氘可来昔替尼适应症,功效与作用,用法用量,副作用,效果,价格？

Deuterated coxitinib China launch information

It has been launched in China on October 18, 2023, but it has not yet been included in medical insurance.

Indications for deuterated colexitinib

Deuterated colexitinib is the world's first oral selective allosteric inhibitor of tyrosine kinase 2 (TYK2) developed by Bristol-Myers Squibb in the United States. It is used to treat adult patients with moderate to severe plaque psoriasis who are suitable for systemic treatment or phototherapy. However, it is not recommended to combine deuterated colexitinib with other powerful immunosuppressants.

Composition and chemical structure of deuterated colexitinib

The main component of Deuterated Colexitinib is Deuterated Colexitinib, whose molecular formula is C20H19D3N8O3. Deuterated Colexitinib is a white to yellow powder. The solubility of deuterated colexitinib is dependent on pH, with solubility decreasing as pH increases.

The inactive ingredients of colexitinib include anhydrous lactose, hypromellose acetate succinate, croscarmellose sodium, microcrystalline cellulose and silicon dioxide, magnesium stearate. Film coatings contain inactive ingredients including polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, etc.

Usage and dosage

1. Recommended evaluation and immunizations before starting treatment:

Patients should be evaluated for active and latent tuberculosis infection before initiating treatment with deuterated colexitinib. If positive, start anti-tuberculosis treatment before using the drug. Additionally, immunizations need to be updated according to current immunization guidelines.

2. Recommended dosage:

Deuterated colexitinib is 6 mg administered orally once daily with or without food. While taking the medicine, do not crush the tablets or chew them.

3. Recommended dosage for patients with liver damage:

Deuterated colexitinib is not recommended for patients with severe hepatic impairment (Child-PughC), and no dose adjustment is required for patients with mild to moderate hepatic impairment.

Deuterated colexitinib dosage forms and specifications

Tablet: 6mg, pink, round, biconvex, with "BMS895" and "6mg" laser printed on one side, and no content on the other side.

Contraindications

Deuterated colexitinib is contraindicated in patients with a history of hypersensitivity to deuterated colexitinib or any of the excipients in deuterated colexitinib.

Hypersensitivity reactions, such as angioedema, have been reported in subjects receiving deuterated colexitinib. If a clinically significant hypersensitivity reaction occurs, initiate appropriate treatment and discontinue deuterated colexitinib.

Effects and functions

1. Efficacy: Deuterated colexitinib has significant efficacy in improving skin lesion clearance, and its safety and tolerability are good. In clinical trials, deuterated colexitinib was shown to have significant therapeutic effects in patients with psoriasis. Patients using deuterated colexitinib can significantly reduce the lesion area and improve skin symptoms within 12 weeks, while also improving the patient's quality of life and psychological state.

2. Effect: Deuterated colexitinib is an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor and is the only TYK2 inhibitor approved by the U.S. Food and Drug Administration (FDA). This drug is the first innovative drug for the treatment of moderate to severe psoriasis. It participates in the treatment of psoriasis by mediating the transcription of key inflammatory mediators through the TYK2/STAT pathway, thereby inhibiting TYK2 and its downstream functions.

Deuterated colexitinib treatment effect

Psoriasis is an immune-mediated disease, and the interleukin (IL)-23/IL-17 axis is currently considered to be its main pathogenic pathway. Tyrosine kinase 2 (TYK2) is responsible for mediating immune signaling by IL-12, IL-23, and type I interferons, without interfering with other key system functions like other JAK proteins.

Deuterated colexitinib is a new oral drug that selectively inhibits TYK2 and has a low risk of off-target effects. Following favorable efficacy and safety results in a Phase II placebo-controlled trial, two Phase III 52-week trials evaluated the efficacy and safety of deuterated colexitinib 6 mg versus placebo and apremilast, an active comparator. POETYKPSO-1 and PSO-2 involved 1,688 patients with moderate to severe psoriasis. After 16 weeks, more than 50% of patients treated with deuterated colexitinib achieved PASI 75 in both studies, significantly better than placebo and apremilast. In POETYKPSO-1, these results improved through week 24 and were maintained through week 52, when more than 65% of patients achieved PASI75. Patients also reported a reduction in signs and symptoms and a greater impact on itching.

Conclusions: Deuterated colexitinib has the potential to be a safe, effective, and well-tolerated treatment for patients with moderate to severe disease.

Deuterated colexitinib side effects

1.: Upper respiratory tract infection (viral, bacterial and unspecified), rhinitis, rhinotracheitis, nasopharyngitis, pharyngitis (including viral, streptococcal and unspecified), laryngitis and tonsillitis (including bacterial, streptococcal), sinusitis (including acute, viral, bacterial), tracheitis.

2. Herpes: including oral herpes, genital herpes, herpes simplex and herpes virus infection.

3. Ulcers: oral ulcers, aphthous ulcers, tongue ulcers and stomatitis.

4. Skin reactions: acne, cystic acne and acneiform dermatitis.

5. Other side effects: such as liver damage, gastrointestinal reactions, hypertension, etc.

Side effects treatment measures

1. Hypertension: Deuterated colexitinib may cause hypertension, so blood pressure should be measured regularly during use for early monitoring of any abnormalities. If blood pressure rises, corresponding antihypertensive measures can be taken, such as adjusting diet and increasing exercise. If blood pressure continues to rise or severe symptoms occur, seek medical attention promptly.

2. Liver function damage: Deuterated colexitinib may affect liver function, so patients should undergo liver function tests monthly to ensure stable liver function. If liver function abnormalities are found, it may be necessary to suspend the use of deuterated colexitinib and take appropriate treatment measures.

3. Infection: Deuterated coxitinib may reduce the patient's immunity and increase the risk of infection. Therefore, patients should avoid contact with sick people, maintain personal hygiene, and follow their doctors’ recommendations for preventive treatment.

4. Digestive tract problems: Deuterated colexitinib may cause minor digestive problems, such as diarrhea, nausea, or vomiting. These symptoms can be alleviated by adjusting diet or using specific medications. If the symptoms are severe or last for a long time, medication can be used under the guidance of a doctor.

pharmacodynamics

In patients with psoriasis, colexitinib reduced psoriasis-related gene expression in psoriatic skin in a dose-dependent manner, including reducing IL-23 pathway and type I IFN pathway regulatory genes. After 16 weeks of once-daily treatment, colexitinib reduced IL-17A, IL-19, and beta-defensins by 47%-50%, 72%, and 81%-84%, respectively. The relationship between these pharmacodynamic markers and the mechanism by which deuterated colexitinib exerts its clinical effects is unclear.

cardiac electrophysiology

Deuterated colexitinib did not prolong the QTc interval to any clinically relevant degree in patients with psoriasis at doses six times the recommended dose of 6 mg once daily.

Deuterated Colexitinib Storage and Handling

Deuterated colexitinib tablets are stored at 20°C-25°C (68°F-77°F), with an allowed fluctuation range of 15°C-30°C (59°F-86°F).

Deuterated colexitinib price

1. The reference price of deuterated colexitinib 6mgx30 tablets produced by Deucrava, a Bangladeshi Ziska pharmaceutical company, is about $550 per box.

2. The reference price of deuterated colexitinib 6mgx30 tablets produced by Bristol-Myers Squibb is approximately $83,415 per box.

However, due to the impact of foreign exchange rate fluctuations, the price of colexitinib has also changed. For specific prices, please consult the medical companion and travel service.

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