Diacerein
Diacerein (INN), also known as diacetylrhein, is a slow-acting medicine of the class anthraquinone used to treat joint diseases such as osteoarthritis (swelling and pain in the joints). It works by inhibiting interleukin-1 beta. An updated 2014 Cochrane review found diacerein had a small beneficial effect on pain. Diacerein-containing medications are registered in some European Union and Asian countries and included as a treatment option on several international therapeutic guidelines. Pharmacology. Diacerein works by blocking the actions of interleukin-1 beta, a protein involved in the inflammation and destruction of cartilage that plays a role in the development  of symptoms of degenerative joint diseases such as osteoarthritis. Due to its specific mode of action, which does not involve the inhibition of prostaglandin synthesis, diacerein has been shown to have anti-osteoarthritis and cartilage stimulating properties in vitro and animal models. Side effects. The most common side effects of diacerein treatment are gastrointestinal symptoms including soft stools and diarrhea. These are generally mild to moderate and occur more frequently in the first 2 weeks, and lessen with continued treatment. Based on review by European Medicines Agency (EMA), diacerein-containing medicines use is restricted due to severe diarrhoea and liver  disorders in patients. An uncommon side effect is hepatic adverse events (most frequently reported as liver function test abnormalities). These have been described as mild/moderate cases of elevated liver enzymes in the blood. Mild skin reactions (rash, pruritus and eczema) have also been reported with diacerein treatment. Discoloration of urine (yellow or pink) is another side effect of diacerein. This effect is due to the elimination of rhein metabolites via the urine and no clinical significance has been found; it may also be dependent on general fluid intake. Special warning. In 2014 the European Medicines Agency (EMA’s) Pharmacovigilance  and Risk Assessment Committee (PRAC) performed a review of diacerein-containing medicines over concerns about its gastrointestinal and liver effects. As a result, the PRAC has introduced additional proposals to manage diacerein’s risks and was satisfied that with new restrictions diacerein’s benefit on pain outweighs the side effects for osteoarthritis treatment. The following recommendations have been made around the use of diacerein: The PRAC concluded that the benefit-risk balance of diacerein-containing medicinal products remained favourable in the symptomatic treatment osteoarthritis, subject to the agreed changes to the product information and conditions. Dosage and administration. The recommended  starting dose is 50 mg once daily with evening meal for the first 2 to 4 weeks of treatment, after which the recommended daily dose is 50 mg twice daily. The treatment should be taken with food, one with breakfast and the other with evening meal. The capsules must be swallowed intact, without opening them, together with a glass of water.