Loxoprofen (Tablets) Instructions for Use

ATC Code

M01AE (Propionic acid derivatives)

Active Substance

Loxoprofen (Rec.INN registered by WHO)

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs; non-steroidal anti-inflammatory and antirheumatic drugs; propionic acid derivatives

Pharmacological Action

Loxoprofen is a prodrug. After oral administration, it is absorbed from the gastrointestinal tract in an unchanged form, exerting a weak stimulating effect on the gastric mucosa, and then is rapidly converted into an active metabolite – the trans-OH form, which has a strong inhibitory effect on the biosynthesis of prostaglandins. Loxoprofen exhibits a pronounced analgesic, anti-inflammatory, and antipyretic effect (with the analgesic effect being the strongest), due to the inhibitory effect on the biosynthesis of prostaglandins as a result of blocking the COX enzyme.

Pharmacokinetics

The binding of loxoprofen and its trans-OH metabolite to plasma proteins was 97% and 92.8%, respectively. When 14C-loxoprofen sodium hydrate was administered orally at a dose of 2 mg/kg to rats on the 14th day after delivery, the concentration of the drug in breast milk was 4.3 times higher after 4 hours and 3.9 times higher after 6 hours than its concentration in maternal blood. In an in vitro metabolism inhibition study using human liver microsomes, Loxoprofen did not affect the metabolism of various drugs that are substrates of cytochrome P450 isoenzymes (CYP 1A1/2, 2A6, 2B6, 2C8/9, 2C19, 2D6, 2E1, and 3A4), even at a concentration approximately 10 times higher than the C_max (200 µmol/L) after a single oral dose of 60 mg in healthy male volunteers.

After a single oral dose of loxoprofen 60 mg in 6 healthy male volunteers, it was rapidly excreted in the urine, and most of the dose excreted in the urine accounted for glucuronide conjugates of unchanged loxoprofen and its trans-OH metabolite.

Indications

As an anti-inflammatory and analgesic for the following diseases and symptoms: rheumatoid arthritis, osteoarthritis, lumbago (low back pain), scapulohumeral periarthritis (shoulder syndrome), cervicobrachial syndrome, toothache (including after tooth extraction), post-traumatic and postoperative pain syndrome.

As an antipyretic and analgesic for the following diseases: acute upper respiratory tract infections (including acute upper respiratory tract infection with acute bronchitis).

Intended for symptomatic therapy, reducing pain and inflammation at the time of use; does not affect the progression of the disease.

ICD codes

Dosage Regimen

Administer Loxoprofen tablets orally, typically after meals to minimize gastrointestinal irritation.

The standard adult single dose is 60 mg, equivalent to one tablet. Take this dose two to three times daily, depending on the severity of symptoms.

Do not exceed the maximum daily dose of 180 mg.

For use as an antipyretic, limit administration to a maximum of three consecutive days.

For use as an analgesic, limit administration to a maximum of five consecutive days.

Adjust the dosage based on the patient’s age and symptoms. For elderly patients or those with renal or hepatic impairment, initiate therapy at the lowest effective dose.

Use the shortest possible duration of therapy and the minimum effective dose required to control symptoms.

Discontinue treatment and consult a physician if symptoms persist or worsen after two to three days of use.

Avoid concomitant use with other NSAIDs or analgesic drugs.

Adverse Reactions

Serious adverse reactions (frequency unknown) anaphylactic shock, agranulocytosis, leukopenia, hemolytic anemia, aplastic anemia, thrombocytopenia; toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme exudativum, acute generalized exanthematous pustulosis; acute renal impairment, nephrotic syndrome, interstitial nephritis; hyperkalemia (which may occur with acute kidney injury); congestive heart failure; interstitial pneumonia with symptoms such as fever, cough, dyspnea, abnormalities on chest X-ray, eosinophilia; peptic ulcer, gastrointestinal bleeding. Severe peptic ulcer or bleeding from the small and/or large intestine may occur with symptoms such as hematemesis, melena, hematochezia, and accompanying shock; gastrointestinal perforation with symptoms such as epigastric pain or pain throughout the abdomen; stenosis or obstruction of the small and large intestine associated with ulcer formation in the small and large intestine, with symptoms such as nausea, vomiting, abdominal pain, abdominal distension; liver function disorders, which include jaundice and increased AST, ALT, GGT activity, fulminant hepatitis; bronchial asthma attacks; aseptic meningitis with symptoms such as fever, headache, nausea, vomiting, neck stiffness, and confusion (aseptic meningitis is especially common in patients with systemic lupus erythematosus or mixed connective tissue disease); rhabdomyolysis with symptoms such as myalgia, weakness, increased CPK levels, increased myoglobin levels in blood and urine.

Blood and lymphatic system disorders rarely – eosinophilia; frequency unknown – anemia, leukopenia, thrombocytopenia.

Nervous system disorders uncommon – drowsiness; rarely – headache, dizziness, numbness.

Cardiac disorders rarely – palpitations, increased blood pressure.

Gastrointestinal disorders uncommon – abdominal pain, stomach discomfort, anorexia, nausea, diarrhea, constipation, heartburn, stomatitis, abdominal distension, dry mouth; rarely – vomiting; frequency unknown – peptic ulcers, ulcers in the small and/or large intestine, dyspepsia.

Hepatobiliary disorders uncommon – increased AST, increased ALT; rarely – increased alkaline phosphatase.

Skin and subcutaneous tissue disorders uncommon – rash, pruritus; frequency unknown – fever, urticaria.

Renal and urinary disorders uncommon – proteinuria; frequency unknown – hematuria, dysuria, decreased diuresis.

General disorders and administration site conditions uncommon – edema, flushing (feeling of heat); frequency unknown – chest pain, malaise, sweating.

Contraindications

Hypersensitivity to loxoprofen; peptic ulcer of the stomach and duodenum in the acute phase; inflammatory bowel disease (Crohn’s disease, ulcerative colitis); erosive and ulcerative lesions of the gastrointestinal tract in the acute phase; history of gastrointestinal bleeding or perforation, including those associated with previous use of NSAIDs; active gastrointestinal bleeding; other active bleeding (including suspected intracranial hemorrhage); severe hematological diseases; severe liver dysfunction; severe renal impairment, progressive kidney disease, confirmed hyperkalemia; severe heart failure (NYHA class IV); period after coronary artery bypass graft surgery; complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history); pregnancy (after 20 weeks); breastfeeding period.

With caution

History of peptic ulcer of the stomach and duodenum (possible relapse of the disease); erosive and ulcerative lesions of the stomach and duodenum caused by long-term use of NSAIDs, with concomitant therapy with misoprostol and the need for long-term use of loxoprofen; Helicobacter pylori infection; impaired liver function (including in history), except for patients with severe liver dysfunction; hepatic porphyria (including acute intermittent porphyria); impaired renal function (including in history), except for patients with severe progressive renal impairment, for which use is contraindicated; hematological diseases (including in history), except for severe hematological diseases, for which use is contraindicated; blood formation disorders; heart failure, except for patients with severe heart failure; coronary artery disease; peripheral arterial disease; arterial hypertension; bronchial asthma or allergic diseases in the acute phase or in history; complications of infectious diseases; age over 65 years, including patients with high body temperature; patients receiving diuretics; debilitated patients and patients with low body weight; dyslipidemia/hyperlipidemia; diabetes mellitus; severe osteoporosis; severe somatic diseases; tuberculosis; cerebrovascular diseases; systemic lupus erythematosus and other systemic connective tissue diseases; nicotine, alcohol dependence; long-term use of NSAIDs; simultaneous use of analgesics, corticosteroids, anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), drugs for the treatment of type 2 diabetes, quinolones/fluoroquinolones; methotrexate, lithium preparations, selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), diuretic and antihypertensive drugs.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy, especially after 20 weeks, and during breastfeeding.

Use in Hepatic Impairment

Contraindicated for use in severe liver dysfunction.

Use in Renal Impairment

Contraindicated for use in severe renal impairment, progressive kidney disease.

Pediatric Use

The safety and efficacy of loxoprofen in children under 18 years of age have not been established. Data are not available.

Geriatric Use

Since elderly patients have a higher risk of adverse reactions, Loxoprofen should be used with caution. It is recommended to start treatment with the lowest dose, carefully monitoring the patient’s condition.

Special Precautions

It is recommended to take Loxoprofen for the shortest possible course and at the minimum effective dose necessary to relieve symptoms. If it is necessary to take for more than 5 days, you should consult a doctor.

If symptoms persist or worsen after taking loxoprofen for 2-3 days, it is necessary to stop treatment and consult a doctor.

Concomitant use of loxoprofen and other NSAIDs or analgesic drugs should be avoided.

During long-term use of NSAIDs, peripheral blood counts should be monitored.

When using loxoprofen for the treatment of chronic diseases (rheumatoid arthritis, osteoarthritis), monitoring of peripheral blood counts and functional state of the liver and kidneys is necessary; other methods of treatment besides drug therapy should be considered.

Special care should be taken in case of acute renal failure due to rhabdomyolysis.

When using loxoprofen for the treatment of acute diseases: the dosing regimen should be chosen taking into account the degree of acute inflammation, pain and fever; long-term use of the same drug should be avoided; if there is etiotropic treatment, it should be prescribed first and Loxoprofen should be used only as indicated. When used for acute infections, there is a risk of the infection transitioning to a subclinical form.

Effect on ability to drive vehicles and machinery

Patients who experience dizziness while taking loxoprofen should refrain from driving vehicles and operating machinery.

Drug Interactions

Coumarin anticoagulants (warfarin): should be used with caution. It is believed that the inhibitory effect of loxoprofen on the biosynthesis of prostaglandins, since Loxoprofen suppresses platelet aggregation, reduces blood clotting ability and enhances the anticoagulant effect of other drugs.

Factor Xa inhibitors (including edoxaban): possible increased risk of bleeding, as it is believed that Loxoprofen enhances the antithrombotic effect.

Oral hypoglycemic agents sulfonylurea derivatives (chlorpropamide): Loxoprofen may enhance the hypoglycemic effect.

It is believed that the binding of loxoprofen to human plasma proteins reaches 97%, and that of its trans-OH metabolite – 92.8%, so when used in combination with a drug with high protein binding, the active fraction of the concomitant drug in the blood increases, and its effect is enhanced.

Quinolones/fluoroquinolones block the binding of GABA, an inhibitory neurotransmitter in the CNS, to receptors and cause convulsive effects. It is believed that the combined use of this drug and quinolones/fluoroquinolones enhances these effects.

Loxoprofen may increase the plasma concentration of methotrexate, thereby enhancing its activity, so if necessary. The exact mechanism of interaction is not known, but it is believed that the inhibitory effect of loxoprofen on the biosynthesis of prostaglandins in the kidneys reduces the renal excretion of these drugs and increases their plasma concentration.

Loxoprofen may increase the plasma concentration of lithium, thereby enhancing its toxicity, so the plasma concentration of lithium should be monitored and, if necessary, the dose of the lithium drug should be reduced.

With simultaneous use, Loxoprofen may reduce the diuretic and antihypertensive effects of hydrochlorothiazide. It is believed that Loxoprofen reduces the excretion of water and sodium due to the inhibitory effect on the biosynthesis of prostaglandins in the kidneys.

Antihypertensive drugs (ACE inhibitors, angiotensin II receptor antagonists): possible reduction of the antihypertensive effect. The inhibitory effect of loxoprofen on the biosynthesis of prostaglandins may weaken the antihypertensive effect.

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

Over-the-Counter

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.