Actamol 120mg/5ml Solution

ACTAMOL is indicated for the symptomatic relief of mild to moderate pain and fever.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE.
Paediatric population
3 months to 1 year: 2,5 - 5 mL (60 u2013 120 mg).
1 to 5 years: 5 u2013 10 mL (120 u2013 240 mg).
6 to 12 years: 10 u2013 20 mL (240 u2013 480 mg).
May be given three to four times daily but with an interval of four hours between each dose.
DO NOT USE CONTINUOUSLY FOR LONGER THAN 10 (TEN) DAYS WITHOUT CONSULTING YOUR DOCTOR.
Method of administration
ACTAMOL is for oral administration.

• Hypersensitivity to the paracetamol or to any of the excipients listed in section 6.1.
• Sever liver function impairment.

• Dosages in excess of those recommended may cause severe liver damage.
• Consult your doctor if no relief is obtained with the recommended dosage or if pain or fever persists or gets worse at the recommended dosage, if new symptoms occur or if redness and swelling is present, as these could be signs of a more serious condition.
• Do not use continuously for longer than ten days without consulting your doctor.
• ACTAMOL should be given with care to patients with impaired kidney or liver function.
• Patients suffering from hepatitis or alcoholism, or recovering from any form of liver disease, should not take excessive quantities of ACTAMOL. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.
• Use ACTAMOL with caution in renal disease, alcohol dependence, chronic malnutrition or dehydration.
• Caution is advised if paracetamol, as in ACTAMOL, 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.
• This product contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or Poison Centre must be contacted immediately.
• Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis (AGEP), eosinophilia and systemic (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines. If a patient develops SCAR, treatment with ACTAMOL must immediately be discontinued and appropriate treatment instituted.
• Paediatric population: Infants under three months: Not recommended.

• The hepatotoxicity of paracetamol, as in ACTAMOL, particularly after overdosage, may be increased by medicines which induce liver microsomal enzymes such as carbamazepine, barbiturates (e.g., phenobarbital), fosphenytoin, phenytoin, primidone, tricyclic antidepressants, and alcohol.
• Chronic alcohol intake can increase the hepatotoxicity of paracetamol overdose and may have contributed to the acute pancreatitis reported in one patient who had taken an overdose of paracetamol. Acute alcohol intake may diminish an individual's ability to metabolise large doses of paracetamol, the plasma half-life of which can be prolonged.
• Hepatotoxic medicines - increased risk of hepatotoxicity of paracetamol, as in ACTAMOL.
• Enzyme inducing medicines - increased risk of hepatotoxicity of paracetamol, as in ACTAMOL. Possible decrease in therapeutic effects of ACTAMOL.
• Metoclopramide - the speed of absorption of paracetamol, as in ACTAMOL, may be increased by metoclopramide.
• Cholestyramine u2013 the absorption of paracetamol, as in ACTAMOL, is reduced if given within one hour of cholestyramine.
• Prolonged concurrent use of paracetamol, as in ACTAMOL, with salicylates increases the risk of adverse renal effects.
• Warfarin and anticoagulants - concurrent, chronic, high-dose administration of paracetamol, as in ACTAMOL, may increase the anticoagulant effect.
• Paracetamol, as in ACTAMOL, is recommended as the general analgesic and antipyretic of choice in patients on oral anticoagulant therapy. However, caution is needed since, although it has no effect on the gastric mucosa or on platelet function, some studies (with warfarin, anisindione, dicoumarol, or phenprocoumon) and isolated reports have found an increased risk of bleeding in patients taking regular doses of paracetamol while on an oral anticoagulant. An increase in INR has also been reported in controlled studies of the use of paracetamol in patients stabilised on warfarin. Increased monitoring of anticoagulant therapy may be appropriate for those also taking paracetamol, as in ACTAMOL, regularly.
• Antiepileptics: The plasma-paracetamol concentrations considered an indication for antidote treatment, should be halved in patients receiving enzyme inducing medicines such as carbamazepine, phenobarbital, phenytoin, or primidone.
• Probenecid: Pre-treatment with probenecid can decrease paracetamol clearance and increase its plasma half-life. Although urinary excretion of the sulphate and glucuronide conjugates of paracetamol are reduced, that of paracetamol is unchanged.
• Antibacterials: The plasma-paracetamol concentrations considered an indication for antidote treatment should be halved in patients receiving enzyme inducing medicines such as rifampicin. Severe hepatotoxicity at therapeutic doses or moderate overdoses of paracetamol has been reported in patients receiving isoniazid, alone or with other medicines for tuberculosis.
• Antivirals: Severe hepatotoxicity has occurred after use of paracetamol in a patient taking zidovudine and co-trimoxazole. However, neither short-term nor long-term studies (the latter also in an individual patient) have shown any alteration of zidovudine elimination in patients taking zidovudine and paracetamol.
• Paracetamol, as in ACTAMOL, has also been found to enhance the antiviral effect of interferon alfa.
• The use of medicines that induce hepatic microsomal enzymes such as anticonvulsants and oral contraceptives may increase the extent of metabolism of paracetamol, as in ACTAMOL, resulting in reduced plasma concentrations of paracetamol and a faster elimination rate.
• Caution should be taken when paracetamol, as in ACTAMOL, 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).

The safety and efficacy of ACTAMOL in pregnancy and lactation have not been established.
Fertility
No data available.

ACTAMOL has no or negligible influence on the ability to drive and use machines.

a) Tabulated list of adverse reactions
The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with paracetamol.
System Organ Class
Frequency
Frequent
Less Frequent
Not known
Blood and lymphatic system disorders
Leucopenia, pancytopenia, neutropenia, anaemia
Blood disorder (including thrombocytopenia and agranulocytosis)
1
Immune system disorders
Anaphylactic reaction, hypersensitivity
Metabolism and nutrition disorders
Pyroglutamic aciduria (5-oxoprolinuria) and high-anion gap metabolic acidosis
Ear and labyrinth disorders
Hearing loss
Cardiac disorders
Possible increase in the risk of hypertension
Gastrointestinal disorders
Pancreatitis
Nausea and vomiting
Hepatobiliary disorders
Hepatitis
Liver injury
2, 6
Skin and subcutaneous tissue disorders
5
Rash, dermatitis, skin rashes, and other allergic reactions such as Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Acute Generalised Exanthematous Pustulosis (AGEP). The rash is usually erythematous or urticarial but sometimes more serious and accompanied by fever and mucosal lesions. More mild rashes and other hypersensitivity reactions also occur occasionally.
Risk of Fixed drug eruptions (FDE)*, Risk of Drug-induced hypersensitivity syndrome (DIHS)*, pruritic, urticaria
Renal and urinary disorders
Renal colic, renal failure and sterile pyuria, nephropathy toxic
Renal papillary necrosis
3
General disorders and administration site conditions
Hypersensitivity reactions characterised by urticaria, dyspnoea, and hypotension.
Investigations
Transaminases increased
4
1 Reported following paracetamol use, but not necessarily causally related to paracetamol.
2 Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year.
3 Reported after prolonged administration.
4 Low level transaminase elevations may occur in some patients taking therapeutic doses of paracetamol; these elevations are not accompanied with liver failure and usually resolve with continued therapy or discontinuation of paracetamol.
5 Very rare cases of serious skin reactions have been reported.
6 Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year and liver damage has been reported after daily ingestion of excessive amounts for shorter periods. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol nor was the control of the disease improved after paracetamol withdrawal.

Prompt treatment is essential. In the event of an overdosage, consult a doctor immediately, or take the person directly to a hospital. A delay in starting treatment may mean that antidote is given too late to be effective. Evidence of liver damage is often delayed until after the time for effective treatment has lapsed.
Susceptibility to paracetamol toxicity is increased in patients who have taken repeated high doses (greater than 5 u2013 10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of medicines that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine.
Symptoms
Symptoms of paracetamol overdosage in the first 24 hours include pallor, nausea, vomiting, anorexia, and possibly abdominal pain (see section 4.8). Mild symptoms during the first two days of acute poisoning do not reflect the potential seriousness of the overdosage.
Liver damage may become apparent 12 to 48 hours, or later after ingestion, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of prothrombin time. Liver damage may lead to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Abnormalities of glucose metabolism and metabolic acidosis may occur. Cardiac arrhythmias have been reported.
Treatment for paracetamol overdosage:
N-acetylcysteine should be administered to all cases of suspected overdosage as soon as possible, preferably within 8 hours of overdosage, although treatment up to 36 hours after ingestion may still be of benefit, especially if more than 150 mg/kg of paracetamol was taken. An initial dose of 150 mg/kg N-acetylcysteine in 200 mL dextrose injection given intravenously over 15 minutes, followed by an infusion of 50 mg/kg in 500 mL dextrose injection over the next 4 hours, and then 100 mg/kg in 1 000 mL dextrose injection over the next 16 hours. The volume of intravenous fluids should be modified for children. Although the oral formulation is not the treatment of choice, 140 mg/kg dissolved in water may be administered initially, followed by 70 mg/kg every 4 hours for 17 doses. A plasma paracetamol level should be determined 4 hours after ingestion in all cases of suspected overdosage. Levels done before 4 hours may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine, can be identified according to their 4-hour plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the nomogram below. The nomogram should be used only in relation to a single acute ingestion. Those whose plasma paracetamol levels are above the u201cnormal treatment lineu201d, should continue N-acetylcysteine treatment with 100 mg/kg IV over 16 hours repeatedly until recovery. Patients with increased susceptibility to liver damage as identified above, should continue treatment if concentrations are above the u201chigh risk treatment lineu201d. Prothrombin index correlates best with survival.
Monitor all patients with significant ingestion for at least 96 hours.