diacerein

Actions and Spectrum: 

diacerein’s primary mechanism of action involves its effects on the inflammatory processes and cartilage metabolism within joints: 

• Inhibition of Interleukin-1 (IL-1): diacerein inhibits the production of interleukin-1 beta (IL-1β), a pro-inflammatory cytokine crucial in promoting inflammation and cartilage degradation in osteoarthritis. By reducing IL-1β levels, diacerein helps decrease inflammation in the joints. 
• Stimulation of Glycosaminoglycan Synthesis: diacerein stimulates the synthesis of glycosaminoglycans (GAGs), essential cartilage components. This action may contribute to maintaining and repairing cartilage within the joints. 
• Modulation of Matrix Metalloproteinases (MMPs): diacerein may also help modulate the activity of matrix metalloproteinases (MMPs), enzymes that break down cartilage. By reducing MMP activity, diacerein may help protect cartilage from degradation. 

diacerein’s spectrum of activity is primarily focused on osteoarthritis: 

• Osteoarthritis: diacerein is approved for treating osteoarthritis, a degenerative joint disorder characterized by the breakdown of cartilage, inflammation, and pain in the affected joints. It is particularly indicated for osteoarthritis of the hip and knee joints. 
• Anti-Inflammatory Effects: diacerein’s ability to inhibit IL-1β production contributes to its anti-inflammatory properties, which can help reduce pain, swelling, and stiffness associated with osteoarthritis. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency not defined 

Stomach discomfort and pain 

Vomiting 

Urine discoloration 

Diarrhea 

Nausea 

Yellowing of eyes and skin 

Black box warning: 

None 

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: Patients with known hypersensitivity or allergy to diacerein or its components should not use this medication. 
• Severe Liver Disorders: diacerein is metabolized by the liver, and patients with severe liver disorders or impaired liver function should use this medication with caution, if at all. 
• Severe Renal Impairment: Patients with severe kidney impairment or end-stage renal disease may need to avoid diacerein due to potential drug clearance and accumulation issues. 
• Children: diacerein’s safety and efficacy in children need to be better established, and its use in pediatric patients is generally discouraged. 
• Inflammatory Bowel Disease (IBD): There have been reports of gastrointestinal side effects associated with diacerein, including diarrhea. Therefore, it is usually not recommended in patients with a history of inflammatory bowel disease or chronic diarrhea. 

Caution: 

• Gastrointestinal Effects: diacerein has been associated with gastrointestinal side effects, including diarrhea. Patients who experience persistent or severe gastrointestinal disturbances while taking diacerein should consult their healthcare provider.  
• Liver Function: diacerein is metabolized by the liver. Patients with liver impairment should use diacerein cautiously, as its metabolism might be affected, potentially leading to altered drug clearance and accumulation. 
• Renal Function: While diacerein’s effects on renal function are generally considered minimal, caution should still be exercised in patients with impaired kidney function. Adequate hydration is recommended to reduce the risk of kidney stone formation. 

Pregnancy consideration: diacerein is generally contraindicated during pregnancy due to concerns about potential effects on the developing fetus. 

Lactation: It is also not recommended during breastfeeding, as the effects on the nursing infant are not well established. 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology: 

diacerein’s mechanism of action is multifaceted and involves several key aspects: 

• Inhibition of IL-1β Production: diacerein inhibits the production of interleukin-1 beta (IL-1β), a pro-inflammatory cytokine. IL-1β plays a significant role in promoting inflammation and cartilage degradation in osteoarthritis. By reducing IL-1β levels, diacerein contributes to reducing inflammation within the joints. 
• Stimulation of GAG Synthesis: diacerein stimulates the synthesis of glycosaminoglycans (GAGs) within cartilage. GAGs are essential components of the extracellular matrix of cartilage, and their enhancement may contribute to the maintenance and repair of cartilage. 

Pharmacokinetics: 

Absorption 

diacerein is absorbed from the gastrointestinal tract after oral administration. It undergoes biotransformation in the liver to its active metabolite, rhein. 

Distribution 

The active metabolite, rhein, is distributed throughout the body, including joint tissues. 

Metabolism 

diacerein is metabolized into rhein through glucuronidation in the liver. Rhein is the compound responsible for the majority of diacerein’s therapeutic effects. 

Elimination and Excretion 

Both diacerein and its active metabolite, rhein, are excreted mainly through the urine. The elimination half-life of diacerein is relatively short, while rhein’s half-life is more prolonged. 

Administration: 

Oral administration 

diacerein is typically taken orally with water, and it is recommended to take it with a meal to help minimize gastrointestinal side effects. Taking it with food can also enhance its absorption. 

Patient information leaflet 

Generic Name: diacerein  

Why do we use diacerein? 

diacerein is primarily used for the treatment of osteoarthritis. It has anti-inflammatory and potential disease-modifying effects on joint structures. Here are the common uses of diacerein: 

• Osteoarthritis: diacerein is mainly prescribed for treating osteoarthritis, a degenerative joint disorder characterized by the breakdown of cartilage, inflammation, and pain in the affected joints. It is commonly used for osteoarthritis of the hip and knee joints. 
• Pain Relief: diacerein’s anti-inflammatory effects help reduce pain, swelling, and stiffness associated with osteoarthritis. 
• Potential Disease-Modifying Effects: By stimulating glycosaminoglycan synthesis and modulating matrix metalloproteinase activity, diacerein may slow down the progression of joint damage and provide disease-modifying benefits.