Nextrim^® Fast (Tablets) Instructions for Use

Marketing Authorization Holder

Polpharma Pharmaceutical Works, Sa (Poland)

ATC Code

N02BA01 (Acetylsalicylic acid)

Active Substance

Acetylsalicylic acid (Ph.Eur. European Pharmacopoeia)

Dosage Form

Nextrim® Fast

Tablets 300 mg: 6 pcs.

Dosage Form, Packaging, and Composition

6 pcs. – blister packs (1) – cardboard packs.

Clinical-Pharmacological Group

NSAID. Antiplatelet agent

Pharmacotherapeutic Group

NSAID

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 vasodilation of the skin 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 unchanged (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 deteriorates, and excretion significantly increases). T_1/2 of acetylsalicylic acid is approximately 15 min. 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), algodysmenorrhea.

ICD codes

Dosage Regimen

Determine the dosage individually based on the indication and patient response.

For fever and mild to moderate pain (e.g., headache, myalgia, algodysmenorrhea), administer a single dose of 300 mg to 1 gram.

The maximum daily dose is 3 grams. Do not exceed this limit.

Administer the medication 2 to 6 times per day as needed. Maintain an interval of at least 4 hours between doses.

For short-term self-medication, limit use to no more than 3 days for fever and no more than 5 days for pain.

Discontinue use and consult a physician if symptoms persist or worsen.

In patients with a history of gastrointestinal disorders, use the lowest effective dose for the shortest possible duration.

Avoid concomitant use with oral anticoagulants and other NSAIDs due to an increased risk of bleeding and gastrointestinal toxicity.

In patients with impaired renal function (creatinine clearance 30-60 ml/min), use with caution and monitor renal function.

Do not administer to children and adolescents under 15 years of age due to the risk of Reye’s Syndrome.

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 polyposis of the nose and paranasal sinuses 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”, 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, 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 renal 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’s age (under 15 years – 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, salicylates should be discontinued 5-7 days before.

During long-term 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, the risk of developing Reye’s syndrome increases under the influence of acetylsalicylic acid. 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 effect of heparin and indirect anticoagulants, hypoglycemic agents of sulfonylurea derivatives, insulins, methotrexate, phenytoin, valproic acid is 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 into 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 high doses of salicylates 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 high doses of acetylsalicylic acid, 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

Rx Only

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.