Acis^® (Powder) Instructions for Use

Marketing Authorization Holder

PharmVILAR NPO, LLC (Russia)

ATC Code

N02BA01 (Acetylsalicylic acid)

Active Substance

Acetylsalicylic acid (Ph.Eur. European Pharmacopoeia)

Dosage Form

Acis®

Powder for oral solution 500 mg: sachets 2 g, 2, 3, 4, 5, 6, 8, 10, 12, 15, 20, 24 or 30 pcs.

Dosage Form, Packaging, and Composition

Powder for oral solution in the form of a mixture of powder, granules, and crystals, white or almost white in color with a characteristic odor; the presence of soft lumps is allowed.

Excipients: anhydrous sodium citrate – 1450 mg, sucralose – 10 mg, Lemon-Lime flavor – 40 mg.

2 g – sachets made of combined material (2) – cardboard packs.
2 g – sachets made of combined material (3) – cardboard packs.
2 g – sachets made of combined material (4) – cardboard packs.
2 g – sachets made of combined material (5) – cardboard packs.
2 g – sachets made of combined material (6) – cardboard packs.
2 g – sachets made of combined material (8) – cardboard packs.
2 g – sachets made of combined material (10) – cardboard packs.
2 g – sachets made of combined material (12) – cardboard packs.
2 g – sachets made of combined material (15) – cardboard packs.
2 g – sachets made of combined material (20) – cardboard packs.
2 g – sachets made of combined material (24) – cardboard packs.
2 g – sachets made of combined material (30) – cardboard packs.

Clinical-Pharmacological Group

Drug with anti-inflammatory and analgesic action

Pharmacotherapeutic Group

Analgesics; other analgesics and antipyretics; salicylic acid and its derivatives

Pharmacological Action

NSAID. It has anti-inflammatory, analgesic, and antipyretic effects, and also inhibits platelet aggregation. The mechanism of action is associated with the inhibition of COX activity, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins that play a major role in the pathogenesis of inflammation, pain, and fever.

A decrease in the content of prostaglandins (mainly E₁) in the thermoregulation center leads to a decrease in body temperature due to the dilation of skin vessels and increased sweating. The analgesic effect is due to both central and peripheral action. It reduces aggregation, platelet adhesion, and thrombus formation by suppressing the synthesis of thromboxane A₂ in platelets.

At a daily dose of 6 g and above, it inhibits prothrombin synthesis in the liver and increases prothrombin time. It increases the fibrinolytic activity of plasma and reduces the concentration of vitamin K-dependent coagulation factors (II, VII, IX, X). It increases the frequency of hemorrhagic complications during surgical interventions and increases the risk of bleeding during therapy with anticoagulants.

In high doses, it stimulates the excretion of uric acid (impairs its reabsorption in the renal tubules). Blockade of COX-1 in the gastric mucosa leads to inhibition of gastroprotective prostaglandins, which can cause erosive and ulcerative lesions of the mucosa and subsequent bleeding.

Pharmacokinetics

When taken orally, it is rapidly absorbed mainly from the proximal part of the small intestine and to a lesser extent from the stomach. The presence of food in the stomach significantly alters the absorption of acetylsalicylic acid.

It is metabolized in the liver by hydrolysis to form salicylic acid, followed by conjugation with glycine or glucuronide. The concentration of salicylates in blood plasma is variable.

About 80% of salicylic acid binds to plasma proteins. Salicylates easily penetrate into many tissues and body fluids, including cerebrospinal, peritoneal, and synovial fluids. Salicylates are found in small amounts in brain tissue, and traces are found in bile, sweat, and feces. It quickly crosses the placental barrier and is excreted in small amounts in breast milk.

In newborns, salicylates can displace bilirubin from its binding with albumin and contribute to the development of bilirubin encephalopathy.

Penetration into the joint cavity is accelerated in the presence of hyperemia and edema and slows down in the proliferative phase of inflammation.

When acidosis occurs, most of the salicylate is converted into a non-ionized acid, which penetrates well into tissues, including the brain.

It is excreted mainly by active secretion in the renal tubules in unchanged form (60%) and in the form of metabolites. The excretion of unchanged salicylate depends on the pH of the urine (when the urine is alkalized, the ionization of salicylates increases, their reabsorption worsens, and excretion significantly increases). The T_1/2 of acetylsalicylic acid is approximately 15 minutes. The T_1/2 of salicylate when taken in low doses is 2-3 hours, and with an increase in dose it can increase to 15-30 hours.

Indications

Fever in infectious and inflammatory diseases; pain syndrome of mild to moderate intensity of various origins (including neuralgia, myalgia, headache), primary dysmenorrhea.

ICD codes

Dosage Regimen

Use the lowest effective dose for the shortest duration necessary to control symptoms.

For oral solution, dissolve the entire contents of one 500 mg sachet in half a glass (100 ml) of warm or cool water. Stir and consume immediately after preparation.

For mild to moderate pain and fever, a single dose for adults and adolescents over 15 years is 500 mg. If pain or fever persists, a repeat dose of 500 mg may be taken. Maintain an interval of at least 4 hours between doses.

Do not exceed a maximum single dose of 1000 mg (1 g). Do not exceed a maximum daily dose of 3000 mg (3 g), which is equivalent to six 500 mg sachets.

The frequency of administration is typically 2 to 4 times per day, depending on symptom severity and response to therapy.

The duration of self-medication as an analgesic must not exceed 7 days. The duration of self-medication as an antipyretic must not exceed 3 days.

Consult a physician if symptoms persist or worsen, or if high doses are required for more than 3 days.

For patients with a history of gastrointestinal disorders, use with caution and only after consulting a physician.

Avoid concomitant use with other oral NSAIDs or anticoagulants due to increased risk of adverse effects.

Adverse Reactions

From the digestive system: nausea, vomiting, anorexia, epigastric pain, diarrhea; rarely – the occurrence of erosive and ulcerative lesions, gastrointestinal bleeding, impaired liver function.

From the nervous system: with prolonged use, dizziness, headache, reversible visual disturbances, tinnitus, aseptic meningitis are possible.

From the hematopoietic system: rarely – thrombocytopenia, anemia.

From the blood coagulation system: rarely – hemorrhagic syndrome, prolonged bleeding time.

From the urinary system: rarely – impaired renal function; with prolonged use – acute renal failure, nephrotic syndrome.

Allergic reactions: rarely – skin rash, angioedema, bronchospasm, “aspirin triad” (a combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid and pyrazolone drugs).

Other: in some cases – Reye’s syndrome; with prolonged use – increased symptoms of chronic heart failure.

Contraindications

Erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, gastrointestinal bleeding, inflammatory bowel diseases in the acute phase (ulcerative colitis, Crohn’s disease), “aspirin triad”, a history of urticaria, rhinitis caused by taking acetylsalicylic acid and other NSAIDs, bleeding, hemophilia, hemorrhagic diathesis, hypoprothrombinemia, dissecting aortic aneurysm, severe hepatic failure, active liver disease, portal hypertension, severe renal failure (creatinine clearance <30 ml/min), vitamin K deficiency, combined use of methotrexate at a dose of ≥15 mg/week, simultaneous use of oral anticoagulants and acetylsalicylic acid at a dose of >3 g/day, Reye’s syndrome, children under 15 years of age (risk of developing Reye’s syndrome in children with hyperthermia due to viral diseases), pregnancy, breastfeeding period, hypersensitivity to acetylsalicylic acid and other salicylates.

With caution

Gout, hyperuricemia, mild to moderate hepatic failure, moderate renal failure (creatinine clearance 30-60 ml/min), in bronchial asthma, a history of erosive and ulcerative lesions and gastrointestinal bleeding, with increased bleeding or simultaneous anticoagulant therapy, decompensated chronic heart failure, COPD, hay fever, nasal polyposis, drug allergy, simultaneous use of oral anticoagulants and acetylsalicylic acid at a dose of <3 g/day, use of methotrexate at a dose of less than 15 mg/week, acyclic uterine bleeding, hypermenorrhea.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in patients with liver diseases.

Contraindicated for use in severe hepatic failure, active liver disease, and portal hypertension.

Use in Renal Impairment

Use with caution in patients with kidney diseases.

Contraindicated for use in severe renal failure (creatinine clearance <30 ml/min).

Pediatric Use

Contraindication: children under 15 years of age (risk of developing Reye’s syndrome in children with hyperthermia due to viral diseases).

Geriatric Use

Use with caution to avoid the risk of exacerbation of chronic diseases.

Special Precautions

Acetylsalicylic acid, even in small doses, reduces the excretion of uric acid from the body, which can cause an acute attack of gout in predisposed patients. During long-term therapy and/or the use of acetylsalicylic acid in high doses, medical supervision and regular monitoring of hemoglobin levels are required.

The use of acetylsalicylic acid as an anti-inflammatory agent in a daily dose of 5-8 g is limited due to the high probability of developing side effects from the gastrointestinal tract.

Before surgery, to reduce bleeding during the operation and in the postoperative period, salicylate intake should be discontinued 5-7 days in advance.

During prolonged therapy, it is necessary to perform a complete blood count and a stool test for occult blood.

The use of acetylsalicylic acid in pediatrics is contraindicated, since in the case of a viral infection in children, under the influence of acetylsalicylic acid, the risk of developing Reye’s syndrome increases. Symptoms of Reye’s syndrome are prolonged vomiting, acute encephalopathy, and liver enlargement.

The duration of treatment (without consulting a doctor) should not exceed 7 days when prescribed as an analgesic and more than 3 days as an antipyretic.

During treatment, the patient should refrain from drinking alcohol.

Drug Interactions

With simultaneous use, antacids containing magnesium and/or aluminum hydroxide slow down and reduce the absorption of acetylsalicylic acid.

With simultaneous use of calcium channel blockers, agents that limit calcium intake or increase calcium excretion from the body, the risk of bleeding increases.

With simultaneous use with acetylsalicylic acid, the effects of heparin and indirect anticoagulants, hypoglycemic agents of sulfonylurea derivatives, insulins, methotrexate, phenytoin, valproic acid are enhanced.

With simultaneous use with glucocorticosteroids, the risk of ulcerogenic action and the occurrence of gastrointestinal bleeding increases.

With simultaneous use, the effectiveness of diuretics (spironolactone, furosemide) is reduced.

With simultaneous use of other NSAIDs, the risk of side effects increases. Acetylsalicylic acid may reduce plasma concentrations of indomethacin and piroxicam.

With simultaneous use with gold preparations, Acetylsalicylic acid may induce liver damage.

With simultaneous use, the effectiveness of uricosuric agents (including probenecid, sulfinpyrazone, benzbromarone) is reduced.

With simultaneous use of acetylsalicylic acid and alendronate sodium, severe esophagitis may develop.

With simultaneous use of griseofulvin, impaired absorption of acetylsalicylic acid is possible.

A case of spontaneous hemorrhage in the iris has been described when taking ginkgo biloba extract against the background of long-term use of acetylsalicylic acid at a dose of 325 mg/day. It is believed that this may be due to an additive inhibitory effect on platelet aggregation.

With simultaneous use of dipyridamole, an increase in C_max of salicylate in blood plasma and AUC is possible.

With simultaneous use with acetylsalicylic acid, the concentrations of digoxin, barbiturates, and lithium salts in blood plasma increase.

With simultaneous use of salicylates in high doses with carbonic anhydrase inhibitors, salicylate intoxication is possible.

Acetylsalicylic acid in doses of less than 300 mg/day has a slight effect on the effectiveness of captopril and enalapril. When using acetylsalicylic acid in high doses, a decrease in the effectiveness of captopril and enalapril is possible.

With simultaneous use, caffeine increases the rate of absorption, concentration in blood plasma, and bioavailability of acetylsalicylic acid.

With simultaneous use, metoprolol may increase the C_max of salicylate in blood plasma.

When using pentazocine against the background of long-term use of acetylsalicylic acid in high doses, there is a risk of developing severe adverse reactions from the kidneys.

With simultaneous use, phenylbutazone reduces the uricosuria caused by acetylsalicylic acid.

With simultaneous use, ethanol may enhance the effect of acetylsalicylic acid on the gastrointestinal tract.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.