Xiamin

• Osteoarthritis (OA):
  • Indicated for symptomatic management of osteoarthritis, particularly in the knee and hip joints.
  • Used to relieve pain, improve joint function, and possibly delay progression of cartilage degeneration in mild to moderate OA.
  • Suitable for patients who require a combined approach with both symptom relief and disease-modifying effects.
• Other Clinically Accepted Uses:
  • Sometimes employed in other degenerative joint diseases where cartilage protection is desired.
  • Adjunct therapy to conventional analgesics or NSAIDs to reduce long-term dependency on anti-inflammatory drugs.
• Not indicated for:
  • Inflammatory arthritides such as rheumatoid arthritis.
  • Acute joint injuries or infections.

• Adults:
  • Glucosamine sulfate: Usually administered as 1,500 mg orally per day, divided into 1-3 doses.
  • Diacerein: Typically 50 mg orally twice daily (total 100 mg/day).
  • Combined fixed-dose preparations may vary; follow specific product labeling.
  • Duration: A minimum of 3 months is recommended to assess efficacy; treatment may continue up to 6 months or longer depending on clinical response.
• Elderly:
  • No routine dose adjustments required; monitor for tolerability and renal function.
• Pediatrics:
  • Safety and efficacy not established; use not generally recommended.
• Renal/Hepatic Impairment:
  • Caution advised; diacerein is contraindicated in severe hepatic or renal impairment.
• Administration:
  • Take orally with meals to reduce gastrointestinal irritation.
  • Tablets should be swallowed whole with sufficient fluid.

Glucosamine sulfate is a natural precursor in the synthesis of glycosaminoglycans and proteoglycans, essential components of cartilage matrix, promoting cartilage repair and maintenance. Diacerein is an anthraquinone derivative that inhibits interleukin-1 beta (IL-1β), a pro-inflammatory cytokine implicated in cartilage degradation and inflammation in osteoarthritis. By blocking IL-1β signaling pathways, diacerein reduces cartilage breakdown, inflammation, and symptoms associated with OA. The combination provides both substrate support for cartilage regeneration (glucosamine) and anti-inflammatory, disease-modifying effects (diacerein), leading to improved joint structure and symptom control.

• Glucosamine Sulfate:
  • Oral bioavailability ~20–30%.
  • Peak plasma concentrations reached in 2–3 hours.
  • Half-life approximately 15–20 hours.
  • Excreted primarily unchanged via renal elimination.
• Diacerein:
  • Rapidly converted in the intestine to active metabolite rhein.
  • Peak plasma concentrations of rhein occur within 2–6 hours post-dose.
  • Half-life of rhein approximately 4–5 hours.
  • Metabolized hepatically via glucuronidation and eliminated primarily via renal and biliary routes.

• Pregnancy:
  • Glucosamine sulfate: FDA Pregnancy Category B; animal studies show no teratogenicity, but human data are limited.
  • Diacerein: Contraindicated in pregnancy due to lack of safety data and potential adverse effects.
  • Overall, the combination should be avoided during pregnancy unless benefits clearly outweigh risks.
• Lactation:
  • Data are insufficient for both components; caution advised.
  • Breastfeeding mothers should consult healthcare providers prior to use.

• Primary Class: Symptomatic slow-acting drugs for osteoarthritis (SYSADOA)
• Subclass: Combination of cartilage precursors (glucosamine sulfate) and anti-inflammatory agents (diacerein)

• Known hypersensitivity to glucosamine sulfate, diacerein, or excipients.
• Severe hepatic impairment.
• Severe renal impairment (eGFR <30 mL/min).
• Inflammatory bowel disease or chronic diarrhea (due to diacerein).
• Pregnancy and lactation unless supervised by a healthcare professional.
• Children and adolescents under 18 years.

• High-risk groups:
  • Patients with liver or kidney disease require close monitoring.
  • Diacerein may cause or worsen diarrhea, especially in elderly patients—monitor bowel function.
  • Patients with gastrointestinal disorders should use cautiously.
• Serious Risks:
  • Rare hepatotoxicity reported with diacerein; monitor liver enzymes during prolonged use.
  • Diacerein-associated diarrhea can be severe and may require treatment discontinuation.
• Monitoring:
  • Liver and renal function tests periodically during therapy.
  • Observe for gastrointestinal adverse effects.

• Common:
  • Gastrointestinal: diarrhea (especially with diacerein), abdominal pain, dyspepsia, nausea.
  • Central nervous system: headache, dizziness.
  • Skin: rash or pruritus.
• Serious/Rare:
  • Hepatotoxicity (rare, diacerein).
  • Severe diarrhea possibly leading to dehydration.
  • Allergic reactions (rare).
• Onset & Dose Dependence:
  • GI side effects often appear within first weeks of treatment; may decrease over time.
  • Diarrhea frequency correlates with diacerein dose.

• Major Interactions:
  • Diacerein may enhance effects of anticoagulants, increasing bleeding risk—monitor coagulation parameters.
  • No significant CYP450-mediated interactions reported.
  • Use caution with other hepatotoxic drugs.
• Food Interactions:
  • Taking with food reduces gastrointestinal irritation, especially diarrhea with diacerein.
• Alcohol:
  • Avoid or limit due to increased risk of hepatotoxicity and GI irritation.

• Clinical Guidelines:
  • Recognized as a combination therapy option for OA in some international guidelines due to synergistic symptomatic and disease-modifying effects.
  • Recent evidence supports long-term safety and improved efficacy over monotherapy, particularly in knee OA.
  • Emphasis on monitoring for GI tolerance and liver function.
• Regulatory Notes:
  • Approved in many countries as fixed-dose combinations or separate agents.
  • Not universally recommended as first-line; often reserved for patients with inadequate response to standard therapies.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from excess moisture, heat, and direct sunlight.
• Keep in tightly closed containers.
• Avoid freezing or exposure to high humidity.
• Keep out of reach of children.