aspirin

Aspirin is a Western medicine. Common dosage forms include tablets, capsules, and powders. It is an antipyretic, analgesic, non-steroidal anti-inflammatory drug, and antiplatelet aggregation drug. It has the effects of relieving pain and inhibiting thrombosis. The medical insurance types of this drug are: aspirin enteric-coated capsules and aspirin enteric-coated tablets are medical insurance Class A; aspirin tablets and aspirin enteric-coated sustained-release tablets are medical insurance Class B; aspirin powder and aspirin effervescent tablets are non-medical insurance.

Element

The main ingredient of this product is aspirin.

Characteristics

Aspirin tablets: white tablets.

Aspirin enteric-coated capsules: enteric-coated pellets, appearing white after removing the coating.

Enteric-coated aspirin tablets: enteric-coated tablets, appear white after removing the coating.

Aspirin enteric-coated sustained-release tablets: enteric-coated tablets, appear white after removing the coating.

Aspirin powder: milky white uniform powder, which becomes a cow-like liquid after being dissolved in warm water and is easily absorbed and decomposed in the air.

Aspirin effervescent tablets: white or light yellow tablets with scattered small yellow dots on the surface.

Indications

Aspirin tablets: suitable for inhibiting platelet aggregation and reducing the incidence of myocardial infarction, transient cerebral ischemia or stroke in patients with atherosclerosis.

Enteric-coated aspirin capsules: can inhibit platelet aggregation and prevent thrombosis. They are used to prevent thrombosis after transient ischemic attack, myocardial infarction, atrial fibrillation, artificial heart valves, arteriovenous fistulas or other surgeries. They can also be used to treat unstable angina.

Enteric-coated aspirin tablets: used for anti-thrombosis. This product has an inhibitory effect on platelet aggregation and can prevent thrombosis. It is clinically used to prevent transient ischemic attacks, myocardial infarction, atrial fibrillation, artificial heart valves, arteriovenous fistulas or thrombosis after other surgeries. It can also be used to treat unstable angina. Enteric-coated sustained-release aspirin tablets: mainly used to inhibit platelet adhesion and aggregation, and reduce the occurrence of myocardial infarction, transient cerebral ischemia or stroke in patients with atherosclerosis. Aspirin powder: used for fever caused by the common cold or influenza, and also used to relieve mild to moderate pain, such as headache, toothache, neuralgia, muscle pain, dysmenorrhea and joint pain.

Aspirin effervescent tablets: used for fever (colds, flu, etc.), pain (headache, toothache, neuralgia, muscle pain and dysmenorrhea, etc.), rheumatism (rheumatoid arthritis, rheumatoid arthritis), and prevention of transient ischemic attack, myocardial infarction or other thrombosis after surgery.

Specification

Aspirin tablets: 50mg; 0.1g; 0.3g; 0.5g.

Aspirin enteric-coated capsules: 75 mg.

Enteric-coated aspirin tablets: 25mg; 40mg; 50mg; 100mg; 300mg.

Aspirin enteric-coated sustained-release tablets: 50 mg.

Aspirin powder: Each package contains 0.5 grams of aspirin.

Aspirin effervescent tablets: 0.1g; 0.3g; 0.5g.

Dosage

The usage and dosage of this product in different dosage forms and specifications may vary. Please read the specific drug instructions for use, or follow the doctor’s advice.

Aspirin tablets: The daily dose is approximately 50-150 mg, taken once or twice, or as directed by a doctor.

Aspirin enteric-coated capsules: used for anti-thrombotic use in small doses, 75-300 mg per day, once a day.

Enteric-coated aspirin tablets: 75mg-160mg per day, once a day, or as directed by a doctor.

Enteric-coated sustained-release aspirin tablets: once a day, 1-3 tablets each time, or as directed by a doctor. This product should be taken with warm water after meals and should not be taken on an empty stomach.

Aspirin powder: Dissolve in warm water and take orally. Adults take 1 pack at a time.

Aspirin effervescent tablets: Dissolve in warm water and take orally. Adults: (1) Antipyretic and analgesic: 0.5g at a time, 0.5-2.0g per day. (2) Anti-rheumatic: 0.5-1.0g at a time, 3-4g per day. (3) Inhibition of platelet aggregation: follow the doctor’s advice. Children: (1) Antipyretic and analgesic: 1-2 years old, 0.05-0.1g at a time, 3 times a day; 3-5 years old, 0.2-0.3g at a time, 3 times a day; 6-12 years old, 0.3-0.5g at a time, 3 times a day. (2) Anti-rheumatic: 0.08-0.1g per kilogram of body weight at a time, divided into 3-4 doses.

Adverse Reactions

The doses generally used for antipyretic and analgesic rarely cause adverse reactions. Long-term and large-scale use of the drug (such as treatment of rheumatic fever) is more likely to cause adverse reactions, especially when the blood concentration of the drug is greater than 200μg/ml. The higher the blood concentration, the more obvious the adverse reactions.

1. The most common gastrointestinal reactions (incidence rate 3%-9%) include nausea, vomiting, upper abdominal discomfort or pain (caused by direct stimulation of the gastric mucosa by this product), which usually disappear after discontinuation of the drug. Long-term or high-dose use may cause gastrointestinal bleeding or ulcers.

2. Central nervous system: reversible tinnitus and hearing loss occur, usually after a certain course of treatment when the blood drug concentration reaches 200-300μg/L.

3. Allergic reaction: It occurs in 0.2% of patients, manifested as asthma, urticaria, angioedema or shock. Most of them are susceptible people, and they will soon have breathing difficulties after taking the medicine. In severe cases, it can cause death, which is called aspirin asthma. Some are aspirin allergy, asthma and nasal polyps triad, which is often related to genetic and environmental factors.

4. Damage to liver and kidney function is related to the dosage, especially when the dosage is too high and the blood drug concentration reaches 250μg/ml. The damage is reversible and can be restored after stopping the drug. However, there are reports of renal papillary necrosis.

Taboo

1. Patients who are known to be allergic to this product.

2. Patients who have asthma, urticaria or allergic reactions after taking aspirin or other non-steroidal anti-inflammatory drugs.

3. It is contraindicated for the treatment of perioperative pain during coronary artery bypass grafting (CABG).

4. Patients with a history of gastrointestinal bleeding or perforation after using non-steroidal anti-inflammatory drugs.

5. Patients with active gastrointestinal ulcers/bleeding, or previous recurrent ulcers/bleeding.

6. Patients with severe heart failure.

7. Hemophilia or thrombocytopenia.

8. It is forbidden for infants under 3 months old.

Precautions

1. Avoid combined use with other nonsteroidal anti-inflammatory drugs, including selective COX-2 inhibitors.

2. According to the need to control symptoms, using the lowest effective dose in the shortest treatment time can minimize adverse reactions.

3. Adverse reactions such as gastrointestinal bleeding, ulcers, and perforations may occur at any time during treatment with all NSAIDs, and the risk may be fatal. These adverse reactions may be accompanied by or without warning symptoms, regardless of whether the patient has a history of gastrointestinal adverse reactions or a history of serious gastrointestinal events. Patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) should use NSAIDs with caution to avoid worsening their condition. When patients develop gastrointestinal bleeding or ulcers while taking the drug, the drug should be discontinued. Elderly patients experience an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.

4. Clinical trials of various COX-2 selective or non-selective NSAIDs lasting up to 3 years have shown that this product may cause an increased risk of serious cardiovascular thrombotic adverse events, myocardial infarction and stroke, which may be fatal. All NSAIDs, including COX-2 selective or non-selective drugs, may have similar risks. Patients with cardiovascular disease or risk factors for cardiovascular disease are at greater risk. Even if there have been no cardiovascular symptoms in the past, doctors and patients should remain vigilant about the occurrence of such events. Patients should be informed of the symptoms and/or signs of serious cardiovascular safety and the steps to be taken if they occur.

Patients should be alert to symptoms and signs such as chest pain, shortness of breath, weakness, and slurred speech, and should seek medical help immediately if any of these symptoms or signs occur.

5. Like all nonsteroidal anti-inflammatory drugs (NSAIDs), this product can cause new hypertension or aggravate existing hypertension symptoms, any of which can lead to an increased incidence of cardiovascular events. When patients taking thiazide or loop diuretics take nonsteroidal anti-inflammatory drugs (NSAIDs), the efficacy of these drugs may be affected. Patients with hypertension should use nonsteroidal anti-inflammatory drugs (NSAIDs), including this product, with caution. Blood pressure should be closely monitored when starting treatment with this product and throughout the treatment process.

6. Patients with a history of hypertension and/or heart failure (such as fluid retention and edema) should use this drug with caution.

7. NSAIDs, including this product, may cause fatal and serious skin adverse reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These serious events may occur without signs. Patients should be informed of the symptoms and signs of severe skin reactions, and this product should be discontinued at the first appearance of skin rash or other signs of allergic reaction.

8. When taking the drug for a long time or in large quantities, the hematocrit, liver function and serum salicylic acid level should be checked regularly.

9. It should be used with caution in the following situations: patients with asthma and other allergic reactions; patients with glucose-6-phosphate dehydrogenase deficiency (this product occasionally causes hemolytic anemia); gout (this product can affect the effects of other uricosuric drugs and may cause uric acid retention at low doses); patients with impaired liver function may aggravate liver toxicity and bleeding tendency, and patients with impaired liver function and cirrhosis are prone to adverse renal reactions; patients with heart failure or hypertension may cause heart failure or pulmonary edema when taking large amounts of the drug; patients with renal impaired function may increase the risk of renal toxicity; patients with thrombocytopenia.

10. Interference with diagnosis:

(1) When the daily dosage exceeds 2.4 g for a long time, a false positive may occur in the copper sulfate urine glucose test and a false negative may occur in the glucose enzyme urine glucose test.

(2) It may interfere with the urine ketone body test.

(3) When the blood drug concentration exceeds 130 µg/ml, the colorimetric method for measuring blood uric acid may produce a falsely high value, but the uricase method is not affected.

(4) This product may interfere with the determination of urinary 5-hydroxyindoleacetic acid (5-HIAA) by fluorescence method.

(5) Determination of urinary vanillylmandelic acid (WMA). The results may be high or low due to different methods used.

(6) Since this product inhibits platelet aggregation, it can prolong bleeding time. A dose as low as 40 mg per day can also affect platelet function, but clinically, it has not been found that at a low dose (250 μg/ml per day, alanine aminotransferase, aspartate aminotransferase and serum alkaline phosphatase may have abnormal changes, which can return to normal when the dose is reduced.

(8) When used in large doses, especially when the blood concentration is >300µg/ml, the prothrombin time may be prolonged.

(9) Serum cholesterol can be lowered when the daily dosage exceeds 5g.

(10) Because this drug acts on the renal tubules, it increases potassium excretion and can lead to a decrease in blood potassium.

(11) When this product is used in large doses, lower results may be obtained by measuring serum thyroxine (T4) and triiodothyronine (T3) using radioimmunoassay.

(12) Since this drug competes with phenolsulfonphthalein for excretion in the renal tubules, the excretion of phenolsulfonphthalein is reduced (i.e., PSP excretion test).

11. Pregnant and lactating women: avoid use as much as possible.

(1) This product easily crosses the placental barrier. Animal tests show that the use of this product in the first month of pregnancy can cause teratogenesis, such as spina bifida, skull cleft, facial cleft, leg deformity, and incomplete development of the central nervous system, internal organs and bones. There are also reports of fetal defects in humans after using this product. In addition, long-term and large-scale use of this product in the third month of pregnancy can prolong the pregnancy period and increase the risk of post-term labor syndrome and prenatal hemorrhage. Use in the last two weeks of pregnancy can increase the risk of fetal hemorrhage or neonatal hemorrhage. Long-term use of the drug in late pregnancy may also cause the fetal ductus arteriosus to contract or close early, leading to persistent pulmonary hypertension and heart failure in the newborn. There have been reports that excessive use or abuse of this product in late pregnancy has increased the incidence of stillbirth or neonatal death (possibly due to ductus arteriosus atresia, prenatal hemorrhage or low body weight). However, the above adverse reactions have not been found when using general therapeutic doses.

(2) This product can be excreted in breast milk. When a lactating woman takes 650 mg orally, the drug concentration in breast milk can reach 173-483 µg/ml 5-8 hours later. Therefore, long-term high-dose use of the drug may cause adverse reactions in infants.

12. Use in children: Pediatric patients, especially those with fever and dehydration, are prone to toxic reactions. The use of this product in children with acute febrile diseases, especially influenza and chickenpox, may be associated with the development of Reye’s Syndrome, which can be fatal in severe cases and is rare in China.

13. Use in the elderly: Elderly patients are more likely to experience toxic reactions when taking this product due to decreased renal function, so the dosage should be reduced.

14. Drug overdose: symptoms of overdose or poisoning

(1) Mild reaction, namely salicylic acid reaction (salicylism), is more common in patients with rheumatism treated with this drug, and manifests as headache, dizziness, tinnitus, deafness, nausea, vomiting, diarrhea, drowsiness, mental disorder, sweating, deep and rapid breathing, thirst, involuntary movements of hands and feet (more common in the elderly) and visual impairment.

(2) Severe cases may include hematuria, convulsions, hallucinations, severe mental disorders, dyspnea, and unexplained fever. Mental and respiratory disorders are more obvious in children. Laboratory tests may show abnormal EEG, changes in acid-base balance (respiratory alkalosis and metabolic acidosis), hypoglycemia or hyperglycemia, ketonuria, hyponatremia, hypokalemia, and proteinuria in case of overdose. Treatment: Rescue according to conventional methods.

Drug interactions

1. The efficacy is not enhanced when used in combination with other non-steroidal anti-inflammatory analgesics, because this product can reduce the bioavailability of other non-steroidal anti-inflammatory drugs. In addition, gastrointestinal side effects (including ulcers and bleeding) are increased; in addition, due to the enhanced inhibition of platelet aggregation, the risk of bleeding in other parts may also increase. Long-term and large-scale use of this product in combination with acetaminophen may cause kidney diseases including renal papillary necrosis, renal cancer or bladder cancer.

2. When used in combination with any drug that can cause hypoprothrombinemia, thrombocytopenia, decreased platelet aggregation function or gastrointestinal ulcer bleeding, there is a risk of aggravating coagulation disorders and causing bleeding.

3. Combination with anticoagulants (coumarin, heparin, etc.) and thrombolytic drugs (streptokinase, urokinase) may increase the risk of bleeding.

4. Urine alkalinizing drugs (sodium bicarbonate, etc.) and antacids (long-term and large-scale use) can increase the excretion of this product in urine and reduce the blood drug concentration. However, when the blood drug concentration of this product has reached a steady state and the alkaline drug is discontinued, the blood drug concentration of this product can rise to a toxic level. Carbonic anhydrase inhibitors can alkalinize urine, but can cause metabolic acidosis, which can not only reduce the blood drug concentration, but also increase the amount of this product that penetrates into the brain tissue, thereby increasing toxic reactions.

5. Uric acid drugs can reduce the excretion of this drug and increase its blood concentration. The addition of uricosides to patients whose blood concentration of this drug has reached a steady state may lead to an increase in the blood concentration of this drug and increased toxic reactions.

6. Glucocorticoids (hormones for short) can increase the excretion of salicylates. In order to maintain the blood concentration of this product when used together, the dosage of this product should be increased if necessary. When this product is used together with hormones for a long time, especially when used in large quantities, salicylic acid reactions may occur when the hormones are reduced or discontinued, and there is even an increased risk of gastrointestinal ulcers and bleeding. For this reason, it is not recommended to use these two drugs at the same time in clinical practice.

7. The hypoglycemic effect of insulin or oral hypoglycemic drugs can be enhanced and accelerated by taking them together with this product.

8. When used in combination with methotrexate (MTX), it can reduce the binding of methotrexate to protein, reduce its excretion from the kidneys, increase blood drug concentration and increase toxic reactions.

9. The uric acid excretion effect of probenecid or sulfinpyrazone can be reduced by the simultaneous use of this product; when the blood concentration of salicylate is >50μg/ml, it will be significantly reduced, and it will be more serious when it is >100-150μg/ml. In addition, probenecid can reduce the clearance rate of salicylate from the kidney, thereby increasing the latter’s blood concentration.

10. Drug interactions may occur if used with other drugs. Please consult your doctor or pharmacist for details.

Pharmacological Action

Aspirin (acetylsalicylic acid) acetylates the cyclooxygenase (i.e., prostaglandin synthase) of platelets, thereby reducing the production of thromboxane A ₂ (TXA _{2 ), producing an irreversible inhibitory effect on TXA 2-} induced platelet aggregation; it also has an inhibitory effect on phase II aggregation induced by ADP or adrenaline; and it can inhibit platelet aggregation and release reactions and spontaneous aggregation caused by low concentrations of collagen, thrombin, antibody-antigen complexes, certain viruses and bacteria, thereby preventing the formation of thrombi. At high concentrations, acetylsalicylic acid can also inhibit PG synthase in the blood vessel wall and reduce the synthesis of prostacyclin (PGI ₂ ), which _is a physiological antagonist of TXA _2. Its reduced synthesis may promote thrombosis.

Pharmacokinetics

Aspirin tablets:

After oral administration, most of this product is absorbed in the upper part of the small intestine, and the blood concentration reaches a peak in about two hours. After absorption, it is quickly distributed to various tissues. Most of this product is quickly hydrolyzed into salicylates in the gastrointestinal tract, liver and blood, and metabolized in the liver. The metabolites are mainly salicylic acid and glucuronic acid conjugates, and a small part is gentisic acid. Most of this product is excreted from the kidneys as conjugated metabolites, and a small part is free salicylic acid.

Aspirin enteric-coated capsules and aspirin enteric-coated tablets:

1. Most of this product can be absorbed in the upper part of the small intestine. However, enteric-coated tablets are absorbed slowly. The protein binding rate of aspirin is low, but the protein binding rate of hydrolyzed salicylate is 65%-90%. The binding rate decreases accordingly when the blood concentration is high. The binding rate is also low during renal insufficiency and pregnancy. The t _{1/2 is 15-20 minutes; the t 1/2} length of salicylate depends on the size of the dose and the pH value of urine. It is about 2-3 hours when taking a small dose at a time; it can reach more than 20 hours when taking a large dose, and it can reach 5-18 hours when taking the drug repeatedly.

2. Most of this product is quickly hydrolyzed into salicylates in the gastrointestinal tract, liver and blood, and then metabolized in the liver. The metabolites are mainly salicylic acid and glucuronic acid conjugates, and a small part is oxidized to gentisic acid. The blood drug peak is reached 1-2 hours after a single dose. The blood drug concentration is 25-50μg/ml when analgesic and antipyretic; 150-300μg/ml when anti-rheumatic and anti-inflammatory. The time required for the blood drug concentration to reach a stable state increases with the daily dose. It generally takes 7 days when taking a large dose of the drug (such as anti-rheumatic), but it takes 2-3 weeks or more to achieve the best effect. For patients who take a large dose of the drug for a long time, because the main metabolic pathway of the drug is saturated, a slight increase in the dose can lead to a significant change in the blood drug concentration. This product is excreted from the kidneys as a combined metabolite and free salicylic acid. When the dosage is large, the excretion of unmetabolized salicylic acid increases. There can be great differences between individuals. The pH value of urine affects the excretion rate. In alkaline urine, the excretion rate is accelerated and the amount of free salicylic acid increases, while the opposite is true in acidic urine.

Enteric-coated sustained-release aspirin tablets:

After oral administration, most of it is absorbed in the upper part of the small intestine. The blood concentration reaches its peak in about 7.3 hours, and it is rapidly hydrolyzed into salicylic acid after absorption. After hydrolysis, it is rapidly distributed to tissues throughout the body in the form of salicylates, and can also enter the joint cavity and cerebrospinal fluid, and can pass through the placenta. Salicylic acid has a high binding rate with plasma proteins, which can reach 80-90%. Salicylic acid is metabolized by the liver, and the metabolites are mainly salicylic acid and glucuronic acid conjugates, and a small part is gentisic acid. Most of this product is excreted from the kidneys as bound metabolites, and a small part is free salicylic acid. The pH value of urine affects the excretion rate, and the excretion rate is accelerated in alkaline urine.

Aspirin effervescent tablets:

1. After oral administration, it is absorbed rapidly and completely. It has already begun to be absorbed in the stomach, and most of it can be absorbed in the upper part of the small intestine. After absorption, most of it is hydrolyzed into salicylate in the liver, and its peak blood concentration appears 1-2 hours after oral administration, which is about 25-50μg/ml. The plasma protein binding rate of salicylate is 65%-90%. It can be distributed in various tissues throughout the body and can also penetrate into the joint cavity and cerebrospinal fluid. Salicylate is metabolized into salicylic acid and glucuronic acid conjugates, and a small part is oxidized to gentisic acid. Free salicylic acid and conjugated metabolites are excreted from the kidneys. The excretion rate is accelerated in alkaline urine; this product can be excreted through breast milk. When taking a small dose, the plasma half-life of the prototype drug is 15-20 minutes, and the plasma half-life of salicylate is 2-3 hours.

2. Long-term high-dose medication (such as anti-rheumatic drugs) because the main metabolic pathway of the drug has been saturated, the excretion of unmetabolized salicylic acid increases. At this time, a slight increase in dose can lead to a large increase in blood drug concentration, and the plasma half-life of salicylate can reach more than 20 hours.

Storage method

Sealed, store in a dry place.

Validity

18-24 months

Implementation Standards

Aspirin tablets: First supplement to the Chinese Pharmacopoeia 2010 edition.

Aspirin enteric-coated capsules: Chinese Pharmacopoeia 2015 Part II.

Enteric-coated aspirin tablets: Part II of the Chinese Pharmacopoeia 2015 edition.

Enteric-coated sustained-release aspirin tablets: National Food and Drug Administration National Drug Standard WS1-(X-058)-2011Z.

Aspirin powder: National Food and Drug Administration National Drug Standard WS1-(X-005)-2002Z.

Aspirin effervescent tablets: Part II of the Chinese Pharmacopoeia 2015 edition.