REMEDOL Suppository Ref.[50371] Active ingredients: Paracetamol

Caution is advised if paracetamol is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as those using maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.

In the presence of the following disorders, this product should be used with great caution (longer interval between doses, reduced dosage) and under careful supervision by a physician:

• Impaired liver function (e.g. due to chronic alcohol abuse, inflammation of the liver).
• Impaired kidney function.
• Gilbert’s syndrome (Meulengracht’s disease).

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risks factors (see section 4.4).

Concomitant use of drugs causing enzyme induction in the liver, such as certain antiepileptics (e.g. carbamazepine, phenobarbital and phenytoin) as well as antitubercular drugs like rifampicin may lead to the liver being damaged by otherwise safe doses of paracetamol. The same applies to alcohol abuse. In addition to a potential toxic effect of paracetamol on the liver in case of chronic alcohol abuse, a paracetamol-alcohol syndrome has been described, which is characterised by an extremely high GOT activity and has been shown to be refractory to treatment with N-acetylcysteine.

From a clinical viewpoint, this observation is irrelevant in the treatment of infants unless they are receiving other medicines containing high concentration of alcohol (e.g. as an excipient).

The clinical significance of interactions between paracetamol and coumarin derivatives cannot be yet assessed. Therefore, long-term Remedol therapy of patients receiving oral anticoagulants requires close medical supervision.

An additive toxic effect on the liver cannot be ruled out when paracetamol and potentially hepatotoxic drugs (e.g. isoniazid) are given concomitantly.

Patients receiving paracetamol in combination with AZT (zidovudine) are more likely to develop neutropenia. This is why these drugs should be used concomitantly only on medical advice.

Concurrent administration of drugs slowing gastric emptying, such as propantheline and of opioid analgesics, may delay the absorption of paracetamol and the onset of its action.

The absorption of paracetamol and its onset of action is accelerated when the drug is given concurrently with products speeding up stomach emptying (e.g. metoclopramide).

Pregnancy

A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.

Paracetamol should not be used for prolonged periods of time, in high doses or in combination with other drugs, since its safety has not been established under these conditions.

Breast-feeding

Paracetamol enters human milk as such, where it reaches concentrations similar to those in plasma. Since no deleterious effects on infants have been reported, discontinuance of breast feeding during treatment is not usually required.

They have no influence on reactivity.

Redness of the skin has rarely been seen. Very rare cases of allergic reactions associated with rash have been reported.

Further hypersensitivity reactions such as Quincke’s oedema, fall in blood pressure including shock have been observed in patients on paracetamol.

Disorders of blood formation (thrombocytopenia, leucopenia, in isolated cases agranulocytosis and pancytopenia) are extremely rare.

In isolated cases, predisposed persons have developed bronchospasm, (analgesic induced asthma). Disorders of renal function may occur when paracetamol is not used properly.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: Cyprus, Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Tel: +357 22608607, Fax: +357 22608669, Website: www.moh.gov.cy/phs.

None.