Aspirin C 400/240 Mg 10 Effervescent Tablets

Aspirin C 400/240 Mg 10 Effervescent Tablets

Acetylsalicylic acid/Ascorbic acid

ACTION AND MECHANISM

Association with anti-inflammatory, analgesic, antipyretic and vitamin factor properties.
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.
Ascorbic acid is a vitamin that is involved in organic oxidation-reduction processes.

INDICATIONS

- [PAIN]: Symptomatic relief of occasional mild or moderate pain, such as [HEADACHE], [DENTISTRY], [DYSMENORRHEA], [CONTRACTURE], [LOW BACKGROUND].
- [FEVER]: Febrile states.

POSOLOGY

Dose expressed in acetylsalicylic acid.
Adults and over 16 years: 500 mg / 4 - 6 hours. It will not exceed 4 g in 24 hours
- Patients with heart failure: reduce the dose (see precautions section).
Always use the lowest dose that is effective.
The administration of this preparation is subject to the appearance of painful or feverish symptoms. As these disappear, this medication should be discontinued.

DOSAGE IN KIDNEY INSUFFICIENCY

* Mild or moderate: Caution. There may be an increased risk of toxicity.
* Severe: Use not recommended.

DOSAGE IN LIVER INSUFFICIENCY

* Severe: Use 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].
- Patients with [ASMA].
- Patients with a history of [SALICYLATE ALLERGY], to any of the components of this specialty, [NSAID ALLERGY] or to tartrazine (cross reaction).
- Patients with diseases that present with [COAGULATION DISORDERS], mainly [HEMOPHILIA] or [HYPOPROTHROMBINEMIA].
- Joint therapy with oral anticoagulants.
- Patients with nasal [POLYPS] associated with asthma that are induced or exacerbated by acetylsalicylic acid.
- Children under 16 years of age with febrile processes, flu or chickenpox, since in these cases the intake of acetylsalicylic acid has been associated with the appearance of Reye's syndrome.

PRECAUTIONS

- [DIABETES]: high doses of ASA can modify blood glucose.
- [DROP]: analgesic doses of ASA may increase serum uric acid levels. High doses of ascorbic acid can precipitate acute attacks of gout.
- [GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY]: Exceptionally, ASA can cause hemolytic anemia, more frequent with doses greater than 1 g / day.
- 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 a day) can cause gastric bleeding.
- Caution is recommended in the elderly, especially with kidney failure, or who have reduced plasma levels of albumin, due to the risk of high toxicity.
- [SURGERY]: The administration of acetylsalicylic acid should be avoided in patients before or after dental extraction or surgical intervention. Suspend its administration one week before surgical interventions.
- High doses of ascorbic acid can precipitate the formation of oxalate kidney stones.
- [DIARRHEA]: doses of ascorbic acid greater than 2 g / day can cause diarrhea.
- Patients with severe [KIDNEY INSUFFICIENCY] or [HEPATIC INSUFFICIENCY].

ADVICE TO THE PATIENT

- Take the medicine with food, a glass of water or milk, especially if you experience digestive discomfort.
- 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. Acetylsalicylic acid 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.
- Warn the patient that during prolonged treatments with acetylsalicylic acid, coagulation disorders (spots on the skin, bleeding gums) may appear.
- 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. Additionally, acetazolamide could lead to systemic acidosis, which could delay the clearance of salicylates. Although no cases of this interaction have been reported 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. A dosage adjustment 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. Also, absorbable antacids could increase the elimination of ASA.
- Platelet antiaggregants. 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 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. Several trials have 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 patient cases have been described in which the administration of heparin together with ASA resulted in 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 controlled.
- Ibuprofen. Experimental data suggest that ibuprofen may inhibit the effect of
low doses of 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. 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 for plasma proteins, as well as reducing renal elimination of some of them, such as chlorpropamide. It is recommended to monitor blood glucose, especially when starting and ending treatment with ASA, readjusting 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 build-up 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. It is recommended to monitor the patient.
- Zafirlukast. In pharmacokinetic studies it has been shown that ASA could increase zafirlukast levels by 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.
- Foods. In pharmacokinetic studies, it has been 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 drinks daily should avoid the use of ASA, replacing it with another NSAID.

PREGNANCY

Acetylsalicylic acid: FDA Category D. Animal studies with salicylates have recorded 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 can 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.
Ascorbic: FDA Category A.

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 recorded 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.
The use of ascorbic acid during breastfeeding is accepted.

ADVERSE REACTIONS

In most cases, the adverse effects of acetylsalicylic acid 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:
- Occasionally (1-9%): [NAUSEA], [DYSPEPSIA], [VOMITING], [GASTRIC ULCER], [DUODENAL ULCER], [GASTROINTESTINAL HEMORRHAGE] ([MELENA], [HEMATEMESIS] ), [ABDOMINAL CRAMPS], [DIARRHEA] (ascorbic doses greater than 2 g), [URTICARIA], [EXHANTEMATIC ERUPTIONS], [ANGIOEDEMA], [RHINITIS], [BRONCHIAL SPASM] and [DYSNEA] severe (due to reactions hypersensitivity); [HYPOPROTHROMBINEMIA] (in high doses). Ascorbic acid can precipitate acute attacks of gout and acidify the urine.
- Rarely (<1%): [HEPATITIS] (particularly in patients with juvenile arthritis), [ANEMIA], [REYE'S SYNDROME] (children).
- With prolonged high doses: [DIZZINESS], [TINNITUS], [DEAFness], [EXCESS SWEATING], [HEADACHE], [CONFUSION], [KIDNEY INSUFFICIENCY] and acute [INTERSTICIAL NEFRITIS]. They can be signs of overdose.
- Treatment should be stopped immediately if the patient experiences an episode of deafness, tinnitus or dizziness.
- In patients with a history of hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs, [ANAFILAXIA] or anaphylactoids may occur. This could also happen in patients who have not previously shown hypersensitivity to these drugs.
- In the event of the appearance of adverse reactions, the treatment should be suspended and notified to the pharmacovigilance systems.

OVERDOSE

- Symptoms: The symptoms of salicism (nausea, vomiting, tinkling, 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 intoxication, both symptoms occur to a certain degree, but the metabolic component tends to predominate in children up to 4 years of age, while respiratory alkalosis is more common in older children and adults.
Signs of acute intoxication 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 event 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. 

Aspirin C 400/240 Mg Leaflet 10 Effervescent Tablets

Technical Sheet Aspirin C 400/240 Mg 10 Effervescent Tablets