Product Data
Properties:
Pharmacokinetics General: Ketolgin® tablets release drug in the stomach whereas the pellets in Ketolgin® S.R. capsules are designed to resist dissolution in the low pH of gastric fluid but release drug at a controlled rate in the higher pH environment of the small intestine. Irrespective of the pattern of release, the systemic availability (Fs) when either oral formulation is compared with IV administration is approximately 90% in humans. For 75 to 200 mg single doses, the area under the curve has been shown to be dose proportional.
Indications And Usage:
Carefully consider the potential benefits and risks of Ketoprofen and other treatment options before deciding to use Ketolgin®. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. Ketolgin® is indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ketolgin® S.R. is not recommended for treatment of acute pain because of its extended-release characteristics. Ketolgin® tablet is indicated for the management of pain and also for treatment of primary dysmenorrhea.
Contraindications:
Ketolgin® is contraindicated in patients who have shown hypersensitivity to ketoprofen. Ketoprofen should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic reactions to ketoprofen have been reported in such patients. Ketoprofen is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. WARNINGS Is not used for children less than 12 years Cardiovascular Risk •NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. • Ketolgin® is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Gastrointestinal Risk • NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal (GI) events. Hypertension NSAIDs, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Ketolgin, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Adverse Reactions:
Minor gastrointestinal side effects predominated; upper gastrointestinal symptoms were more common than lower gastrointestinal symptoms. The incidence of peptic ulceration in patients on NSAIDs is dependent on many risk factors including age, sex, smoking, alcohol use, diet, stress, concomitant drugs such as aspirin and corticosteroids, as well as the dose and duration of treatment with NSAIDs. Gastrointestinal reactions were followed in frequency by central nervous system side effects, such as headache, dizziness, or drowsiness. The incidence of some adverse reactions appears to be dose-related. Rare adverse reactions (incidence less than 1%) were collected from one or more of the following sources: foreign reports to manufacturers and regulatory agencies, publications, U.S. clinical trials, and/or U.S. postmarketing spontaneous reports. Reactions are listed below under body system, then by incidence or number of cases in decreasing incidence. Incidence Greater than 1% (Probable Causal Relationship) Digestive: Dyspepsia (11%):Nausea, abdominal pain, diarrhea, constipation, flatulence, anorexia, vomiting, stomatitis. Nervous System: Headache, dizziness, CNS inhibition (i.e., pooled reports of somnolence, malaise, depression, etc.) or excitation (i.e., insomnia, nervousness, dreams, etc.). Special Senses: Tinnitus, visual disturbance. Skin and Appendages: Rash. Urogenital: Impairment of renal function (edema, increased BUN), signs or symptoms of urinary-tract irritation. Incidence Less than 1% (Probable Causal Relationship) Body as a Whole: Chills, facial edema, infection, pain, allergic reaction, anaphylaxis. Cardiovascular: Hypertension, palpitation, tachycardia, congestive heart failure, peripheral vascular disease, vasodilatation
Dosage & Administration:
Carefully consider the potential benefits and risks of Ketolgin® and other treatment options before deciding to use Ketolgin®. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. After observing the response to initial therapy with Ketolgin, the dose and frequency should be adjusted to suit an individual patient's needs. If minor side effects appear, they may disappear at a lower dose which may stil have an adequate therapeutic effect. If well tolerated but not optimally effective, the dosage may be increased. Individual patients may show a better response to 300 mg of Ketoprofen daily as compared to 200 mg. They did, however, show an increased frequency of upper- and lower-GI distress and headaches. It is of interest that women also had an increased frequency of these adverse effects compared to men. When treating patients with 300 mg/day, the physician should observe suffcient increased clinical benefit to offset potential increased risk. In patients with mildly impaired renal function, the maximum recommended total daily dose of Ketolgin® is 150 mg. In patients with a more severe renal impairment (GFR less than 25 mL/min/1.73 m2 or endstage renal impairment), the maximum total daily dose of Ketolgin should not exceed 100 mg. In elderly patients, renal function may be reduced with apparently normal serum creatinine and/or BUN levels. Therefore, it is recommended that the initial dosage of Ketolgin should be reduced for patients over 75 years of age. It is recommended that for patients with impaired liver function and serum albumin concentration less than 3.5 g/dL, the maximum initial total daily dose of Ketolgin should be 100 mg. All patients with metabolic impairment, particularly those with both hypoalbuminemia and reduced renal fuction, may have increased levels offree (biologically active) ketoprofen and should be closely monitored. The dosage may be increased to the range recommended for the general population, if necessary, only after good individual tolerance has been ascertained. Because hypoalbuminemia and reduced renal function both increase the fraction of free drug (biologically active form), patients who have both conditions may be at greater risk of adverse effects. Therefore, it is recommended that such patients also be started on lower doses of Ketolgin and closely monitored. Rheumatoid Arthritis and Osteoarthritis The recommended starting dose of ketoprofen in otherwise healthy patients is 75 mg three times or 50 mg four times a day, or Ketolgin® SR 200 mg administered once a day. Smaller doses of Ketoprofen should be utilized initially in small individuals or in debilitated or elderly patients. The recommended maximum daily dose of ketoprofen is 300 mg/day. Dosages higher than 300 mg/day are not recommended because they have not been studied. Management of Pain and Dysmenorrhea The usual dose of Ketolgin® recommended for mild-to-moderate pain and dysmenorrhea is 25 to 50 mg every 6 to 8 hours as necessary. A smaller dose should be utilized initially in small individuals, in debilitated or elderly patients, or in patients with renal or liver disease. A larger dose may be tried if the patient's response to a previous dose was less than satisfactory, but doses above 75 mg have not been shown to give added analgesia. Daily doses above 300 mg are not recommended because they have not been adequately studied. Because of its typical nonsteroidal anti-inflammatory drug-side-effect profile, including as its principal adverse effect GI side effects, higher doses of Ketolgin should be used with caution and patients receiving them observed carefully. Ketolgin® SR is not recommended for use in treating acute pain because of its extended-release characteristics.
Drug Interactions:
The following drug interactions were studied with ketoprofen doses of 200 mg/day. The possibility of increased interaction should be kept in mind when Ketolgin doses greater than 50 mg as a single dose or 200 mg of ketoprofen per day are used concomitantly with highly bound drugs. 1. ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors. 2. Antacids: Concomitant administration of magnesium hydroxide and aluminum hydroxide does not interfere with the rate or extent of the absorption of ketoprofen administered. 3. Aspirin: Ketoprofen does not alter aspirin absorption; however, however, as with other NSAIDs, concomitant administration of ketoprofen and aspirin is not generally recommended because of the potential of increased adverse effects. 4. Diuretics: NSAIDs can reduce the natriuetic effect of furosemide and thiazides in some patients. Hydrochlorothiazide, given concomitantly with ketoprofen, produces a reduction in urinary potassium and chloride excretion compared to hydrochlorothiazide alone. Patients taking diuretics are at a greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy. 5. Digoxin: ketoprofen did not alter the serum levels of digoxin. 6. Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. 7. Methotrexate: Ketoprofen, like other NSAIDs, may cause changes in the elimination of methotrexate leading to elevated serum levels of the drug and increased toxicity. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate. 8. Probenecid: Probenecid increases both free and bound ketoprofen by reducing the plasma clearance of ketoprofen to about one-third, as well as decreasing its protein binding. Therefore, the combination of ketoprofen and probenecid is not recommended. 9. Warfarin: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone. In a short-term controlled study in 14 normal volunteers, ketoprofen did not significantly interfere with the effect of warfarin on prothrombin time. Bleeding from a number of sites may be a complication of warfarin treatment and GI bleeding a complication of ketoprofen treatment. Because prostaglandins play an important role in hemostasis and ketoprofen has an effect on platelet function as well, concurrent therapy with ketoprofen and warfarin requires close monitoring of patients on both drugs. Drug/Laboratory Test Interactions: Effect on Blood Coagulation Ketoprofen decreases platelet adhesion and aggregation. Therefore, it can prolong bleeding time by approximately 3 to 4 minutes from baseline values. There is no significant change in platelet count, prothrombin time, partial thromboplastin time, or thrombin time.
How Supplied:
Ketolgin® (ketoprofen) tablets: Strips of 10 tablets (25 mg, 50 mg) in packs of 1, 2 or 3 strips. Ketolgin® (ketoprofen) SR capsules: Strips of 10 capsules (200 mg) in packs of 1 strip Keep tightly closed.
Precautions:
General Ketoprofen cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. If steroid dosage is reduced or eliminated during therapy, it should be reduced slowly and the patients observed closely for any evidence ofadverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis. The pharmacological activity of Ketoprofen in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions. Ketoprofen and other nonsteroidal anti-inflammatory drugs cause nephritis in mice and rats associated with chronic administration. Rare cases of interstitial nephritis or nephrotic syndrome have been reported in humans with ketoprofen since it has been marketed.
Pregnancy & Lactation:
Teratogenic Effects: Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Ketoprofen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided. Labor and Delivery The effects of ketoprofen on labor and delivery in pregnant women are unknown. Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of ductus arteriosus), use of ketoprofen during late pregnancy should be avoided. Nursing Mothers It is not known whether this drug is excreted in human milk. Data on secretion in human milk after ingestion of ketoprofen do not exist. Upon administration to lactating dogs, the milk concentration of ketoprofen was found to be 4 to 5% of the plasma drug level. As with other drugs that are excreted in milk, ketoprofen is not recommended for use in nursing mothers
Overdosage:
Signs and symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Respiratory depression, coma, or convulsions have occurred following large ketoprofen overdoses. Gastrointestinal bleeding, hypotension, hypertension, or acute renal failure may occur, but are rare. Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Gut decontamination may be indicated in patients with symptoms seen within 4 hours (longer for sustained-release products) or following a large overdose (5 to 10 times the usual dose). This should be accomplished via emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) with a saline cathartic or sorbitol added to the first dose. Forced diuresis, alkalinization of the urine, hemodialysis or hemoperfusion would probably not be useful due to ketoprofen's high protein binding.
