Index of drugs

Treatment of patients with pulmonary arterial hypertension (PAH) classified according to WHO to functional class II and III in order to improve exercise capacity. The efficacy of ambrisentan in idiopathic PAH (IPAH) as well as in PAH associated with connective tissue diseases has been demonstrated.

1 tabl powl. contains 5 mg or 10 mg of ambrisentan. The product contains lactose and soy lecithin.

A hypotensive drug, a highly selective endothelin A receptor antagonist (ET_AND), a propionic acid derivative. Ambrisentan blocks the ET receptor subtype_AND, mainly found in the muscle vasculature and myocardial myocytes, thus preventing the activation of a second system of messengers that leads to vasospasm and smooth muscle cell proliferation. The selectivity of ambrisentan to ET receptors is expected_AND compared to ET receptors_B it will not affect the production of ET receptors_B, substances causing vasodilatation - nitric oxide and prostacyclin. Ambrisentan is rapidly absorbed from the gastrointestinal tract. The maximum plasma concentration usually occurs approximately 1.5 hours after administration of the drug, both on an empty stomach and after a meal. Steady state is usually achieved after 4 days of administration. It binds to plasma proteins in 98.8%. Ambrisentan and its metabolites are mainly excreted in the bile. About 22% of the administered dose is excreted in the urine, including 3.3% unchanged. T_0,5 ranges from 13.6-16.5 hours.

Hypersensitivity to the active substance, soy or any auxiliary substances. Pregnancy. Women of childbearing age who do not use effective methods of contraception. Lactation. Severe liver dysfunction (with or without liver cirrhosis). Baseline AST and / or (ALT)> 3 x ULN. Idiopathic pulmonary fibrosis with and without secondary pulmonary hypertension.

In clinical trials, patients with IPF had higher rates of hospitalization for respiratory reasons, fatal events, and respiratory depression in patients receiving ambrisentan compared to the placebo group. Patients with IPF who have already started therapy with ambrisentan should be carefully monitored, alternative therapeutic options should be considered. The benefit / risk ratio in WHO functional class I PAH has not been established. The efficacy of monotherapy was not determined in patients classified as WHO functional class IV PAH. If the patient's clinical condition worsens, treatment recommended in severe stages of disease (eg epoprostenol) should be considered. Accidents similar to autoimmune hepatitis have been observed with ambrisentan, including possible exacerbation of pre-existing autoimmune hepatitis, liver damage, and elevation of liver enzymes potentially associated with the treatment. Therefore, the activity of ALT and AST should be checked before initiating treatment with the preparation. Patients should be monitored to rule out symptoms of liver damage and ALT and AST are recommended every month. If patients develop persistent, unexplained, clinically significant increases in ALT and / or AST, or if ALT and / or AST elevation is accompanied by signs or symptoms of liver damage (eg jaundice), discontinuation should be discontinued. In patients without clinical signs of liver injury or jaundice, re-initiation of treatment may be considered when liver enzyme activity returns to normal. It is recommended to consult a hepatologist. It is not recommended to start treatment with patients with clinically significant anemia. It is recommended to check hemoglobin and / or hematocrit values, eg after 1 month, 3 months of treatment, and then periodically. If clinically significant reductions in hemoglobin or hematocrit are observed, other causes should be considered or a dose reduction or discontinuation of therapy should be considered. If patients have fluid retention, it should be treated before starting to use ambrisentan.In the event of clinically significant fluid retention associated with or unrelated to weight gain, the cause of this symptom, which may be ambrisentan or concomitant heart failure, should be determined and the need for specific treatment or discontinuation of ambrisentan should be determined. If patients develop acute pulmonary edema while using ambrisentan, the possibility of pulmonary veno-occlusive disease should be considered. Due to the lactose content, patients with rare hereditary diseases related to galactose intolerance, lactase deficiency (Lapp type) or malabsorption of Glucose and galactose should not use the drug. The tablets contain aluminum dye, Allura AC red (E129), which may cause hypersensitivity reactions. There are no data on the safety and efficacy of the drug in children under 18 years.

The drug is contraindicated during pregnancy. Animal studies have shown that ambrisentan has teratogenic effects. Do not start treatment with ambrisetan in women of childbearing age until a negative pregnancy test result is obtained and unless effective contraception is used. In case of any doubts, what effective method of contraception should be used in the patient, consult a gynecologist. During the treatment, a check-up pregnancy test is recommended every month. Women receiving ambrisentan should be informed about the risk of fetal harm and if they become pregnant, alternative treatment should be started. It is not known if ambrisentan is excreted in breast milk, therefore breast-feeding is contraindicated.
Chronic use of ERA, including ambrisentan, was associated with the loss of seminal tubules in experimental animals. The effect of this phenomenon on reproduction in men is unknown. The deterioration of spermatogenesis can not be ruled out. In clinical studies, the long-term use of ambrisentan was not associated with changes in serum testosterone levels.

Very common: headache (including sinus pain, migraine) - more often after a dose of 10 mg, peripheral edema and fluid retention - more often after a dose of 10 mg and patients ≥65 years. Common: heart failure - in most cases associated with fluid retention, palpitations, anemia - more often after a dose of 10 mg, dizziness, hypotension, redness of the skin (especially the face), nosebleeds, shortness of breath, congestion of the upper respiratory tract (eg nasal , sinus), sinusitis, inflammation of the nose and throat, runny nose, stomach pain, constipation, nausea, vomiting, diarrhea, increased liver transaminases, chest pain / discomfort, asthenia and fatigue. Uncommon: hypersensitivity reactions (including angioedema, rash, pruritus), fainting, liver damage, autoimmune hepatitis. Frequency unknown: blurred vision, blurred vision. Most cases of hemoglobin decrease and hematocrit values ​​were found in the first 4 weeks of treatment, later the hemoglobin level was usually stabilized. In a long-term study, the mean reduction in hemoglobin values ​​from baseline values ​​was maintained during treatment with ambrisentan for up to 4 years. Following post-marketing experience, cases of anemia requiring transfusion of blood cells have been observed.

Treatment should only be started by a doctor who has experience in the treatment of PAH.
Orally. Adults: 5 mg once a day. An increased efficacy of ambrisentan at a dose of 10 mg was found in patients in the functional class III, while an increase in peripheral edema was observed. For patients with PAH associated with connective tissue diseases, a 10-mg dose may be necessary. Before increasing the dose, make sure that the 5 mg dose is well tolerated by the patient. A limited number of data indicate that the rapid discontinuation of the drug does not cause deterioration of the course of PAH. When co-administered with ciclosporin A, the dose of ambrisentan should be limited to 5 mg once a day, the patient's condition should be carefully monitored. In patients with severe renal impairment (creatinine clearance <30 ml / min), treatment should be started cautiously and special attention should be given when increasing the dose to 10 mg.
The tablets should be swallowed whole, regardless of meals.