Otezla pills, 30mg 56pcs

Composition

Active ingredient:

apremilast-30 mg

Pharmacological action

Mechanism of action Apremilast is a small molecule inhibitor of PDE-4, which acts inside the cell, modulating pro-inflammatory and anti-inflammatory mediators. PDE-4 is a specific cAMP PDE that dominates PDE in inflammatory cells. Inhibition of PDE4 increases the amount of cAMP, which, in turn, leads to suppression of the inflammatory response by modulating the expression of TNF-α, IL-23, IL-17, and other inflammatory cytokines. cAMP also modulates the levels of certain anti-inflammatory cytokines, such as IL-10. These pro-and anti-inflammatory mediators are involved in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Pharmacodynamic effects In clinical studies in patients with PsA, apremilast significantly modulated, but did not completely inhibit, plasma proteins: IL-1a, IL-6, IL-8, monocyte chemoattractive protein-1 (MXE-1), macrophage inflammatory protein-1β (MBB-1β), matrix metalloproteinase-3 (MMP-3), and TNF-α. After 40 weeks of apremilast treatment, there was a decrease in the concentration of IL-17 and IL-23 and an increase in the concentration of IL-10 in blood plasma. In patients with psoriasis, apremilast reduced focal epidermal thickening of the affected skin areas, infiltration by inflammatory cells, and expression of pro-inflammatory genes, including genes for induced nitric oxide synthase (iNOS), IL-12/IL-23p40, IL-17A, IL-22, and IL-8. Apremilast at doses up to 50 mg twice daily does not prolong the QT interval in healthy subjects. 1,493 patients with active PsA (≥3 swollen joints and ≥3 painful joints), despite previous therapy with low-molecular-weight or biological disease-modifying drugs (BMLS) lasting at least 6 months, received placebo, apremilast 20 mg or apremilast 30 mg twice daily. Apremilast was used as monotherapy (34.8%) or in combination with stable doses of low-molecular-weight BMLS (65.2%).76.4% of patients previously received only low-molecular-weight BMLS, and 22.4% of patients were previously treated with biological BMLS, among which 7.8% of this therapy was ineffective. The average duration of PsA is 5 years. Apremilast therapy resulted in a significant improvement in PsA symptoms compared to placebo. The effectiveness of apremilast treatment did not differ in patients receiving concomitant or non-concomitant BMLS, including methotrexate. In patients who received BMLS or biological BMLS prior to apremilast therapy, the therapeutic effects of apremilast were more pronounced than in those who took placebo. During apremilast therapy, there was a significant, statistically significant improvement in functional activity. A total of 1,257 patients with moderate to severe plaque psoriasis who were scheduled for phototherapy or systemic therapy were randomly assigned to the placebo or apremilast group (oral,30 mg twice daily). Approximately 30% of patients have not previously received phototherapy, standard systemic or biologics. Patients with moderate to severe psoriasis showed a significant improvement in apremilast therapy compared to placebo. The effectiveness of apremilast was shown in relation to a complex of clinical manifestations of psoriasis, including itching, nail and scalp damage, as well as quality of life. The clinical efficacy of apremilast was confirmed in various subgroups of patients based on baseline demographic and clinical characteristics (including the duration of psoriasis and the presence of PsA in the anamnesis). The positive clinical effect of the drug did not depend on previous drug therapy of psoriasis and its results. The response to apremilast treatment was rapid and resulted in a significant reduction in psoriasis symptoms by the 2nd week of treatment, compared to placebo.

Indications

Psoriatic arthritis Treatment of active psoriatic arthritis (PsA) in adults in monotherapy or in combination with basic anti-inflammatory drugs (DMARDs) with insufficient response or intolerance to previous therapy with DMARDs. Psoriasis Treatment of moderate to severe plaque psoriasis in adults with insufficient response, contraindications, or intolerance to basic anti-inflammatory therapy, including cyclosporine, methotrexate, or medications used together with ultraviolet-A radiation (PUVA).

Contraindications

• Hypersensitivity to apremilast or other components that make up the drug;

• pregnancy;

• children under 18 years of age (insufficient clinical experience).

Side effects

The most common adverse drug reactions (NLR) in phase III clinical trials were gastrointestinal disorders – diarrhea (15.7%) and nausea (13.9%). Most of these disorders were mild or moderate in severity, and only 0.3% of each of these NLRs were considered severe. These NLRs occurred primarily in the first 2 weeks of treatment and usually resolved within 4 weeks. Other common NLRs were upper respiratory tract infections (8.4%), headache (7.9%), and tension headache (7.2%). Overall, most NLRs were mild to moderate in severity. Hypersensitivity reactions have rarely been reported in clinical trials of apremilast. NLRs were registered in clinical trials of apremilast in psoriatic arthritis (1945 patients) and psoriasis (1184 patients). Infectious and parasitic diseases: bronchitis, upper respiratory tract infections, nasopharyngitis. Immune system disorders: hypersensitivity reactions. Metabolic and nutritional disorders: decreased appetite. Mental disorders: insomnia, depression. Nervous system disorders: migraine, tension headache, headache. Respiratory, thoracic and mediastinal disorders: cough. Gastrointestinal disorders: diarrhea, nausea, vomiting, dyspepsia, frequent stools, upper abdominal pain, gastroesophageal reflux, gastrointestinal bleeding. Skin and subcutaneous tissue disorders: skin rash. Musculoskeletal and connective tissue disorders: back pain. General disorders and disorders at the injection site: fatigue. Laboratory and instrumental data: weight loss.

Interaction

Combined use with a powerful inducer of the cytochrome P450 3A4 (CYP3A4) isoenzyme, rifampicin, leads to a weakening of the systemic effect of apremilast and a decrease in its effectiveness. Therefore, the combined use of powerful inducers of the CYP3A4 isoenzyme (for example, rifampicin, phenobarbital, carbamazepine, phenytoin and St. John’s wort preparations) with apremilast is not recommended. With simultaneous repeated use of apremilast and rifampicin, the AUC and Cmax of Apremilast are reduced by 72 and 43%, respectively. When apremilast is used in combination with powerful inducers of the CYP3A4 isoenzyme (for example, rifampicin), the clinical response may be reduced. During clinical trials, apremilast was combined with topical therapies (corticosteroids, tar shampoo, salicylic acid preparations for the treatment of the scalp) and with UV-B phototherapy. There was no clinically significant drug interaction between ketoconazole and apremilast. Apremilast can be combined with strong inhibitors of the CYP3A4 isoenzyme, such as ketoconazole. There was no pharmacokinetic drug interaction between apremilast and methotrexate in patients with PsA. Apremilast can be combined with methotrexate. There was no pharmacokinetic drug interaction between apremilast and oral contraceptives containing ethinyl estradiol and norgestimate. Apremilast can be combined with oral contraceptives.

How to take, course of use and dosage

For oral use. Treatment with Otezla can only be prescribed by a specialist who has sufficient experience in the diagnosis and treatment of psoriasis and psoriatic arthritis. Coated tablets should be swallowed whole, preferably with water. Take regardless of the meal time. The recommended dose of apremilast is 30 mg orally 2 times a day, morning and evening, with an interval of approximately 12 hours. Initial dose titration is required. After the initial titration, no re-titration is required.

Overdose

Apremilast was studied in healthy volunteers at a maximum daily dose of 100 mg (50 mg 2 times a day) for 4.5 days without signs of dose-limiting toxicity. In case of overdose, it is recommended to monitor the symptoms and signs of NLR. If necessary, prescribe symptomatic and supportive treatment.

Special instructions

Patients with rare hereditary problems of galactose intolerance, congenital lactase deficiency, or glucose-galactose malabsorption should not take this medicine. Psychiatric disorders: Apremilast use is associated with an increased risk of developing psychiatric disorders such as insomnia and depression. Cases of suicidal thoughts and behaviors, including suicide, have been reported in patients with or without a history of depression (see section “Side effects”). The risks and benefits of starting and continuing apremilast therapy should be carefully evaluated in those patients who report having or having a history of mental disorders, or if the patient is planning to take other concomitant medications that may cause mental disorders. The patient and caregivers should inform the prescriber of any changes in the patient’s behavior or mood, as well as any suicidal thoughts.Severe renal insufficiency: in patients with severe renal insufficiency, the dose of Otezla should be reduced to 30 mg once a day (see section “Pharmacokinetics ” and”Dosage and use”). Patients with insufficient body weight: in patients with insufficient body weight at the beginning of the course of therapy, it is necessary to regularly monitor their body weight during treatment. In case of unexplained or clinically significant weight loss, a thorough medical examination of the patient should be performed and discontinuation of treatment should be considered. Influence on the ability to drive vehicles and mechanisms: apremilast does not affect or slightly affects the ability to drive vehicles or work with mechanisms.

Form of production

Tablets

Storage conditions

Store at a temperature not exceeding 30°C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Apremilast

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adult Doctor’s prescription