Indications
Treatment of symptoms in patients with osteoarthritis of the hip or knee, with delayed effect.
Treatment with diacerein is not recommended in patients with rapidly progressive hip osteoarthritis, as
they may have a weaker response to diacerein.
Dosage and administration
The treatment should be started by specialists experienced in the treatment of osteoarthritis.
Usual adult dose: Because some patients may develop loose stools or diarrhea, the recommended starting dose is 50 mg once daily with evening meal for the first 2 – 4 weeks of treatment. Thereafter the recommended daily dose is 50 mg twice daily. The capsule should be taken with meal (one with breakfast and the other with evening meal).
Agdicerin must be swallowed intact (without opening them) with a glass of water.
However, diacerein exhibits late onset of action and its beneficial effect is observed after 2-4 weeks of treatment, patients should be advised not to discontinue the treatment before the effectiveness of diacerein is apparently observed. Since diacerein does not inhibit prostaglandin synthesis, it causes no harm to the stomach. Diacerein may be safely associated with a nonsteroidal anti-inflammatory drug (NSAID) for the first 2-4 weeks of treatment.
Diacerein is not recommended in patients older than 65 years.
Contraindications
Patients with a history of hypersensitivity to diacerein or any excipients of this product and anthraquinone derivatives.
Patients with current and/or a history of liver disease.
The benefit/risk ratio of diacerein use in patients with previous episodes of enterocolic disturbances, especially irritable colon, must be considered.
Pregnant women and breastfeeding mothers.
Warnings and Precautions
Diarrhea:
Regular administration of diacerein can cause diarrhea (see undesirable effects), resulting in dehydration and hypokalaemia. Patients should be advised to stop diacerein treatment in case of diarrhoea and contact their doctor to discuss treatment alternatives.
Caution should be exercised in patients taking diuretics due to increased risk of dehydration and hypokalaemia. Particular caution should be taken to prevent hypokalaemia in patients receiving concomitantly cardiac glycosides (digitoxin, digoxin).
Avoid concurrent use of diacerein with laxatives.
Hepatotoxicity:
Increased serum hepatic enzyme levels and symptoms of acute hepatic injury have been reported with diacerein in the post-marketing phase (see undesirable effects).
Before starting the treatment with diacerein, the patient should be questioned about possible comorbid
conditions and past or concurrent liver disease and screened for major causes of active hepatic disease.
If a diagnosis of liver disease is determined, diacerein is contraindicated (see contraindications).
Signs of hepatic injury should be closely monitored and caution should be taken when diacerein is used
concomitantly with other medicinal products associated with hepatic injury. Patients should be advised
to limit their alcohol intake during the treatment with diacerein.
Diacerein should be discontinued if elevated hepatic enzymes or suspected signs or symptoms of liver damage are detected. Patients should be advised about the signs and symptoms of hepatotoxicity and must be suggested to immediately contact their physician in case of detecting symptoms of liver damage.
Renal insufficiency modifies the pharmacokinetics of diacerein and therefore a dose reduction is recommended in such cases (creatinine clearance < 30 ml/min).
Diacerein should not be prescribed to children below 15 years old as no clinical studies have been undertaken in this age-group.
Interactions
Diacerein can cause diarrhea and hypokalaemia. Caution should be used concurrently with diuretics (diuretics and thiazide) or with cardiac glycosides (digitoxin, digoxin), due to increases the risk of arrhythmias (see warning and precaution).
Coadministration of diacerein and medicines containing oxide or hydroxide of aluminum, calcium or magnesium should be avoided because they reduce the absorption of diacerein. These medicines may be used at different time (more than 2 hours) after taking diacerein.
Undesirable effects
Gastrointestinal disorders.
Accelerated intestinal transit and abdominal pain are the most frequently reported side-effect associated with diacerein treatment. These symptoms may appear within the first few days of treatment and in most cases:
Very common (> 1/10): Diarrhea, abdominal pain.
Common (> 1/100 and <1/10): Increased intestinal motility, flatulence.
These effects will improve with continued use. In some cases, complicated diarrhea such as dehydration and electrolyte imbalance occur.
Hepatobiliary disorders
Uncommon (> 1/1000 and <1/100): Increased serum liver enzymes.
Skin and subcutaneous tissue disorders
Common (1/100 and <1/10): Itching, skin rash, eczema.
Intense yellow coloring of urine may observed in patients taking diacerein. This is typical sign of the type of compound contained in Agdicerin and it is not clinically significant.
Inform the doctor about undesirable effects encountered while taking this medication.
Pharmacodynamic properties
Diacerein is an anti-osteoarthritis and anti-inflammatory drug used for the treatment of degenerative joint disease (osteoarthritis and other related disease). Diacerein is well tolerated from the stomach because it does not inhibit prostaglandin synthesis.
Diacerein is one of current anti-osteoarthritis drugs capable of affecting both cartilage catabolism and anabolism and reducing proinflammatory cytokines. Results of in vitro and in vivo studies showed that diacerein and rhein, its active metabolite, inhibited the production and activity of proinflammatory and procatabolic cytokines IL-1b, both in the shallow and deep layers of cartilage, in the synovial membrane and synovial fluid whereas they stimulated the production of transforming growth factor beta (TGF-b) and the basic components of the extracellular substances such as proteoglycan, aggrecan, hyaluronic acid and collagen type II. In addition, these agents also showed the inhibition of macrophage migration and phagocytosis. Studies in animal models of osteoarthritis showed that diacerein reduced constantly cartilage degeneration compared with untreated group.
The clinical study showed that there was a significant decrease of pain and joint function was improved significantly compared with placebo group after 1 month treatment period. Other studies proved that beneficial effect of diacerein treatment persisted for at least 2 months after stopping treatment. A randomized, double-blind study between the placebo group and the control group was conducted at many centers for 3 years (ICHODIAH study) in 507 patients with hip osteoarthritis showed that diacerein significantly slowed down the degradation of cartilage.
Pharmacokinetic properties
After oral administration, diacerein is well absorbed through gastrointestinal tract.
Diacerein is distributed to both the shallow and deep layers of cartilage, the synovial membrane and synovial fluid.
Diacerein is very rapidly metabolized to rhein, an active metabolite.
Diacerein is excreted mainly via the urine.
Over dosage and management
The accidental or voluntary ingestion of high doses of diacerein may cause diarrhoea. Symptomatic treatment is required. If diarrhoea persists, move the patient to emergency room immediately. Emergency treatment consists of restoring the hydroelectrolytic balance if necessary.
KEEP OUT OF REACH OF CHILDREN
READ CAREFULLY THE INSTRUCTIONS BEFORE USE
FOR FURTHER INFORMATIONS, CONSULT YOUR PHYSICIAN
USE ONLY UNDER A DOCTOR’S PRESCRIPTION
Storage: Protect from humidity and light, below 300C.
Shelf – life: 36 months from the manufacturing date.
Do not use after the expiry date printed on the box.
