Oxicamox (Tablets) Instructions for Use

Marketing Authorization Holder

Sandoz, d.d. (Slovenia)

Manufactured By

Cipla Ltd. (India)

ATC Code

M01AC06 (Meloxicam)

Active Substance

Meloxicam (Rec.INN registered by WHO)

Dosage Forms

	Oxicamox	Tablets 7.5 mg: 10, 20, 50 or 100 pcs.
		Tablets 15 mg: 10, 20, 50 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets from light yellow to light yellow with a slight greenish tint, round, flat, with a score on one side and a bevel.

Excipients: corn starch – 22 mg, pregelatinized starch – 9.5 mg, colloidal anhydrous silicon dioxide – 0.8 mg, sodium citrate dihydrate – 10 mg, lactose monohydrate – 43 mg, microcrystalline cellulose – 66.4 mg, magnesium stearate – 0.8 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Tablets from light yellow to light yellow with a slight greenish tint, round, flat, with a score on one side and a bevel.

Excipients: corn starch – 44 mg, pregelatinized starch – 19 mg, anhydrous silicon dioxide – 1.6 mg, sodium citrate dihydrate – 20 mg, lactose monohydrate – 86 mg, microcrystalline cellulose – 132.8 mg, magnesium stearate – 1.6 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID with analgesic, anti-inflammatory and antipyretic effects. The mechanism of the pronounced anti-inflammatory action of meloxicam is associated with the selective suppression of the COX-2 enzyme, which is involved in the biosynthesis of prostaglandins in the area of inflammation.

Ex vivo studies have established that Meloxicam (in doses of 7.5 mg and 15 mg) more actively inhibited COX-2, exerting a greater inhibitory effect on the production of prostaglandin E2 (a reaction controlled by COX-2) than on the production of thromboxane involved in the blood clotting process (a reaction controlled by COX-1). These effects were dose-dependent. Ex vivo studies have shown that Meloxicam in recommended doses did not affect platelet aggregation and bleeding time, unlike indomethacin, diclofenac, ibuprofen and naproxen, which significantly suppressed platelet aggregation and increased bleeding time. When prescribed in high doses, with long-term use and due to individual characteristics, COX-2 selectivity decreases.

It suppresses the synthesis of prostaglandins in the area of inflammation to a greater extent than in the gastric mucosa or kidneys, which is associated with relatively selective inhibition of COX-2. It less often causes erosive and ulcerative lesions of the gastrointestinal tract. Meloxicam has a lesser effect on COX-1, which is involved in the synthesis of prostaglandins that protect the gastrointestinal mucosa and are involved in the regulation of renal blood flow.

Pharmacokinetics

Absorption

Meloxicam is well absorbed from the gastrointestinal tract, oral bioavailability is 89%, food intake does not affect absorption. The equilibrium concentration in plasma is reached 3-5 days after the start of taking the drug. When taken orally, C_max in plasma is reached after 5-6 hours. Does not accumulate.

Distribution

Plasma protein binding is more than 99%. The range of differences between maximum and basal concentrations of meloxicam when taken once a day is relatively small and is in the range of 0.4-1 µg/ml for a dose of 7.5 mg and 0.8-2 µg/ml for a dose of 15 mg (C_min and C_max values are given, respectively). Meloxicam penetrates through histohematic barriers, the concentration in the synovial fluid reaches 50% of the C_max of the drug in plasma.

Metabolism

Almost completely metabolized in the liver with the formation of four pharmacologically inactive derivatives. The main metabolite, 5′-carboxymeloxicam (60% of the dose), is formed by oxidation of an intermediate metabolite, 5′-hydroxycarboxymeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies have shown that the isoenzyme CYP2C9 plays an important role in this metabolic transformation, and the isoenzyme CYP3A4 is of additional importance. Peroxidase, whose activity probably varies individually, is involved in the formation of two other metabolites (constituting 16% and 4% of the drug dose, respectively).

Excretion

It is excreted through the intestines and kidneys in equal proportions, mainly in the form of metabolites. 5% of the daily dose is excreted unchanged through the intestines; in urine, the drug is found unchanged only in trace amounts. T_1/2 of meloxicam is 15-20 hours.

Plasma clearance averages 8 ml/min (decreases in the elderly). V_d is low and averages 11 L.

Pharmacokinetics in special clinical cases

Mild to moderate hepatic and renal impairment do not significantly affect the pharmacokinetic parameters of meloxicam. In severe renal failure, due to reduced drug excretion, the daily dose should not exceed 7.5 mg.

Indications

Symptomatic therapy of the following diseases

• Osteoarthritis;
• Acute and chronic rheumatoid arthritis;
• Ankylosing spondylitis;
• Gout and other inflammatory and degenerative joint diseases accompanied by pain syndrome.

ICD codes

Dosage Regimen

The drug is taken orally with meals at a daily dose of 7.5-15 mg. The drug should be taken during or after meals with water or milk (fluid volume not less than 100 ml). The recommended daily dose is 7.5 mg; maximum -15 mg. In elderly patients and in patients with severe renal failure on hemodialysis, the daily dose should not exceed 7.5 mg. In moderate renal failure (creatinine clearance more than 25 ml/min), as well as in moderate hepatic impairment, dose adjustment is not required.

Adverse Reactions

The frequency of adverse effects is characterized as common (≥1/10), uncommon (≥1/1000, <1/10), rare (≥1/1000).

From the digestive system common – dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea; uncommon – gastrointestinal bleeding (including occult), peptic ulcers, gastroduodenal ulcer, esophagitis, stomatitis, transient increase in liver transaminase activity, hyperbilirubinemia, belching; rare – gastrointestinal perforation, gastritis, colitis, hepatitis.

From the CNS common – dizziness, headache; uncommon – tinnitus, drowsiness; rare – confusion, disorientation, insomnia, emotional lability.

From the hematopoietic organs common – anemia; uncommon – changes in blood count, leukopenia, thrombocytopenia; rare – agranulocytosis.

Allergic reactions rare – angioedema, anaphylactoid/anaphylactic reactions.

From the cardiovascular system common – peripheral edema; uncommon – increased blood pressure, palpitations, flushing.

From the respiratory system rare – bronchospasm.

From the skin common – itching, skin rash; uncommon – urticaria; rare – bullous eruptions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, photosensitivity.

From the sense organs rare – conjunctivitis, visual disturbances, including blurred vision.

From the urinary system uncommon – hypercreatininemia and/or increased serum urea, sodium and water retention, hyperkalemia; rare – acute renal failure in patients at increased risk; connection with meloxicam intake not established – interstitial nephritis, albuminuria, hematuria.

Contraindications

• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption;
• Complete or incomplete combination of bronchial asthma, recurrent nasal and sinus polyposis and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including history);
• Erosive and ulcerative changes in the gastric or duodenal mucosa;
• Gastrointestinal, cerebrovascular and other bleeding, including history (or suspicion of bleeding);
• Inflammatory bowel diseases (ulcerative colitis, Crohn’s disease);
• Severe hepatic failure or active liver disease;
• Chronic renal failure in patients not undergoing dialysis (creatinine clearance less than 30 ml/min), progressive kidney diseases, including confirmed hyperkalemia;
• Condition after coronary artery bypass grafting;
• Decompensated heart failure;
• Pregnancy;
• Breastfeeding period;
• Children under 15 years of age;
• Hypersensitivity to meloxicam or any other component of the drug and other NSAIDs.

With caution: coronary artery disease, cerebrovascular diseases, congestive heart failure, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial diseases, smoking, chronic renal failure with creatinine clearance 30-60 ml/min.

History of gastrointestinal ulcer disease, presence of Helicobacter pylori infection, elderly age, long-term use of NSAIDs, frequent alcohol consumption, severe somatic diseases, concomitant therapy with the following drugs: anticoagulants (e.g., warfarin), antiplatelet agents (acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline).

To reduce the risk of adverse events, the minimum effective dose should be used for the shortest possible duration.

Use in Pregnancy and Lactation

In the first and second trimesters of pregnancy, the drug can be prescribed only if the intended benefit to the mother outweighs the potential risk to the fetus. If it is necessary to prescribe the drug during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure or active liver disease.

Use in Renal Impairment

Contraindicated in chronic renal failure in patients not undergoing dialysis (creatinine clearance less than 30 ml/min), in progressive kidney diseases, including confirmed hyperkalemia.

With caution: chronic renal failure with creatinine clearance 30-60 ml/min.

In patients with severe renal failure on hemodialysis, the daily dose should not exceed 7.5 mg. In moderate renal failure (creatinine clearance more than 25 ml/min), dose adjustment is not required.

Pediatric Use

Contraindicated in children under 15 years of age.

Geriatric Use

Use with caution in the elderly.

In elderly patients, the daily dose should not exceed 7.5 mg.

Special Precautions

During long-term treatment, monitoring of the peripheral blood picture, electrolyte balance, blood coagulation system and functional state of the liver and kidneys is necessary. When using the drug, an increase in the concentration of liver enzymes and urea in the blood serum may be observed. These changes are mild and transient. In case of pronounced changes, the drug should be discontinued.

Caution should be exercised when using the drug in patients with a history of gastric and duodenal ulcers, as well as in patients on anticoagulant therapy. Such patients have an increased risk of erosive and ulcerative lesions of the gastrointestinal tract.

If symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, blood test with determination of hemoglobin, hematocrit, stool test for occult blood.

To prevent the development of gastropathy, it is recommended to combine with protective drugs, for example, misoprostol or proton pump inhibitors.

Long-term use of Oxicamox by patients with uncontrolled high blood pressure, heart failure, concomitant coronary artery disease, occlusive lesions of peripheral arteries and/or cerebrovascular diseases, with risk factors for the development of cardiovascular diseases (for example, high blood pressure, hyperlipidemia, diabetes mellitus, smoking), should be carried out only after a thorough examination.

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

Patients taking diuretics and Meloxicam simultaneously should take sufficient amounts of fluid.

In patients with mild or moderate renal impairment (creatinine clearance more than 30 ml/min), no adjustment of the dosing regimen is required.

Meloxicam, like other NSAIDs, may mask the symptoms of infectious diseases.

If allergic reactions occur during treatment (itching, skin rash, urticaria, photosensitivity), it is necessary to consult a doctor to decide whether to discontinue the drug. In patients with an increased risk of adverse effects, treatment is started with a dose of 7.5 mg.

In patients with dehydration of various etiologies, chronic heart failure, liver cirrhosis, nephrotic syndrome, taking diuretics, with clinically significant kidney diseases, daily diuresis and kidney function should be monitored.

The use of meloxicam, like other drugs that block the synthesis of prostaglandins, may affect fertility, so it is not recommended for women planning pregnancy.

During treatment, it is not recommended to take ethanol.

Special precautions for the disposal of unused medicinal product

No special precautions are required for the disposal of unused Oxicamox.

Effect on ability to drive vehicles and operate machinery

No specific studies have been conducted regarding the effect of the drug on the ability to drive vehicles and operate machinery, nevertheless, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms dizziness, nausea, vomiting, pain in the epigastric region. Gastrointestinal bleeding, acute renal failure, acute liver failure, respiratory arrest, asystole are possible.

Treatment gastric lavage no later than 6 hours after ingestion, forced diuresis, symptomatic therapy. There is no specific antidote. Hemodialysis is ineffective.

Drug Interactions

Concomitant use of meloxicam and other NSAIDs or acetylsalicylic acid is not recommended, as it may increase the risk of gastrointestinal ulceration and bleeding.

Concomitant use of meloxicam with lithium preparations may lead to an increase in the concentration of these drugs in the serum.

NSAIDs may weaken the effect of diuretics and antihypertensive drugs. In patients with impaired renal function (e.g., dehydrated or elderly patients), concomitant use of ACE inhibitors or angiotensin II receptor antagonists with drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible development of acute renal failure, which in most cases is reversible.

When meloxicam is used concomitantly with glucocorticosteroids, selective serotonin reuptake inhibitors (citalopram, fluoxetine, paroxetine, sertraline), the risk of gastrointestinal ulcers and serious gastrointestinal bleeding increases.

Concomitant use of meloxicam with methotrexate may lead to an increase in the concentration of the latter in the blood serum and an increase in its toxic effects (risk of anemia and leukopenia, periodic complete blood count is recommended).

The risk of nephrotoxic effects associated with the use of cyclosporine, gold preparations, increases with concomitant use with meloxicam. Concomitant use also increases the hepatotoxicity of cyclosporine.

When meloxicam is used concomitantly with anticoagulants (warfarin) or thrombolytics (alteplase, streptokinase, urokinase), the risk of bleeding increases.

Inducers of microsomal oxidation (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, increasing the risk of severe intoxication.

Inhibitors of microsomal oxidation reduce the risk of hepatotoxic action of meloxicam.

When used concomitantly with intrauterine contraceptive devices, the effectiveness of the latter may be reduced.

Caffeine enhances the analgesic effect of meloxicam.

Cholestyramine reduces the absorption of meloxicam.

Storage Conditions

Store the drug in a place inaccessible to children, dry, protected from light, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 2.5 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

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.