SERTOFEN

 

TRADE NAME

Sertofen

 

INTERNATIONAL NONPROPRIETARY NAME

Dexketoprofen

 

CHEMICAL NAME

2- amino-2-(hydroxymethyl)propan-1,3-diol; 2-(3-benzoylphenyl)propionic acid

 

PHARMACEUTICAL FORM

Solution for injections/concentrate for preparation of solution for infusions.

Description: clear colorless solution.

 

COMPOSITION

1 ampoule of the medicine contains

Active substance: dexketoprofen (as dexketoprofen trometamol) 50 mg.

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

 

АТС CODE      М01АЕ17

 

PHARMACOTHERAPEUTIC GROUP

Nonsteroidal antiinflammatory drugs (NSAIDs). Propionic acid derivatives.

 

PHARMACOLOGIC PROPERTIES

PHARMACODYNAMICS

Sertofen is a nonsteroidal antiinflammatory drug (NSAID), a propionic acid derivative. It exerts analgesic, antiinflammatory, and antipyretic actions. The mechanism of action is associated with inhibition of the activity of cyclooxygenase-1 and cyclooxygenase-2 and with a decrease in the biosynthesis of prostaglandins that play a key role in the pathogenesis of inflammation, pain and fever.

The analgesic effect of the drug occurs within 30 minutes after parenteral administration. The duration of analgesic effect following injection of 50 mg is 4-8 hours.

In a combined therapy with opioid analgesics, dexketoprofen trometamol significantly (up to 30-45%) reduces the need for opioids.

pharmacokinetics

Absorption

Following intramuscular injection of dexketoprofen trometamol, peak serum concentration is achieved after an average 20 minutes (10-45 minutes). After a single injection in a dose of 25-50 mg, AUC is dose proportional following both intramuscular and intravenous administration. The relevant pharmacokinetic parameters are similar after a single and repeated intramuscular or intravenous injection, indicating that no drug accumulation occurs.

Distribution

Dexketoprofen trometamol is characterized by a high plasma protein binding (99%). Mean value of V_d is below 0.25 L/kg.

Elimination

The main elimination route for dexketoprofen is its conjugation with glucuronic acid followed by renal excretion. The elimination half-life of dexketoprofen trometamol is about 1-2.7 hours.

Pharmakokinetics in special populations

In elderly subjects, there is an increase in the duration of elimination half-life (both after single and repeated intramuscular or intravenous injection) up to an average of 48%, and a decrease in total body clearance was observed.

 

therapeutic indicationS

- relief of pain syndrome of different genesis (including postoperative pains, pain from bone metastases, posttraumatic pains, renal colic pain, algodismenorrhea, ischialgia, radiculitis, neuralgic pains, toothache);

- symptomatic treatment of acute and chronic inflammatory, inflammatory-degenerative and metabolic diseases of the musculoskeletal system (including rheumatoid arthritis, spondylarthritis, arthrosis, osteochondrosis).

 

POSOLOGY AND ADMINISTRATION

Sertofen is indicated for intramuscular and intravenous injection.

Adults

The recommended dose is 50 mg dexketoprofen every 8-12 hours. If necessary, the administration can be repeated every 6 hours. The total daily dose should not exceed 150 mg dexketoprofen.

The drug is intended for short-term (not more than 2 days) administration in acute pain syndrome period. Subsequently it is possible to switch the patient to an oral analgesic treatment.

Elderly

No dose adjustment is generally required in elderly patients. However because of the physiological decline in renal function a lower dose is recommended: usual daily dose in elderly patients with mild renal function impairment should not exceed 50 mg a day.

Hepatic dysfunction

The total daily dose should be reduced to 50 mg in patients with mild to moderate compromised liver function (Child-Pugh score 5 - 9), and hepatic function should be closely monitored. Sertofen is contraindicated for patients with severe hepatic impairment.

Renal dysfunction

Total daily dose should not exceed 50 mg in patients with moderate renal impairment (creatinine clearance 50 – 80 ml/min). The drug should not be used in patients with severe renal dysfunction (creatinine clearance <50 ml/min).

Method of administration of solution for injections/concentrate for preparation of solution for infusions

Sertofen may be mixed in small volumes (e.g., in a syringe) with injectable solutions of heparin, lidocaine, morphine and theophylline.

Intramuscular injection

The content of one ampoule (2 mL) should be injected slowly deep into the muscle.

Intravenous infusion

The content of one ampoule (2 mL) is dissolved in 30-100 mL saline solution, glucose solution or Ringer's solution (lactate). The solution should be diluted aseptically and protected from natural daylight. The prepared solution (should be clear) is injected as a slow intravenous infusion for 10-30 minutes.

The solution of Sertofen diluted in 100 mL saline or glucose solution may be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.

The drug is intended for a single use only and any unused solution should be discarded. Prior to administration, the solution should be inspected visually to make sure it is clear and colorless. The solution containing particulate matters should not be used.

Intravenous injection (bolus injection)

If necessary, the content of one ampoule (2 mL) is injected intravenously over no less than 15 seconds.

 

CONTRAINDICATIONS

- hypersensitivity to dexketoprofen or other NSAIDs, or to any of the excipients of the drug;

- history of attacks of asthma, bronchospasm, acute rhinitis, urticaria or angioneurotic oedema that were caused by previous use of substances with a similar mechanism of action (e.g. acetylsalicylic acid and other NSAIDs);

- patients with active peptic ulcer or history of recurrent episodes of peptic ulcer (two or more episodes);

- gastrointestinal bleeding (including those related to previous NSAIDs therapy), other active bleeding;

- Crohn's disease, nonspecific ulcerative colitis;

- severely impaired hepatic function (Child-Pugh score 10 - 15);

- severe renal dysfunction (creatinine clearance <50 ml/min);

- bronchial asthma (including in past medical history);

- severe heart failure;

- hemorrhagic diathesis or other coagulopathies;

- the third trimester of pregnancy and lactation period;

- pediatric use.

The drug is contraindicated for epidural, subthecal or intrathecal injection due to its ethanol content.

 

SIDE EFFECTS

Hematopoietic system disorders: rare - anemia.

Central nervous system disorders: uncommon - headache, dizziness, somnolence; rare - paraesthesia.

Disorders of sensory organs: uncommon - blurred vision; rare - tinnitus.

Cardiac disorders: uncommon - arterial hypotension, flushing, skin hyperemia; rare - extrasystole, tachycardia, arterial hypertension, peripheral edema, superficial thrombophlebitis.

Respiratory disorders: rare - bradypnoea.

Digestive system disorders: common - nausea, vomiting; uncommon - abdominal pain, dyspepsia, diarrhea, constipation, haematemesis, dry mouth; rare - erosive ulcerative lesions of gastrointestinal tract, including bleeding and perforation, anorexia, increased activity of hepatic enzymes, jaundice.

Urinary disorders: rare - polyuria, renal colic, proteinuria, ketonuria.

Reproductive system disorders: rare – in women -   menstrual disorder, in men - prostate dysfunction.

Musculoskeletal disorders: rare - muscle spasm, joint movement difficulty.

Dermatologic reactions: sometimes - dermatitis, rash, sweating increased; rare - acne.

Allergic reactions: rare - urticaria.

Metabolic disorders: rare - hyperglyceaemia, hypoglyceaemia, hypertriglyceridaemia.

Laboratory tests: rare - ketonuria, proteinuria.

Local and general reactions: common - injection site pain; uncommon -             inflammatory response, hematoma, injection site hemorrhage, feeling of having a fever, feeling cold, fatigue; rare - back pain, syncope, fever.

Other: aseptic meningitis, which might predominantly occur in patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease, hematological reactions (purpura, aplastic and hemolytic anemia, rare - agranulocytosis and bone marrow hypoplasia).

 

SPECIAL INDICATIONS

Sertofen solution for intramuscular and intravenous injection must not be mixed in a small volume (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, pethidine or hydroxyzine, as this will result in a precipitation of the solution. The diluted solutions for infusion should not be mixed with promethazine or pentazocine.

Sertofen should not be co-administered (in one syringe, in one bottle, etc.) with other drugs (solvents), other than those specified in this instruction.

The use of Sertofen with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided.

Before starting treatment with dexketoprofen trometamol and in case of any history of esophagitis, gastritis and/or peptic ulcer, one should make sure of their remission. Patients with symptoms of GIT pathology and history of gastrointestinal diseases should be monitored for digestive disorders, especially gastrointestinal bleeding.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding: oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.

Caution should be exercised when prescribing the drug to patients with hepatic and/or renal dysfunction, as well as to patients with arterial hypertension and/or heart failure, as they may experience renal function deterioration, fluid retention and edemas in association with NSAID therapy.

 

INFLUENCE ON ABILITY TO DRIVE AND OPERATE MECHANISMS

The treatment with the drug may lead to a reduced ability to concentrate and to a decreased psychomotor speed due to the possibility of dizziness and drowsiness.

 

ADMINISTRATION DURING PREGNANCY AND LACTATION

Sertofen is contraindicated during the third trimester of pregnancy and during lactation. During the first and the second trimester of pregnancy Sertofen may be administered if strictly necessary, on doctor's prescription, the dose should be kept as low and duration of treatment as short as possible.

 

PEDIATRIC USE

The efficacy and safety of Sertofen have not been established in children.

 

interaction WITH OTHER DRUGS

Inadvisable combinations

The concurrent administration of several NSAIDs, including high doses of salicylates (more than 3 g a day) increases the risk of gastrointestinal bleeding and ulcers due to the synergistic effect.

The concurrent administration with oral anticoagulants, heparin in doses higher than the preventive ones and ticlopidine increases the risk of bleeding due to the inhibition of platelet aggregation and gastrointestinal mucosal damage.

NSAIDs increase blood lithium levels, which may reach toxic values; therefore, this parameter requires monitoring during the prescription, dose adjustment and after withdrawal of treatment with NSAIDs.

In co-administration with methotrexate in high doses (15 mg a week and more) there is an increase in hematological toxicity of methotrexate due to a decrease in its renal clearance against the treatment with NSAIDs.

In concurrent administration with hydantoines and sulphonamides there is a risk of increased toxic effects of these substances.

Combinations requiring precautions

If it is necessary to co-administer the drug with diuretics, ACE inhibitors, consideration must be given to the fact that NSAID therapy is associated with a risk of acute renal failure in dehydrated patients (a decrease in glomerular filtration caused by inhibition of prostaglandin synthesis). NSAIDs may reduce the hypotensive effect of some drugs. In case of combined prescription with diuretics, it is necessary to ensure that the patient is adequately hydrated and to monitor renal function before NSAID prescription.

The concurrent administration with methotrexate in low doses (less than 15 mg a week) may increase hematological toxicity of methotrexate due to a decrease in its renal clearance by NSAIDs. Weekly blood count checks should be done during the first weeks of the combination. Enhanced monitoring should take place in the presence of even mildly impaired renal function, as well, as in elderly.

The concurrent administration with pentoxyfylline increases the risk of bleeding. Intensive clinical monitoring and frequent control of bleeding time (coagulation time) are required.

In co-administration with zidovudine there is a risk of increased red blood cell toxicity due to action on reticulocytes, with severe anemia occurring one week after NSAID prescription. It is necessary to check all blood cells and reticulocytes 1-2 weeks after the beginning of NSAID treatment.

NSAIDs can increase the hypoglycaemic effect of sulfonylureas by displacement from plasma protein binding sites.

There is an increased risk of bleeding upon concurrent administration with low molecular weight heparins.

 

 

Combinations requiring to be taken into account

NSAIDs may reduce the hypotensive effect of beta-adrenergic blocking agents, which is caused by inhibition of prostaglandin synthesis.

Upon concurrent administration with cyclosporine and tacrolimus, NSAIDs may enhance nephrotoxicity, which is mediated by the action of renal prostaglandins. During the combination therapy, renal function has to be measured.

In concurrent administration with thrombolytics there is an increased risk of bleeding.

The co-administration with probenecid may increase plasma NSAID concentrations due to inhibition of renal secretion and/or glucuronoconjugation. This requires a dose adjustment of NSAIDs.

NSAIDs may increase plasma concentrations of cardiac glycosides.

Because of a theoretical risk that prostaglandin synthetase inhibitors may alter the efficacy of mifepristone, NSAIDs should not be used earlier than 8-12 days after mifepristone withdrawal.

 

OVERDOSE

The symptomatology following overdose is not known. Similar medicinal products have produced gastrointestinal (vomiting, anorexia, abdominal pain) and neurological (somnolence, vertigo, disorientation, headache) disorders.

In case of accidental overdose, immediately institute symptomatic treatment depending on the patient's state.

Dexketoprofen trometamol may be removed from the body by dialysis.

 

PACKAGING

Solution for injections/concentrate for preparation of solution for infusions.

5 amber glass ampoules of 2 mL are in a contour tray.

1 or 2 contour trays with a leaflet are in a carton box.

 

storage conditions

Store in a protected from light place at temperature not exceeding 25ºС.

Keep out of reach of children!

 

SHELF LIFE

3 years from the date of manufacture.

Do not use after the expiry date.

 

SALES TERMS

Sold under prescription.

 

MANUFACTURER

The holder of Marketing Authorization is

“DR SERTUS İLAÇ SANAYİ VE TİCARET LİMİTED ŞİRKETİ”, TURKEY.

Manufactured by

“PharmaVision Sanayi ve Ticaret A.Ş.”, Turkey

(Davutpaşa Caddesi No.145, Topkapı, İstanbul).