Rebofen

BRAND NAME:

Rebofen

INTERNATIONAL NONPROPRIETARY NAME:

Dexketoprofen

DOSAGE FORM:

Solution for intravenous and intramuscular administration/concentrate for solution for infusion preparation.

Description: clear, colorless solution.

COMPOSITION:

1 ampoule contains:

Active substance: dexketoprofen (in a form of dexketoprofen trometamol) – 50.0 mg;

Excipients: sodium chloride, sodium hydroxide, ethanol 96%, water for injection.

PHARMACOTHERAPEUTIC GROUP:

Non-steroid anti-inflammatory drugs. Propionic acid derivative.

ATC code: M01AE17.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics

Dexketoprofen trometamol is a painkiller, an anti-inflammatory, antipyretic drug from the group of non-steroidal anti-inflammatory drugs (NSAIDs).

Dexketoprofen trometamol possesses the pronounced analgesic activity. The analgesic effect starts quickly with its maximum in the first 45 minutes. Usually analgesic effect duration after dexketoprofen 50 mg injection is 8 hours.

Combination therapy of dexketoprofen trometamol with opioid analgesics significantly (up to 30-45%) reduces the need for opioids.

Pharmacokinetics

After dexketoprofen trometamol intramuscular injection maximum concentration (C_max) is obtained in about 20 minutes (10-45 minutes). Both with a single intramuscular injection and single intravenous injection of 25-50 mg, the area under the concentration-time curve (AUC) is proportional to the dose. C_max and AUC after the repeated intramuscular or intravenous injection do not differ from the similar parameters determined after a single administration demonstrating no drug cumulation.

Dexketoprofen trometamol at a high degree binds to plasma proteins (99%) with an average distribution volume of 0.25 l/kg. The drug’s distribution half-life is 0.35 hours.

The drug half-life is 1-2.7 hours. Dexketoprofen metabolism is mainly occurs by conjugation with glucuronic acid, followed by excretion through the kidneys.

In elderly patients there is an increase in half-life (both: after a single and repeated intramuscular or intravenous injection) to an average of 48% and a decrease in the drug total clearance observed.

INDICATIONS FOR USE:

-       symptomatic treatment of acute medium to high intensity pain in cases where oral drugs administration is impractical – for example, in postoperative pain, renal colic and low back pain (lumbago).

CONTRAINDICATIONS:

hypersensitivity to drug components or any NSAIDs;

- when substances with a similar action (for example, acetylsalicylic acid and other NSAIDs) provoke asthma attacks aggravation, bronchospasm, acute rhinitis or cause nasal polyps formation, urticaria or angioedema;

- ulcer/bleeding (two or more cases confirmed) or chronic dyspepsia;

- gastrointestinal bleeding, other site with active bleeding or excessive bleeding;

- gastrointestinal bleeding or a history of perforation associated with previous NSAID therapy;

- Crohn disease or ulcerative colitis;

- bronchial asthma in history;

- severe heart failure;

- moderate to severe renal function impairment (CC <50 ml/min);

- severe liver function impairment (10-15 points on Child-Pugh score);

- hemorrhagic diathesis and other blood coagulation disorders;

- the third trimester of pregnancy and breastfeeding.

Due to ethanol content Rebofen is contraindicated for neuraxial (intrathecal or epidural) administration.

SIDE EFFECT:

Gastrointestinal tract disorders: nausea, vomiting, abdominal pain, dyspepsia, diarrhea, constipation, vomiting with blood, dry mouth.

Skin and subcutaneous adipose tissue disorders: dermatitis, rash, hyperhidrosis, itching, urticaria, acne.

General and local site disorders: pain at injection site, injection site reactions (including inflammation, hematoma, bleeding).

DOSAGE AND ADMINISTRATION:

Rebofen is used for intravenous and intramuscular administration.

Adult patients: the recommended dose is 50 mg with 8-12 hours interval.

If necessary, the dose is repeated in 6 hours.

Total daily dose should not exceed 150 mg.

In case of postoperative pain of moderate to severe intensity Rebofen can be used at the same recommended doses indicated in a leaflet in combination with opioid analgesics.

Elderly patients: dose adjustment is usually not required; however due to physiological decline in kidney function a lower dose is recommended: the total daily dose is 50 mg for mild renal impairment.

Patients with liver function impairment: in patients with mild to moderate liver impairment the total daily dose should be reduced to 50 mg and liver function should be monitored. Rebofen is contraindicated in patients with severe liver dysfunction.

Patients with renal function impairment: in patients with renal function impairment the total daily dose should be reduced to 50 mg and liver function should be monitored. Rebofen is contraindicated in patients with moderate to severe renal failure.

Children and adolescents: Rebofen safety and efficacy has not been studied. Rebofen should not be used in this group of patients.

Mode of application:

Intramuscular injection: the content of one Rebofen ampoule should be injected slowly and deep into muscle. The solution should be injected immediately avoiding daylight exposure.

Intravenous administration:

- intravenous infusion: the diluted solution is injected slowly in 10-30 minutes; the solution should not be exposed to daylight;

- intravenous injection (bolus): the content of one ampoule should be injected in at least 15 seconds; the solution should be injected immediately avoiding daylight exposure.

Injection Preparation

For use in the form of intravenous infusion the contents of one ampoule (2 ml) should be diluted into 30-100 ml of saline solution, glucose solution or Ringer-lactate solution. The solution is prepared under aseptic conditions, avoiding daylight exposure. The prepared solution should be transparent.

Rebofen diluted in 100 ml saline or glucose solution can be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.

Rebofen is designed for a single use only. Before injection it is necessary to make sure that the solution is clear and colorless; solution contained solid particles should be discarded.

Solution prepared in accordance with recommendations retains its chemical properties for 24 hours period at a temperature 25°C and should be protected from daylight.

PRECAUTIONARY MEASURES:

Rebofen should be used with caution in patients with a history of allergy.

Combination of Rebofen with NSAIDs including cyclooxygenase-2 inhibitors should be avoided.

NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn disease) due to the risk of these diseases exacerbation.

Before the treatment with dexketoprofen trometamol similar to other NSAIDs, in case of esophagitis, gastritis and/or peptic ulcer in history, it is necessary to be sure that these diseases are in remission. In patients with a history of gastrointestinal pathology and gastrointestinal diseases it is necessary to monitor the digestive tract condition, especially for gastrointestinal bleeding.

Rebofen should be used with caution in patients on other drugs therapy as thy may increase the risk of ulceration or bleeding: oral corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors, antiplatelet agents (e.g. aspirin).

When using NSAIDs, body fluid retention and edema are possible, therefore, patients with mild or moderate severity of arterial hypertension and/or congestive heart failure should be closely monitored by a doctor.

Similar to other NSAIDs dexketoprofen trometamol may increase the level of plasma urea nitrogen and creatinine, temporary and slight increase in some liver function parameters, as well as significant increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level. In case of certain increase in value of these indicators Rebofen therapy should be discontinued.

Careful consideration is advisable for this drug prescription to patients with impaired liver and/or kidney function, as well as to patients with arterial hypertension and/or heart failure, as NSAIDs may affect the renal function, cause body fluid retention and edema.

Like other NSAIDs, dexketoprofen trometamol may reduce female fertility so it is not recommended for use in women planning to conceive.

Each Rebofen ampoule contains 200 mg of ethanol. Ethanol should be carefully considered when prescribing the drug in pregnancy and breastfeeding, in children and high-risk patient group, for example, with liver diseases and epilepsy.

EFFECT ON ABILITY TO DRIVE AND OPERATE MACHINERY:

During the therapy with Rebofen dizziness and drowsiness may occur, therefore a weak or moderate effect on ability to drive and operate machinery can’t be excluded.

PREGNANCY AND LACTATION:

Rebofen is contraindicated in the third trimester of pregnancy and a lactation period. Dexketoprofen trometamol administration in the first and second trimester of pregnancy is acceptable only if proved necessary. When dexketoprofen trometamol prescribed to women planning to conceive or in the first and second trimester of pregnancy, the lowest possible dose should be chosen with minimal treatment duration.

PEDIATRIC USE:

Rebofen is not recommended for use in patients under 18 years due to insufficient data on the drug safety and efficacy. Dizziness, drowsiness and vision abnormalities may occur during the therapy.

INTERACTION WITH OTHER DRUGS

The following interactions are common for all NSAIDs.

Not recommended for use with:

- other NSAIDs, including salicylates at high doses (≥3 g/day); combined use of several NSAIDs, the risk of ulcer and gastrointestinal bleeding increases;

- NSAIDs enhance the effect of anticoagulants;

- heparin: increased risk of bleeding;

- corticosteroids: increased risk of ulceration and gastrointestinal bleeding;

- lithium: NSAIDs increase lithium plasma concentration which may lead to intoxication,

- methotrexate at high doses (≥15 mg per week): enhances the harmful effect on the blood system;

- hydantoin and sulfonamides derivatives: toxic properties of these substances may increase.

It is recommended to use with caution with:

- diuretics, ACE inhibitors, aminoglycoside group antibacterial drugs and angiotensin II receptor antagonists: dexketoprofen weakens their effect;

- zidovudine: increased risk of toxic effects on red blood cells,

- sulfonylurea: NSAIDs are able to enhance the hypoglycemic effect of these drugs.

Rebofen should not be mixed with of dopamine, promethazine, pentazocine, pethidine and hydroxyzine solutions in small volume objects (for example, in a syringe) due to precipitation. The prepared solution for infusion should not be mixed with promethazine and pentazocine.

STORAGE CONDITIONS:

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

Keep out of reach of children!

SHELF LIFE:

Shelf life is 3 years. It should not be used after the expiration date indicated on the label.

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,