregnancy and lactation

The use of the drug during pregnancy and during breastfeeding is contraindicated.

Application for violations of liver function

The use of the drug is contraindicated in severe hepatic insufficiency.

With care: mild to moderate hepatic impairment, viral hepatitis, alcoholic liver damage, benign hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes).

Application for impaired renal function

The use of the drug is contraindicated in severe renal failure.

With caution: renal failure.

Application in children

The use of the drug in children and adolescents under 18 years of age is contraindicated.

Use in elderly patients

The drug should be prescribed with caution to elderly patients.

special instructions

Avoid the simultaneous use of the drug with other drugs containing paracetamol and / or other NSAIDs, incl. with remedies to relieve the symptoms of colds, flu and nasal congestion.

When using the drug for more than 5-7 days, the peripheral blood parameters and the functional state of the liver should be monitored.

Paracetamol distorts the results of laboratory tests of the content of glucose and uric acid in the blood plasma.

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

It should be borne in mind that naproxen increases bleeding time.

The effect of caffeine on the central nervous system depends on the type of the nervous system and can manifest itself as arousal and inhibition of higher nervous activity.

During the period of treatment, the patient should avoid drinking alcohol.

Influence on the ability to drive vehicles and use mechanisms

In some cases, it is possible to reduce the concentration of attention and the speed of psychomotor reactions, therefore, during the period of treatment, the patient should be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interactions

With the simultaneous use of the drug with barbiturates, tricyclic antidepressants, rifampicin, ethanol, the risk of hepatotoxic action increases (these combinations should be avoided).

Paracetamol

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

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

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

Inhibitors of microsomal oxidation (including cimetidine) reduce the risk of hepatotoxic effects of paracetamol.

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

Naproxen

Naproxen is capable of reducing the diuretic effect of furosemide.

Enhances the effect of indirect anticoagulants.

Increases the toxicity of sulfonamides and methotrexate.

Reduces the excretion of lithium and increases its concentration in the blood plasma.

Caffeine

With the combined use of caffeine and barbiturates, primidone, anticonvulsants (hydantoin derivatives, especially phenytoin), it is possible to increase metabolism and increase the clearance of caffeine.

With the simultaneous administration of caffeine and cimetidine, oral contraceptives, disulfiram, ciprofloxacin, norfloxacin, it is possible to reduce the metabolism of caffeine in the liver (slowing down its excretion and increasing its concentration in the blood).

The simultaneous use of caffeinated beverages and other drugs that stimulate the central nervous system can lead to overstimulation of the central nervous system.

Drotaverin

With the simultaneous use of drotaverine can weaken the antiparkinsonian effect of levodopa.

Pheniramine

With the simultaneous use of pheniramine with tranquilizers, hypnotics, MAO inhibitors, ethanol, an increase in the inhibitory effect on the central nervous system is possible.