Instructions for use of the drug for medical use
• Save this instruction, it may be required again. • If you have any questions, consult your doctor.
Trade name of the drug:
International non-proprietary name:
solution for intravenous and intramuscular administration.
1 ampoule contains: active ingredient: ketoprofen – 100 mg; excipients: propylene glycol – 800 mg; ethanol – 200 mg; benzyl alcohol – 40 mg; water for injection – up to 2 ml.
Transparent, colorless or slightly yellowish solution.
Nonsteroidal anti-inflammatory drug (NSAIDs).
ATX code: MO1AE03 – ketoprofen.
Pharmacodynamics Ketoprofen is a non-steroidal anti-inflammatory drug. Ketoprofen has anti-inflammatory, analgesic and antipyretic effects. Ketoprofen blocks the action of the enzyme cyclooxygenase 1 and 2 (COX1 and COX2) and, in part, lipoxygenase, which leads to the suppression of the synthesis of prostaglandins (including in the central nervous system, most likely in the hypothalamus). In vitro and in vivo stabilizes liposomal membranes; at high concentrations in vitro, ketoprofen inhibits the synthesis of bradykinin and leukotrienes. Ketoprofen does not adversely affect the state of the articular cartilage. Pharmacokinetics. Absorption When intravenous ketoprofen is administered, the average plasma concentration after 5 min from the beginning of the infusion and up to 4 min after its termination is 26.4 ± 5.4 μg / ml. Bioavailability is 90%. With a single intramuscular injection of 100 mg of ketoprofen, the drug is detected in the blood plasma 15 minutes after the start of the infusion, and the peak concentration (1.3 μg / ml) is reached after 2 hours. The bioavailability of the drug increases linearly with increasing dose. The distribution of Ketoprofen is 99% bound to plasma proteins, mainly from the albumin fraction. The volume of distribution in the tissues is 0.1-0.2 l / kg. Ketoprofen enters the synovial fluid, and with intravenous administration of 100 mg after 3 h, its concentration reaches 1.5 μg / ml, which is 50% of the concentration in blood plasma (about 3 μg / ml). After 9 hours, the concentration in the synovial fluid is 0.8 μg / ml, and in the blood plasma — 0.3 μg / ml, which means that ketoprofen penetrates the synovial fluid more slowly and is withdrawn more slowly from it. Stationary plasma concentrations of ketoprofen are determined even 24 hours after its administration. After a single intramuscular injection of 100 mg of ketoprofen, the drug is detected in the cerebrospinal fluid, like blood serum, after 15 minutes. Metabolism Ketoprofen is subjected to intensive metabolism with the participation of microsomal liver enzymes. It binds to glucuronic acid and is excreted from the body as a glucuronide. There are no active metabolites of ketoprofen. Withdrawal The half-life (T1 / 2) of ketoprofen is 2 hours. Up to 80% of ketoprofen is excreted by the kidneys within 24 hours, mostly (>90%) in the form of ketoprofen glucuronide, and about 10% through the intestines. In patients with renal insufficiency, ketoprofen is eliminated more slowly, its T1 / 2 increases by 1 hour. In patients with hepatic insufficiency, T1 / 2 increases, therefore accumulation of ketoprofen in tissues is possible. In elderly patients, ketoprofen metabolism and elimination proceed more slowly, which is of clinical importance only for patients with severe renal failure.
Indications for use
Symptomatic therapy of pain, in
• hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other nonsteroidal anti-inflammatory drugs (NSAIDs); • complete or incomplete combination of asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history); • peptic ulcer or duodenal ulcer in the acute stage; • ulcerative colitis, Crohn’s disease; • hemophilia and other bleeding disorders; • children’s age (up to 15 years); • severe liver failure; • severe renal failure: severe renal insufficiency (creatinine clearance (CC) less than 30 ml / min), confirmed hyperkalemia, progressive kidney disease; • decompensated heart failure; • the postoperative period after coronary artery bypass surgery; • gastrointestinal, cerebrovascular and other bleeding (or suspected bleeding); • chronic dyspepsia; • III trimester of pregnancy; • breastfeeding period.
• history of peptic ulcer disease, Helicobacter pylori infection; • history of bronchial asthma; • clinically significant cardiovascular, cerebrovascular diseases and peripheral artery diseases; • dyslipidemia, liver failure, hyperbilirubinemia, alcoholic cirrhosis of the liver; • chronic renal failure (CC 30-60 ml / min); • chronic heart failure, arterial hypertension, blood diseases; • dehydration, diabetes; • smoking; • elderly age; • long-term use of NSAIDs, simultaneous administration of anticoagulants (in
Use during pregnancy and during breastfeeding
Inhibition of prostaglandin synthesis may have an undesirable effect on the course of pregnancy and / or on embryonic development. The data obtained during epidemiological studies with the use of inhibitors of prostaglandin synthesis in early pregnancy confirm the increased risk of spontaneous abortion and the formation of heart defects (up to 1.5%) and congenital defects of the anterior abdominal wall. The risk increases with increasing dose and duration of treatment. It is possible to prescribe the drug to pregnant women in the I and II trimesters of pregnancy only when the advantages for the mother justify the possible risk to the fetus. In this case, it is necessary to apply the minimum effective dose of the shortest possible course. Ketoprofen is contraindicated in pregnant women during the third trimester of pregnancy due to the possible development of weak uterus labor, increased bleeding time, antiplatelet effect (even when taken in small doses), and effects on the fetus (cardiopulmonary toxicity,
Dosage and administration
Intravenous, intramuscularly. To reduce the frequency of adverse reactions, it is recommended to use the minimum effective dose of the drug. The maximum daily dose is 200 mg. It is necessary to carefully evaluate the ratio of the expected benefits and risks before starting ketoprofen at a dose of 200 mg / day. Intramuscular administration: 100 mg (1 ampoule) 1-2 times a day. Intravenous infusion of ketoprofen should be carried out only in a hospital. The duration of the infusion should be from 0.5 to 1 hour. The intravenous route of administration should be used within no more than 48 hours. Short intravenous infusion: from 100 (up to 200) mg (1-2 ampoules) of ketoprofen diluted in 100 ml of 0.9% solution sodium chloride, injected within 0.5-1 hours. Continuous intravenous infusion: from 100 (up to 200) mg (1-2 ampoules) of ketoprofen, diluted in 500 ml of infusion solution (0.9% sodium chloride solution, lactate-containing Ringer’s solution , 5% dextrose solution), is introduced within 8 hours; possible re-introduction after 8 hours. The maximum daily dose is 200 mg. Ketoprofen can be combined with centrally acting analgesics; it can be mixed with opioids (for example, morphine) in one vial, pharmaceutically incompatible with tramadol solution due to precipitation. Parenteral administration of the drug Ketonal ® can be combined with the use of oral forms (tablets, capsules) or rectal suppositories.
According to the World Health Organization (WHO), adverse effects are classified according to their frequency of development as follows: very often (≥1 / 10), often (≥1 / 100,