Caldolor™ (ibuprofen) Injection

CALDOLOR (ibuprofen) Injection, for intravenous use

DESCRIPTION

Caldolor contains the active ingredient ibuprofen, which is (±)-2-(p-isobutylphenyl) propionic acid. Ibuprofen is a white powder with a melting point of 74-77°C. It has a molecular weight of 206.28. It is very slightly soluble in water (<1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone.

Each 1 mL of solution contains 100 mg of ibuprofen in Water for Injection, USP. The product also contains 78 mg/mL arginine at a molar ratio of 0.92:1 arginine:ibuprofen. The solution pH is about 7.4.

Caldolor is sterile and is intended for intravenous administration only.

Mechanism of Action
Ibuprofen's mechanism of action, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition. Caldolor possesses anti-inflammatory, analgesic, and antipyretic activity.

Pharmacokinetics
Ibuprofen is a racemic mixture of [-]R- and [+]S-isomers. In vivo and in vitro studies indicate that the [+]S-isomer is responsible for clinical activity. The [-]R-form, while thought to be pharmacologically inactive, is slowly and incompletely (~60%) interconverted into the active [+]S species in adults. The [-]R-isomer serves as a circulating reservoir to maintain levels of active drug.

Analgesia (Pain)
Caldolor is indicated in adults for the management of mild to moderate pain and the management of moderate to severe pain as an adjunct to opioid analgesics.

Antipyretic (Fever)
Caldolor is indicated for the reduction of fever in adults.

-- Known hypersensitivity to ibuprofen or other NSAIDs
--Asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
--Use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery

--Serious and potentially fatal CV thrombotic events: Use lowest effective dose of Caldolor for shortest possible duration.

--Serious and potentially fatal GI reactions: Use lowest effective dose of Caldolor for shortest possible duration. Use with caution in patients with prior history of ulcer disease or GI bleeding.

--Hepatic effects: Range from transaminase elevations to liver failure. Discontinue Caldolor immediately if abnormal liver tests persist or worsen.

--Hypertension: Can occur with NSAID treatment. Monitor blood pressure closely during treatment with Caldolor.

--Congestive heart failure and edema: Fluid retention and edema can occur with NSAID treatment. Use Caldolor with caution in patients with fluid retention or heart failure.

--Renal effects: Long-term administration of NSAIDs can result in renal papillary necrosis and other renal injury. Use Caldolor with caution in patients at risk (e.g., the elderly, those with renal impairment, heart failure, liver impairment, and those taking diuretics or ACE inhibitors).

-- Anaphylactoid reactions: May occur in patients with the aspirin triad or in patients without prior exposure to Caldolor. Discontinue Caldolor immediately if an anaphylactoid reaction occurs.

--Serious skin reactions: Include exfoliative dermatitis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis, which can be fatal. Discontinue Caldolor if rash or other signs of local skin reaction occur.

To report SUSPECTED ADVERSE REACTIONS, contact Cumberland Pharmaceuticals Inc. at 1-877-484-2700 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS
--ACE inhibitors: NSAIDs may diminish the antihypertensive effect of ACE inhibitors.
--Aspirin: Concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential for increased adverse effects.

USE IN SPECIFIC POPULATIONS
--Pregnancy: Avoid use after 30 weeks gestation because premature closure of the ductus arteriosus in the fetus may occur. (8.1)
--Nursing Mothers: Use with caution as it is not known if ibuprofen is excreted in human milk. (8.3)
--Pediatric Use: Safety and effectiveness not established in patients less than 17 years of age. (8.4)

To reduce the risk of renal adverse reactions, patients must be well hydrated prior to administration of Caldolor.

Analgesia (Pain)
Administer 400 mg to 800 mg intravenously every 6 hours as necessary. Infusion time must be no less than 30 minutes.

Antipyretic (Fever)
Administer 400 mg intravenously, followed by 400 mg every 4 to 6 hours or 100-200 mg every 4 hours as necessary. Infusion time must be no less than 30 minutes.

Preparation and Administration
Caldolor must be diluted prior to intravenous infusion. Dilute to a final concentration of 4 mg/mL or less. Appropriate diluents include 0.9% Sodium Chloride Injection USP (normal saline), 5% Dextrose Injection USP (D5W), or Lactated Ringers Solution.

-- 800 mg dose: Dilute 8 mL of Caldolor in no less than 200 mL of diluent.
-- 400 mg dose: Dilute 4 mL of Caldolor in no less than 100 mL of diluent.

Visually inspect parenteral drug products 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.

Diluted solutions are stable for up to 24 hours at ambient temperature (approximately 20 to 25° C) and room lighting.

Infusion time must be no less than 30 minutes.

Vials: 400 mg/4 mL or 800 mg/8 mL

400 mg/4 mL
(100 mg/mL)

NDC 66220-247-04
400 mg/4 mL

For
Intravenous
Use

CUMBERLAND®
PHARMACEUTICALS