PARACONICA Solution for infusion Ref.[50645] Active ingredients: Paracetamol

Paracetamol should be used with caution in cases of:

• hepatocellular insufficiency,
• severe renal insufficiency (creatinine clearance ≤30 mL/min; see “Pharmacokinetics”),
• chronic alcoholism,
• concomitant administration of potentially hepatotoxic medicinal products, with liver enzyme inducers or excessive alcohol consumption. In these cases, the benefit/risk ratio should be carefully reviewed, taking therapeutic alternatives into consideration,
• anorexia, bulimia or cachexia; chronic malnutrition (low reserves of hepatic glutathione),
• dehydration, hypovolaemia.

Caution is advised in cases of excessive alcohol consumption. Alcohol can increase the hepatotoxicity of paracetamol, particularly during concomitant fasting. In such cases, even a therapeutic paracetamol dose can lead to liver damage.

To avoid the risk of an overdose, it must be ensured that other administered medicinal products contain no paracetamol.

Higher than recommended dosages carry the risk of very severe liver damage.

The concomitant use of Paraconica with other medicines can increase the likelihood of undesirable effects.

Co-medication with phenytoin can lead to decreased efficacy of paracetamol and, due to the increase in toxic paracetamol metabolites, an increased risk of hepatotoxicity. Patients on phenytoin therapy should therefore avoid the use of high and/or chronic doses of paracetamol. At the same time, the patients should be monitored for signs of hepatotoxicity.

The dose-dependent potential hepatotoxicity of paracetamol may be increased when coadministering cytochrome P450 system inducers (such as isoniazid, rifampicin, anticonvulsants, barbiturates, zidovudine, anticoagulants, amoxicillin/clavulanic acid and alcohol).

Hepatotoxicity can also be increased by salicylamide, as it prolongs the elimination half-life of paracetamol.

Paracetamol prolongs the elimination half-life of chloramphenicol by 5-fold.

The tendency for neutropenia is increased by the concomitant use of zidovudine and paracetamol.

Probenecid inhibits the conjugation of paracetamol with glucuronic acid, thereby reducing paracetamol clearance by about one-half. When co-administering probenecid, the dose of paracetamol should therefore be reduced.

The concomitant use of paracetamol with oral anticoagulants can lead to an increase in the INR value. More intensive monitoring of the INR value should therefore take place during concomitant use and for one week after discontinuation of paracetamol treatment.

Pregnancy

Animal reproductive toxicity studies have not been conducted with the intravenous form of paracetamol. However, studies on oral administration revealed no malformations or foetotoxic effects.

Clinical experience with the intravenous use of paracetamol is limited. However, epidemiological data on the use of oral therapeutic paracetamol doses show no adverse effects on the course of pregnancy or on the health of the foetus/newborn infant.

Prospective data on overdose in pregnancy revealed no increased risk of malformations. Nevertheless, Paraconica should be used during pregnancy only after careful benefit-risk assessment. The recommended dosage and duration of administration must be strictly observed in this case.

Breast-feeding

In breast-feeding mothers, less than 1% of the administered paracetamol dose is excreted in breast milk. No undesirable effects on breast-fed infants have been reported to date.

No such studies have been performed.

Blood and lymphatic system disorders

Rare: allergy-related thrombocytopenia, haemolysis, leukopenia, pancytopenia, neutropenia, agranulocytosis

Immune system disorders

Very rare: allergic reactions such as angioedema, breathing difficulties, bronchospasm, sweating, nausea, hypotension and even anaphylactic shock

A small proportion (5-10%) of patients with acetylsalicylic acid-induced asthma or other manifestations of so-called acetylsalicylic acid intolerance may also respond in a similar fashion to paracetamol (analgesic asthma).

Vascular disorders

Rare: hypotension

Hepatobiliary disorders

Rare: elevated liver transaminase levels

In the event of an overdose, hepatic necrosis may occur.

Skin and subcutaneous tissue disorders

Uncommon: skin rash (erythema or urticaria)

Rare: exfoliation, toxic epidermal necrolysis, Stevens-Johnson syndrome

Renal and urinary disorders

In the event of an overdose, nephrotoxicity can occur.

General disorders and administration site conditions

Rare: malaise

Post-marketing experience

During the post-marketing observation phase, the following undesirable effects have also been reported (frequency not known):

Blood and lymphatic system disorders: Haemolytic anaemia (especially in patients with G-6-PD deficiency)

Cardiac disorders: Tachycardia

Gastrointestinal disorders: Vomiting, pancreatitis

Hepatobiliary disorders: Cholestasis, jaundice, fulminant hepatitis, hepatic necrosis, hepatic failure, elevated liver enzyme levels

Skin and subcutaneous tissue disorders: Pruritus, flushing

General disorders and administration site conditions: Injection site reaction (erythema, pruritus)

It is recommended not to mix Paraconica with other medicinal products without first checking compatibility.