Aspirin Plus 500/50 Mg 20 Tablets

Aspirin Plus 500/50 Mg 20 Tablets

ACTION AND MECHANISM

Acetylsalicylic acid belongs to the group of antipyretic and non-steroidal anti-inflammatory analgesic drugs (NSAIDs). The analgesic effect of acetylsalicylic acid is performed peripherally because of the inhibition of prostaglandin synthesis, which prevents the stimulation of pain receptors by bradykinin and other substances. Also, in pain relief central effects on the hypothalamus are possible.
The antipyretic effect appears to be due to the inhibition of prostaglandin synthesis, although the nuclei of the hypothalamus play a significant role in the control of these peripheral mechanisms.
Acetylsalicylic acid inhibits the formation of thromboxane A2, by acetylation of platelet cyclooxygenase. This antiplatelet effect is irreversible during the life of the platelets.
Caffeine is pharmacologically similar to other xanthines such as theobromine and theophylline. Caffeine stimulates the Central Nervous System by antagonizing adenosine receptors.

INDICATIONS

- [PAIN]: Symptomatic relief of mild or moderate pain, [HEADACHE], [ODONTALGIA], [DYSMENORRHEA], [CONTRACTURE], [LUMBALGIA].
- [FEVER]: Febrile states.

POSOLOGY

- Adults, oral: dose of 500 mg of acetylsalicylic acid (1 tablet) every 4-6 hours. Acetylsalicylic acid 4 g (eight tablets) will not be exceeded in 24 hours.
If the pain persists for more than 5 days, the fever for more than 3 days, either worsens or other symptoms appear, the clinical situation should be evaluated.
-Children: Do not use in children under 16 years of age.
- Patients with renal and hepatic insufficiency: reduce the dose (see precautions section).

DOSAGE IN KIDNEY INSUFFICIENCY

* CrCl <10 ml / min: Not recommended.

DOSAGE IN LIVER INSUFFICIENCY

* Severe: Not recommended.

RULES FOR CORRECT ADMINISTRATION

Take the medicine with food or milk, especially if digestive discomfort is noted.

CONTRAINDICATIONS

Acetylsalicylic acid should not be administered in the following cases:
- Patients with active, chronic or recurrent [PEPTIC ULCER], [ACUTE GASTRITIS]: it can cause a worsening of the disease or exacerbation of gastric bleeding or recurrence of gastrointestinal lesions.
- Patients with [ASMA]: there is an increased risk of bronchospastic hypersensitivity reactions.
- Patients with a history of [SALICYLATE ALLERGY], any of the components of this specialty, [NSAID ALLERGY] or tartrazine (cross reaction).
- Patients with [XANTHINE ALLERGY] (aminophylline, theophylline, ...) may also be sensitive to caffeine.
- Patients with diseases that present with [COAGULATION DISORDERS], mainly [HEMOPHILIA] or [HYPOPROTHROMBINEMIA].
- Joint therapy with oral anticoagulants.
- Patients with nasal [NASAL POLYPS] associated with asthma that are induced or exacerbated by acetylsalicylic acid.
- Children under 16 years of age, since in these cases the intake of acetylsalicylic acid has been associated with Reye's syndrome.

PRECAUTIONS

- [DIABETES]: high doses of acetylsalicylic acid can cause alterations in blood glucose. Caffeine can raise blood glucose levels so it should be considered in diabetic patients.
- [GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY]: risk of hemolytic anemia with high doses of ASA.
- Alcohol: Alcohol should not be ingested as it increases the gastrointestinal adverse effects of acetylsalicylic acid, and is a triggering factor in the chronic irritation produced by it. The use of acetylsalicylic acid in patients who regularly consume alcohol (three or more alcoholic drinks -beer, wine, liquor, ...- a day) can cause gastric bleeding.
- [KIDNEY INSUFFICIENCY]: Acetylsalicylic acid and its metabolites are mainly excreted in the urine. Additionally, patients with kidney failure are at greater risk of kidney toxicity.
- [HEPATIC INSUFFICIENCY]: salicylates are metabolized in the liver. In liver cirrhosis and in severe liver failure, there is, respectively, an increased risk of renal adverse effects and bleeding.
- Due to its caffeine content, it should be administered with caution in patients with severe heart disease, [ARRHYTHMIA, CARDIAC], due to the risk of tachycardia and extrasystole, [HYPERTHYROIDISM], [ANXIETY]. In these patients, do not administer more than 100 mg / day of caffeine.
- Medicines containing acetylsalicylic acid should not be administered to children, particularly those under 16 years of age and adolescents suffering from viral illnesses with or without fever, without consulting a doctor or pharmacist. In some viral diseases, especially influenza A, influenza B and chickenpox, there is a risk of the appearance of Reye's Syndrome. The risk of suffering from this disease increases with the concomitant intake of acetylsalicylic acid, however no cause-effect relationship between them has been proven. In some children, acetylsalicylic acid may be, among others, a triggering factor in the development of Reye's syndrome. If continuous vomiting or lethargy occurs, this could be a symptom of suffering from Reye's syndrome and treatment should be discontinued immediately.

ADVICE TO THE PATIENT

- Take the medicine with food, especially if you experience digestive discomfort. If you take a tablet, keep your torso upright for at least 15 minutes, to prevent the drug from damaging your esophagus.
- Do not drink alcoholic beverages, as alcohol increases the gastrointestinal adverse effects of acetylsalicylic acid.
- It is advisable to suspend its administration one week before surgical interventions. Administration of acetylsalicylic acid should be avoided before or after tooth extraction or surgery.
- Keep the medicine out of the reach of children. Aspirin poisoning is common in children.
- Store the medicine in a dry place. Moisture can make the medicine less effective.

SPECIAL WARNINGS

- If the pain persists for more than 10 days, the fever for more than 3 days either worsens or other symptoms appear, the clinical situation should be evaluated.
- Do not administer systematically as a preventive of possible discomfort caused by vaccinations.
- Advise the patient that during prolonged acetylsalicylic acid treatments, watch for signs of coagulation disturbances (skin spots, bleeding gums, black stools).
- Acetylsalicylic acid can interfere with some analytical tests.

INTERACTIONS

- Acetazolamide. ASA has led to increases in acetazolamide levels of up to 80-200%, probably due to displacement of plasma protein binding. There is a risk of poisoning, so it is recommended to avoid administration. Furthermore, acetazolamide could lead to systemic acidosis, which could delay the elimination of salicylates. Although no cases of this interaction have been recorded with other carbonic anhydrase inhibitors, it cannot be ruled out.
- Urinary acidifiers (ascorbic acid, ammonium chloride, methionine) or urinary alkalinizers (absorbable antacids). ASA is a weak acid whose elimination in urine depends on urinary pH. Those drugs that lower the pH will decrease renal elimination, while those that increase the pH will lead to increased elimination.
- Tiludronic acid. The interaction has been detected in pharmacokinetic terms, since ASA could decrease the bioavailability of tiludronate by up to 50% when taken within one hour of tiludronate. It is recommended to distance the administrations of these drugs at least 2 hours.
- Valproic acid. There have been cases of increased levels of valproate associated with the administration of ASA. The interaction could be due to competition between both drugs for the same renal elimination mechanism. Posology readjustment may be necessary.
- NSAIDs. Co-administration of ASA with other NSAIDs, including coxibes, could increase the risk of peptic ulcer and gastric bleeding. In addition, it has been proven that ASA could reduce the plasma levels of other NSAIDs, especially those with an arylpropionic structure such as ibuprofen.
-Aliskiren. Possible reduction of the antihypertensive effect of aliskiren (NSAIDs act on the renin-angiotensin system). In patients with compromised renal function (dehydrated or elderly), deterioration of renal function may be precipitated (possible acute renal failure, usually reversible). Caution, especially in the elderly, monitoring the antihypertensive effect and kidney function.
- Antacids. Antacids may delay and decrease the absorption of ASA. Additionally, absorbable antacids may increase the elimination of ASA.
- Antiplatelet agents. Clopidogrel and ticlopidine could potentiate the antiplatelet effects of ASA. For its part, dipyridamole has increased in pharmacokinetic studies an increase in Cmax and AUC of 31.5% and 37% respectively, probably due to the inhibition of metabolism, with the consequent risk of toxicity. In the case of prasugrel, concomitent administration is indicated, since the efficacy and safety of prasugrel was studied in patients receiving ASA.
- Oral anticoagulants. ASA has led to a potentiation of the effects of anticoagulants such as acenocoumarol, with the consequent risk of bleeding, especially of gastric origin. This interaction could be due to the hypoprothrombinemic effects of ASA at high doses (more than 3 g) or to the inhibition of platelet aggregation. The administration of punctual doses of ASA does not appear to pose a great risk. However, it is advisable to avoid association in patients treated with ASA for long periods, using salicylates or other NSAIDs without antiplatelet effects, and if this is not possible, to exercise extreme caution and control the INR.
- Antiulcer. Pharmacokinetic studies have shown that the increase in gastric pH produced by h3 antihistamines or hydrogen ions pump inhibitors could increase the absorption of ASA, with the possible risk of poisoning. In the case of patients receiving high doses of ASA, a decrease in dosage may be necessary.
- Barbiturates. ASA could increase barbiturate concentrations, with the consequent risk of poisoning.
- Beta-blockers. Administration of ASA at high doses, greater than 2 g, has resulted in a decrease in the antihypertensive effects of beta-blockers. Although the cause is unknown, it could probably be due to inhibition of prostaglandin synthesis, which appear to mediate the antihypertensive effects of beta-blockers. It is therefore recommended to avoid treatment with high doses of ASA in patients treated with a beta-blocker.
- Cyclosporine. NSAIDs may increase cyclosporine nephrotoxicity. It is recommended to periodically evaluate kidney function, especially in the elderly.
- Corticosteroids. There is an increased risk of damage to the gastric mucosa. Furthermore, it appears that corticosteroids could reduce plasma levels of ASA, although the mechanism is unclear. However, it is believed that it could be due to an increase in glomerular filtration and a decrease in tubular reabsorption. For its part, ASA could displace corticosteroids from their protein binding, leading to toxic effects.
- Digoxin. ASA could increase digoxin concentrations, increasing the risk of poisoning. Dosage readjustment may be necessary.
- Diuretics. In several trials it has been shown that ASA could slightly reduce the diuretic effects of drugs such as furosemide, and the natriuretics of spironolactone. In addition, the appearance of acute renal failure could be more frequent, especially in dehydrated patients treated with thiazide diuretics.
- Ototoxic drugs. ASA could increase the ototoxicity of drugs such as aminoglycosides, cisplatin, erythromycin, furosemide, or vancomycin, especially at high doses.
- Phenytoin. ASA could, at high doses, displace phenytoin from its protein binding sites, leading to toxic effects. However, symptoms of this interaction do not usually appear, since free phenytoin undergoes a redistribution in the tissues, decreasing its plasma concentrations. It is recommended to monitor the patient.
- Griseofulvin. Griseofulvin could intensely decrease the absorption of ASA, so it is recommended to avoid the association.
- Heparin. A large number of cases of patients have been described in which the administration of heparin together with ASA resulted in a potentiation of the anticoagulant effects, with an increased risk of bleeding. Although heparin has been associated with ASA to reduce mortality associated with postoperative thromboembolism, the risk in each patient must be evaluated, and their coagulation parameters must be controlled.
- Ibuprofen. Experimental data suggest that ibuprofen may inhibit the effect of
low-dose ASA on platelet aggregation when administered concomitantly. However, there is no clinical evidence and it is likely that there is no relevant effect with the occasional use of ibuprofen.
- ACEI. There are studies in which it has been possible to verify an antagonistic effect of NSAIDs at doses greater than 1 g, on ACE inhibitors, probably due to the inhibition of prostaglandin synthesis, which have vasodilator effects. Regular monitoring of blood pressure is recommended.
- SSRI. There is an increased risk of bleeding in general, and gastric in particular, so it is recommended to avoid the association.
- Lithium. ASA could decrease lithium clearance, increasing the risk of poisoning. Dosage readjustment may be necessary.
- Methotrexate. Numerous cases have been described in which the administration of ASA potentiated the effects of methotrexate. The effects could be due to the displacement of methotrexate from its protein binding sites by ASA, or due to decreased renal clearance due to inhibition of tubular secretion. This effect is especially important in elderly patients with kidney failure. Extreme precautions are recommended, given the risk of severe pancytopenia.
- Nitroglycerin. In pharmacokinetic studies, it has been shown that ASA could increase plasma nitroglycerin levels by up to 54%, perhaps due to decreased hepatic flux and nitroglycerin metabolism. On the contrary, prolonged treatments with ASA led to an increase in the need for nitroglycerin for the same effect, perhaps due to a decrease in the production of vasodilator prostaglandins. It is recommended to monitor the patient.
- Pentazocine. A case of reversible renal toxicity of ASA has been described when adding pentazocine. It is recommended to evaluate the renal function of the patient.
- Sulfonylureas. The administration of ASA at high doses, greater than 2 g, could potentiate the hypoglycemic effects of sulfonylureas. The mechanism is unknown, but ASA could displace sulfonylureas from their binding sites to plasma proteins, while it could reduce the renal elimination of some of them, such as chlorpropamide. It is recommended to monitor blood glucose, especially when starting and ending treatment with ASA, adjusting the sulfonylurea dosage if necessary.
- Uricosuric. ASA has uricosuric effects at high doses, greater than 3 g, but at low doses, it has been shown that it can antagonize the effects of probenecid or sulfinpyrazone. In addition, uricosuric drugs may decrease the elimination of AAS. A buildup of uric acid and ASA can occur. It is therefore recommended to avoid association.
- Verapamil. Cases of potentiation of the antiplatelet effects of ASA by verapamil have been described. Monitoring the patient is recommended.
- Zafirlukast. In pharmacokinetic studies it has been shown that ASA could increase the levels of zafirlukast up to 45%, with the possible risk of toxicity. It is recommended to monitor the patient.
- Zidovudine. Zidovudine plasma concentrations can be increased by competitively inhibiting glucuronidation or directly by inhibiting
hepatic microsomal metabolism , reaching toxic levels. Caution must be exercised. It also increases the toxicity of acetylsalicylic acid.
- Food. Pharmacokinetic studies have shown that the administration of ASA after meals could reduce absorption by up to 50%. Therefore, if rapid effects are desired, it is advisable to administer ASA on an empty stomach. However, administration with meals reduces the risk of gastric irritation.
- Ethyl alcohol. There is an increased risk of gastric damage, so it is recommended to avoid alcohol consumption, especially in the 8-10 hours after a dose of ASA. Those patients who ingest more than three alcoholic beverages daily should avoid the use of ASA, replacing it with another NSAID.

PREGNANCY

Acetylsalicylic acid: FDA Category D. Animal studies with salicylates have reported teratogenic and embryocidal effects. Salicylates quickly cross the placenta. Controlled studies with acetylsalicylic acid (ASA) in humans have not demonstrated teratogenicity. Chronic use with high doses of salicylates during the 3rd trimester may prolong pregnancy, which could lead to fetal damage or death due to decreased placental function, and increase the risk of maternal antenatal bleeding. The use of salicylates, especially ASA, during the last 2 weeks of pregnancy may increase the risk of fetal or neonatal bleeding. Regular or excessive use during late pregnancy could theoretically lead to premature closure of the fetal ductus arteriosus,The risk of stillbirth or neonatal death is also increased (possibly due to antenatal hemorrhage, premature closure of the ductus arteriosus and lower newborn weight); however, this was not observed in studies with therapeutic doses. Chronic treatment with high doses of salicylates during late pregnancy can prolong and complicate labor and increase the risk of maternal or fetal bleeding. The use of ASA (analgesic doses) is only accepted in the absence of safer therapeutic alternatives; Chronic use or high doses are not recommended, especially during the 3rd trimester.Chronic treatment with high doses of salicylates during late pregnancy can prolong and complicate labor and increase the risk of maternal or fetal bleeding. The use of ASA (analgesic doses) is only accepted in the absence of safer therapeutic alternatives; Chronic use or high doses are not recommended, especially during the 3rd trimester.Chronic treatment with high doses of salicylates during late pregnancy can prolong and complicate labor and increase the risk of maternal or fetal bleeding. The use of ASA (analgesic doses) is only accepted in the absence of safer therapeutic alternatives; Chronic use or high doses are not recommended, especially during the 3rd trimester.
Caffeine: FDA Category C.

LACTATION

Acetylsalicylic acid, as well as other salicylates, are excreted in human milk in low amounts. There is a potential risk of effects on platelet function in the newborn, although these have not been reported with the use of ASA. In general, it is recommended to suspend breastfeeding in nursing mothers with long-term therapy and / or high doses; however, some experts determine that occasional single doses do not appear to have significant risk to the infant.
Caffeine is excreted with breast milk in small amounts.

CHILDREN

Contraindicated in children under 16 years of age since the use of acetylsalicylic acid has been related to Reye's Syndrome, a rare but serious disease.

SENIORS

The elderly may be more sensitive to the toxic effects of acetylsalicylic acid, probably due to decreased kidney function.

ADVERSE REACTIONS

The adverse effects of acetylsalicylic acid, in most cases, are a consequence of the mechanism of its pharmacological action and mainly affect the digestive system. 5 7% of patients experience some type of adverse effect.
The most characteristic adverse effects are:
- Gastrointestinal: Common (19%): [NAUSEA], [DYSPEPSIA], [VOMITING], [GASTRIC ULCER], [DUODENAL ULCER]. Less frequently, [GASTROINTESTINAL HEMORRHAGE] ([MELENA], [HEMATEMESIS]).
- Dermatological / hypersensitivity: [URTICARIA], [EXANTEMATIC ERUPTIONS], [ANGIOEDEMA], [RHINITIS], [BRONCHIAL SPASM] paroxysmal and [DYSNEA] severe. [EXCESSIVE SWEATING] (with high doses). In patients with a history of hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs, anaphylactic or anaphylactoid reactions may occur. This could also happen in patients who have not previously shown hypersensitivity to these drugs.
- Hepatic: Uncommon (<1%): [HEPATOTOXICITY] reversible (particularly in patients with juvenile arthritis, systemic lupus erythematosus, rheumatic fever and a history of hepatic impairment), alteration of liver function parameters. Very rarely, [REYE'S SYNDROME] (in children under 16 years old) of very serious consequences.
- Central nervous system: With high doses, [DIZZINESS], [HEADACHE], [CONFUSION], [NERVIOSISM], [ANXIETY].
- Otolaryngological: [TINNITUS], [DEAF] (with high doses).
- Renal: [KIDNEY INSUFFICIENCY] and acute [INTERSTICIAL NEFRITIS] (with high doses).
- Blood: [HYPOPROTHROMBINEMIA] (in high doses), [LEUCOPENIA], [THROMBOPENIA] and prolonged bleeding time and [ANEMIA].
Treatment should be stopped immediately in the event that the patient experiences an episode of deafness, tinnitus, or dizziness.
Due to the presence of caffeine in the preparation, adverse reactions may appear as a result of CNS stimnulation with symptoms such as nervousness or restlessness or mild gastrointestinal irritation. These adverse effects depend on the sensitivity to caffeine and the daily dose. Vegetatively labile individuals can react even to low doses of caffeine with insomnia, restlessness, rapid heartbeat, and possibly gastrointestinal upset.

OVERDOSE

Symptoms: The symptoms of salicism - nausea, vomiting, ringing, deafness, sweating, vasodilation and hyperventilation, headache, blurred vision, and occasionally diarrhea - are indications of overdose. Most of these reactions are produced by the direct effect of the compound. However, vasodilation and sweating are the result of an accelerated metabolism. Alterations in the acid-base balance are common, which can influence the toxicity of salicylates, changing their distribution between plasma and tissues. Stimulation of respiration produces hyperventilation and respiratory alkalosis. Impaired oxidative phosphorylation produces metabolic acidosis. In salicylate poisoning, both symptoms occur to a certain degree, but the metabolic component tends to predominate in children up to 4 years of age.while in older children and adults respiratory alkalosis is more common. Signs of acute poisoning are neurological disorders, such as confusion, delirium, seizures, and coma. Signs of salicism appear when plasma salicylate concentrations exceed 300 mg / l. Supportive measures are needed for adults with plasma salicylate concentrations greater than 500 mg / L and for children when concentrations exceed 300 mg / L. Treatment: There is no antidote to salicylate poisoning. In the case of a suspected overdose, the patient should be kept under observation for at least 24 hours, since the symptoms and blood levels of salicylate may not become evident for several hours. Treat overdose with gastric lavage, forced alkaline diuresis, and supportive therapy.Restoration of acid-base balance may be required along with hemodialysis in acute cases. The symptoms that appear in case of caffeine overdose are as a result of excessive stimulation of the CNS (insomnia, restlessness, vomiting, seizures and symptoms of excitement) and gastrointestinal irritation (nausea, vomiting, diarrhea, abdominal pain). 

Aspirin Plus Leaflet 500/50 Mg 20 Tablets

Technical Data Sheet Aspirin Plus 500/50 Mg 20 Tablets