Ketoprofen suppositories 100mg, No. 10

• Symptomatic therapy of pain syndrome, incl. with inflammatory processes of various origins: rheumatoid arthritis;

• seronegative arthritis: ankylosing spondylitis (ankylosing spondylitis), psoriatic arthritis, reactive arthritis (Reiter's syndrome);

• gout, pseudogout;

• degenerative diseases of the musculoskeletal system, incl. osteoarthritis; weak, moderate and severe pain syndrome with headache, migraine, tenditis, bursitis, myalgia, neuralgia, radiculitis;

• post-traumatic and postoperative pain syndrome, incl. accompanied by inflammation and fever;

• pain syndrome in cancer;

• algodismenorrhea.

Rectally - 100 mg 1-2 times / day.

Rectal suppositories are white or almost white, torpedo-shaped.

1 supp. ketoprofen 100 mg

Excipients: solid fat (Witepsol N-15) - 1850 mg, glyceryl caprilocaprate (miglyol 812) - 200 mg.

• for rectal use - inflammatory diseases of the rectum and / or bleeding from the rectum.

pharmachologic effect

NSAIDs. It has anti-inflammatory, analgesic and antipyretic effects. Ketoprofen blocks the action of the enzyme COX-1 and COX-2 and, in part, lipoxygenase, which leads to suppression of the synthesis of prostaglandins (including in the central nervous system, most likely in the hypothalamus).

Stabilizes in vitro and in vivo liposomal membranes, at high concentrations in vitro inhibits the synthesis of bradykinin and leukotrienes. Ketoprofen does not adversely affect the condition of the articular cartilage.

Pharmacokinetics

When taken orally, ketoprofen is rapidly absorbed from the gastrointestinal tract. Bioavailability is 90%. At a dose of 100 mg in a dosage form with a normal release, Cmax in blood plasma is 10.4 ?g / ml and is reached after 1 hour and 22 minutes.

With intravenous administration of ketoprofen, the average plasma concentration after 5 minutes from the start of the infusion and up to 4 minutes after its termination is 26.4 ± 5.4 ?g / ml. Bioavailability is 90%.

With a single intramuscular injection at a dose of 100 mg, ketoprofen is detected in the blood plasma 15 minutes after the start of the injection, and Cmax (1.3 ?g / ml) is achieved after 2 hours. Bioavailability increases linearly with increasing dose.

Plasma clearance of ketoprofen is approximately 0.08 l / kg / h.

The binding of ketoprofen to blood plasma proteins is 99%, mainly to the albumin fraction. Vd is 0.1 l / kg. Ketoprofen penetrates into the synovial fluid and, after oral administration, reaches a concentration there equal to 30% of the concentration in blood plasma. With the on / in the introduction of 100 mg after 3 hours, its concentration reaches 1.5 ?g / ml, which is 50% of the concentration in the blood plasma (about 3 ?g / ml). After 9 hours, the concentration in the synovial fluid is 0.8 ?g / ml, and in the blood plasma - 0.3 ?g / ml, which means that ketoprofen penetrates into the synovial fluid more slowly and is excreted from it more slowly. Css of ketoprofen in blood plasma are determined even 24 hours after its administration. After a single intramuscular injection of 100 mg of ketoprofen, the drug is found in the cerebrospinal fluid, as in the blood serum, after 15 minutes.

Ketoprofen is extensively metabolized by liver microsomal enzymes. T1 / 2 is less than 2 hours. Ketoprofen binds to glucuronic acid and is excreted from the body as glucuronide. There are no active metabolites of ketoprofen. Up to 80% of ketoprofen is excreted by the kidneys within 24 hours, mainly in the form of ketoprofen glucuronide.

Side effect

From the hematopoietic system: rarely - hemorrhagic anemia, hemolytic anemia, leukopenia; frequency unknown - agranulocytosis, thrombocytopenia, bone marrow dysfunction.

From the immune system: the frequency is unknown - anaphylactic reactions (including anaphylactic shock).

From the nervous system: often - insomnia, depression, asthenia; infrequently - headache, dizziness, drowsiness; rarely - paresthesia, confusion or loss of consciousness, peripheral polyneuropathy; the frequency is unknown - convulsions, impaired taste, emotional lability.

From the senses: rarely - blurred vision, tinnitus, conjunctivitis, dryness of the mucous membrane of the eye, pain in the eyes, hearing loss; frequency unknown - optic neuritis.

From the side of the cardiovascular system: infrequently - tachycardia; the frequency is unknown - heart failure, increased blood pressure, vasodilation.

From the respiratory system: rarely - exacerbation of bronchial asthma, nosebleeds, laryngeal edema; frequency unknown - bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.

From the digestive system: often - nausea, vomiting, dyspepsia, abdominal pain, NSAID gastropathy; infrequently - constipation, diarrhea, bloating, gastritis; rarely - peptic ulcer, stomatitis; very rarely - exacerbation of ulcerative colitis or Crohn's disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of the gastrointestinal tract; frequency unknown - gastrointestinal discomfort, stomach pain.

From the liver and biliary tract: rarely - hepatitis, increased activity of liver enzymes in the blood, increased concentration of bilirubin in the blood.

From the urinary system: rarely - cystitis, urethritis, hematuria; very rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values ??of indicators of renal function.

On the part of the skin and subcutaneous tissues: infrequently - skin rash, itching; frequency unknown - photosensitivity, alopecia, urticaria, exacerbation of chronic urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, purpura.

Others: infrequently - peripheral edema, fatigue; rarely - hemoptysis, menometrorrhagia, shortness of breath, thirst, muscle twitching.

Local reactions: with rectal application - burning sensation, loose stools, irritation of the rectal mucosa.

Application during pregnancy and lactation

Contraindicated for use in the third trimester of pregnancy. Application in the I and II trimesters of pregnancy is possible only when the expected benefit of therapy for the mother outweighs the existing risk to the fetus. In this case, ketoprofen should be used in the minimum effective dose for the shortest possible course.

Use during breastfeeding is contraindicated.

The use of ketoprofen can affect female fertility, therefore, the use is not recommended for patients with infertility (including those undergoing examination).

Application for violations of liver function

Use is contraindicated in severe hepatic insufficiency.

The drug should be prescribed with caution in liver failure, hyperbilirubinemia, alcoholic cirrhosis of the liver.

Application for impaired renal function

Contraindicated in severe renal failure (CC less than 30 ml / min), confirmed hyperkalemia, progressive kidney disease.

It should be used with caution in chronic renal failure (CC 30-60 ml / min).

Application in children

Contraindicated in children and adolescents under 15 years of age.

Use in elderly patients

Use with caution in elderly patients.

special instructions

With long-term use of NSAIDs, it is necessary to periodically evaluate the clinical blood test, as well as monitor the function of the kidneys and liver, especially in elderly patients (over 65 years old), conduct a fecal occult blood test. Care must be taken and blood pressure should be monitored more often when using ketoprofen to treat patients with arterial hypertension, cardiovascular diseases that lead to fluid retention in the body.

In the event of violations on the part of the organ of vision, treatment should be stopped immediately.

Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. In case of detection of signs of infection or deterioration of health while using the drug, the patient should immediately consult a doctor.

If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer), in the case of long-term therapy and the use of ketoprofen in high doses, the patient should be under close medical supervision.

Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when using ketoprofen in patients with heart or renal failure, as well as in the treatment of elderly patients taking diuretics and patients who, for any reason, have a decrease in BCC (for example , after surgery).

Influence on the ability to drive vehicles and mechanisms

During the treatment period, drowsiness, dizziness or other discomfort from the nervous system, including visual impairment, may occur. When using ketoprofen, patients should be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interactions

The combined use of ketoprofen with other NSAIDs (including selective COX-2 inhibitors and high-dose salicylates) is not recommended due to an increased risk of gastrointestinal bleeding and ulceration of the gastrointestinal mucosa.

Simultaneous use with anticoagulants (heparin, warfarin), antiplatelet agents (ticlopidine, clopidogrel) increases the risk of bleeding. If the use of such a combination is unavoidable, the patient's condition should be carefully monitored.

With simultaneous use with lithium preparations, it is possible to increase the concentration of lithium in the blood plasma up to toxic values. It is necessary to carefully monitor the concentration of lithium in the blood plasma and promptly adjust the dose of lithium preparations during and after the use of NSAIDs.

Ketoprofen increases the hematological toxicity of methotrexate, especially when used in high doses (more than 15 mg / week). The time interval between stopping or starting therapy with ketoprofen and taking methotrexate should be at least 12 hours.

On the background of ketoprofen therapy, patients taking diuretics, especially with the development of dehydration, have a higher risk of developing renal failure due to a decrease in renal blood flow caused by inhibition of prostaglandin synthesis. Before starting the use of ketoprofen in such patients, rehydration measures should be taken. After starting treatment, it is necessary to monitor kidney function.

The combined use of ketoprofen with ACE inhibitors and angiotensin II receptor antagonists (ARA II) in patients with impaired renal function (with dehydration, in elderly patients) can lead to an aggravation of renal impairment, including the development of acute renal failure.

During the first weeks of the simultaneous use of ketoprofen and methotrexate at a dose not exceeding 15 mg / week, a blood test should be monitored weekly. In elderly patients or if any signs of impaired renal function occur, the study should be performed more often.

Ketoprofen can weaken the hypotensive effect of antihypertensive drugs (beta-blockers, ACE inhibitors, diuretics).

The simultaneous use of ketoprofen with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding.

Concomitant use with thrombolytics increases the risk of bleeding.

The simultaneous use of ketoprofen with potassium salts, potassium-sparing diuretics, ACE inhibitors, ARA II, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus and trimethoprim increases the risk of hyperkalemia.

With simultaneous use with cyclosporine, tacrolimus, the risk of developing an additive nephrotoxic effect is possible, especially in elderly patients.

The simultaneous use of several antiplatelet drugs (tirofiban, eptifibatide, abciximab, iloprost) increases the risk of bleeding.

Ketoprofen increases the plasma concentration of cardiac glycosides, slow calcium channel blockers, cyclosporine, methotrexate and digoxin.

The combined use of ketoprofen with corticosteroids, ethanol increases the risk of developing adverse events from the gastrointestinal tract.

Ketoprofen may increase the effect of oral hypoglycemic and some anticonvulsants (phenytoin).

Concomitant use with probenecid significantly reduces the plasma clearance of ketoprofen.

NSAIDs can reduce the effectiveness of mifepristone. NSAIDs should be started no earlier than 8-12 days after discontinuation of mifepristone.

Ketoprofen is pharmaceutically incompatible with tramadol solution due to precipitation.