Ketoprofen

Pronunciation: (KEY-toe-PRO-fen)
Class: NSAID

Trade Names

Ketoprofen
- Capsules 50 mg
- Capsules 75 mg
- Capsules, extended-release 100 mg
- Capsules, extended-release 150 mg
- Capsules, extended-release 200 mg

APO-Keto (Canada)
APO-Keto-E (Canada)
APO-Keto SR (Canada)

Pharmacology

Decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis.

Pharmacokinetics

Absorption

Immediate-release form is released in the stomach; T _max is 0.5 to 2 h. Sustained-release form is released in the small intestine; T _max is 6 to 7 h. Bioavailability is approximately 90%. Food does not change AUC, but the rate of absorption for either form is slowed.

Distribution

More than 99% protein bound, mainly to albumin. Vd is 0.1 L/kg.

Metabolism

Metabolic pathway is glucuronide conjugation. The metabolite is acylglucuronide, which can be converted back to the parent drug. There are no known active metabolites.

Elimination

Oral immediate release t _½ is 2 to 4 h. Sustained-release t _½ is approximately 5.4 h. Cl is approximately 0.08 L/kg/h.

Onset

Within 30 min.

Duration

Persisted for up to 6 h.

Special Populations

Elderly

Plasma and renal Cl are reduced and the unbound fraction increases.

Hypoalbuminemia and Renal Function Impairment

Patients with these conditions may be at greater risk of adverse reactions due to increased fractions of free drug. Give these patients lower doses of the drug and monitor them closely.

Indications and Usage

Treatment of rheumatoid arthritis and osteoarthritis.

Immediate-release form only

Treatment of mild to moderate pain and primary dysmenorrhea.

OTC Use

Temporary relief of minor aches and pains associated with common cold, headache, toothache, muscular aches, backache, minor arthritis pain, menstrual cramps, and reduction of fever.

Unlabeled Uses

Treatment of juvenile rheumatoid arthritis, sunburn, migraine prophylaxis.

Contraindications

Patients in whom aspirin, iodides, or any NSAID have caused allergic-type reactions.

Dosage and Administration

Rheumatoid Arthritis or Osteoarthritis
Adults Immediate-release

PO 75 mg 3 times daily or 50 mg 4 times daily; do not exceed 300 mg/day.

Maintenance dose

Reduce initial dosage to 75 to 150 mg/day in elderly or disabled patients or those with renal function impairment.

Sustained-release

PO 200 mg once daily can be used in patients already stabilized on that dose.

Mild to Moderate Pain, Primary Dysmenorrhea
Adults

PO 25 to 50 mg every 6 to 8 h as needed; do not exceed 300 mg/day.

OTC Use
Adults

PO 12.5 mg with a full glass of liquid every 4 to 6 h. If pain or fever persists after 1 h, follow with 12.5 mg. Do not exceed 25 mg in a 4- to 6-h period or 75 mg in a 24-h period. Use the smallest effective dose.

Children

PO Do not give to children younger than 16 yr of age unless directed by a health care provider.

Mild To Severe Renal Function Impairment

Maximum recommended total daily dose is 150 mg. In patients with more severe renal function impairment (GFR less than 25 mL/min or end-stage renal impairment), the max total daily dose should not exceed 100 mg.

Hepatic Function Impairment

For patients with impaired hepatic function and serum albumin concentration less than 3.5 g/dL, the max initial total daily dose should be 100 mg.

Storage/Stability

Store at room temperature in tightly closed, light-resistant container.

Drug Interactions

Anticoagulants

Increased risk of gastric erosion and bleeding.

Aspirin

Additive GI toxicity.

Cyclosporine

Nephrotoxicity of both agents may be increased.

Lithium

Serum lithium levels may be increased.

Methotrexate

Increased methotrexate levels.

Laboratory Test Interactions

May prolong bleeding time.

Adverse Reactions

Cardiovascular

Peripheral edema; fluid retention; CHF.

CNS

Headache; dizziness; lightheadedness; drowsiness; vertigo.

Dermatologic

Rash; pruritus.

EENT

Visual disturbances; stomatitis.

GI

Peptic ulcer; GI bleeding; dyspepsia; nausea; diarrhea; constipation; abdominal pain; flatulence; anorexia; vomiting.

Genitourinary

Menorrhagia.

Respiratory

Bronchospasm; laryngeal edema; rhinitis; dyspnea.

Precautions

Warnings

NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with length of therapy. Patients with CV disease or risk factors for CV disease may be at greater risk. NSAIDs cause an increased risk of serious GI adverse reactions, including bleeding, inflammation, perforation of the stomach or intestines, and ulceration, which can be fatal. These events can occur any time during use and without warning symptoms. Elderly patients are at greater risk of serious GI events.

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Increased risk of adverse reactions.

Hypersensitivity

Hypersensitivity may occur; use caution in aspirin-sensitive individuals because of possible cross-sensitivity.

Renal Function

Lower doses may be necessary.

Hepatic Function

Avoid sustained-release product.

GI

Bleeding, ulceration or perforation can occur at any time, with or without warning symptoms.

GU

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia and renal papillary necrosis may occur.

Overdosage

Symptoms

Drowsiness, dizziness, confusion, disorientation, lethargy, numbness, vomiting, gastric irritation, nausea, abdominal pain, headache, tinnitus, convulsions, acute renal failure.

Patient Information

Advise patient to take medication with food, milk, or antacids. Capsule should be swallowed whole, not chewed or crushed.
Warn patient not to take aspirin or other NSAIDs.
Caution patient to report changes in stool (eg, color, consistency, frequency), fluid retention and shortness of breath.
Instruct patient to report the following symptoms to health care provider: skin rash, itching, visual disturbances, weight gain, edema, black stools, or persistent headache.
Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
Caution patient to avoid exposure to sunlight and other sources of ultraviolet light and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.
Instruct patient not to ingest alcohol or take OTC medications without notifying health care provider.