Acetylsalicylic acid + Caffeine + Paracetamol - instructions for use, dose, side effects, contraindications

Combined drug. Acetylsalicylic acid has antipyretic and anti-inflammatory effect, relieves pain, especially caused by the inflammatory process, and also moderately inhibits platelet aggregation and thrombosis, improves microcirculation in the inflammatory focus.

Caffeine increases the excitability of spinal cord reflex, excites the respiratory and vasomotor centers, dilates blood vessels in skeletal muscle, brain, heart, kidneys, reducing platelet aggregation; reduces drowsiness, a feeling of fatigue, increases mental and physical performance. In this combination caffeine in a small dose practically does not have a stimulating effect on the central nervous system, but it contributes to the normalization of the tone of the vessels of the brain and the acceleration of blood flow.

Paracetamol has an analgesic, antipyretic and extremely weak anti-inflammatory effect, which is related to its effect on the thermoregulatory center in the hypothalamus and a weak ability to inhibit the synthesis of prostaglandins in peripheral tissues.

Pharmacokinetics:

Acetylsalicylic acid

At intake the absorption is complete. During absorption, it undergoes presystemic elimination in the intestinal wall and systemic in the liver (deacetylated). The resorbed part is rapidly hydrolyzed by cholinesterases and albumin esterase, therefore the elimination half-life is no more than 15-20 minutes.
In the body it circulates (75-90% in association with albumin) and is distributed in tissues as an anion of salicylic acid. The time to reach the maximum concentration is 2 hours.
Metabolized mainly in the liver with the formation of 4 metabolites, found in many tissues and urine.
It is excreted mainly by active secretion in the renal tubules in the form of salicylate (60%) and its metabolites. Excretion of unchanged salicylate depends on the hydrogen index of urine (with alkalinization of urine ionization of salicylates increases, their reabsorption worsens and the excretion increases significantly).The rate of excretion depends on the dose: when taking small doses, the elimination half-life is 2-3 hours, with an increase in the dose it can increase to 15-30 hours. In newborns, the elimination of salicylates is much slower than in adults.

Paracetamol

Adsorption is high, the maximum concentration is achieved after 0.5-2 hours; the maximum concentration is 5-20 μg / ml. Connection with plasma proteins - 15%. Penetrates through the blood-brain barrier. Less than 1% of the dose of paracetamol taken by the lactating mother penetrates into breast milk. The therapeutically effective concentration of paracetamol in plasma is achieved when it is administered at a dose of 10-15 mg / kg.
Metabolised in the liver (90-95%): 80% enters the conjugation reaction with glucuronic acid and sulfates with the formation of inactive metabolites; 17% undergoes hydroxylation with the formation of 8 active metabolites, which are conjugated with glutathione with the formation of already inactive metabolites. With a lack of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. In the metabolism of the drug, the isoenzyme CYP2E1 also participates. The half-life is 1-4 hours.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 the half-life increases.

Caffeine

When ingested absorption is good, occurs throughout the intestine. Absorption occurs mainly due to lipophilicity, and not water solubility. The time to reach the maximum concentration is 50-75 minutes after ingestion, the maximum concentration is 1.58-1.76 mg / l. Quickly distributed in all organs and tissues of the body; easily penetrates the blood-brain barrier and the placenta. The volume of distribution in adults is 0.4-0.6 l / kg. Communication with blood proteins (albumins) is 25-36%.

Metabolism in the liver is more than 90%, in children of the first years of life - up to 10-15%. About 80% of the dose of caffeine is metabolized to paraxanthin, about 10% to theobromine and about 4% to theophylline. These compounds are subsequently demethylated into monomethylxanthines, and then into methylated uric acids. The half-life is 3.9-5.3 hours (sometimes up to 10 hours). The excretion of caffeine and its metabolites is carried out by the kidneys (in an unchanged form - 1-2%).

Indications:

Pain syndrome of mild and moderate severity (of various origins): headache, migraine, toothache, neuralgia, myalgia, arthralgia, algodismenorea.Feverish syndrome: with acute respiratory infections, influenza.

ICD-10

VI.G40-G47.G43 Migraine

XI.K00-K14.K13.7 Other and unspecified lesions of the oral mucosa

XVIII.R50-R69.R52.2 Another constant pain

XVIII.R50-R69.R51 Headache

XIII.M20-M25.M25.5 Pain in the joint

XIII.M70-M79.M79.1 Myalgia

XIII.M70-M79.M79.2 Neuralgia and neuritis, unspecified

XIV.N80-N98.N94.6 Dysmenorrhea, unspecified

XVIII.R50-R69.R50 Fever of unknown origin

Contraindications:

Hypersensitivity; erosive and ulcerative lesions of the gastrointestinal tract (in the phase of exacerbation), gastrointestinal bleeding; A bronchial asthma, a urticaria or an acute rhinitis, provoked by reception of an acetylsalicylic acid or non-steroidal anti-inflammatory agents; hemophilia, hemorrhagic diathesis, hypoprothrombinemia, portal hypertension; avitaminosis K; kidney failure; pregnancy (I and III trimesters), lactation period; deficiency of glucose-6-phosphate dehydrogenase, severe arterial hypertension, severe course of ischemic heart disease, glaucoma, increased excitability, sleep disturbances; surgical interventions accompanied by bleeding, children's age (up to 15 years - the risk of developing Reye's syndrome in children with hyperthermia on the background of viral diseases).

Carefully:

Gout or arthritis; liver disease; headaches associated with head trauma; reception of anticoagulants, hypoglycemic agents, as well as simultaneous administration of drugs containing acetylsalicylic acid or other analgesic and antipyretic components.

Pregnancy and lactation:

Recommendations Food and Drug Administration (US Food and Drug Administration) - Category D (for acetylsalicylic acid), C (for caffeine).

Despite the fact that acetylsalicylic acid can be used in the second trimester of pregnancy, the safety of this combination in pregnant and breast-feeding has not been studied, so the drug is contraindicated in pregnancy (in all trimesters) and breastfeeding.

Acetylsalicylic acid has a teratogenic effect; when applied in the first trimester of pregnancy leads to malformations - the cleavage of the upper palate; in the third trimester - to inhibition of labor (inhibition of the synthesis of prostaglandins), to the closure of the arterial duct in the fetus, which causes hyperplasia of the pulmonary vessels and hypertension in the vessels of the small circle of blood circulation.

Isolated with breast milk, which increases the risk of bleeding in the child due to impaired platelet function.

Dosing and Administration:

Inside (during or after a meal), 1 tablet every 4 hours, with a pain syndrome - 1-2 tablets; at the first signs of migraine take 2 tablets.

The average daily dose is 3-4 tablets, the maximum daily dose is 8 tablets. The course of treatment is no more than 7-10 days.

With pain syndrome, the drug should not be taken for more than 5 days without consulting a doctor; When migraine, the drug should not be taken more than 3 days without consulting a doctor.

Side effects:

Gastralgia, nausea, vomiting, hepatotoxicity, nephrotoxicity, erosive and ulcerative lesions of the gastrointestinal tract, allergic reactions, tachycardia, increased blood pressure, bronchospasm.

With prolonged use - dizziness, headache, blurred vision, tinnitus, platelet aggregation reduction, hypocoagulation, hemorrhagic syndrome (epistaxis, bleeding gums, purpura), kidney disease with papillary necrosis, deafness, malignant erythema multiforme (Stevens-Johnson syndrome ), toxic epidermal necrolysis (Lyell's syndrome), Reye's syndrome in children (hyperpyrexia, metabolic acidosis, disorders of the nervous system and psyche, vomiting, liver dysfunction).

Overdose:

Symptoms caused by the presence of acetylsalicylic acid: with light intoxication - nausea, vomiting, gastralgia, dizziness, ringing in the ears; severe intoxication - retardation, drowsiness, collapse, convulsions, bronchospasm, shortness of breath, anuria, bleeding. Initially, the central hyperventilation leads to respiratory alkalosis (shortness of breath, dyspnea, cyanosis, perspiration). As the intoxication progressive paralysis and respiratory uncoupling of oxidative phosphorylation causes respiratory acidosis.

Symptoms caused by the presence of paracetamol (when taken at doses of more than 10-15 g per day): during the first 24 hours pallor of the skin, nausea, vomiting, anorexia, abdominal pain, impaired glucose metabolism, metabolic acidosis. Symptoms of liver dysfunction may appear 12-48 hours after an overdose.

Symptoms caused by the presence of caffeine (when taken in doses of more than 300 mg per day): gastralgia, agitation, anxiety, agitation, motor anxiety, confusion, delirium, dehydration, tachycardia, arrhythmia, hyperthermia, frequent urination, headache,increased tactile or pain sensitivity, tremor or muscle twitching; nausea and vomiting, sometimes with blood; ringing in the ears, epileptic seizures (with acute overdose - tonic-clonic).

Treatment: control of acid-base state and electrolyte balance. Depending on the state of metabolism - the introduction of sodium bicarbonate, sodium citrate or sodium lactate. Increasing alkalinity increases the excretion of acetylsalicylic acid due to alkalinization of urine. Gastric lavage in the first 4 hours, induction of emesis, administration of activated carbon, laxative drugs, administration of SH-group donors and glutathione-methionine synthesis precursors for 8-9 hours after an overdose and acetylcysteine for 8 hours.

Interaction:

It is not recommended to combine with barbiturates, anticonvulsants, salicylates, rifampicin, alcohol. For the duration of treatment, breastfeeding should be stopped.

Strengthens the action of heparin, indirect anticoagulants, reserpine, steroid hormones and hypoglycemic drugs.

Simultaneous appointment with others non-steroidal anti-inflammatory agents, methotrexate increases the risk of side effects.

Reduces the effectiveness of spironolactone, furosemide, antihypertensive drugs, as well as anti-arthritis drugs that promote the excretion of uric acid.

Barbiturates, rifampicin, salicylamide, antiepileptic drugs and other stimulants of microsomal oxidation contribute to the formation of toxic metabolites of paracetamol that affect liver function.

Metoclopramide accelerates the absorption of paracetamol.

Under the influence of paracetamol, the half-elimination (half-life) of chloramphenicol increases five-fold. At repeated reception paracetamol can enhance the effect of anticoagulants (derivatives of dicumarin).

Caffeine accelerates the absorption of ergotamine.

Simultaneous reception of paracetamol, acetylsalicylic acid and alcoholic beverages increases the risk of hepatotoxic effects.

Special instructions:

Because the acetylsalicylic acid, which is part of the drug, reduces coagulability of the blood, patients who are preparing for surgical interventions, should stop taking the drug and warn the attending physician.

If symptoms persist after taking the drug, worsening or new symptoms occur, immediately consult a doctor. When taking the drug at the recommended dose, the same amount of caffeine is fed into the body as it is contained in one cup of coffee, so you should reduce the consumption of caffeine-containing products when treated with this drug in order to avoid the development of nervous excitement, irritability, insomnia and rapid heartbeat against caffeine overdose. If you suspect an overdose, you should immediately seek medical help, even if you have no symptoms.

One should refrain from usingalcohol intake when taking the drug in connection with an increased risk of liver damage and gastrointestinal bleeding.

Because the acetylsalicylic acid slows the clotting of blood, the patient, who is to undergo surgery, must warn the doctor in advance about taking the drug. Acetylsalicylic acid in low doses reduces the excretion of uric acid, and therefore in patients with a predisposition the drug can trigger a gout attack.With continued use of the drug, control of peripheral blood and the functional state of the liver is necessary.

Instructions

Acetylsalicylic acid + Caffeine + Paracetamol (Acidum acetylsalicylicum + Coffeinum + Paracetamolum)