Otesla, 10 mg+20 mg+30 mg+30 mg 14 pcs

Mechanism of action
Apremilast, is a small molecule – FDE-4 inhibitor, which acts inside the cell, modulating pro-inflammatory and anti-inflammatory mediators. FDE-4 is a specific FDE-cAMP, the dominant FDE in inflammatory cells. Inhibition of FDE-4 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 some 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 PsA patients, apremilast significantly modulated but did not completely inhibit plasma proteins: IL-1α, IL-6, IL-8, monocyte chemoattract protein-1 (MXE-1), macrophage inflammatory protein-1β (MBB-1β), matrix metalloproteinase-3 (MMP-3) and TNF-α. After 40 weeks of treatment with apremilast, a decrease in IL-17 and IL-23 concentrations and an increase in plasma IL-10 concentrations were observed. In psoriasis patients, apremilast reduced focal epidermal thickening of affected skin areas, inflammatory cell infiltration and expression of proinflammatory genes including inducible nitric oxide synthase (iNOS), IL-12/IL-23p40, IL-17A, IL-22 and IL-8 genes.
Apremilast when administered in doses up to 50 mg twice daily does not prolong the QT interval in healthy subjects.
1493 patients with active PsA (≥3 swollen joints and ≥3 painful joints), despite prior therapy with low-molecular-weight or biological disease-modifying drugs (DMARDs) for at least 6 months, received oral placebo, apremilast 20 mg or apremilast 30 mg 2 times daily. Apremilast was used as monotherapy (34.8%) or in combination with stable doses of LMWH (65.2%). 76.4% of patients had previously received only low-molecular-weight BMLS, and 22.4% of patients had been previously treated with biological BMLS, among whom 7.8% found this therapy ineffective. The average duration of PsA was 5 years.
Apremilast therapy resulted in a significant improvement in PsA symptoms compared with placebo.
The effectiveness of apremilast treatment did not differ among patients receiving or not receiving concomitant BMLS, including methotrexate. The therapeutic effects of apremilast were more pronounced in patients who received BMLS or biological BMLS prior to apremilast therapy than in those who received placebo. There was a significant, statistically significant improvement in functional activity on apremilast therapy.
A total of 1257 patients with moderate to severe plaque psoriasis who were scheduled for phototherapy or systemic therapy were randomized to the placebo or apremilast group (oral, 30 mg twice daily). Approximately 30% of patients had not previously received phototherapy, standard systemic or biological drugs.
On the background of apremilast therapy, patients with moderate to severe psoriasis showed significant improvement compared with placebo. The efficacy of apremilast was manifested with respect to the complex of clinical manifestations of psoriasis, including itching, nail and scalp lesions, as well as quality of life.
The clinical effectiveness of apremilast was confirmed in various patient subgroups formed by initial demographic and clinical characteristics (including the duration of psoriasis and a history of PsA). The positive clinical effect of the drug was independent of the previous drug therapy of psoriasis and its results. Response to apremilast treatment was rapid and was expressed in a significant reduction of psoriasis symptoms already by the 2nd week of treatment, compared to placebo.

Indications

Active ingredient

Composition

The active ingredient:

apremilast – 10/20/30 mg

How to take, the dosage

For oral administration.

The treatment with Otesla should only be prescribed by a specialist with sufficient experience in the diagnosis and treatment of psoriasis and psoriatic arthritis.

The coated tablets should be swallowed whole, preferably with water. It should be taken regardless of the time of meals.

Doses

The recommended dose of apremilast is 30 mg orally twice daily, morning and evening, about 12 hours apart. Initial dose titration is required. No retitration is required after initial titration.

Interaction

Special Instructions

Patients with rare hereditary disorders of galactose intolerance, congenital lactase deficiency or glucose-galactose absorption disorders should not take this drug.

Mental disorders: use of apremilast is associated with an increased risk of mental disorders such as insomnia and depression. Cases of suicidal thoughts and behavior, including suicide, have been reported in patients with and without a history of depression (see section “Side effects”).

The risks and benefits of initiating and continuing therapy with apremilast should be carefully evaluated in patients who report or have a history of mental disorders or if the patient plans to take other concomitant medications that may cause mental disorders.

The patient and the patient’s caregivers should tell the prescribing physician about any behavioral or mood changes or suicidal ideation. Severe renal failure: In patients with severe renal failure, the dose of Otesla should be reduced to

30 mg once daily (see section “Pharmacokinetics” and “Dosage and administration”). Patients with insufficient body weight: in patients with insufficient body weight at the beginning of therapy it is necessary to monitor body weight regularly during treatment. In case of unexplained or clinically significant decrease in body weight it is necessary to conduct a thorough medical examination of the patient and consider discontinuation of therapy.

Impact on driving and operating machinery: Apremilast has no or negligible effect on the ability to drive vehicles or operate machinery.

Contraindications

Side effects

The most common adverse drug reactions (ADRs) in phase III clinical trials were gastrointestinal disorders – diarrhea (15.7%) and nausea (13.9%). For the most part, these disorders were mild to moderate in severity, and only 0.3% of each of these IUDs were considered severe. These NLDs occurred predominantly in the first 2 weeks of treatment and usually resolved within 4 weeks. Other common NLDs were upper respiratory tract infections (8.4%), headache (7.9%), and tension headache (7.2%). Overall, most NERs were mild to moderate in severity.

Hypersensitivity reactions have rarely been reported in clinical trials of apremilast. NLRs have been reported 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 system disorders, chest and mediastinal organs: cough. Gastrointestinal tract disorders: diarrhea, nausea, vomiting, dyspepsia, frequent stools, pain in the upper abdomen, 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.

Overdose