ACTION AND MECHANISM

Analgesic, antipyretic and anti-inflammatory.

CONTRAINDICATIONS

- [SALICYLATE ALLERGY] or [NSAID ALLERGY]. Hypersensitivity to any component of the medication, such as [SALICYLATE ALLERGY].
- Patients with [ASTHMA], [NASAL POLYPS] or [IDIOPATHIC CHRONIC URTICARIA].
- [PEPTIC ULCER] active, chronic or recurrent, or in any other process that increases the risk of [GASTROINTESTINAL HEMORRHAGE], as well as in patients with a history of bleeding or [GASTRIC PERFORATION] associated with treatment with acetylsalicylic acid. Acetylsalicylic acid has an ulcerogenic effect, which increases the risk of upper gastrointestinal bleeding and gastric perforation.
- [COAGULATION DISORDERS], especially [HEMOPHILIA] or [HYPOPROTHROMBINEMIA], as well as [VITAMIN K DEFICIENCY].
- Severe renal (CLcr < 30 ml/minute) or severe hepatic (Child-Pugh C) impairment.
- Children under 16 years of age with fever, since in these cases the intake of aspirin has been associated with the onset of Reye's syndrome.
- Third trimester of pregnancy.
- [LIVER DISEASE] (with or without liver failure), viral [HEPATITIS]: increases the risk of hepatotoxicity.
- Administration together with methotrexate.
- [INSOMNIA] or [ANXIETY], due to the stimulating action of caffeine on the Central Nervous System.
- Mental disorders that present with nervous excitement and [EPILEPSY], since it may increase the risk of seizures.

EFFECTS ON DRIVING

Some patients may experience drowsiness or dizziness when taking paracetamol, so patients should exercise caution when performing activities that require alertness.

PREGNANCY

Animal studies with salicylates have shown teratogenic and embryocidal effects. Salicylates rapidly cross the placenta. Epidemiological studies suggest an increased risk of miscarriage and congenital malformations (including cardiac malformations and gastroschisis). During the first and second trimesters of pregnancy, aspirin should not be administered unless strictly necessary, with the lowest possible dose and the shortest possible treatment duration. During the third trimester of pregnancy, the use of prostaglandin synthesis inhibitors may expose the fetus to cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension) and renal failure, which may lead to renal failure and oligohydramniosis. It may also expose the mother and child at the end of pregnancy to a possible prolongation of bleeding time, an antiplatelet effect that may occur even at very low doses, and an inhibition of uterine contractions, leading to delayed or prolonged labor. Chronic treatment with high doses of salicylates during late pregnancy may prolong and complicate labor and increase the risk of maternal or fetal hemorrhage. Therefore, salicylates should only be used during pregnancy after a careful benefit-risk assessment, and are contraindicated during the third trimester.

INDICATIONS

- Symptomatic relief of occasional mild or moderate [PAIN] such as headache, toothache or menstrual pain, and [FEVER].

INTERACTIONS

Due to acetylsalicylic acid:
- NSAID. Simultaneous administration with an NSAID may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect. Do not administer concomitantly.
- Corticosteroids. Simultaneous administration with corticosteroids may increase the risk of
ulcers and gastrointestinal bleeding, due to a synergistic effect, so concomitant administration is not recommended
- Diuretics. This causes a decrease in glomerular filtration rate, as it produces a decrease in the synthesis of renal prostaglandins. NSAIDs can cause acute renal failure, especially in dehydrated patients. It is necessary to ensure adequate
proper hydration of the patient and monitoring of kidney function when starting treatment.
- Selective serotonin reuptake inhibitors. Increased risk of bleeding in general, and upper gastrointestinal bleeding in particular, due to a synergistic effect; therefore, concomitant use should be avoided.
- Anticoagulants. Increased risk of bleeding, so concomitant use is not recommended.
- ACE inhibitors and ARBs. Reduction in glomerular filtration rate, which may be exacerbated by impaired renal function. Administration of this combination to elderly or dehydrated patients may lead to acute renal failure. Monitoring is recommended.
of kidney function at the beginning of treatment as well as regular hydration of the patient.
- Beta-blockers. May reduce the antihypertensive effect due to inhibition of vasodilatory prostaglandins.
- Antidiabetics. Concomitant administration with insulin and sulfonylureas increases the latter's hypoglycemic effect. Due to the hypoglycemic effect of aspirin, sulfonylureas are displaced from their plasma-binding protein at high doses of aspirin.
- Cyclosporine. Increased nephrotoxicity of cyclosporine due to renal prostaglandin-mediated effects. Monitoring of renal function is recommended, especially in elderly patients.
- Vancomycin. Increased risk of vancomycin otoxicity.
- Interferon alpha. Decreased activity of interferon alpha.
- Ethyl alcohol. Increased risk of damage to the gastrointestinal mucosa and increased bleeding time due to the additive effect of alcohol and aspirin.
- Lithium. Decreased lithium excretion, increasing blood lithium levels, which can reach toxic levels. Concomitant use of lithium is not recommended.
- Methotrexate. Decreased tubular secretion of methotrexate, increasing its plasma concentrations and thus its toxicity. Concomitant use is not recommended.
- Uricosurics. Decrease in the effect of uricosurics by competition of
Renal elimination of uric acid and decreased excretion of salicylic acid
reaching high plasma levels.
- Antacids. Increased renal excretion of salicylates due to alkalinization of urine.
- Digoxin: Increased plasma levels of digoxin that can reach levels
toxic due to a decrease in renal excretion. Use is not recommended.
- Zidovudine. Increases plasma concentrations of zidovudine by competitively inhibiting glucuronidation or by directly inhibiting microsomal metabolism.
hepatic and therefore increase its toxicity.
- Valproic acid. Decreased plasma protein binding and inhibition of valproic acid metabolism, increasing its toxicity.
- Phenytoin. Increased plasma levels of phenytoin due to displacement of protein receptors.
Due to paracetamol:
- Ethyl alcohol: The toxicity of paracetamol is potentiated, due to possible
induction of hepatic production of hepatotoxic products derived from paracetamol.
- Oral anticoagulants (acenocoumarol, warfarin). Potentiation of the anticoagulant effect by inhibiting hepatic synthesis of coagulation factors, leading to an increased risk of bleeding. Paracetamol should not be taken for prolonged periods without medical supervision.
- Anticonvulsants (phenytoin, phenobarbital, methylphenobarbital, primidone). Decreased
of the bioavailability of paracetamol as well as potentiation of hepatotoxicity
overdose, due to induction of hepatic metabolism.
- Metoclopramide and domperidone: Increased absorption of paracetamol in the intestine
thin, due to the effect of these medications on gastric emptying and therefore a delay in the onset of action.
- Zidovudine. Increased risk of neutropenia. Should not be administered.
- Propranolol: Increased plasma levels of paracetamol, due to possible inhibition of
your hepatic metabolism.
- Isoniazid: decreased clearance of paracetamol, with possible enhancement of its
action and/or toxicity, due to inhibition of its hepatic metabolism.
- Lamotrigine: Decreased bioavailability of lamotrigine, with possible reduction in
its effect, due to possible induction of its hepatic metabolism.
Due to caffeine:
- Oral contraceptives (estrogens): Studies have shown a decrease in caffeine clearance, with possible potentiation of its action and/or toxicity due to inhibition of its hepatic metabolism.
- Cimetidine: There are studies in which a decrease in caffeine clearance has been recorded, with possible potentiation of its action and/or toxicity, due to inhibition of its hepatic metabolism.
- Clozapine: There are some studies in which inhibition of the antipsychotic effect of clozapine has been recorded, due to antagonism of its actions at the level of dopaminergic receptors.
- Disulfiram: There are some studies in which a decrease in caffeine clearance has been recorded, with possible potentiation of its action and/or toxicity, due to possible inhibition of its hepatic metabolism.
- Methoxsalen: There are some studies in which a decrease in caffeine clearance has been recorded, with possible potentiation of its action and/or toxicity, due to inhibition of its hepatic metabolism.
- Mexiletine: Studies have shown a decrease in caffeine clearance, with possible potentiation of its action and/or toxicity.
- Quinolones (pipemidic acid, ciprofloxacin, enoxacin): there are studies in which an increase in plasma caffeine levels has been recorded, with possible potentiation of its action and/or toxicity, due to inhibition of its hepatic metabolism.

LACTATION

Aspirin, salicylates, and their metabolites are excreted in breast milk in small amounts. Paracetamol is excreted in breast milk, but not in clinically significant amounts. Caffeine is excreted in breast milk in very small amounts, approximately 1%.
Administration of this medication should be avoided as far as possible during breastfeeding.

RULES FOR CORRECT ADMINISTRATION

The tablets are dissolved in a glass of water after the bubbling has stopped. Take the medication with food or milk, especially if you experience digestive discomfort. Do not take it on an empty stomach.

If fever persists for more than 3 days, pain persists for more than 5 days, or the patient worsens or other symptoms appear, the clinical situation should be evaluated.

POSOLOGY

- Adults and adolescents 16 years and older, oral: 1 tablet every 8 hours. Maximum dose: 3 tablets/24 h.

- Children and adolescents under 16 years of age: do not use this medicine due to its caffeine content.

PRECAUTIONS

- [CHRONIC ALCOHOLISM]: Chronic alcohol consumption (more than 3-4 drinks/day) may increase the liver toxicity of paracetamol. Chronic alcoholics should avoid prolonged treatment or excessive doses of paracetamol (no more than 2 g/day). An increased incidence of hepatotoxicity and gastrointestinal bleeding has been observed in patients treated with fixed doses of paracetamol plus aspirin.
- [HEMORRHAGE], [ULCER], and [GASTRIC PERFORATION]. Treatment with nonsteroidal anti-inflammatory drugs is associated with the development of bleeding, ulceration, and perforation of the upper gastrointestinal tract. If any of these events occur, treatment should be discontinued immediately.
- [GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY ANEMIA]: cases of hemolysis have been observed.
- [RENAL FAILURE] In severe cases with creatinine clearance less than 10 ml/min, the interval between doses should be at least 8 hours. In patients with severe or moderate renal impairment, accumulation of conjugated paracetamol derivatives may occur. Prolonged treatment with high doses increases the risk of renal toxicity.
- [SALICYLATE ALLERGY]: Paracetamol as an analgesic and antipyretic is a very valid alternative for patients allergic to salicylate. However, bronchospastic reactions have been observed in some asthmatic patients hypersensitive to aspirin or other NSAIDs. Although the incidence of cross-reaction is low (less than 5%), clinical monitoring is advisable in patients allergic to salicylates treated with paracetamol.
- Medications containing aspirin should not be given to children under 16 years of age or to adolescents suffering from viral illnesses with or without fever. With some viral illnesses, especially influenza A, influenza B, and chickenpox, there is a risk of developing Reye's syndrome. The risk of developing this illness increases with concomitant use of aspirin; however, no cause-and-effect relationship has been proven between the two. If persistent vomiting or lethargy occurs, this could be a symptom of Reye's syndrome, so treatment should be discontinued and a specialist consulted.
- If pain persists for more than 10 days (5 days for children) or fever for more than 3 days, or worsens or other symptoms appear, the clinical situation should be re-evaluated.
- [DIABETES]. Caution is advised in diabetic patients, as caffeine may raise blood glucose levels.
- Patients sensitive to other xanthines (aminophylline, theophylline, etc.) may also be sensitive to caffeine and should therefore not take this medication.
- [HEPATOTOXICITY]. Due to paracetamol, it should not be taken at higher doses or for longer periods of time than recommended. Using paracetamol for longer periods than recommended can cause serious liver damage, such as liver cirrhosis. Therapeutic doses of paracetamol can cause elevated transaminases.
- [ISCHEMIC HEART DISEASE]. In patients with a history of myocardial ischemia, especially when exercising or at high altitudes.
- In patients with thyroid hyperfunction and those with a previous history of cardiac arrhythmias, peptic ulcers, or gastritis, caffeine should be administered with caution.
- In some patients, despite the presence of caffeine, sedation or
Drowsiness. Sedation may be potentiated by other nervous system depressants.
Central.

PRECAUTIONS RELATED TO EXCIPIENTS

- This medicinal product contains sodium salts. For the exact sodium content, please check the composition. Oral and parenteral dosage forms with sodium levels greater than 1 mmol (23 mg)/maximum daily dose should be used with caution in patients on or following a low-sodium diet.

ADVERSE REACTIONS

Adverse reactions are described according to each frequency interval, considering very frequent (>10%), frequent (1-10%), unfrequent (0.1-1%), rare (0.01-0.1%), very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data).

* Due to acetylsalicylic acid:

- Hematological: Common: [HEMORRHAGE] (increased risk), perioperative bleeding, [HEMATOMA], [GINGIVAL BLEEDING], [GENITOURINARY BLEEDING], [HYPOPROTHROMBINEMIA] (with high doses). Uncommon: [ANEMIA]. Rare: Chronic post-hemorrhagic anemia due to hemorrhage or occult bleeding, which will present with typical symptoms such as [ASTHENIA], [PALENESS], hypoperfusion. Very rare: [CEREBRAL HEMORRHAGE], especially in patients with uncontrolled hypertension and concomitantly taking anticoagulant agents.

- Respiratory: Common: Paroxysmal [BRONCHIAL SPASM], severe [DYSPNEA], [RHINITIS], [ASTHMA], [NASAL CONGESTION]. Very rare: [ANAPHYLAXIS].

- Digestive: Common: [GASTRIC ULCER], [DUODENAL ULCER], [MELA], [HEMATEMESIS], [ABDOMINAL PAIN], [DYSPEPSIA], [NAUSEA], [VOMITING]. Rare: [INFLAMMATION] gastrointestinal. Very rare: [GASTRIC PERFORATION]

- Dermatological: Frequent: [URTICARIA], [EXANTHEMATOUS RASHES], [ANGIOEDEMA], [PRURITUS]. Frequency unknown: [EXCESSIVE SWEATING].

- Hepatic: Uncommon: [HEPATITIS] (particularly in patients with juvenile arthritis). Very rare: Transient [LIVER FAILURE] with [ELEVATED TRANSAMINASES].

- Neurological/psychological: Unknown frequency: [HEADACHE], [DIZZINESS], [CONFUSION].

- Otics: Unknown frequency: [TINNITUS], [DEAFNESS].

- Genitourinary: Unknown frequency: [ACUTE RENAL FAILURE], [ACUTE TUBULOINTERSTITIAL NEPHRITIS].

- General: Uncommon: [REYE'S SYNDROME] (in children under 16 years of age with fever, flu or chickenpox).

* Due to paracetamol:

- Hematological: exceptionally, blood disorders, such as [THROMBOPENIA], [LEUKOPENIA], [PANCYTOPENIA], [NEUTROPENIA], [AGRANULOCYTOSIS] and [HEMOLYTIC ANEMIA] (in patients with G6PD deficiency).

- Dermatological: [EXANTHEMATOUS ERUPTIONS], [URTICARIA], [ALLERGIC CONTACT DERMATITIS], [FEVER].

- Metabolic: exceptionally, [HYPOGLYCEMIA], especially in children.

- Hepatic: rarely, [JAUNDICE], [ELEVATED TRANSAMINASES], [HEPATOTOXICITY] (associated with cases of overdose, either by ingesting 1 toxic dose or several excessive doses).

- Genitourinary: may cause [NEPHROPATHY] which in turn may develop into kidney failure, sterile [PYURIA] (cloudy urine), adverse kidney effects (with high doses).

- Cardiovascular: rarely, [HYPOTENSION].

* Due to caffeine:

- Frequently: [INSOMNIA], [AGITATION] and [EXCITABILITY].

- Occasionally: [NAUSEA], [VOMITING], [DIARRHEA], [GASTRALGIA], [HEADACHE], [TINNITUS], [DISORIENTATION], [EXTRASYSTOLE], [PALPITATIONS], [TACHYCARDIA], [CARDIAC ARRHYTHMIA], [IRRITABILITY], [HOT FLASHES], [TACHYPNEA], [POLYURIA]; with high doses: [ANXIETY] symptoms.

COMPOSITION

ACETYLSALICYLIC ACID: 267 MILLIGRAMS
CAFFEINE: 40 MILLIGRAMS
PARACETAMOL: 133 MILLIGRAMS
SODIUM SALTS (EXCIPIENT): 440 MILLIGRAMS