DIARIN PLUS

Indications

• Osteoarthritis
• Degenerative joint disease

Dosage

Children: Paediatric dosing guidelines for diacerein are not well established, and it is generally not recommended for children. Refer to the BNF for Children for specific information.

Adults: The usual adult dosage is 50 mg taken orally once or twice daily, as directed by a healthcare professional. It is recommended to take diacerein with food to minimize gastrointestinal side effects.

Mechanism of action

Diacerein's active metabolite rhein reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)-1 and -3, while upregulating tissue inhibitor of matrix metalloproteinases. This action helps to mitigate the activity of several MMPs. Additionally, rhein has anti-inflammatory properties that lower the activity of interleukin-1 beta, a cytokine that contributes to inflammation and cartilage degradation. Furthermore, rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism.

Pharmacodynamics

Diacerein decreases inflammation and cartilage destruction, correcting altered osteoblast activity. Its effects are particularly beneficial in the treatment of osteoarthritis, where it helps to slow the progression of joint damage and improve mobility.

Pharmacokinetics

Diacerein is absorbed from the gastrointestinal tract and is metabolized to rhein, which is responsible for its therapeutic effects. The onset of action may take several weeks, reflecting its role as a slow-acting drug in osteoarthritis therapy. The elimination half-life and specific pharmacokinetic parameters can vary based on individual patient factors, but detailed pharmacokinetic data should be referenced in specific clinical guidelines or drug literature.

Contra-indications

• Hypersensitivity to diacerein or any of its components
• Severe liver impairment
• Pregnancy

Adverse effects

• Diarrhea
• Abdominal pain
• Nausea
• Vomiting
• Rash
• Dyspepsia

Interactions

• May enhance the effects of other anti-inflammatory medications
• Caution is advised when taken with other drugs that affect liver metabolism

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor liver function tests periodically during therapy
• Not recommended for use in children

Pregnancy

Diacerein is contraindicated in pregnancy due to potential risks to the fetus.

Breast-feeding

It is not known whether diacerein is excreted in human breast milk; caution is advised.

Storage

Store in a cool, dry place, away from light and moisture.

Formulations

• Capsules: 50 mg

Indications

• Symptomatic relief of mild to moderate osteoarthritis of the knee

Dosage

Children: Refer to the BNF for Children for

Adults: 200–400 mg daily, maximum 6.5 mg/kg per day, or 1250 mg once daily, or 1500 mg once daily dissolved in at least 250 mL of water; review treatment if no benefit after 2–3 months.

Mechanism of action

The mechanism of action of glucosamine in joint health is not entirely clear, but it is believed to involve several pathways. Glucosamine is a precursor for glycosaminoglycans, which are essential for cartilage integrity. It may also reduce inflammation by inhibiting interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), which could improve symptoms of arthritis and joint pain. Upon uptake by living cells, glucosamine reacts with ATP to form glucosamine-6-phosphate, further contributing to glycosaminoglycan synthesis.

Pharmacodynamics

Glucosamine is theorized to provide essential building blocks for the synthesis of glycosaminoglycans, potentially slowing the progression of osteoarthritis and alleviating joint pain. Although some studies have indicated modest improvements in joint pain and function among users, the overall evidence remains inconclusive. Glycosaminoglycans are critical for maintaining cartilage elasticity, strength, and flexibility, which are vital for joint health.

Pharmacokinetics

After oral administration, glucosamine is absorbed in the gastrointestinal tract and transported into the bloodstream, where it is metabolized into various forms, including glucosamine-6-phosphate. The exact pharmacokinetics, such as absorption rate and half-life, remain largely undefined, and much of the data is derived from animal studies. Further research is required to clarify its pharmacokinetic profiles in humans.

Adverse effects

• Constipation
• Diarrhoea
• Fatigue
• Gastrointestinal discomfort
• Headache
• Nausea
• Flushing
• Skin reactions

Interactions

• Glucosamine + warfarin: Severe (increases anticoagulant effect)
• Glucosamine + coumarins: Severe (increases anticoagulant effect)
• Glucosamine + acenocoumarol: Unknown (decreases anticoagulant effect)
• Glucosamine + coumarins: Unknown (decreases anticoagulant effect)

Precautions

• Asthma
• Impaired glucose tolerance
• Predisposition to cardiovascular disease

Pregnancy

Safety during pregnancy has not been established; consult with a healthcare provider.

Breast-feeding

Safety during breastfeeding has not been established; consult with a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Alateris®
• Dolenio®
• Glusartel®

Mechanism of action

Diacerein's active metabolite rhein [DB13174] reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)-1 and -3 as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs. The anti-inflammatory action of rhein reduces the level of interleukin-1beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism.

Pharmacodynamics

Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity.

Mechanism of action

The mechanism of action of glucosamine in joint health is unclear, however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis. Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time. When taken up by living cells, glucosamine reacts with ATP to form glucosamine-6-phosphate, the natural precursor of glycosaminoglycans (GAGs) that contain N-acetylglucosamine (keratan sulfate and Hyaluronan) and those that have N-acetylgalactosamine (heparan sulfate and chondroitin sulfate). These GAGs are polysaccharides composed of hexosamines and monosaccharides (e.g., galactose and glucuronic acid) arranged as a linear chain of repeating disaccharide units (such as the glucuronic acid and N-acetylgalactosamine-6-sulfate of chondroitin sulfate). With the exception of hyaluronan, GAGs do not exist alone in nature but are attached to specific "core" proteins, and the composite structures are called proteoglycans (protein-glycosaminoglycans). Both hyaluronan and many different kinds of proteoglycans (such as aggrecan, versican, and syndecan) are abundant throughout the body where they perform diverse functions.

Pharmacodynamics

The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.