The following undesirable phenomena (AEs) are presented in accordance with the following grades of their incidence according to the classification of the World Health Organization: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely (<1/10000, including individual messages), unknown frequency (it is not possible to determine the incidence of AE from the available data).
In clinical AE studies, patients treated with irbesartan / hydrochlorothiazide for 6 months and one year or more were usually mild and transient, and their incidence was not related to the dose taken. The incidence of AEs also did not depend on the age, sex and race of the patients.
In placebo-controlled studies in patients receiving the combination
irbesartan / hydrochlorothiazide (the usual duration of treatment is 2-3 months),
discontinuation of treatment due to any clinical or laboratory AEs was
significantly less frequent in patients taking the combination
irbesartan / hydrochlorothiazide than in patients taking placebo.
BUT, observed with the combination of irbesartan / hydrochlorothiazide in
clinical trials in patients with AH
Impaired nervous system:
often: dizziness, headache;
infrequently: orthostaticheskos dizziness.
Heart Disease:
infrequently: tachycardia, changes in the electrocardiogram. Vascular disorders:
infrequently: excessive decrease in blood pressure, peripheral edema, in particular, swelling of the lower extremities, "tides" of blood to the skin of the face, syncopal conditions.
Disorders from the gastrointestinal tract:
often: nausea / vomiting;
infrequently: diarrhea, dryness of the oral mucosa, abdominal pain.
Disorders from the kidneys and urinary tract:
often: changes in frequency of urination.
Violations of the genitals and breast:
infrequently: sexual dysfunction (weakening of libido, erectile dysfunction).
Common disorders and disorders together:
often: increased fatigue;
infrequently: weakness.
Disturbances from the skin and subcutaneous tissues: infrequent: skin rash, itchy skin.
Disturbances from the musculoskeletal and connective tissue: infrequently: myalgia, bone pain, weakness in the extremities.
BUT, observed in the placebo-koptroliruemyh studies with the combination of irbesartan / gidrohyurotiazid as initial treatment for patients with severe hypertension and moderate
Initial treatment with irbesartan / hydrochlorothiazide
The following AEs combination irbesartan / hydrochlorothiazide in clinical trials conducted in patients with severe hypertension or moderate severity, were similar to those described above AEs observed in earlier clinical studies in hypertension.
In a clinical study conducted at moderate hypertension (mean diastolic blood pressure (DBP), in the "sitting" 90-110 mm Hg. V.), The types and frequency of adverse events observed in patients treated with a combination of irbesartan / hydrochlorothiazide as initial therapy were similar to the AE profile in patients who received initial treatment as monotherapy with irbesartan or hydrochlorothiazide. There were no cases of syncopal conditions in the combination therapy group, and in the monotherapy group with hydrochlorothiazide, one case of syncope was recorded.
The frequency of the above-mentioned AEs in combination with irbesartan / hydrochlorothiazide, irbesartan monotherapy and hydrochlorothiazide monotherapy, respectively, was 0.9%, 0%, and 0% for excessive reduction in blood pressure, 3.0%, 3.8%, and 1, 0% for dizziness, 5.5%, 3.8% and 4.8% for headache, 1.2%, 0% and 1.0% for hyperkalemia and 0.9%, 0% and 0 % - for hypokalemia.
The frequency of cancellation due to AEs in combination with irbesartan / hydrochlorothiazide, irbesartan monotherapy and hydrochlorothiazide monohydrate was 6.7%, 3.8%, and 4.8%, respectively. In a clinical study conducted with severe hypertension (DBP in the "sitting" position> 110 mm Hg), the overall pattern of AE during 7 observation cycles was similar in patients treated with irbesartan / hydrochlorothiazide as the initial therapy, and in patients , received as an initial therapy irbesartan. The frequency of the above-mentioned AE for the combination irbesartan / hydrochlorothiazide and irbesartan was, respectively: 0% and 0% for syncopal conditions, 0.6% and 0% for excessive blood pressure lowering, 3.6% and 4.0% for vertigo, 4.3% and 6.6% for headache, 0.2% and 0% for hyperkalemia and 0.6%, and 0.4% for hypokalemia, respectively.
The frequency of cancellation of treatment due to AEs when taking the combination irbesartan / hydrochlorothiazide and with monotherapy with irbesartan was 2.1% and 2.2%, respectively.
Laboratory and instrumental data
Clinically significant changes in the results of laboratory studies during controlled clinical trials of irbesartan / hydrochlorothiazide combination have not been revealed.
Experience of post-registration application
Irbesartan
As in the case of other ARA II, extremely rare cases of development of hypersensitivity reactions (angioedema, urticaria) were observed with monotherapy with irbesartan. In addition, the following AEs were observed after the post-promotion of irbesartan: vertigo, asthenia, hyperkalemia, jaundice, myalgia, increased functional hepatic samples, hepatitis, ringing in the ears, and renal dysfunction, including acute renal failure in patients at risk.
Hydrochlorothiazide
In monotherapy with hydrochlorothiazide, the following AEs were observed (regardless of their association with hydrochlorothiazide): anorexia, irritation of the gastric mucosa, diarrhea, constipation,jaundice (associated with intrahepatic cholestasis), pancreatitis, sialoadenitis, vertigo, paresthesia, xanthopsy, leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, photosensitivity reactions, fever, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), respiratory distress -syndrome (including pneumonitis and pulmonary edema), anaphylactic reactions, toxic epidermal necrolysis, hyperglycemia, glucosuria, hyperuricemia, water-electrolyte balance disorders (including hyponatremia and hypokalemia), renal dysfunction, interstitial nephritis, muscle spasms, weakness, anxiety, transient visual impairment.