Diaflex Chondro (Capsules) Instructions for Use

Marketing Authorization Holder

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

ATC Code

M01AX (Other non-steroidal anti-inflammatory drugs)

Active Substances

Chondroitin sulfate sodium (Ph.Eur.)

Diacerein (Rec.INN)

Dosage Form

Diaflex Chondro

Capsules 25 mg+200 mg: 30, 60 or 90 pcs.

Dosage Form, Packaging, and Composition

Capsules with a brown cap and a white body; the capsule contents are a granular powder ranging from yellow or yellowish-greenish to yellowish-brown in color.

Excipients: anhydrous lactose, povidone K30, colloidal silicon dioxide, magnesium stearate.

Capsule shell composition body: titanium dioxide (E171), gelatin; cap: titanium dioxide (E171), red iron oxide (E172), gelatin.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.
10 pcs. – blisters (9) – cardboard packs.

Clinical-Pharmacological Group

Drug used for inflammatory and inflammatory-dystrophic diseases of the musculoskeletal system

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs; non-steroidal anti-inflammatory and antirheumatic drugs; other non-steroidal anti-inflammatory and antirheumatic drugs

Pharmacological Action

Diacerein inhibits the synthesis and activity of interleukin-1 (IL-1), which plays an important role in the development of inflammation, degradation, and subsequent destruction of cartilage in osteoarthritis.

Furthermore, Diacerein inhibits the action of other cytokines that cause inflammation, including interleukin-6 (IL-6), TNFα. Diacerein also slows down the synthesis of metalloproteinases (collagenase, elastase), which are involved in the process of cartilage tissue damage.

With long-term use, Diacerein stimulates the synthesis of proteoglycans and does not affect the synthesis of prostaglandins.

Chondroitin sulfate affects metabolic processes in hyaline and fibrous cartilage, reduces degenerative changes in the articular cartilage tissue, and stimulates the biosynthesis of glycosaminoglycans.

It slows down bone tissue resorption and reduces calcium loss, accelerating bone tissue repair processes.

When chondroitin sulfate is used, pain decreases and mobility of the affected joints improves. The therapeutic effect persists for a long time after the end of the course of therapy.

Pharmacokinetics

Diacerein

After oral administration, Diacerein is rapidly absorbed from the gastrointestinal tract. Simultaneous administration with food increases the bioavailability of diacerein by 25%.

It is completely metabolized (deacetylated) to the active metabolite, rhein. C_max of rhein in plasma is reached after 144 minutes.

After a single dose of 50 mg, C_max reaches 3.15 mg/L. With repeated administration of the drug, C_max increases due to the accumulation of diacerein.

The binding of rhein to plasma proteins (albumin) is almost 100%. Rhein crosses the placental barrier and the blood-brain barrier. T_1/2 from plasma is 255 min.

Rhein is excreted by the kidneys unchanged (20%) and in the form of glucuronide (60%) and sulfate (20%).

Chondroitin sulfate

Exogenous chondroitin sulfate is absorbed after oral administration in the form of a high molecular weight polysaccharide along with derivatives resulting from partial depolymerization and/or desulfation.

After absorption, the original substance and its fragments reach the synovial fluid and articular cartilages.

The majority of the oral dose of chondroitin sulfate is metabolized both before and after absorption by hydrolysis to monosaccharides, and to a lesser extent to di-, oligo-, and polysaccharides.

Chondroitin sulfate is excreted in urine and feces in the form of monosaccharides and oligosaccharides.

Indications

Symptomatic treatment of osteoarthritis of the knee and hip joints.

ICD codes

Dosage Regimen

Take orally. The standard adult dosage is one capsule twice daily, providing a total daily dose of 50 mg diacerein and 400 mg chondroitin sulfate sodium.

Administer with meals to improve tolerability and increase diacerein bioavailability.

Initiate treatment with one capsule once daily for the first 2-4 weeks to assess gastrointestinal tolerance, particularly to diacerein.

For long-term symptomatic treatment of osteoarthritis, continue the twice-daily regimen. The therapeutic effect develops slowly and may take several weeks to manifest.

The duration of treatment is long-term, based on clinical response. Regularly reassess the need for continued therapy.

In patients over 65 years, use with caution; no specific dosage adjustment is required but monitor for adverse effects more frequently.

Discontinue immediately if severe diarrhea or abdominal pain occurs. Do not use in patients with a history of liver disease.

For moderate renal impairment (creatinine clearance 30-60 mL/min), use with caution. It is contraindicated in severe renal impairment (creatinine clearance less than 30 mL/min).

Adverse Reactions

Digestive system diarrhea, abdominal pain, nausea, flatulence.

Metabolism water-electrolyte imbalance due to diarrhea.

Liver and biliary tract acute liver damage, including increased activity of liver enzymes in the blood serum.

Nervous system dizziness.

Skin and subcutaneous tissues itching, rash, eczema, erythema.

Immune system urticaria, facial edema, angioedema.

Other during treatment, intense coloration of urine from yellow to brown (depending on pH) may occur, which does not require dose reduction (discontinuation) of this agent.

Contraindications

Hypersensitivity to diacerein, chondroitin sulfate; hypersensitivity to anthraquinone derivatives, e.g., laxative drugs; inflammatory bowel diseases (ulcerative colitis, Crohn’s disease); intestinal obstruction or pseudo-obstruction; abdominal pain syndrome of unclear etiology; current liver diseases and/or history of liver diseases; severe renal failure (creatinine clearance less than 30 ml/min) and history of kidney diseases; children and adolescents under 18 years of age.

With caution

Patients with bleeding or tendency to bleeding; moderate renal failure (creatinine clearance 30-60 ml/min) or chronic renal failure; irritable bowel syndrome; age over 65 years.

Use in Pregnancy and Lactation

There are no data on the use of diacerein and chondroitin sulfate in pregnant women. Use during pregnancy is not recommended.

Diacerein is capable of being excreted in breast milk. It is unknown whether chondroitin sulfate or its metabolites pass into breast milk. A possible risk to newborns/infants cannot be excluded. Use of this combination during breastfeeding is not recommended. If use during lactation is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindicated in liver diseases and/or history of liver diseases.

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance less than 30 ml/min) and history of kidney diseases.

Use with caution in moderate renal failure (creatinine clearance 30-60 ml/min) or in chronic renal failure.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients over 65 years of age.

Special Precautions

The duration of treatment, depending on the result achieved, can be long.

Periodic monitoring of blood counts, liver enzymes, and urine is necessary.

If kidney function worsens, the dose of this agent should be reduced.

The use of diacerein in rapidly progressive osteoarthritis is not recommended due to the slow development of the clinical effect.

If diarrhea develops, the intake of this agent should be discontinued.

Caution should be exercised when used concomitantly with diuretics, as dehydration and hypokalemia may develop. Particular caution should be exercised in case of hypokalemia in patients receiving cardiac glycosides (digoxin, digitoxin).

Before starting treatment, an examination should be performed to identify disorders of the functional state of the liver.

It is necessary to monitor laboratory and clinical manifestations of liver damage, and to take precautions when used concomitantly with other drugs with a characteristic risk of hepatotoxic reactions.

Patients should be advised to limit alcohol consumption during treatment.

Treatment should be discontinued if an increase in liver enzyme activity is detected or if symptoms of liver damage are suspected.

Drug Interactions

Medicinal products containing aluminum hydroxide and/or magnesium hydroxide (antacids) reduce the absorption of diacerein.

When taken concomitantly with antibiotics or chemotherapeutic drugs that affect the intestinal microflora, the frequency of adverse intestinal reactions may increase.

When used concomitantly with diuretics (“loop” and thiazide) and/or cardiac glycosides (digoxin, digitoxin), the risk of arrhythmia increases.

Concomitant use with laxatives, as well as with substances that increase the volume of intestinal contents and the rate of its emptying (e.g., a large amount of fiber), is not recommended.

It is possible to enhance the effect of indirect anticoagulants, antiplatelet agents, and fibrinolytics when used concomitantly with chondroitin sulfate, which will require more frequent monitoring of blood coagulation parameters.

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.