Aspirin C 400/240 Mg 20 Effervescent Tablets

Aspirin C 400/240 Mg 20 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 non-steroidal antipyretic and 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 the relief of pain, central effects on the hypothalamus are possible.
The antipyretic effect seems to be due to the inhibition of prostaglandin synthesis, although the hypothalamus nuclei have a significant role in controlling these peripheral mechanisms.
Acetylsalicylic acid inhibits the formation of thromboxane A2, by acetylation of platelet cyclooxygenase. This antiaggregant effect is irreversible during the life of platelets.
Ascorbic acid is a vitamin that is involved in organic oxide-reduction processes.

INDICATIONS

- [PAIN]: Symptomatic relief of occasional mild or moderate pain, such as [CEFALEA], [ODONTALGIA], [DISMENORREA], [CONTRACTURE], [LUMBALGIA].
- [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 febrile symptoms. As these disappear, this medication should be discontinued.

POSOLOGY IN RENAL INSUFFICIENCY

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

POSOLOGY IN HEPATIC INSUFFICIENCY

* Serious: Use not recommended.

RULES FOR THE CORRECT ADMINISTRATION

Take the medication with meals or with milk, especially if digestive discomfort is noticed.

CONTRAINDICATIONS

Acetylsalicylic acid should not be administered in the following cases:
- Patients with active, chronic or recurrent [ULCERA PEPTICA].
- Patients with [ASMA].
- Patients with a history of [SALICILATOS ALLERGY], any of the components of this specialty, [NSAID ALLERGY] or tartrazine (cross reaction).
- Patients with diseases with [COAGULATION CHANGES], mainly [HEMOPHILIA] or [HYPOPROTROMBINEMIA].
- Joint therapy with oral anticoagulants.
- Patients with nasal [POLIPOS] associated with asthma that are induced or exacerbated by acetylsalicylic acid.
- Children under 16 with febrile processes, influenza or chicken pox, 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.
- [DEFICIENCY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE]: Exceptionally, ASA can cause hemolytic anemia, more frequent with doses greater than 1 g / day.
- Alcohol should not be taken as it increases the gastrointestinal adverse effects of acetylsalicylic acid, and is a trigger in the chronic irritation caused by it. The use of acetylsalicylic acid in patients who regularly consume alcohol (three or more alcoholic beverages per day) can cause gastric bleeding.
- Caution is recommended in the elderly, especially with renal impairment, or with reduced albumin plasma levels, due to the risk of high toxicity.
- [SURGERY]: The administration of acetylsalicylic acid should be avoided in patients before or after a dental extraction or surgical intervention. Discontinue administration one week before surgery.
- High doses of ascorbic acid can precipitate the formation of renal oxalate stones.
- [DIARREA]: Ascorbic acid doses greater than 2 g / day can cause diarrhea.
- Patients with [RENAL INSUFFICIENCY] or [HEPATIC INSUFFICIENCY] severe.

PATIENT ADVICE

- Take the medicine with food, with a glass of water or with milk, especially if you notice 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 surgery. The administration of acetylsalicylic acid should be avoided before or after a dental extraction or surgical intervention.
- Keep the medicine out of the reach of children. Acetylsalicylic acid poisoning is common in children.
- Keep the medicine in a dry place. Moisture may decrease the effectiveness of the medication.

SPECIAL WARNINGS

- If the pain persists for more than 10 days, the fever for more than 3 days either gets worse or other symptoms appear, the clinical situation should be evaluated.
- Do not systematically administer as a preventative of possible discomfort caused by vaccinations.
- Warn the patient that during prolonged treatments with acetylsalicylic acid, coagulation abnormalities may appear (skin blemishes, bleeding gums).
- Acetylsalicylic acid may interfere with some analytical tests.

INTERACTIONS

- Acetazolamide. The 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. In addition, acetazolamide could lead to systemic acidosis, so it may delay the elimination of salicylates. Although there have been no cases of this interaction 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 an increase in elimination.
- Tiludronic acid. Interaction has been detected in pharmacokinetic terms, since ASA could decrease the bioavailability of tiludronate up to 50% when taken in the hour following tiludronate. It is recommended to distance administrations of these medications 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 mechanism of renal elimination. A dose adjustment may be necessary.
- NSAID. Co-administration of ASA together with other NSAIDs, including coxibes, could increase the risk of peptic ulcer and gastric hemorrhage. In addition, it has been proven that ASA could reduce the plasma levels of other NSAIDs, especially those with 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 (possible acute renal failure, usually reversible) may be precipitated. Caution, especially in the elderly, monitoring the antihypertensive effect and renal function.
- Antacids. Antacids may delay and decrease the absorption of ASA. In addition, absorbable antacids could increase the elimination of ASA.
- Platelet antiaggregants. Clopidogrel and ticlopidine may potentiate the antiaggregant effects of ASA. On the other hand, 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, concomitant administration is indicated, since the efficacy and safety of prasugrel was studied in patients receiving ASA.
- Oral anticoagulants. The 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 hypoprothrombinémic effects of ASA at high doses (more than 3 g) or to the inhibition of platelet aggregation. The administration of specific doses of ASA does not seem 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 platelet antiaggregant effects, and if not possible, exercise caution and control the INR.
- Antiulcer. Pharmacokinetic studies have shown that the increase in gastric pH produced by h3 antihistamines or hydrogenation pump inhibitors could increase the absorption of ASA, with the possible risk of poisoning. In case of patients receiving high doses of ASA, a decrease in dosage may be necessary.
- Barbiturates. The ASA could increase barbiturate concentrations, with the consequent risk of poisoning.
- Beta-blockers. The 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 the inhibition of prostaglandin synthesis, which seems to mediate the antihypertensive effects of beta-blockers. It is therefore recommended to avoid treatments with high doses of ASA in patients treated with a beta-blocker.
- Cyclosporine. NSAIDs may increase cyclosporine nephrotoxicity. It is recommended to periodically evaluate renal functionality, especially in the elderly.
- Corticosteroids. There is an increased risk of damage to the gastric mucosa. In addition, it seems that corticosteroids may reduce ASA plasma levels, 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, the ASA could displace corticosteroids from their protein binding, leading to toxic effects.
- Digoxin. ASA may increase digoxin concentrations, increasing the risk of poisoning. A dose adjustment 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 occurrence of acute renal failure may be more frequent, especially in dehydrated patients treated with thiazide diuretics.
- Ototoxic drugs. ASA may 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 points, leading to toxic effects. However, symptoms of such interaction do not usually appear, since free phenytoin undergoes a redistribution in the tissues, decreasing their plasma concentrations. It is recommended to monitor the patient.
- Griseofulvin. Griseofulvin may greatly decrease the absorption of ASA, so it is recommended to avoid 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 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 assessed, and its coagulation parameters monitored.
- 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 there is probably no relevant effect with the occasional use of ibuprofen.
- IECA. There are studies in which it has been possible to verify an antagonistic effect of NSAIDs at doses greater than 1 g, on ACEIs, probably due to the inhibition of prostaglandin synthesis, which have vasodilator effects. Periodic 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 association.
- Lithium The AAS could decrease the clearance of lithium, increasing the risk of poisoning. A dose adjustment may be necessary.
- Methotrexate. Numerous cases have been described in which the administration of ASA enhanced the effects of methotrexate. The effects could be due to the displacement of methotrexate from its protein binding points by the ASA, or by the decrease in renal clearance due to the inhibition of tubular secretion. This effect is especially important in elderly patients with renal insufficiency. Extreme precautions are recommended, given the risk of severe pancytopenia.
- Nitroglycerin. Pharmacokinetic studies have shown that ASA could increase plasma nitroglycerin levels up to 54%, perhaps due to a decrease in liver flow and nitroglycerin metabolism. On the contrary, prolonged treatments with ASA resulted in an increase in nitroglycerin needs for the same effect, perhaps due to decreased production of vasodilator prostaglandins. It is recommended to monitor the patient.
- Pentazocine. A case of reversible renal toxicity of ASA has been described by adding pentazocine. It is recommended to evaluate the patient's renal functionality.
- Sulfonylureas. The administration of ASA at high doses, greater than 2 g, could enhance the hypoglycemic effects of sulfonylureas. The mechanism is unknown, but ASA could displace sulfonylureas from their plasma protein binding points, while reducing renal elimination of some of them, such as chlorpropamide. It is recommended to monitor blood glucose, especially when starting and finishing an ASA treatment, readjusting the sulfonylurea dosage if necessary.
- Uricosuric. The ASA has uricosuric effects at high doses, greater than 3 g, but at low doses, it has been found that it can antagonize the effects of probenecid or sulfinpyrazone. In addition, uricosuric agents may decrease the elimination of ASA. An accumulation of uric acid and ASA can occur. It is therefore recommended to avoid association.
- Verapamil. Cases of potentiation of platelet antiaggregant effects of ASA by verapamil have been described. It is recommended to monitor the patient.
- Zafirlukast. Pharmacokinetic studies have shown that ASA could increase zafirlukast levels up to 45%, with the possible risk of toxicity. It is recommended to monitor the patient.
- Zidovudine. Plasma zidovudine concentrations can be increased by competitively inhibiting glucuronidation or directly inhibiting microsomal metabolism.
Hepatic, being able to reach toxic levels. Caution must be taken. It also increases the toxicity of acetylsalicylic acid.
- Foods. Pharmacokinetic studies have shown that administration of ASA after meals could reduce absorption up to 50%. Therefore, if rapid effects are desired, it is advisable to administer the 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 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. Studies on animals with salicylates have recorded teratogenic and embryogenic effects. Salicylates quickly cross the placenta. Studies controlled 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 hemorrhage. The use of salicylates, especially ASA, during the last 2 weeks of pregnancy may increase the risk of fetal or neonatal hemorrhage. Regular or excessive use during the final phase of pregnancy could theoretically result in premature closure of the fetal ductus arteriosus, and the risk of delivery with dead product or neonatal death is increased (possibly due to antenatal hemorrhage, premature closure of the ductus arteriosus and less newborn weight); however, this was not observed in studies with therapeutic doses. Chronic treatment with high doses of salicylates during the final phase of pregnancy can prolong and complicate labor and increase the risk of maternal or fetal hemorrhage. The use of ASA (analgesic dose) is only accepted in the absence of safer therapeutic alternatives; not recommending chronic use or high doses, especially during the 3rd trimester.
Ascorbic: FDA Category A.

LACTATION

Acetylsalicylic acid, as well as other salicylates, are excreted with breast milk in low amounts. There is a potential risk of effects on the platelet function of the newborn, although they have not been registered 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 for the infant.
The use of ascorbic acid during lactation 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%): [NAUSEAS], [DYSPEPSY], [VOMITES], [GASTRIC ULCERA], [DUODENAL ULCERA], [GASTROINTESTINAL HEMORRAGY] ([MELENA], [HEMATEMESIS]), [ABDOMINAL CALAMBRES], [DIARRHEA] (ascorbic doses greater than 2 g), [URTICARY], [EXANTEMATIC ERUPTIONS], [ANGIOEDEMA], [RHINITIS], [BRONCHIAL SPASM] and [DISNEA] severe (due to hypersensitivity reactions); [HYPOPROTROMBINEMIA] (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], [KING SYNDROME] (children).
- With prolonged high doses: [MAREO], [TINNITUS], [WAITING], [EXCESS OF SWEATING], [CEFALEA], [CONFUSION], [RENAL INSUFFICIENCY] and [INTERSTICIAL NEFRITIS] acute. They can be signs of overdosing.
- The treatment should be suspended immediately if the patient experiences any 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.
- If the occurrence of adverse reactions is observed, the treatment should be suspended and notified to pharmacovigilance systems.

OVERDOSE

- Symptoms: The symptoms of salicism (nausea, vomiting, chimes, 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 compound. However, vasodilation and sweats 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. Breathing stimulation produces hyperventilation and respiratory alkalosis. Impaired oxidative phosphorylation produces metabolic acidosis.
In the case of salicylate poisoning the two symptoms occur to a certain degree but the metabolic component tends to predominate in children up to 4 years, 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 concentrations of salicylate exceed 300 mg / l. Supportive measures are needed for adults with plasma concentrations of salicylate of more than 500 mg / l and for children when the concentrations exceed 300 mg / l.
- Treatment: There is no antidote against salicylate poisoning. In the case of an alleged overdose, the patient should be kept under observation for at least 24 hours, since for several hours the symptoms and blood salicylate levels may not be evident. Overdose is treated with gastric lavage, forced alkaline diuresis and supportive therapy. Acid-base balance restoration may be required along with hemodialysis, in acute cases.

See leaflet Aspirin C 400/240 Mg 20 Effervescent Tablets

See Technical Data Sheet Aspirin C 400/240 Mg 20 Effervescent Tablets