Matsitentan - instructions for use, doses, side effects, contraindications

Clinical and pharmacological group: & nbsp

Vasodilators

Included in the formulation

Opsamit

pills inwards

Actelion Pharmaceuticals Co., Ltd. Switzerland

Stellanin

drops locally inwards

FARMPREPARAT, LLC Russia

АТХ:

C.02.K.X.04 Matsitentan

Pharmacodynamics:

Matsitentan - a drug for the treatment of arterial pulmonary hypertension, belongs to the class of antagonists of endothelin receptors, is a vasodilator.

Matsitentan is an oral dual ARE designed to improve the efficacy and safety of therapy due to the tissue specificity of the drug. Belongs to the class of sulfonamides.

Matsitentan blocks the receptors of ET type A and B, affecting the endothelium of the vessels and smooth musculature. Stimulation of these receptors is associated with narrowing of the vessels, causing fibrosis, proliferation, hypertrophy and inflammation. Matsitentan expands pulmonary arteries, reduces vascular pulmonary resistance, thereby facilitates the work of the heart, reduces arterial blood pressure without affecting the heart rhythm. Matsitentan improves hemodynamic parameters, which leads to a positive dynamics in the change in the functional class of chronic heart failure by NYHA.

Pharmacokinetics:

The pharmacokinetics of macitanthane is characterized by its slow adsorption and the slow formation of the active metabolite.The half-life of macitantan is 16 h, the active metabolite is 48 h, respectively. The maximum plasma concentration is observed 8 hours after taking the drug.

Matsitentan and its active metabolite binds intensively to plasma proteins (albumin) by 99%. It is well distributed in tissues (the volume of distribution is about 50 liters). The metabolism of macitentan occurs with the participation of cytochrome P450 (CYP) and its isoenzymes CYP3A4 and CYP2C8, CYP2C9 and CYP2C19.

Urinary excretion (~ 50%), feces (~ 24%).

Indications:Matsitentan as monotherapy or in combination is indicated for long-term treatment of adult patients with pulmonary arterial hypertension (PAH) II-III functional class (FC) according to WHO classification. Treatment should be conducted under the constant supervision of an experienced doctor.

ICD-10

IX.I26-I28.I27.0 Primary pulmonary hypertension

Contraindications:

Hypersensitivity to the active substance macitentan or any of the excipients
Children under 12 years old
Pregnancy or Pregnancy Planning
Lactation
Women of childbearing age not using reliable contraception
Pulmonary vein-occlusive disease
Severe hepatic insufficiency (with or without cirrhosis or cirrhosis)
Clinically significant increase in liver transaminases (3 times higher than the upper limit of the norm)

Carefully:Matsitentan can have a negative effect on spermatogenesis.

Precautions should be given to patients with anemia, renal failure, HIV infection, lactose intolerance, lactase deficiency and glucose-galactose malabsorption, and with a history of allergic reactions associated diseases. When appointing macetitane should take into account the reception of other medicines.

Pregnancy and lactation:

Contraindicated in pregnancy. The course of treatment for women of childbearing age is prescribed only after confirmation of the absence of pregnancy. During treatment, the drug requires effective contraception. Monthly pregnancy testing is recommended during drug treatment macitentan to identify early pregnancy. A woman should not become pregnant a month after stopping the drug macitentan.

There is no data on the isolation of macetitanium with breast milk. Matsitentan contraindicated during lactation.

Dosing and Administration:

Matsitentan take 10 mg (1 tablet) per day during meals or regardless of it.Tablets are not chewed, but swallowed whole, washed down with water. You can not break a tablet in half.

Matsitentan taken daily at the same time. If the patient misses the appointment, he should take the pill as soon as possible, and then take the next dose at the scheduled time, but in no case should not take two doses at a time. If the patient has accidentally taken more pills than prescribed, you should immediately inform your doctor to avoid complications.

In patients aged 65 years, dose adjustment is not required. Based on pharmacokinetic (PK) data, dose adjustment is necessary for patients with mild, moderate or severe hepatic insufficiency.

Side effects:

Very frequent side effects: anemia, a decrease in hemoglobin, a rise in the serum of liver transaminases, peripheral edema, difficulty urinating, headache, bronchitis, nasopharyngitis.

Common side effects: pharyngitis, influenza, urinary tract infections, gastrointestinal infections, menstrual disorders in women (bleeding), ovarian cyst.

Overdose:

Symptoms: signs of liver damage - nausea, vomiting, fever (high body temperature),pain in the stomach, yellowing of the skin or whites of the eyes (jaundice), dark urine, itching, unusual tiredness or flu-like fatigue symptoms (joint and muscle pains with fever); severe asthenia, dyspnea, excessive weight gain, swelling of the extremities, bruising, dysuria, or difficulty urinating.

Treatment: gastric lavage, activated charcoal, infusion therapy. Because of the high degree of binding of macetitanium to proteins, dialysis will be ineffective.

Interaction:

Aprepitant: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Boszentan: There may be a decrease in serum concentrations of CYP3A4 substrates. Monitor therapy

Conivaptan: May increase serum concentrations of CYP3A4 substrates. Avoid the combination

Dabrafenib: It is possible to reduce serum concentrations of CYP3A4 substrates.

Dasatinib: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Deferazirox: A decrease in serum concentrations of CYP3A4 substrates is possible. Monitor therapy

Fosaprepitant: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Fusidic acid: May increase serum concentrations of CYP3A4 substrates.Avoid the combination

Idelisib: May increase serum concentrations of CYP3A4 substrates. Avoid the combination

Iwafactor: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Luliconazole: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Mifepristone: May increase serum concentrations of CYP3A4 substrates. Minimize the dose of CYP3A4 substrates, and monitor for increased concentrations / toxicity, for 2 weeks and after treatment with mifepristone. Avoid prescribing: ciclosporin, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and ciclosporin.

Nepupitant: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Ozymertinib: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Palbosiclib: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Syltximab: A decrease in serum concentrations of CYP3A4 substrates is possible. Monitor therapy

Simeprevir: May increase serum concentrations of CYP3A4 substrates. Monitor therapy

Stiripentol: May increase serum concentrations of CYP3A4 substrates.It should be avoided because of the increased risk of side effects and toxicity.

Tocilizumab: It is possible to reduce serum concentrations of CYP3A4 substrates. Monitor therapy

Special instructions:

Matsitentan has little effect on the ability to drive vehicles and potentially dangerous mechanisms. The clinical condition of the patient and the degree of adverse reactions (such as headache, hypotension) should be taken into account when assessing a patient's ability to drive a car or operate machinery.

It is important to monitor the clinical signs and symptoms of liver damage (for example, abdominal pain, loss of appetite, dark urine, fatigue, fever, itching, jaundice, nausea, vomiting), hemoglobin and hematocrit to cancel the drug in time.

It is necessary to inform the patient about signs of hyperreaction (for example, dyspnea, chest tightness, fever, itching, severe coughing, blue skin, convulsions, swelling of the face, lips, tongue or throat).

If there are signs of pulmonary edema, find out whether this is a consequence of pulmonary veno-occlusive disease and stop taking the medication if the disease is confirmed.

Instructions

Matsitentan (Macitentan)