COMBOGESIC IV

Posology For intravenous administration and short term use only for a maximum of two days. 4). Adults (weighing >50 kg) Administer one vial (100 ml) Combogesic IV as a 15-minute infusion every 6 hours, as necessary. Do not exceed a total daily dose of four vials (400 ml), which equates to 4000 mg (4 g) paracetamol and 1200 mg ibuprofen.

5 ml/kg, as a 15-minute infusion every 6 hours, as necessary. This equates to a maximum single dose of 75 ml (discard remaining medicine in vial), and a total daily dose of 3000 mg (3 g) paracetamol and 900 mg ibuprofen. 3). Special populations Elderly Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used for the shortest possible duration. Treatment should be reviewed at regular intervals and discontinued if no benefit is seen or intolerance occurs.

The patient should be monitored regularly for gastrointestinal bleeding during NSAID therapy. Renal impairment Caution should be taken with ibuprofen dosage in patients with renal impairment. 3). The dosage should be assessed individually.

The initial dose should be reduced in patients with mild to moderate renal impairment. The dose should be kept as low as possible and be used for the shortest possible duration necessary to control the symptoms. 2). Hepatic impairment The use of paracetamol at higher than recommended doses can lead to hepatotoxicity and even hepatic failure and death.

In patients with additional risk factors for hepatotoxicity, like hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of glutathione in the liver), or dehydration, a total daily dose of 3000 mg (3 g) paracetamol should not be exceeded.

3). A patient with symptoms and/or signs suggesting liver dysfunction, or with abnormal liver test values, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with ibuprofen and Combogesic IV should be discontinued.

g. ), Combogesic IV should be discontinued. Method of administration Combogesic IV should be administered as a 15-minute intravenous infusion. 8 mm needle (21 gauge needle) and vertically perforate the stopper at the spot specifically indicated.

6). As for all solutions for infusion presented in glass vials, it should be remembered that close monitoring is needed notably at the end of the infusion, regardless of administration route. This monitoring at the end of the infusion applies particularly for central route infusion, in order to avoid air embolism.

Clinical trials with Combogesic IV and paracetamol 500 mg/ibuprofen 150 mg film- coated tablets have not indicated any other undesirable effects other than those for paracetamol alone or ibuprofen alone. g. development of necrotising fasciitis) coinciding with the use of NSAIDs has been described.

Blood and lymphatic system disorders Uncommon:

Decrease in haemoglobin and haematocrit. g. epistaxis, menorrhagia) have been reported in during therapy with the drug.

Very Rare:

Haematopoietic disorders (agranulocytosis, anaemia, aplastic anaemia, haemolytic anaemia leucopenia, neutropenia, pancytopenia and thrombocytopenia with or without purpura) have been reported following ibuprofen use, but were not necessarily causally related to the drug.

Immune system disorders Very Rare:

Hypersensitivity reactions including skin rash and cross- sensitivity with sympathomimetics have been reported.

Uncommon:

Other allergic reactions have been reported but a causal relationship has not been established: Serum sickness, lupus erythematosus syndrome, Henoch-Schönlein vasculitis, angioedema.

Metabolic and nutrition disorders Very Rare:

In the case of metabolic acidosis, causality is uncertain as more than one drug was ingested. 95 grams of acetylsalicylic acid, and a small amount of a liquid household cleaner. The patient also had a history of seizures which the authors reported may have contributed to an increased lactate level indicative of metabolic acidosis.

Metabolic side effects including metabolic acidosis have been reported following a massive overdose of paracetamol.

Uncommon:

Gynaecomastia, hypoglycaemic reaction.

Not Known:

Hypokalaemia1, High anion gap metabolic acidosis3.

Nervous system disorders Common:

Dizziness, headache, nervousness.

Uncommon:

Depression, insomnia, confusion, emotional lability, somnolence, aseptic meningitis with fever and coma.

Rare:

Paraesthesia, hallucinations, dream abnormalities.

Very Rare:

Paradoxical stimulation, optic neuritis, psychomotor impairment, extrapyramidal effects, tremor and convulsions.

Eye disorders Uncommon:

Amblyopia (blurred and/or diminished vision, scotomata and/or changes in colour vision) have occurred but is usually reversed after cessation of therapy. Any patient with eye complaints should have an ophthalmological examination which includes central vision fields.

Ear and labyrinth disorders Very Rare:

Vertigo.

Common:

Tinnitus (for medicines containing ibuprofen).

Cardiac disorders Common:

Oedema, fluid retention; fluid retention generally responds promptly to discontinuation of the drug.

Very Rare:

Palpitations; tachycardia; arrhythmia and other cardiac dysrhythmias have been reported. 2 Respiratory and thoracic and mediastinal disorders Uncommon: Thickened respiratory tract secretions. In children undergoing tonsillectomy, stridor has been reported.

Hypoxemia has been reported.

Very Rare:

Respiratory reactivity including: asthma, exacerbation of asthma, bronchospasm and dyspnoea.

Gastrointestinal Disorders Common:

Abdominal pain, diarrhoea, dyspepsia, nausea, stomach discomfort and vomiting, flatulence, constipation, slight gastrointestinal blood loss that may cause anaemia in exceptional cases.

Uncommon:

Peptic/gastrointestinal ulcer, perforation or gastrointestinal haemorrhage, with symptoms of melaena haematemesis sometimes fatal, particularly in the elderly. Ulcerative stomatitis and exacerbation of colitis and Crohn's disease have been reported following administration.

Less frequently gastritis has been observed and pancreatitis reported. Acid peptic disease has been reported.

Very rare:

Oesophagitis, formation of intestinal diaphragm-like strictures.

Hepatobiliary disorders Very Rare:

Hepatic damage, especially during long-term treatment, hepatic failure. Abnormal liver function, hepatitis and jaundice. In overdose paracetamol can cause acute hepatic failure, hepatic failure, hepatic necrosis and liver injury.

Skin and subcutaneous tissue disorders Common:

Rash (including maculopapular type), pruritus.

Very Rare:

Alopecia. Hyperhidrosis, purpura and photosensitivity. Exfoliative dermatoses. Bullous reactions including erythema multiforme, Stevens Johnson Syndrome and Toxic Epidermal Necrolysis. Very rare cases of serious skin reactions have been reported.

In exceptional cases, severe skin infections and soft-tissue complications may occur during varicella infection.

Not known:

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalised exanthematous pustulosis (AGEP).

Renal and urinary disorders Uncommon:

Urinary retention Rare: Kidney tissue damage (papillary necrosis), particularly in long-term therapy.

Very Rare:

Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic renal failure. Adverse renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with paracetamol- related hepatotoxicity.

Acute tubular necrosis usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases. A possible increase in the risk of renal cell carcinoma has been associated with chronic paracetamol use as well.

One case-control study of patients with end-stage renal disease suggested that long term consumption of paracetamol may […]

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms. This medicine is for short term use and is not recommended for use beyond 2 days. The use of Combogesic IV with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided.

Do not give anything else containing paracetamol while giving this medicine. 2). Cardiovascular thrombotic events Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

g. 1200 mg/day) is associated with an increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA II- III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.

g. hypertension, hyperlipidaemia, diabetes mellitus, and smoking), particularly if high doses of ibuprofen (2400 mg/day) are required. Hepatic impairment The use of paracetamol at higher than recommended doses can lead to hepatotoxicity and even hepatic failure and death.

Also, patients with impaired liver function or a history of liver disease, and who are on long term ibuprofen therapy or paracetamol treatment, should have hepatic function monitored at regular intervals, as ibuprofen has been reported to have a minor and transient effect on liver enzymes.

Dose reduction is recommended in patients showing signs of worsening hepatic function. 3). Severe hepatic reactions, including jaundice and cases of fatal hepatitis, though rare, have been reported with ibuprofen as with other NSAIDs.

g. ), ibuprofen should be discontinued. Both active drugs have been reported to cause hepatotoxicity and even hepatic failure, especially paracetamol. Renal impairment Paracetamol can be used in patients with chronic renal disease without dosage adjustment.

There is minimal risk of paracetamol toxicity in patients with moderate to severe renal failure. However, for the ibuprofen component of this product, caution should be used when initiating treatment with ibuprofen in patients with dehydration.

The two major metabolites of ibuprofen are excreted mainly in the urine and impairment of renal function may result in their accumulation. The significance of this is unknown. NSAIDs have been reported to cause nephrotoxicity in various forms: interstitial nephritis, nephritic syndrome and renal failure.

Renal impairment from ibuprofen use is usually reversible. In patients with renal, cardiac or hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly, caution is required since the use of NSAIDs may result in deterioration of renal function.

The dose should be kept as low as possible and renal function should be monitored in these patients. 3). Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.

Combination use of ACE inhibitors or angiotensin receptor antagonists, anti- inflammatory drugs, diuretics and thiazide diuretics The use of an ACE inhibiting drug (ACE-inhibitor or angiotensin receptor antagonist), an anti-inflammatory drug (NSAID or COX-2 inhibitor) and thiazide diuretic at the same time increases the risk of renal impairment.

This includes use in fixed-combination products containing more than one class of drug. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination.

The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment. Elderly No reduction in recommended dosage is necessary. However, caution should be taken with regard to the use of ibuprofen as it should not be taken by adults over the age of 65 without consideration of co-morbidities and co-medications because of an increased risk of adverse effects, in particular heart failure, gastrointestinal ulceration and renal impairment.

Haematological effects Blood dyscrasias have been rarely reported. Patients on long-term therapy with ibuprofen should have regular haematological monitoring. Anaphylactoid reactions As standard practice during intravenous infusion, close patient monitoring is recommended, especially at the beginning of the infusion to detect any anaphylactic reaction caused by the active substance or the excipients.

g. anaphylactic shock) are very rarely observed. At the first signs of a hypersensitivity reaction following the administration of Combogesic IV, therapy must be stopped and symptomatic treatment must be established. Medically required measures, in line with the symptoms, must be initiated by specialist personnel.

Coagulation defects Like other NSAIDs, ibuprofen can inhibit platelet aggregation. Ibuprofen has been shown to […]

6); • in patients under the age of 18 years.