Clinical stidies have demonstrated the absence of interaction between diacerein and drugs such as warfarin, tolbutamide,aspirin (acetyl salicylic acid), chlorpromazine, and indomethicin.

Hence it is safe to use these drugs concomittantly

Osteoarthiritis of hip or knee

Diacerin is well tolerated. The prinicipal adverse events observed with diacerein are mild to moderate diarrhoea, which generally abate as treatment continues.

Other adverse effects include abdominal pan, and urine discoloration.

Hypersensitivity to diacerein or any components of the product Combined use of diacerein with laxitives is contraindicated

Special precautions-

It is recommended that diacerein be initiated during night time for the first 2 to 4 weeks since the use of the drug can initially produce an accelration of the intestinal transit time.

As with other prolonged treatment, it is recommended to monitor laboratory parameters including hepatic enzymes, every six months. Not recommeded to be used in pregnancy and lactation and in the pediatric population. Diacerein should be used with caution in elderly.

Daily doses exceeding 100mg warrant close monitoring In patients with severe hepatic insufficiency close clinical monitoring is advised, since cirrhosis may influence drug accumulation after multiple doses.

Diacerein dose should also be reduced by half in patients with a creatinine clearance less than 2.4 litres/hr.

Laxatives should not be taken with diacerein

Indication

Osteoarthiritis of the hip or knee

Dosage-

For initial 4 weeks , Diaceretin is administered as 50mg once daily after meals at nightbtime by BID.

Oral absorption is greatest when administered with food.

Not recommeded to be used in pregnancy and lactation and in the pediatric population. Diacerein should be used with caution in elderly.

Do not use with laxatives

Pharmacology-

The mechanism of action of diacerein differs from the NSAIDs since it is not related to the inhibition of the synthesis of the prostaglandins. anti-osteoartriritic and cartilage -stimulating properties have been demonstrated in the vitro and in animal models.

Diacerein have shown to inhibit the production of interleukin- 1 Beta by monocytes and the effects of the cytokine on chondrocytes in vivo. They exert chondroproterctive efects in cultured articular cartilage and reduce severity of cartilage bone, and synovial membrane damage in osteoarthiritis

Pharmacokinetics-

Oral bioavailability of diacerein is 35% to 58% . Concurrent intake of food delays the time of peak concentartion from 2.4 hours to 5.2 hours, but is assiciated with a increase of 25% in absorption. Therefore diacerein is best given with food.

Diacerein is excreted in urine in the form of its metabolites 35- 60% with approximately 20% as free rhein and 80% as congates of rhein.

Concurrent intake of food delays the time of peak concentartion from 2.4 hours to 5.2 hours, but is associated with a increase of 25% in absorption.

Therefore diacerin is best given with food.

Not recommeded to be used in pregnancy and lactation and in the pediatric population.

Children-

Should not be prescribed to children below 15 years age as no clinical studies have been undertaken in this age group.

Geriatric Use-

Safety and effectiveness in geriatric patients have not been established. The pharmacokinetics of diacerein is about the same in young healthy volunteers and elderly people with normal renal function both after a single ( 50mg ) or repeated doses of 25-75 mg twice daily)

Elderly patients with congestive heart failure with or without hepatic failure, had similar plasma rhein concentrations ( after administration of diacerein 50mg twice daily for 5 days) to heathy elderly patients with osteoarthiritis.