ACTION AND MECHANISM

A non-opioid analgesic and antipyretic, combined with vitamin C. Paracetamol peripherally blocks pain impulses through the reversible inhibition of cyclooxygenase, an enzyme involved in prostaglandin synthesis. Its antipyretic effect is due to the inhibition of prostaglandins at the thermoregulatory center located in the hypothalamus. It has demonstrated weak anti-inflammatory properties in some non-rheumatic conditions. In other circumstances, anti-inflammatory action is not expected. At the same dose, the analgesic and antipyretic potency of paracetamol is similar to that of acetylsalicylic acid (aspirin).

SPECIAL WARNINGS

- During prolonged treatment, periodic monitoring of liver function and complete blood counts is recommended. - Although it does not significantly reduce inflammation, very positive effects have been observed in arthritic knee conditions, probably due to its analgesic effect. - Food delays the absorption of paracetamol.

PATIENT ADVICE

- High doses of paracetamol or prolonged treatment without medical supervision can cause liver damage, especially in patients who regularly consume alcoholic beverages. - Do not use this medicine for more than 10 consecutive days without medical supervision. Prolonged treatment or high doses should be taken under a doctor's supervision. - Do not exceed the recommended daily dose (maximum 4 g/day; 2 g/day for alcoholics). - Do not use paracetamol with non-steroidal anti-inflammatory drugs (NSAIDs) without medical advice. - Phenacetin (a metabolite of paracetamol) can darken urine.

CONTRAINDICATIONS

- [PARACETAMOL ALLERGY].

- [LIVER DISEASE] (with or without liver failure), viral [HEPATITIS]: increases the risk of hepatotoxicity.

ADVANCED AGE

No specific problems have been described in elderly patients that would require a dosage adjustment.

PREGNANCY

- Paracetamol: the use of short-term therapeutic oral doses is generally accepted at all stages of pregnancy.

- Ascorbic acid: acceptable use at low doses (Caution at high doses).

INDICATIONS

- [PAIN] of mild or moderate intensity.- [FEVER]. Alternative to acetylsalicylic acid in peptic ulcer, treatment with oral anticoagulants and in salicylate allergy.

INTERACTIONS

Paracetamol is metabolized in the liver, producing hepatotoxic metabolites, and therefore can interact with drugs that use the same metabolic pathways. Clinical data on interactions at this level exist with the following drugs:

- Oral anticoagulants (acenocoumarol, warfarin): possible potentiation of the anticoagulant effect, with apparently little clinical relevance; they are considered a therapeutic alternative to salicylates when anticoagulant therapy is already in use. However, the dose and duration of treatment should be as low as possible, with periodic INR monitoring.

- Ethyl alcohol: potentiation of paracetamol toxicity, due to possible induction of hepatic production of hepatotoxic products derived from paracetamol.

- Anticonvulsants (phenytoin, phenobarbital, methylphenobarbital, primidone): decreased bioavailability of paracetamol as well as potentiation of hepatotoxicity in overdose, due to induction of hepatic metabolism.

- Busulfan: Because paracetamol can decrease available glutathione, busulfan clearance may be reduced and its body levels increased. It is recommended to minimize or avoid paracetamol administration before (< 72 hours) or during busulfan treatment.

- Estrogens: decreased plasma levels of paracetamol, with possible inhibition of its effect, due to possible induction of its metabolism.

- Exenatide: The absorption of paracetamol may be reduced by exenatide, as it slows gastric emptying. This interaction can be avoided if the analgesic is administered 1 hour before exenatide.

- Isoniazid: decreased clearance of paracetamol, with possible potentiation of its action and/or toxicity, due to inhibition of its hepatic metabolism.

- Lamotrigine: decrease in the area under the curve (20%) and half-life (15%) of lamotrigine, with possible inhibition of its effect, due to possible induction of its hepatic metabolism.

- Propranolol: increased plasma levels of paracetamol, due to possible inhibition of its hepatic metabolism.

- Rifampicin: increased clearance of paracetamol due to possible induction of its hepatic metabolism.

In addition, there is clinical data on interactions with other mechanisms:

- Anticholinergics (glycopyrronium, propantheline): decreased absorption of paracetamol, with possible inhibition of its effect, due to the decreased speed of gastric emptying.

- Ion exchange resins (cholestyramine): decreased absorption of paracetamol, with possible inhibition of its effect, due to the binding of paracetamol in the intestine.

- Drugs that predispose to nephrolithiasis (acetazolamide, calcium salts, saquinavir, topiramate, triamterene). Concomitant administration could lead to a higher incidence of nephrolithiasis. This combination should be avoided.

LACTATION

Paracetamol is excreted in breast milk in low concentrations. No adverse effects have been reported in newborns following oral administration to the mother, except for one isolated case of an infant with a reversible maculopapular rash on the upper trunk and face.

The safety and efficacy of high-dose vitamin C supplements in breastfeeding mothers have not been evaluated.

GUIDELINES FOR PROPER ADMINISTRATION

Dissolve the tablet in half a glass of water, then drink it.

POSOLOGY

- Adults: 1 tablet every 4 hours. Do not exceed 3 g of paracetamol/day (6 doses/day)

A dosage regimen may also be established for adult patients weighing less than 50 kg, patients with mild or moderate hepatic impairment, chronic alcoholism or chronic malnutrition (low hepatic glutathione reserves) and dehydration, not to exceed 2 g/24 hours

PRECAUTIONS

- [CHRONIC ALCOHOLISM]: Chronic alcohol consumption (more than 3-4 drinks/day) may potentiate the liver toxicity of paracetamol. Chronic alcoholics should avoid prolonged treatment or excessive doses of paracetamol (no more than 2 g/day should be administered). An increased incidence of hepatotoxicity and gastrointestinal bleeding has been observed in patients treated with fixed doses of paracetamol plus acetylsalicylic acid.

- [ANEMIA]: Due to the possible occurrence of blood disorders such as thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia, etc., caution is advised in patients with anemia, avoiding prolonged treatment. In these patients, there is a risk that cyanosis may not manifest despite elevated methemoglobin levels.

Prolonged treatments will also be avoided in patients with heart or lung disorders.

- [ANEMIA DUE TO GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY]: cases of hemolysis have been observed.

- In severe renal impairment 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 salicylates. However, bronchospastic reactions have been observed in some asthmatic patients hypersensitive to acetylsalicylic acid or other NSAIDs. Although the incidence of cross-reactivity is low (less than 5%), clinical monitoring is advised in patients allergic to salicylates treated with paracetamol.

- [KIDNEY STONES] and a history of kidney stones. Ascorbic acid can acidify the urine and cause urate crystals to precipitate, which could trigger the formation of kidney stones. Extreme caution should be exercised in patients with this condition.

PRECAUTIONS RELATING TO EXCIPIENTS

- This medicine contains sodium salts, which should be taken into account in patients on low sodium diets.

ADVERSE REACTIONS

"ADRs RELATED TO PARACETAMOL"

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

- Dermatological: [SKIN RASHES], [URTICARIA], [ALLERGIC CONTACT DERMATITIS], [FEVER].

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

- Hepatobiliary: rarely, [JAUNDICE], [INCREASE TRANSAMINASES], [HEPATOTOXICITY] (associated with cases of overdose, either from the ingestion of 1 toxic dose or several doses of excessive doses).

- Genitourinary: may cause [NEPHROPATHY] which in turn may evolve into a state of renal failure, sterile [PYURIA] (cloudy urine), adverse renal effects (with high doses).

- Cardiovascular: rarely, [HYPOTENSION].

"RAMS RELATED TO ASCORBIC ACID"

It does not usually cause adverse reactions, except in particularly sensitive individuals.

- Digestive. The most common symptom is diarrhea, although it usually occurs at high doses, above 1 g for adults and 500 mg for children. This diarrhea could be due to the osmotic effects of ascorbic acid in the intestinal lumen. Nausea, vomiting, gastric hyperacidity, abdominal spasm, and flatulence have also been reported, but these usually occur at doses higher than 1 g.

- Genitourinary. The administration of large amounts of vitamin C has been associated with the production of [KIDNEY STONES], although these have only appeared in individuals with a history of kidney stones.

- Hematological. Cases of [HEMOLYTIC ANEMIA] have been described in patients with glucose-6-phosphate dehydrogenase deficiency, especially in neonates.

ADVERSE REACTIONS RELATED TO EXCIPIENTS

This medicine contains sorbitol. Daily doses above 10 g of sorbitol taken orally may have a mild laxative effect and lead to diarrhea.