Combogesic® IV

COMBOGESIC^® IV is contraindicated in:

• COMBOGESIC IV is contraindicated in patients who are hypersensitive to acetaminophen, ibuprofen or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
• Patients with a history of asthma, urticaria, or allergic-type reactions after taking ASA or other NSAIDs (i.e. complete or partial syndrome of ASA-intolerance – rhinosinusitis, urticaria/ angioedema, nasal polyps, asthma).
• The peri-operative setting of coronary artery bypass graft surgery (CABG).
• Patients with severe uncontrolled heart failure.
• Patients with cerebrovascular bleeding or other bleeding disorders.
• Patients with severe liver impairment or active liver disease.
• Patients with active gastric/duodenal/peptic ulcer, active GI bleeding.
• Patients with inflammatory bowel disease.
• Patients with severe renal impairment (creatinine clearance <30 mL/min or 0.5 mL/sec) or deteriorating renal disease (individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored).
• Patients with systemic lupus erythematosus, as an anaphylaxis-like reaction with fever may occur, particularly when ibuprofen has been administered previously.
• Patients with known hyperkalemia.
• Patients with blood formation disturbances.
• Patients with active alcoholism as chronic excessive alcohol ingestion may predispose patients to hepatotoxicity.
• The third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus and prolonged parturition.
• Women who are breastfeeding, because of the potential for serious adverse reactions in nursing infants.
• Children and adolescents less than 18 years of age.

Dosing Considerations
For intravenous administration and short-term use for up to two days.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
The safety and efficacy of COMBOGESIC IV has been evaluated in treatment of post-operative pain for up to 2 days (8 doses) with additional safety data in a small number of patients treated for up to 5 days (20 doses). Patients who require longer treatment may be dosed to a maximum of 5 days if justified by ongoing benefit-risk assessments.
Lower total daily doses may be used. Clinical pharmacology data using an oral COMBOGESIC formulation show that using half or even quarter of the total daily dose could achieve comparable pain relief.
Prolonged or frequent use is discouraged. It is recommended that a suitable analgesic oral treatment be used as soon as this route of administration is possible.
The maximum daily dose of acetaminophen or ibuprofen includes all routes of administration (intravenous, oral and rectal) and all products containing acetaminophen/ibuprofen (oral solutions/drops, syrup, pills, capsules, suppositories, etc.). In order to avoid the risk of overdose, check that other medicines administered do not contain either ibuprofen, acetaminophen or its prodrug. Adjust dose as required.
Take care when prescribing and administering COMBOGESIC IV to avoid dosing errors due to confusion between milligram (mg) and millilitre (mL), which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume. Ensure the dose is measured and administered accurately.

Recommended Dose and Dosage Adjustment
Adults (weighing > 50 kg)
Administer one vial (100 ml) COMBOGESIC IV as 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) acetaminophen and 1200 mg (1.2 g) ibuprofen.
Adults (weighing ≤ 50 kg)
Adults weighing 50 kg or under should be dosed according to their weight, at a dosage of 1.5 ml/kg (15 mg/kg acetaminophen + 4.5 mg/kg ibuprofen), 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) acetaminophen and 900 mg ibuprofen.
Pediatrics (< 18 years of age):
Safety and effectiveness of COMBOGESIC IV in pediatric and adolescent patients have not been established; therefore, Health Canada has not authorized an indication for pediatric use.
Geriatrics (≥ 65 years of age):
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. The use of a lower dose for a shorter duration should be considered.
Hepatic Impairment:
COMBOGESIC IV should not be used in patients with severe hepatic impairment. In patients with impaired hepatic function or additional risk factors for hepatoxicity, longer dosing intervals and/or reduced total daily dose may be warranted.
Renal Impairment:
COMBOGESIC IV should not be used in patients with severe renal impairment (creatinine clearance _ 30 mL/min). Caution should be taken in patients with renal insufficiency, dehydrated patients, patients on salt restricted diets, those with congestive heart failure, cirrhosis, liver dysfunction, taking angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, cyclosporin, diuretics, and those who are elderly. In these patients, longer dosing intervals and/or reduced total daily dose may be warranted.
Reconstitution
COMBOGESIC IV is a single-use solution for infusion, which does not require re-constitution. Any unused portion of the solution must be discarded.
Administration

• COMBOGESIC IV is administered as a 15-minute infusion every 6 hours, as necessary.
• DO NOT USE if particulate matter, cloudiness or change in color of the solution is observed.
• In the absence of compatibility studies, COMBOGESIC IV should not be mixed with diluents or with other medicines.
• The solution should be used in one patient on one occasion only. It contains no antimicrobial preservative. Any unused solution should be discarded.
• If less than a full vial is required for a single dose, the correct amount should be infused and the remaining solution discarded.

Missed Dose
If a dose is missed, it should be administered as soon as remembered. If it is almost time for the next dose, the missed dose should not be administered, and the next scheduled dose should be given. Do not try to make up for the missed dose by taking a double dose next time.

COMBOGESIC IV is a combination product. The clinical presentation of overdose may include the signs and symptoms of acetaminophen toxicity, ibuprofen toxicity, or both.
Symptoms
Acetaminophen
In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia also occur. Plasma acetaminophen levels > 300 mcg/mL at 4 hours after oral ingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are < 150 mcg/mL or < 37.5 mcg/mL at 12 hours after ingestion.
Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.
Ibuprofen
Symptoms include nausea, abdominal pain and vomiting, dizziness, convulsion and rarely, loss of consciousness. Clinical features of overdose with ibuprofen which may result are depression of the central nervous system and the respiratory system.
Treatment
Acetaminophen
Acetylcysteine (chemical name N-acetyl-L-cysteine or NAC) is the antidote for acetaminophen. If an acetaminophen overdose is evident, administer the entire course of NAC treatment. If an acetaminophen overdose is suspected, obtain a serum acetaminophen assay at approximately 4 hours following acetaminophen administration. Obtain liver function studies initially and repeat at 24-hour intervals. As a guide to the treatment of overdose, the acetaminophen level can be plotted against time on a nomogram (Rumack-Matthew) which can be used to predict acetaminophen toxicity, and therefore the need for NAC treatment. The lower toxic line on the nomogram is equivalent to 150 mcg/mL at 4 hours and 37.5 mcg/mL at 12 hours. If serum level is above the lower line, administer the entire course of NAC treatment. Withhold NAC therapy if the acetaminophen level is below the lower line.
Ibuprofen
Treatment should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable.

For management of a suspected drug overdose, contact your
regional poison control centre or Health Canada’s toll-free number,
1-844 POISON-X (1-844-764-7669)

Description
COMBOGESIC IV is a sterile clear, colourless, non pyrogenic, isotonic solution free from visible particles. Each 100 mL vial contains acetaminophen 1000 mg and ibuprofen (as ibuprofen sodium) 300 mg intended for intravenous infusion. It has a pH of 6.3-7.3 and an osmolality of 285-320 mOsmol/kg.
COMBOGESIC IV is available in cartons of 10 vials of 100 mL.
The stopper is not made with natural rubber latex.

Store at controlled room temperature, 15°C to 25°C.
Do not refrigerate or freeze. Store in the original carton in order to protect from light.
Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit. If visibly opaque particles, discoloration or other foreign particulates are observed, the
solution should not be used.
In the absence of compatibility studies, this medicine should not be mixed with diluents and with other medicines.
If less than a full vial is required for a single dose, the correct amount should be infused and the remaining solution discarded.
The solution should be used in one patient on one occasion only. It contains no antimicrobial preservative. Any unused solution should be discarded.