Each capsule contains: Diacerein (Manufacturer's Specs.) 50 mg.
Pharmacology: Pharmacodynamics: The mechanism of action differs from the nonsteroidal anti inflammatory drugs since it is not related to the inhibition of the synthesis of the prostaglandins. Antiosteoarthritic and cartilage-stimulating properties have been demonstrated in vitro and in animal models. Diacerein and its active metabolite have been shown to inhibit the production of interleukin-1 beta by human monocytes and the effects of the cytokine on chondrocytes in vivo. They exert chondro protective effects in cultured articular cartilage and reduce severity of cartilage, bone, and synovial membrane damage in osteoarthritis. There appear to be some inhibitory effects on leucocyte migration and activation, contributing to the weak anti-inflammatory activity of the drug. Studies indicate that Diacerein does not block the synthesis of prostaglandins, thromboxanes, or leukotrienes but may actually stimulate prostaglandin synthesis, especially PGF-2 alpha, a prostaglandin with cytoprotective effect on the gastric mucosa.
Diacerein in therapeutic doses inhibits the stimulation of interleukin-1 beta production and production of nitrous oxide. It also significantly reduces severity of pathological changes of osteoarthritis compared to placebo and increases the expression of transforming growth factor (TGF)-beta1 and TGF-beta 2, with potential cartilage repairing properties. Diacerein does not alter renal or platelet cyclo-oxygenase activity and may therefore be tolerated by patients with prostaglandin-dependent renal function.
Pharmacokinetics: Absorption: Oral bioavailability of Diacerein is 35% to 56%. Concurrent intake of food delays the time to peak concentration from 2.4 hours to 5.2 hours (p less than 0.05), but is associated with a 25% increase in absorption. Therefore, Diacerein is best given with food.
Distribution: Total protein binding of the active metabolite is about 99% to plasma albumin and in a lesser percentage to lipoproteins and gamma-immunoglobulins. It achieves synovial fluid concentration of 0.3 to 3.0 milligrams/liter.
Metabolism: Diacerein is metabolized extensively (100%) in liver following oral dosing, to the deacetylated active metabolite rhein, prior to entering systemic circulation. Major active metabolites include rhein glucuronide and rhein sulfate with half-life being 7 to 8 hours.
Excretion: Urinary excretion of Diacerein in the form of its metabolites has ranged between 35% and 60%, with approximately 20% as free rhein and 80% as conjugates of rhein.
Diacerein is indicated for the treatment of osteoarthritis of the hip or knee.
KARTY 50 mg is to be administered orally, twice daily, for the treatment of osteoarthritis of the hip or knee. Initiate the treatment with one capsule night time for 2 to 4 weeks; gradually adjust the dose to two capsules twice daily. Oral absorption is greatest when administered with food.
In case of overdose it can produce a profuse diarrhea. The treatment must be symptomatic with correction of any electrolyte imbalance, which may be necessary.
Hypersensitivity to diacerein or any of the components.
Renal Impairment: In patients with mild-to-severe renal impairment, there was a significant increase in the area-under-the-curve and a decrease in the total apparent clearance compared to the healthy adults. Severe renal failure (creatinine clearance 10 to 27 milliliters/minute) showed a significantly decreased renal clearance of rhein, therefore, a 50% reduction in the dose of Diacerein should be made in patients with severe renal insufficiency.
Hepatic Impairment: No significant difference in pharmacokinetic parameters of rhein between patients with liver impairment and healthy volunteers was observed either in plasma or in urine assessments. However, since cirrhosis may influence drug accumulation after multiple doses, close clinical monitoring is advised for patients with hepatic insufficiency.
Use in Pregnancy: Use of Diacerein is not recommended in women attempting to conceive. No clinical data on exposed pregnancies are available for Diacerein. The potential for human risk in pregnancy is unknown.
Use in Lactation: Pharmacokinetics of Diacerein has not been studied in lactating women and its administration is not recommended.
Use in Children: Pharmacokinetics of Diacerein has not been studied in pediatric population and its administration is not recommended in pediatric population.
Use in the Elderly: Daily doses exceeding 100 milligrams may warrant close clinical monitoring in geriatric patients.
Pregnancy: Use of Diacerein is not recommended in women attempting to conceive. No clinical data on exposed pregnancies are available for Diacerein. The potential for human risk in pregnancy is unknown.
Lactation: Pharmacokinetics of Diacerein has not been studied in lactating women and its administration is not recommended.
Generally, the drug has been well tolerated.
The commonest reported adverse reaction was acceleration of the time of intestinal transit (diarrhea 37% of patients). Few cases of abdominal pains have been described. The modification of the dose in the initial periods of the treatment (2 to 4 weeks) has allowed to surpass or to diminish these adverse events.
Other adverse events reported are urine discoloration in 14.4% cases and single case of hypokalemia, hepatotoxicity resulting into acute hepatitis and fatal toxic epidermal necrolysis (Lyell's syndrome).
The clinical studies have demonstrated the absence of interaction with the drugs such as: warfarin, tolbutamide, aspirin (acetylsalicylic acid), chlorpromazine, indomethacin.
General: It is recommended to initiate therapy with one capsule at night for the first 2 to 4 weeks as use of the drug can produce an acceleration of the intestinal transit time initially.
It is recommended to continue treatment for at least 6 months. The clinical studies have demonstrated that the drug can be used for 2 years without serious adverse effects.
As with any other long term therapy, it is recommended to monitor laboratory parameters, including hepatic enzymes, every 6 months.
Combined use with laxatives is contraindicated.
Instructions: Store below 30°C.
Protect from heat, sunlight & moisture.
M01AX21 - diacerein ; Belongs to the class of other non-steroidal antiinflammatory and antirheumatic products.