The following undesirable phenomena are presented in accordance with the following gradations of the frequency of their occurrence according to WHO classification: 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 (according to available data, it is not possible to determine the frequency of occurrence of an undesirable phenomenon).
Combination of irbesartan / hydrochlorothiazide
In clinical studies, the safety of the combination of irbesartan and hydrochlorothiazide was estimated in approximately 2750 patients, including 1540 patients with hypertension who received this medication for 6 months and more than 960 patients who received it for one year or more. Adverse events in patients receiving Coaprovel® were usually mild and transitory, and their frequency was not related to the dose taken.The incidence of adverse events also did not depend on age, gender and race.
In placebo-controlled trials of 898 patients treated with irbesartan / hydrochlorothiazide (the usual duration of treatment was 2-3 months), discontinuation of treatment due to any clinical or laboratory adverse event was significantly less frequent in patients taking irbesartan combinations and hydrochlorothiazide (3.6%) than in patients taking placebo (6.8%).
The adverse events observed with the combination of irbesartan and hydrochlorothiazide in placebo-controlled studies in patients with hypertension
Disturbances from the nervous system
Often: dizziness, headache.
Infrequent: orthostatic dizziness.
Heart Disease
Infrequent: tachycardia, changes in the electrocardiogram.
Vascular disorders
Infrequent: excessive blood pressure lowering; 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.
Infrequent: diarrhea, dryness of the oral mucosa, abdominal pain.
Disorders from the kidneys and urinary tract
Often: change in frequency of urination.
Violations of the genitals and mammary gland
Infrequent: sexual dysfunction (weakening of libido, erectile dysfunction).
General disorders and disorders at the site of administration
Often: increased fatigue.
Infrequently: weakness.
Disturbances from the skin and subcutaneous tissues
Infrequent: skin rash, itching.
Disturbances from musculoskeletal and connective tissue
Infrequently: myalgia, pain in the bones, weakness in the limbs.
The adverse events observed in placebo-controlled studies with the combination of irbesartan and hydrochlorothiazide as initial treatment in patients with severe and moderate arterial hypertension
Initial treatment with a combination of irbesartan and hydrochlorothiazide
The following undesirable effects of the combination of irbesartan and hydrochlorothiazide in studies conducted in patients with severe and moderate arterial hypertension were similar to those described above in adverse events observed in previous studies with hypertension.
In a clinical study conducted with moderate arterial hypertension (mean DBP, in the "sitting" position 90-110 mm Hg), the types and frequency of adverse events observed in patients receiving Coaprovel®
as initial therapy, were similar to the profile of adverse events 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 adverse events with Coaprovel®, monotherapy with irbesartan 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 of treatment due to adverse events with Coaprovel, monotherapy with irbesartan and monotherapy with hydrochlorothiazide was 6.7%, 3.8%, and 4.8%.
In a clinical study conducted with severe arterial hypertension (DBP in a sitting position> 110 mm Hg), the overall picture of adverse events during 7 weeks of follow-up was similar in patients receiving Coaprovel® as an initial therapy, and patients who received as initial therapy irbesartan. The frequency of the above undesirable phenomena for the preparation Coaprovel® and irbesartan was, respectively: 0% and 0% for the syncopal condition; 0.6% and 0% for excessive lowering of blood pressure; 3.6% and 4.0% for dizziness; 4.3% and 6.6% for headache; 0.2% and 0% for hyperkalemia and 0.6% and 0.4% for hypokalemia.
The frequency of cancellation of treatment due to adverse events with Coaprovel® and 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 Coaprovel® were not detected.
Experience of postmarketing application
Irbesartan
As with other antagonists of angiotensin II receptors, extremely rare cases of development of hypersensitivity reactions (angioedema, urticaria) have been observed with monotherapy with irbesartan.In addition, with the use of irbesartan after its release on the market, the following adverse reactions were observed: vertigo, asthenia, hyperkalemia, jaundice, myalgia, increased functional hepatic test, hepatitis, ringing in the ears and renal dysfunction, including cases
development of acute renal failure in patients at risk.
Hydrochlorothiazide
In monotherapy with hydrochlorothiazide, the following adverse events were observed (regardless of their relationship to hydrochlorothiazide): anorexia, gastric mucosal irritation, diarrhea, constipation, jaundice (associated with intrahepatic cholestasis), pancreatitis, sialadenitis, vertigo, paresthesia, xanthopsia, leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, photosensitization reactions, fever, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), respiratory distress -sindrom (including pneumonitis and pulmonary edema), anaphylactic reactions, toxic epidermal necrolysis, hyperglycemia, glycosuria, hyperuricemia, disorders of water and electrolyte balance (including hyponatremia and hypokalemia)impaired renal function, interstitial nephritis, muscle spasms, weakness, anxiety, transient visual impairment.