Ascophen ULTRA, 250 mg+65 mg+250 mg 10 pcs

Pharmacotherapeutic group: analgesic combined (non-steroidal anti-inflammatory agent + analgesic non-narcotic agent + psychostimulant).

The ATX code: [N02BA71].

Pharmacological properties

Pharmacodynamics:

A combined drug containing paracetamol, acetylsalicylic acid and caffeine.

Acetylsalicylic acid has antipyretic and anti-inflammatory effects, reduces pain, especially caused by inflammation, and inhibits platelet aggregation and thrombosis, improves microcirculation in the inflamed area.

Caffeine increases reflex excitability of the spinal cord, stimulates respiratory and vasomotor centers, increases blood vessels of skeletal muscles, brain, heart and kidneys; it decreases platelet aggregation; it reduces sleepiness and fatigue and increases mental and physical performance.

In this combination, a small dose of caffeine has practically no stimulating effect on the central nervous system, but it increases the tone of cerebral blood vessels and accelerates blood flow.

Paracetamol has analgesic, antipyretic and very weak anti-inflammatory activity, due to its effect on the thermoregulation center in the hypothalamus and weak ability to inhibit the synthesis of prostaglandins (Pg) in peripheral tissues.

Pharmacokinetics

Acetylsalicylic acid

When taken orally, absorption is complete. During absorption it undergoes presystemic elimination in the intestinal wall and systemic elimination in the liver (deacetylated). It is rapidly hydrolyzed by cholinesterases and albumin esterase, therefore half-life period is not more than 15-20 minutes.

In the body it circulates (75-90% in connection with albumin) and is distributed in the tissues as salicylic acid anion. The time of reaching maximum concentration is 2 hours. It is metabolized mainly in liver with formation of 4 metabolites found in many tissues and urine.

Extracted mainly by active secretion in the renal tubules as salicylate (60%) and its metabolites. Excretion of unchanged salicylate depends on urine pH (when urine is alkaline, ionization of salicylates increases, their reabsorption is impaired and excretion significantly increases).

The elimination rate depends on the dose: when taking small doses, the elimination half-life is 2-3 hours, with increasing doses it may increase to 15-30 hours. In infants the elimination of salicylates is much slower than in adults.

Caffeine

When taken orally absorption is good, occurs throughout the intestine. Absorption is mainly due to lipophilicity rather than water solubility.

The time to reach maximum concentration is 50-75 minutes after oral administration, the maximum concentration is 1.6-1.8 mg/l. It is rapidly distributed in all organs and tissues of the body; easily penetrates through the blood-brain barrier and the placenta.

The volume of distribution in adults is 0.4 – 0.6 l/kg, in infants 0.78-0.92 l/kg. Binding with blood proteins (albumin) is 25-36%. More than 90% is metabolized in liver, in children during first years of life up to 10-15%. In adults about 80% of caffeine dose is metabolized to paraxanthine, about 10% to theobromine and about 4% to theophylline.

These compounds are subsequently demethylated to monomethylxanthines and then to methylated uric acids. The elimination half-life in adults is 3.9-5.3 h (sometimes up to 10 h). Excretion of caffeine and its metabolites is carried out by kidneys (1-2% in adults is excreted unchanged).

Paracetamol

The absorption is high, the maximum concentration is reached after 0.5-2 hours; the maximum concentration is 5-20 mcg/ml. Binding with plasma proteins is 15%. Penetrates through the blood-brain barrier. Less than 1% of the dose taken by a nursing mother passes into breast milk.

The therapeutic effective concentration of paracetamol in plasma is achieved when administered at a dose of 10-15 mg/kg. It is metabolized in liver (90-95%): 80% enters into conjugation reactions to form inactive glucuronides and sulfates; 17% undergoes hydroxylation to form 8 active metabolites, which conjugate with glutathione to form already inactive metabolites.

With a lack of glutathione these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. CYP2E1, CYP1A2 isoenzymes are also involved in metabolism of the drug, and to a lesser extent CYP3A4 isoenzyme. The elimination half-life is 1-4 hours. Excreted by the kidneys as metabolites, mainly conjugates, less than 5% unchanged. In elderly patients the drug clearance is decreased and the elimination half-life is increased.

Indications

Pain syndrome of moderate to mild intensity of different origin in adults and children over 15 years:

Fever syndrome in adults: in acute respiratory diseases, influenza.

Active ingredient

Composition

Active ingredients:

Acetylsalicylic acid – 250.0 mg,

Paracetamol – 250.0 mg,

Caffeine (caffeine anhydrous) – 65.0 mg.

Auxiliary substances:microcrystalline cellulose – 66.01 mg, hyprolose (low-substituted hydroxypropyl cellulose) – 21.50 mg, talc – 10.00 mg, hyprolose (hydroxypropyl cellulose) – 7.30 mg, colloidal silicon dioxide (aerosil) – 3.40mg, stearic acid – 2.50 mg, calcium stearate – 1.29 mg.

Shell: Opadray 20A28380 WHITE – 13.5 mg [hypromellose (hydroxypropyl methylcellulose 2910) – 4.556 mg, hydroxypropylcellulose – 4.556 mg, talc – 2.700 mg, titanium dioxide – 1.688 mg].

How to take, the dosage

Interaction

Special Instructions

Contraindications

Side effects

Many of the listed adverse reactions are clearly dose-dependent and vary from patient to patient. The frequency of adverse drug reactions is classified according to the recommendations of the World Health Organization: very common (>1/10), common (>1/100 to ≤1/10), infrequent (>1/1000 to ≤1/100), rare (>1/10000 to ≤1/1000), very rare (≤1/10000), frequency unknown (frequency of occurrence cannot be determined based on available data).

Infections and invasions:
rarely – pharyngitis.

Metabolic and nutritional disorders:
rarely – decreased appetite.

Mental disorders:
often – nervousness;
infrequently – insomnia;
rarely – anxiety, euphoric mood, inner tension.

Nervous system disorders:
often – dizziness;
infrequently – tremor, paresthesias, headache;
rarely – taste disorder, attention disorder, amnesia, impaired movement coordination, hyperesthesia, pain in the paranasal sinuses.

Visual organ disorders:
rarely – visual impairment.

Hearing organ disorders:
infrequent – tinnitus.

Cardiovascular system disorders:
infrequent – arrhythmia.

Vascular disorders:
rarely – hyperemia, peripheral circulation disorders.

Respiratory system disorders, thoracic and mediastinal organs:
rarely – nasal bleeding, hypoventilation, rhinorrhea.

Disorders of the digestive system:
frequently – nausea, abdominal discomfort;
infrequently – dry mouth, diarrhea, vomiting;
rarely – belching, flatulence, dysphagia, paresthesias in the mouth, increased salivation.

Skin and subcutaneous tissue disorders:
rarely – hyperhidrosis, itching, urticaria.

Musculoskeletal system disorders:
rarely – musculoskeletal stiffness, neck pain, back pain, muscle spasms.

General disorders:
infrequently – fatigue, increased excitability;
rarely – asthenia, heaviness in the chest.

Other:
infrequent – increased heart rate.

Post-registration follow-up data

System-organ class
Immune system side Hypersensitivity Mental disorders Anxiety Nervous system disorders Migraine, somnolence Skin and subcutaneous tissue disorders Erythema, rash, angioedema, erythema multiforme Cardiovascular system disorders Heart palpitations Vascular disorders Decreased blood pressure Respiratory system, thoracic and mediastinal organ disorders Shortness of breath, bronchospasm Liver and biliary tract disorders Hepatic insufficiency General disorders Malaise, discomfort

Overdose

Acetylsalicylic acid.

In mild intoxication – dizziness, tinnitus, deafness, increased sweating, nausea, vomiting, headache and confusion. Occurs at plasma concentrations of 150-300 µg/ml.

The treatment is dose reduction or discontinuation of therapy.

At concentrations above 300 µg/ml, more severe intoxication occurs, manifesting as hyperventilation, fever, anxiety, ketoacidosis, respiratory alkalosis, and metabolic acidosis. Central nervous system depression may lead to coma, and cardiovascular collapse and respiratory failure may also occur.

The highest risk of chronic intoxication is seen in children and the elderly when more than 100 mg/kg/day is taken for several days.

Treatment- If ingestion of more than 120 mg/kg of salicylates is suspected, activated charcoal is given repeatedly orally within the last hour.If more than 120 mg/kg of salicylates are taken, their plasma concentration should be determined, although it is impossible to predict its severity based on this indicator alone; clinical and biochemical parameters should also be considered.

If plasma concentrations exceed 500 µg/ml (350 µg/ml for children younger than 5 years), intravenous sodium bicarbonate administration effectively removes salicylates from plasma. If plasma concentrations exceed 700 µg/ml (lower concentrations in children and the elderly) or in severe metabolic acidosis, hemodialysis or hemoperfusion is the therapy of choice.

Paracetamol overdose. In overdose intoxication is possible, especially in elderly patients, children, patients with liver disease (caused by chronic alcoholism), in patients with nutritional disorders, as well as in patients taking microsomal liver enzyme inducers, in which lightning hepatitis, liver failure, cholestatic hepatitis, cytolytic hepatitis may develop, in the above cases – sometimes with fatal outcome.

The clinical picture of acute overdose develops within 24 hours after taking paracetamol. Symptoms: gastrointestinal disorders (nausea, vomiting, decreased appetite, abdominal discomfort and (or) abdominal pain), pale skin.

Hepatocyte cytolysis with complete and irreversible liver necrosis, liver failure, metabolic acidosis and encephalopathy occurs when administered to adults 7.5 g or more or children more than 140 mg/kg at one time, which may lead to coma and death.

12-48 hours after administration of paracetamol an increase in the activity of microsomal liver enzymes, lactate dehydrogenase, bilirubin concentration and prothrombin decrease is noted. Clinical symptoms of liver damage appear 2 days after overdose of the drug and reach their maximum on the 4th-6th day.

The treatment is immediate hospitalization. Determination of plasma paracetamol quantification before starting treatment as soon as possible after overdose.

The administration of SH-group donators and precursors of glutathione synthesis-methionine and acetylcysteine-is most effective in the first 8 hours. The need for additional therapeutic measures (further administration of methionine, intravenous (IV) administration of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its administration.

Symptomatic treatment. Laboratory studies of the activity of microsomal liver enzymes should be performed at the beginning of treatment and then – every 24 hours. In most cases, microsomal liver enzyme activity normalizes within 1-2 weeks. In very severe cases, liver transplantation may be necessary.

Caffeine.Common symptoms are gastralgia, agitation, delirium, anxiety, nervousness, restlessness, insomnia, mental agitation, muscle twitching, confusion, seizures, dehydration, rapid urination, hyperthermia, headache, increased tactile or pain sensitivity, nausea and vomiting (sometimes with blood), tinnitus.

In severe overdose, hyperglycemia may occur. Cardiac disorders are manifested by tachycardia and arrhythmia.

Treatment – dose reduction or abolition of caffeine.

Pregnancy use

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