Ketodexal (Solution) Instructions for Use

Marketing Authorization Holder

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

M01AE17 (Dexketoprofen)

Active Substance

Dexketoprofen (Rec.INN registered by WHO)

Dosage Form

Ketodexal

Solution for intravenous and intramuscular injection 25 mg/1 ml: amp. 2 ml 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular injection transparent, colorless.

Excipients : ethanol 96% – 100 mg, sodium chloride – 4 mg, 1M sodium hydroxide solution – to pH 7.4±0.1, water for injections – to 1 ml.

2 ml – dark glass ampoules (5) – blister packs (1) – cardboard boxes.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID. It has analgesic, anti-inflammatory and antipyretic effects. The mechanism of action is associated with the inhibition of prostaglandin synthesis at the level of COX-1 and COX-2.

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

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

Pharmacokinetics

After intramuscular administration, the C_max of dexketoprofen in plasma is reached on average after 20 minutes (10-45 minutes). AUC after a single administration of 25-50 mg is proportional to the dose, both with intramuscular and intravenous administration. The corresponding pharmacokinetic parameters are similar after single and repeated intramuscular or intravenous administration, indicating no accumulation of the drug. Plasma protein binding is 99%. The mean V_d value is less than 0.25 l/kg, the distribution half-life is about 0.35 hours. The main route of elimination of dexketoprofen is its conjugation with glucuronic acid followed by renal excretion. The T_1/2 of dexketoprofen trometamol is about 1-2.7 hours. In elderly individuals, an increase in the duration of T_1/2 (both after single and repeated intramuscular or intravenous administration) is observed, on average up to 48%, and a decrease in the total clearance of dexketoprofen.

Indications

Relief of pain syndrome of various origins (including postoperative pain, pain from bone metastases, post-traumatic pain, pain from renal colic, algodysmenorrhea, sciatica, radiculitis, neuralgia, toothache).

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

ICD codes

Dosage Regimen

For intravenous and intramuscular administration.

The recommended dose is 50 mg every 8-12 hours. If necessary, repeated administration is possible at 6-hour intervals. The daily dose is 150 mg.

In elderly patients and patients with impaired liver and/or kidney function, therapy should be started with lower doses; the daily dose is 50 mg.

Dexketoprofen for parenteral use is intended for short-term (no more than 2 days) use during acute pain syndrome. Subsequently, the patient can be switched to oral analgesics.

Adverse Reactions

From the hematopoietic system rarely – anemia; very rarely – neutropenia, thrombocytopenia.

From the nervous system: infrequently – headache, dizziness, insomnia, drowsiness; rarely – paresthesia.

From the sensory organs: infrequently – blurred vision; rarely – tinnitus.

From the cardiovascular system infrequently – arterial hypotension, feeling of heat, skin hyperemia; rarely – extrasystole, tachycardia, arterial hypertension, peripheral edema, superficial thrombophlebitis.

From the respiratory system rarely – bradypnea; very rarely – bronchospasm, dyspnea.

From the digestive system frequently – nausea, vomiting; infrequently – abdominal pain, dyspepsia, diarrhea, constipation, hematemesis, dry mouth; rarely – erosive and ulcerative lesions of the gastrointestinal tract, including bleeding and perforations, anorexia, increased activity of liver enzymes, jaundice; very rarely – pancreatic damage, liver damage.

From the urinary system: rarely – polyuria, renal colic; very rarely – nephritis or nephrotic syndrome.

From the reproductive system: rarely – in women – menstrual cycle disorders, in men – impaired prostate function.

From the musculoskeletal system rarely – muscle spasm, difficulty in joint movement.

From the skin and subcutaneous tissues: sometimes – dermatitis, rash, sweating; rarely – acne; very rarely – photosensitivity.

Allergic reactions: rarely – urticaria; very rarely – severe skin reactions (Stevens-Johnson syndrome, Lyell’s syndrome), angioedema, allergic dermatitis.

From the metabolism rarely – hyperglycemia, hypoglycemia, hypertriglyceridemia.

From laboratory parameters: rarely – ketonuria, proteinuria.

Local and general reactions: frequently – pain at the injection site; infrequently – inflammatory reaction, hematoma, hemorrhage at the injection site, feeling of heat, chills, fatigue; rarely – back pain, fainting, fever; very rarely – anaphylactic shock, facial edema.

Other aseptic meningitis, occurring mainly in patients with systemic lupus erythematosus or mixed connective tissue diseases, hematological disorders (purpura, aplastic and hemolytic anemia, rarely – agranulocytosis and bone marrow hypoplasia).

Contraindications

Hypersensitivity to dexketoprofen or other NSAIDs or to any of the excipients included in the drug used; peptic ulcer of the stomach and duodenum; history of gastrointestinal bleeding, other active bleeding (including suspected intracranial bleeding), anticoagulant therapy; gastrointestinal diseases (Crohn’s disease, ulcerative colitis); severe liver dysfunction (10-15 points on the Child-Pugh scale); severe renal dysfunction (creatinine clearance <50 ml/min); bronchial asthma (including history); severe heart failure; treatment of pain syndrome during coronary artery bypass grafting; hemorrhagic diathesis or other coagulation disorders; children and adolescents under 18 years of age; for epidural, subarachnoid or intrathecal administration.

With caution

History of allergic conditions; disorders of the hematopoietic system; with systemic lupus erythematosus or mixed connective tissue diseases; simultaneously with other drugs; in case of predisposition to hypovolemia; with coronary artery disease; in elderly patients over 65 years of age.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

In patients with impaired liver function, therapy should be started with lower doses.

Contraindicated in severe liver dysfunction (10-15 points on the Child-Pugh scale).

Use in Renal Impairment

In patients with impaired renal function, therapy should be started with lower doses.

Contraindicated in severe renal dysfunction (creatinine clearance <50 ml/min).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

The drug should be used with caution in elderly patients (over 65 years of age).

Special Precautions

In patients with disorders of the digestive system or a history of gastrointestinal diseases, constant monitoring is necessary. In case of gastrointestinal bleeding or ulcerative lesions, dexketoprofen therapy should be discontinued.

Dexketoprofen did not affect coagulation parameters. Nevertheless, with simultaneous use with other drugs that affect blood clotting, careful medical supervision is necessary.

Like other NSAIDs, Dexketoprofen can lead to an increase in plasma creatinine and nitrogen levels.

Like other inhibitors of prostaglandin synthesis, Dexketoprofen can have an adverse effect on the urinary system, which can lead to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure.

During therapy with dexketoprofen, as with other NSAIDs, a slight transient increase in some liver parameters, as well as a significant increase in the activity of AST and ALT in the blood serum, may be observed. In this case, monitoring of liver and kidney functions is necessary in elderly patients. In case of a significant increase in the corresponding indicators, Dexketoprofen should be discontinued.

Like other NSAIDs, Dexketoprofen can mask the symptoms of infectious diseases. If symptoms of a bacterial infection appear or if the condition worsens during therapy, the patient should inform the doctor.

Effect on ability to drive vehicles and operate machinery

Due to possible dizziness and drowsiness during treatment with dexketoprofen trometamol, a decrease in the ability to concentrate and the speed of psychomotor reactions is possible.

Drug Interactions

The drug interactions described below are characteristic of all NSAIDs, including Dexketoprofen.

Undesirable combinations

Simultaneous use of several NSAIDs, including salicylates in high doses (more than 3 g/day), increases the risk of gastrointestinal bleeding and ulcers due to the synergy of action.

When used simultaneously with oral anticoagulants, heparin in doses exceeding prophylactic doses, and ticlopidine, the risk of bleeding increases due to inhibition of platelet aggregation and damage to the gastrointestinal mucosa.

NSAIDs increase the plasma concentration of lithium, up to toxic levels, so this indicator must be monitored when prescribing, changing the dose and after discontinuation of NSAIDs.

When used with methotrexate in high doses (15 mg/week and more), the hematological toxicity of methotrexate increases due to a decrease in its renal clearance during NSAID therapy.

When used simultaneously with hydantoins and sulfonamide drugs, there is a risk of increased toxic effects of these drugs.

Combinations requiring caution

If simultaneous use with diuretics and ACE inhibitors is necessary, it should be taken into account that NSAID therapy is associated with the risk of developing acute renal failure in patients with dehydration (decreased glomerular filtration due to inhibition of prostaglandin synthesis). NSAIDs may reduce the hypotensive effect of some drugs. When prescribing simultaneously with diuretics, it is necessary to ensure that the patient’s water balance is adequate and to monitor renal function before prescribing NSAIDs.

When used simultaneously with methotrexate in low doses (less than 15 mg/week), an increase in the hematological toxicity of methotrexate is possible due to a decrease in its renal clearance during NSAID therapy. It is necessary to monitor the blood cell count weekly during the first weeks of simultaneous therapy. If there is impaired renal function, even mild, as well as in elderly individuals, careful medical supervision is necessary.

When used simultaneously with pentoxifylline, the risk of bleeding increases. Intensive clinical monitoring and frequent monitoring of bleeding time (blood clotting time) are necessary.

When used simultaneously with zidovudine, there is a risk of increased toxic effects on red blood cells, due to the effect on reticulocytes, with the development of severe anemia a week after the prescription of NSAIDs. It is necessary to monitor all blood cells and reticulocytes 1-2 weeks after the start of NSAID therapy.

It is possible to enhance the hypoglycemic effect of sulfonylurea derivatives due to their displacement from plasma protein binding sites under the influence of NSAIDs.

When used simultaneously with low molecular weight heparin preparations, the risk of bleeding increases.

Combinations that must be taken into account

NSAIDs may reduce the hypotensive effect of beta-blockers, which is due to inhibition of prostaglandin synthesis.

When used simultaneously with cyclosporine and tacrolimus, NSAIDs may enhance nephrotoxicity, which is mediated by the action of renal prostaglandins. During combination therapy, renal function should be monitored.

When prescribed simultaneously with thrombolytics, the risk of bleeding increases.

When used simultaneously with probenecid, an increase in NSAID concentrations in plasma is possible, which may be due to inhibition of renal secretion and/or conjugation with glucuronic acid. This requires adjustment of the NSAID dose.

NSAIDs can cause an increase in the plasma concentration of cardiac glycosides.

Due to the theoretical risk of changing the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should not be prescribed earlier than 8-12 days after discontinuation of mifepristone.

Data obtained from experimental animal studies indicate a high risk of seizures when prescribing NSAIDs during therapy with high doses of ciprofloxacin.

Pharmaceutical interactions

Dexketoprofen trometamol should not be mixed in the same syringe with a solution of dopamine, promethazine, pentazocine, pethidine or hydroxyzine (a precipitate forms).

Dexketoprofen trometamol can be mixed in the same syringe with a solution of heparin, lidocaine, morphine and theophylline.

The diluted solution of dexketoprofen trometamol for infusion should not be mixed with promethazine or pentazocine.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.