Clinical data | |
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Other names | Diacetylrhein; Diacerhein; 2-Anthracenecarboxylic acid, 4,5-bis(acetyloxy)-9,10-dihydro-9,10-dioxo-; 2-Anthroic acid, 9,10-dihydro-4,5-dihydroxy-9,10-dioxo-, diacetate; 9,10-Dihydro-4,5-dihydroxy-9,10-dioxo-2-anthroic acid, diacetate |
AHFS/Drugs.com | International Drug Names |
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Routes of administration | Oral |
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Pharmacokinetic data | |
Protein binding | 99% |
Metabolism | Hepatic: deacetylation to rhein, later glucuronidation and sulfate conjugation |
Elimination half-life | 4 to 5 hours |
Excretion | Renal (30%) |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.033.904 |
Chemical and physical data | |
Formula | C19H12O8 |
Molar mass | 368.297 g·mol−1 |
3D model (JSmol) | |
Solubility in water | Practically insoluble in water 0.01 mg/mL (20 °C) |
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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). [1] It works by inhibiting interleukin-1 beta. An updated 2014 Cochrane review found diacerein had a small beneficial effect on pain. [2] Diacerein-containing medications are registered in some European Union and Asian countries[ which? ] and included as a treatment option on several international therapeutic guidelines.[ which? ][ citation needed ]
There are many known methods synthesis of diacerein, most of which use aloin as a starting material. It's hydroxyl groups undergo acetylation, and then the intermediates are oxidised with chromic anhydride using acetic acid as a solvent. [3]
A less common method uses rhein as the starting compound. It involves diacetylation of the hydroxyl groups at positions C4 and C5 of rhein. [4]
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.[ citation needed ]
The most common side effects of diacerein treatment are gastrointestinal symptoms including soft stools and diarrhea. [5] 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. [6] [7]
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.
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. [8] 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.
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. [8]
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.
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