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

Use of the product Paraconica 1 g I.V. is restricted to patients weighing more than 33 kg.

Administration

Paraconica is a ready-to-use solution. It is administered as a 15-minute I.V. infusion. Efficacy and safety of slower or faster administration have not been investigated. In children, the volume of solution for infusion is 1.5 mL/kg per administration. As with all solutions for infusion in glass vials, it must be remembered that the infusion must be carefully monitored, regardless of the route of infusion, particularly towards the end of the infusion. Monitoring at the end of the infusion is particularly important in central venous infusions, in order to avoid an air embolism.

Posology

Adults >50 kg

1 g paracetamol per administration, up to 4 times daily. The minimum interval between two administrations must be 4 hours and the maximum daily dose must not exceed 4 g.

Adults and children weighing more than 33 kg and less than 50 kg

15 mg paracetamol per kg body weight per administration, up to 4 times daily. The minimum interval between two administrations must be 4 hours and the maximum daily dose must not exceed 60 mg/kg (no more than 3 g).

Special dosage instructions

In severe renal insufficiency (creatinine clearance 10-30 mL/min), the minimum interval between two administrations should be extended to 6 hours (see “Kinetics in special patient groups”).

In patients with chronic or active liver disease, especially with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione) or dehydration, the daily dose must not exceed 3 g paracetamol.

Maximum duration of therapy

Duration of treatment in adults and children: max. 2 days.

There is a risk of intoxication especially in elderly subjects, in young children, in patients with liver disease, in cases of chronic alcoholism, in chronically malnourished patients and in patients receiving enzyme inducers. In these cases, intoxication can be fatal.

An overdose, 7.5 g paracetamol or more in a single dose in adults or 140 mg/kg body weight in a single dose in children, causes cytolytic hepatitis, which may induce complete and irreversible hepatic necrosis. This can lead to acute or fulminant liver failure, hepatic insufficiency, metabolic acidosis and encephalopathy, which can result in coma and death. Simultaneously, elevated plasma levels of liver transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with a decreased prothrombin level 12-48 hours after administration. Clinical symptoms of liver damage normally occur for the first time after 2 days and reach their peak after 4-6 days.

During the first 24 hours, there are no specific early symptoms. Anorexia, nausea, vomiting and malaise, pallor and abdominal pain may occur and persist. Hepatic damage can occur 24 hours to 5 days after administration.

Occurrence of a massive overdose, the main risk of paracetamol (especially with tablets), seems unlikely with Paraconica (I.V. administration in hospital).

Emergency measures

In all cases, regardless of how large the suspected amount of administered paracetamol is, N-acetylcysteine (NAC) must be administered I.V. or orally as soon as possible (preferably within 10 hours post overdose). NAC may afford some protection even after 10 hours; however, prolonged treatment is required in these cases. The paracetamol concentration in plasma must be determined as soon as possible (no sooner than 3 hours after the overdose). However, the results do not have to be available before starting treatment with NAC.

Plasma concentrations of >200 µg/mL after 4 hours, of >100 µg/mL after 8 hours, of >50 µg/mL after 12 hours and of >30 µg/mL after 15 hours can cause liver damage and even hepatic coma with a fatal outcome. Hepatotoxicity is directly dependent on the plasma concentration.

Liver tests must be performed from the outset and repeated every 24 hours. An increase in liver enzymes (ALT and AST) is usually observed, which normalises after one to two weeks. Supplemental symptomatic treatment (after N-acetylcysteine I.V. or orally) should be determined on the basis of blood paracetamol levels and the length of time since the Paraconica overdose.

Note the expiry date. The solution for infusion contains no preservatives and should, for microbiological reasons, be used immediately after opening. Any remaining solution must be discarded.

Stability studies show that Paraconica can be diluted up to 10-fold with 0.9% sodium chloride solution or 5% glucose solution. After such dilution, the solution should be inspected visually and must not be used if cloudiness, particles or precipitates are visible. Furthermore, the diluted solution should likewise be used immediately, but no more than one hour (including the infusion time) after dilution.

Store at room temperature (15-25°C). Must not be stored in the refrigerator. Do not freeze.

Protect from light.

Paraconica 1 g I.V. solution for infusion: 10 × 100 mL vials (hospital pack).

Notes on handling

Prior to use, Paraconica should be checked for particles and discolouration. The solution should be clear and colourless.

Impact of diagnostic methods

Paracetamol can cause false results when determining blood uric acid via the phosphotungstic acid reduction method and when measuring blood sugar via the glucose oxidase method.