Sandetofen

Dexketoprofen.

FC tab: Each film-coated tablet contains: Dexketoprofen Trometamol equivalent to Dexketoprofen 25 mg.
Inj: Each mL contains: Dexketoprofen Trometamol equivalent to Dexketoprofen 25 mg.

Pharmacology: FC tab: Dexketoprofen Trometamol is a tromethamine salt of S-(+)-2-(3-benzoylphenyl) propionic acid, which belongs to the nonsteroidal anti-inflammatory group of drugs (NSAIDs). Dexketoprofen Trometamol has pharmacologic actions similar to those of other prototypical NSAIDs. The drug exhibits anti-inflammatory, analgesic and antipyretic activity. The exact mechanisms have not been clearly established, but many of the actions appear to be associated principally with the inhibition of prostaglandin synthesis. The drug inhibits the synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2), have been identified that catalyze the formation of prostaglandins in the arachidonic acid pathway.
Inj: Dexketoprofen Trometamol is a tromethamine salt of S(+)-2-(3-benzoylphenyl) propionic acid, is an analgesic, anti-inflammatory and antipyretic belong to non-steroidal anti-inflammatory drugs (NSAIDs).
Mechanism of action of nonsteroidal anti-inflammatory drugs are associated with a reduction of prostaglandin synthesis by inhibition of cyclooxygenase pathway. Inhibition of the transformation of arachidonic acid into cyclic endoperoxide, PGG₂ and PGH₂, which produce prostaglandins; PGE₁, PGE₂, PGF_2α and PGD₂ and also prostacyclin PGI₂ and thromboxane (TxA₂ and TxB₂) specifically occur. Furthermore, inhibition of prostaglandin synthesis can affect other inflammatory mediators such as kinin, causing indirect action that strengthen direct action.
Pharmacokinetics: FC tab: Dexketoprofen Trometamol, given as tablet, is rapidly absorbed (90% bioavailability), with a time to maximum plasma concentration (t_max) of between 0.25 and 0.75 hours. The C_max of Dexketoprofen Trometamol in human is reached at 30 minutes (range 15 to 60 minutes).
The distribution half-life and the elimination half-life were approximately 0.35 hours and 1.65 hours, respectively. Dexketoprofen is strongly bound to plasma proteins (99%), particularly albumin. The volume of distribution has a mean value below 0.25 L/kg.
Dexketoprofen is eliminated following extensive biotransformation to inactive glucuroconjugated metabolites. No (R)-(-)-ketoprofen is found in the urine after administration of Dexketoprofen, confirming the absence of bioinversion of the (S)-(+)-enantiomer in human. Conjugates are excreted in urine, and virtually no drug is eliminated unchanged.
Dexketoprofen Trometamol did not show any accumulation phenomena after repeated doses and was well tolerated.
The profile of absorption was changed when Dexketoprofen is ingested with food, reducing both the rate of absorption (t_max) and the maximal plasma concentration; however the AUC did not change.

FC tab: Symptomatic treatment of mild to moderate pain such as acute musculoskeletal pain, dysmenorrhea, dental pain and postoperative pain.
Inj: Treatment of the symptoms with acute pain intensity, where per oral administration is inadequate, such as post operative pain.

FC tab: Absorption is delayed if the drug is taken with food and therefore recommends that in acute pain, Dexketoprofen should be given at least 30 minutes before food.
Usual doses: Usual doses are 12.5 mg every 4 to 6 hours or 25 mg every 8 hours. The total daily dose should not exceed 75 mg. The dosage should be considered according to the nature and severity of pain.
SANDETOFEN may not be used for long-term period and the treatment must be limited to the symptomatic period.
Elderly: Elderly patients should be started on a total daily dose not exceeding 50 mg.
The dosage may be increased to usual dosage for general population if the drug can be tolerated well.
Hepatic impairment: A reduced initial daily dose of 50 mg orally is recommended in patients with mild to moderate hepatic impairment.
Renal impairment: A reduced initial daily dose of 50 mg orally is recommended in patients with mild renal impairment (creatinine clearance 50-80 mL/minute).
Inj: Dosage: 50 mg every 8-12 hours. If needed, the administration can be repeated every 6 hours. The total dosage per day may not exceed 150 mg.
SANDETOFEN Injection is not addressed for prolong administration, and the therapy should be limited for acute symptomatic period only.
For post operative pain, SANDETOFEN injection can be used with the opioid analgesic for the pain, particularly severe pain in the initial period after surgery.
Elderly: Adjustment doses usually not required in elderly patients. However, due to decreased physiological kidney function in the elderly patients, lower doses is recommended in the case of mild impairment of kidney functions. The total doses per day is 50 mg.
Hepatic Dysfunction: In patients with mild to moderate hepatic impairment (Child-Pugh Score 5-9), the doses should be lowered to 50 mg total daily dose, and the hepatic function be monitored strictly. SANDETOFEN Injection solution or concentrate solution for infusion should not be given for patient with severe hepatic dysfunction (Child-Pugh score 10-15).
Renal Dysfunction: In patients with reduced mild kidney function condition (creatinine clearance 50-80 mL/minutes), the doses should be lowered to 50 mg total daily dose. SANDETOFEN Injection or concentrate solutions concentrates for infusion should not be given to the patients with moderate to severe renal dysfunction (creatinine clearance 50 mL/minutes).
Children: This drug should not be used in children.
Administration: SANDETOFEN can be administered IM or IV route.
IM: SANDETOFEN Injection should be given with slow injection to the muscle.
IV Infusion: SANDETOFEN Injection should be diluted into 30 to 100 mL NaCl, Glucose or Ringer Lactate solution. Diluted solution should be given with slow intravenous infusion for 10 until 30 minutes. The solution must be protected from direct sunlight.
IV bolus: If needed, SANDETOFEN Injection can be administered as slow bolus intravenous with not more than 15 seconds administration.
When SANDETOFEN Injection is administered as IM or IV bolus, the solution should be directly injected after being removed from amber ampoules. In i.v. infusion administration, the solution should be diluted aseptically and protected form direct sunlight.

FC tab: Drowsiness, vomiting, and abdominal pain have been reported in a few individuals following acute overdosage of the drug.
In acute overdosage, general measures should include immediately emptying the stomach by inducing emesis or by gastric lavage, followed by initiation of supportive and symptomatic treatment.

FC tab: Patients with known hypersensitivity to Dexketoprofen Trometamol, other NSAIDs or any excipients in this product.
Patients in whom asthma, urticaria, or other sensitivity reactions are precipitated by Aspirin or other NSAIDs.
Patients with active peptic or suspected peptic ulcer/hemorrhage or history recurrent peptic ulcer/hemorrhage.
Patients with hemorrhagic disorders.
Patients with moderate to severe renal impairment, severe hepatic impairment, and in those with severe heart failure.
Pregnant and nursing women.
Dexketoprofen Trometamol is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (see Precautions).
Inj: Patients with a history of hypersensitivity to Dexketoprofen, other NSAIDs, or excipients contained in the preparation.
Patients who have had an asthma attack, bronchospasm, acute rhinitis, or nasal polyps, urticaria or angioneurotic edema that are triggered by other drugs in similar ways (eg Aspirin, or other NSAIDs).
Patients with a history of suffering from gastric ulcer (active or new suspicion only), or chronic dyspepsia, gastric bleeding or other active bleeding, Crohn's disease or ulcerative colitis, history of bronchial asthma, severe heart failure, moderate to severe renal dysfunction (Creatinine clearance < 50 mL/minutes), damage severe liver function (Child-Pugh score 10-15).
Patients with haemorrhagic diathesis and other coagulation disorders, or patients treated with anticoagulants.
Pregnancy and breast-feeding.
Neuraxial administration (Intrathecal or epidural) regarding alcohol content in the product.

Cardiovascular risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (See Precautions).
SANDETOFEN is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (See Precautions).
Gastrointestinal risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk of serious gastrointestinal events (See Precautions).

FC tab: Cardiovascular effects: Cardiovascular thrombotic events: Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of Aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of Aspirin and an NSAID does increase the risk of serious GI events (see Gastrointestinal effects as follows).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see Contraindications).
Hypertension: NSAIDs, including Dexketoprofen Trometamol, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Dexketoprofen Trometamol, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Congestive heart failure and edema: Fluid retention and edema have been observed in some patients taking NSAIDs. Dexketoprofen Trometamol, should be used with caution in patients with fluid retention or heart failure.
Gastrointestinal effects-risk of ulceration, bleeding, and perforation: NSAIDs, including Dexketoprofen Trometamol, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a grater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
The drug should be used with caution in patients with a history of allergic conditions, esophagitis, and gastritis.
The drug should be used with caution in patients who may be adversely affected by a prolongation of bleeding time (e.g., patients receiving anticoagulant therapy), since the drug may inhibit platelet function.
Like other NSAIDs, urea nitrogen and creatinine plasma level may increase. Some NSAIDs have been associated with nephrotoxicity such as glomerulonephritis, interstitial nephritis and nephrotic syndrome. Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Elevations of serum SGPT or SGOT concentration have occurred in patients receiving NSAIDs. Therapy should be discontinued if signs or symptoms of a severe hepatic reaction occur.
The drug should be used with caution in patients with hematopoietic disorders, systemic lupus erythematosus, or mixed-type of connective tissue disease. The use of NSAIDs may mask the usual signs and symptoms of infection or other diseases.
The drug is not recommended in patients with advanced renal disease. If the drug is used in patients with severe renal impairment, close monitoring of renal function is recommended.
The safety of the drug in children has not been established.
NSAIDs should be used with caution in the geriatric patients and may need to be given in reduced doses. Geriatric patients appear to tolerate gastrointestinal ulceration or bleeding less well than other individuals. The recent use of NSAIDs in geriatric patients has been associated with an increased risk of developing heart failure.
Inj: The safety of its use in children has not been established.
Caution in patients with a history of drug allergy and bronchial asthma.
Patients with diseases of the gastrointestinal symptoms should be monitored, specifically the gastrointestinal bleeding. If bleeding or gastrointestinal peptic occur, treatment must be discontinued immediately.
As with other NSAIDs, it could potentially inhibit aggregation of platelets and prolong bleeding time through the inhibition of prostaglandins synthesis. Concomitant use of Dexketoprofen Trometamol with preventive dose of lower molecular weight of Heparin in postoperative shows that there is no effect for the coagulation parameter that already determined. However, the patients who have other therapy that affect hemostasis should be monitored carefully.
Increase of urea nitrogen and plasma creatinine can happen like other NSAIDs. As inhibitors of prostaglandin synthesis, side effects can occur in the renal system: glomerulonephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure.
As with other NSAIDs, these drugs can increase liver enzymes (temporary), if occur a significant increase in SGPT and SGOT, discontinue therapy immediately. Caution in patients with hematopoietic disorders, systemic lupus erythematosus, or a mixed connective tissue disease. The use of NSAIDs may mask the symptoms of the infection.
Caution in patients with impaired liver function, kidney or heart failure and other conditions that would cause fluid retention. In these patients, NSAID treatment can decrease kidney function and fluid retention. Caution in patients that already have diuretic therapy or hypovolemia incidence that can increase nephrotoxicity risk.
Caution in elderly patients, are more susceptible to side effects: gastrointestinal bleeding and/or perforation, depending on the doses. While therapy, sometimes it can be more serious and occurring without warning or previous history. In elderly patients, the risk of kidney, cardiovascular and liver damage is increasing so their function should be monitored.

FC tab: Cardiovascular effects: Peripheral edema, palpitation, hypertension, tachycardia, facial edema, angioedema, hypotension, hot flushes.
Gastrointestinal effects: Dyspepsia, gastrointestinal bleeding or perforation, peptic ulcer, nausea, diarrhea, abdominal pain, constipation, flatulence, vomiting, anorexia, dry mouth, pancreatitis, gastritis.
Nervous system effects: Headache, insomnia, anxiety, dizziness, malaise, drowsiness, fatigue, paresthesia, asthenia, vertigo.
Hepatic effects: Hepatic dysfunction, elevation of serum SGPT or SGOT concentration.
Hematologic effects: Anemia, purpura, agranulocytosis, thrombocytopenia, neutropenia.
Dermatologic effects: Rash, pruritus, urticaria, photosensitivity reaction, sweating, toxic epidermal necrolysis, Stevens-Johnson syndrome.
Other adverse effects: Dyspnea, bronchospasm, pain, anaphylaxis, visual disturbances, tinnitus, aseptic meningitis.
Inj: Nausea, vomiting, pain at the administration site, anemia, headache, dizziness, insomnia, drowsiness, blurred vision, hypotension, hot flushes, abdominal pain, dyspepsia, diarrhea, constipation, vomiting blood, dry mouth, dermatitis, pruritus, skin rashes, excessive sweating, reaction in injection area, inflammatory bruise or bleeding, fever, fatigue, pain, coldness, hyperglycemia, hypoglycemia, hypertriglyceridemia, paresthesia, tinnitus, extrasystole, tachycardia, hypertension, peripheral edema, thrombophlebitis, superficial, bradypnea, peptic ulcers, bleeding or gastroduodenal perforation, anorexia, elevated liver enzyme, liver disorders, jaundice, urticaria, acne, stiff joints, muscular cramp, polyuria, kidney pain, menstrual disorders, prostatic disorder, back pain, syncope, chills, ketonuria, proteinuria, neutropenia, thrombocytopenia, bronchospasm, dyspnea, pancreatic damage, liver damage, severe mucocutaneous skin reaction (Stevens-Johnson syndrome, Lyell syndrome), angioedema, dermatology reaction, photosensitivity reaction, pruritus, kidney damage (nephritis or nephrotic syndrome), anaphylaxis, face edema.
The following adverse reactions may occur because of the side effects appear in other NSAID and may be related to prostaglandin synthesis inhibitors: Aseptic meningitis: will primarily occur in patients with SLE (Systemic Lupus Erythematosus) or mixed connective tissue disease.
Hematological reactions: purpura, hemolytic and aplastic anemia, and rarely, agranulocytosis and medullar hypoplasia.

FC tab: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists: Concomitant use of NSAIDs with ACE inhibitors or angiotensin II receptors antagonists may reduce the blood pressure response to the antihypertensive agent.
Anticoagulant and thrombolytic agents: Concomitant use of this drug and anticoagulant or thrombolytic agents is associated with a higher risk of gastrointestinal bleeding compared with use of either agent alone.
Cardiac glycosides: Concomitant use of this drug and cardiac glycosides may increase plasma concentration of cardiac glycosides.
Diuretics: Patients receiving diuretics may have an increased risk of developing renal failure secondary to decrease renal blood flow resulting from prostaglandin inhibition by NSAIDs. There may also be an increased risk of hyperkalemia with ACE inhibitors and some diuretics, including potassium-sparing diuretics.
Nonsteroidal anti-inflammatory agents: Concomitant use of Aspirin and NSAID increases the risk for serious gastrointestinal effects.
Probenecid: Probenecid delays the excretion of this drug and decreases its extent of protein binding resulting in increased concentrations of this drug in plasma.
Methotrexate: Severe, sometimes fatal, toxicity has occurred following administration of an NSAID, concomitantly with Methotrexate (principally high-dose therapy) in patients with various malignant neoplasms or rheumatoid arthritis. The toxicity was associated with elevated and prolonged blood concentrations of Methotraxate.
Lithium: NSAIDs have been reported to increase serum Lithium concentrations. NSAIDs appear to decrease renal clearance of Lithium.
Quinolones: Convulsion may occur due to an interaction with quinolones.
Zidovudine: There may be increased risk of hematotoxicity if Zidovudine is used with NSAIDs.
Mifepristone: NSAIDs may alter the efficacy of Mifepristone.
Cyclosporine and Tacrolimus: The risk of nephrotoxicity may be increased if the drug given with Cyclosporine or Tacrolimus.
Phenytoin and sulfonylurea antidiabetics: NSAIDs may increase the effects of Phenytoin and sulfonylurea antidiabetics.
Inj: Ulcers and gastrointestinal bleeding may occur in the concomitant use with other NSAIDs, for their synergistic effect.
There may be an increased risk of bleeding and damage to the gastrointestinal mucosa on the concomitant use with anticoagulant drugs, above Heparin prophylaxis dose parenterally, as well as Ticlopidine.
NSAIDs can increase lithium level in the blood until toxic levels, so it needs to be monitored.
On the use of Methotrexate above 15 mg/week or more, NSAIDs may increase Methotrexate toxicity in blood because of clearance through the kidney decreased.
There may be an increase in the toxicity of hydantoins and sulfonamides, if used concomitantly with NSAIDs.
Reduction of antihypertensive effects of diuretics and β-blockers group (keep out as there is no dehydration).
There is an increased risk of bleeding in concomitant use with Pentoxifylline and thrombolytic drugs.
An increase in poisoning of red blood cells (reticulocytes influence) on the concomitant use with Zidovudine.
An increase in hypoglycaemic effect of sulfonylurea class of drugs.
An increase of nephrotoxicity in the use of Cyclosporine and Tacrolimus by NSAIDs. During combination therapy, renal function should be monitored.
An increase in the blood levels of Dexketoprofen on concomitant use with Probenecid.
Cardiac glycosides: NSAIDs may increase blood levels of glycosides.
Mifepristone: NSAIDs should not be used within 8-12 days after Mifepristone use. Because theoretically an inhibitor of prostaglandin synthesis can change the efficacy of Mifepristone.
Quinolone antibiotics: high doses of quinolone and NSAIDs may increase the risk of convulsions.

FC tab: Store at temperature below 30°C.
Inj: Store below 30°C, away from light.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AE17 - dexketoprofen ; Belongs to the class of propionic acid derivatives of non-steroidal antiinflammatory and antirheumatic products.

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