Keto-Reb

Keto-Reb

INTERNATIONAL NONPROPRIETARY NAME

Ketoprofen

DRUG FORM: solution for intramuscular injections

Description: clear colourless solution

COMPOSITION:

1 ampule contains:

Active ingredients: Ketoprofen – 100 mg

PHARMACOTHERAPEUTIC CATEGORY:

Non-steroidal anti-inflammatory drugs. Propionic acid derivatives

ATC code: М01АE03.

PHARMACOLOGICAL PROPERTIES

PHARMACODYNAMICS:

Mechanism of action

Ketoprofen inhibits prostaglandins and leukotrienes synthesis and block the enzyme cyclooxygenase (COX-1 and COX-2) which catalyzes prostaglandins synthesis in arachidonic acid metabolism.

In some female patients ketoprofen reduces the symptoms of primary dysmenorrhea by inhibiting prostaglandins synthesis and/or effectiveness.

Pharmacokinetics

Ketoprofen average plasma concentration determined in 5 minutes after 100 mg intravenous infusion started and 4 minutes after the injection completion is 26.4 ± 5.4 μg/ml. Bioavailability of ketoprofen is 90%. In most patients with intramuscular administration ketoprofen was detected in blood in 15 minutes and the peak plasma concentration was obtained in 2 hours after its administration. Being injected ketoprofen bioavailability increases proportionally with the drug dose increase. 99% of ketoprofen binds to plasma proteins, mainly with albumin. Ketoprofen slowly penetrates into synovial fluid and excretes slowly, within the continuous decrease in plasma concentration. Ketoprofen equilibrium concentrations are established in 24 hours of its administration. In elderly patients equilibrium concentration was reached in 8.7 hours.

Ketoprofen was detected in synovial fluid in 15 minutes of intramuscular injection with its peak concentration reached in 2 hours. Ketoprofen is intensively metabolized with hepatic microsomal enzymes. It binds to glucuronic acid and in that form excreted from the body. Due to its fast metabolism biological half-life is only two hours. Since ketoprofen is metabolized mainly in the liver, liver failure can cause half-life prolongation; in these circumstances, possible drug cumulation should be considered. Up to 80% of ketoprofen is excreted into the urine, mainly (over 90%) in a form of ketoprofen glucuronide and about 10% is excreted with the feces. In patients with renal failure ketoprofen is excreted more slowly with its biological half-life increased by an hour.

Pharmacokinetics in special patients group.

In patients with hepatic insufficiency ketoprofen may accumulate in tissues. Its metabolism and elimination is slowed down in elderly patients. It is clinically significant only in patients with impaired renal function.

INDICATIONS FOR USE:

Symptomatic treatment in episodes of acute pain observed during skeletomuscular system inflammatory processes.

CONTRAINDICATIONS:

-          Increased hypersensitivity to ketoprofen or any of drug excipients;

-          the history of bronchial asthma, urticaria, rhinitis, bronchospasm or allergic reactions after the use of ketoprofen or similar active substances such as other NSAIDs or salicylates (for example, acetylsalicylic acid);

-          severe heart failure;

-          pain treatment in perioperative period during coronary artery bypass grafting (CABG);

-          active phase of peptic ulcer as well as gastrointestinal bleeding, ulcer or perforation in history;

-          gastrointestinal, cerebrovascular or other active bleeding;

-          chronic dyspepsia in anamnesis;

-          severe renal impairment;

-          severe liver function impairment;

-          predisposition to bleeding;

-          last trimester of pregnancy;

-          children;

-          blood coagulation disorders or the current treatment with anticoagulants.

SIDE EFFECTS:

Nervous system disorders: headache, dizziness, drowsiness;

Gastrointestinal tract disorders: nausea, vomiting, constipation, diarrhea, gastritis.

Skin and subcutaneous tissues disorders: rash, itching.

General disorders and administration site conditions: edema

DOSAGE AND ADMINISTRATION:

For Intramuscular injections only!

Maximum daily dose is 200 mg. It is recommended not to inject for more than 3 days. Once satisfactory response is observed ketoprofen should be prescribed in a form for oral administration.

Instructions for use

One ampoule (100 mg) once or twice a day intramuscularly

If necessary the drug can be combined with ketoprofen in oral, rectal or transdermal route of administration.

Undesirable effects can be minimized by taking the lowest effective drug dose for the shortest time needed for symptoms elimination.

Maximum daily dose of ketoprofen (regardless of dosage form) is 200 mg. Before initial treatment with 200 mg of ketoprofen per day benefits and possible risks should be carefully estimated. Higher doses are not recommended.

Elderly patients: in elder patients adverse reactions can often lead to serious consequences. Treatment of the elderly is recommended with the smallest effective doses available.

Patients with impaired renal function: in patients with mild renal impairment (creatinine clearance below 0.33 ml/s (20 ml/min)) the dose of ketoprofen should be reduced. Ketoprofen is contraindicated in patients with severe renal impairment.

Patients with impaired liver function: in patients with chronic liver disease with a reduced serum albumin level the dose of ketoprofen should be reduced. Ketoprofen is contraindicated in patients with severe liver function abnormality.

Children: ketoprofen safety and effectiveness in children has not been studied.

PRECAUTIONS:

For Intramuscular injections only!

Simultaneous drug administration with other NSAIDs, including selective cyclooxygenase-2 inhibitors should be avoided.

Undesirable effects can be minimized by taking the lowest effective drug dose for the shortest time needed for symptoms elimination.

Gastrointestinal tract bleeding, ulcers and perforations

According to epidemiological data ketoprofen may be associated with a high risk of severe gastrointestinal toxicity, characteristic for some other NSAIDs, especially taken at high doses.

If gastrointestinal bleeding or ulcers occur in patients treated with ketoprofen, the drug therapy should be discontinued.

Cardiovascular and cerebrovascular effects

Patients with a history of arterial hypertension and/or congestive heart failure of mild to moderate severity require appropriate monitoring and consultation as since fluid retention and edema have been reported with NSAIDs administration.

In patients with heart failure, cirrhosis and nephrotic syndrome, as well as in patients on diuretics therapy and in patients with chronic renal failure, especially in elderly the use of ketoprofen can cause renal blood flow decrease due to prostaglandin synthesis inhibition and lead to renal function decompensation.

Ketoprofen should be canceled in case of skin rash, mucous membranes lesions or other signs of hypersensitivity appeared. With prolonged treatment it is necessary to control the whole blood cells count, as well as liver and kidneys function.

As all NSAIDs, ketoprofen due to its anti-inflammatory, analgesic or antipyretic effect can mask the signs of infectious diseases development, e.g. fever.

Prior to extensive surgical interventions the drug therapy should be discontinued.

Hyperkalemia in case of diabetes mellitus or concomitant therapy with potassium-sparing drugs

In these circumstances potassium plasma concentration should be checked regularly. For severe pain relief ketoprofen can be used in combination with morphine derivatives.

EFFECT ON ABILITY TO DRIVE AND OPERATE MACHINERY:

Patients should be warned that the drug may cause drowsiness, dizziness or convulsions and advise not to drive or operate machinery in these symptoms appearance. Patients should be warned about the possible occurrence of visual abnormalities. In this case it is prohibited to drive and operate machinery.

PREGNANCY AND LACTATION:

Ketoprofen should not be prescribed in the first and second trimesters of pregnancy unless it is absolutely necessary. If ketoprofen is prescribed to a woman trying to conceive or in the first or second trimester of pregnancy the dose should be as low as possible and the treatment duration should be as short as possible.

Ketoprofen administration is contraindicated in the third trimester of pregnancy.

Data on drug penetration into breast milk are not available; ketoprofen is not recommended for therapy in nursing women.

PEDIATRIC USE:

Keto-Reb safety and efficacy in children has not been established.

INTERACTION WITH OTHER DRUGS:

Not recommended combinations

Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates: increased risk of gastrointestinal ulcers and bleeding.

Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors (e.g. ticlopidine, clopidogrel): increased risk of bleeding.

If necessary, combined administration requires close medical supervision.

Methotrexate at doses higher than 15 mg/week: increased risk of methotrexate haematotoxicity, especially when used at high doses (> 15 mg/week).

At least 12 hours should be maintained between the final or initial stages of ketoprofen and methotrexate therapy.

STORAGE CONDITIONS:

Store in a place protected from sun at temperature not above 25 °C.

Keep out of the reach of children!

SHELF LIFE:

Shelf life is 3 years. Do not use after an expiration date indicated on the package.

PRESCRIPTION STATUS

By prescription

Manufacturer Information

Foreign production and trade unitary enterprise “Reb-Pharma”, 223216, Republic of Belarus, Minsk region, Chervensky district, Smilovichi, Sadovaya st., 1, tel./fax: (+375) 17 240 26 35,

e-mail: rebpharma@rebpharma.by, http://www.rebpharma.by