Состав:
Применяется при лечении:
Страница осмотрена фармацевтом Милитян Инессой Месроповной Последнее обновление 22.03.2022
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Гипертония
Ломир СРО® (изодрадипин) показан при лечении гипертонии. Может использоваться отдельно или одновременно с диуретиками тиазидного типа.
Дозировка таблеток контролируемого высвобождения Ломира СРО® (изорадипин) должна быть индивидуализирована. Рекомендуемая начальная доза Ломира СРО® (изорадипин) составляет 5 мг один раз в день в качестве монотерапии или в сочетании с тиазидным диуретиком. Антигипертензивный ответ обычно происходит в течение 2 часов,с пиковым антигипертензивным ответом, возникающим через 8-10 часов после введения дозы; снижение артериального давления поддерживается в течение не менее 24 часов после введения препарата. При необходимости,доза может корректироваться с шагом 5 мг с интервалом 2-4 недели до максимальной дозы 20 мг / день. Неблагоприятные события увеличиваются в частоте выше 10 мг / день.
Ломир СРО® (изодрадин) Контролируемые таблетки выпуска следует проглатывать целиком и не следует укусить или разделить.
Биодоступность (увеличение AUC) немедленного высвобождения DynaCirc® (изорадипин) повышается у пожилых пациентов (старше 65 лет), пациентов с печеночной функциональной недостаточностью и пациентов с легкой почечной недостаточностью. Обычно у этих пациентов следует использовать начальную дозу Ломира СРО® (израдипина) 5 мг один раз в день.
Ломир СРО® (изодрадипин) противопоказан лицам, которые проявили повышенную чувствительность к любому из ингредиентов в составе.
WARNINGS
None
PRECAUTIONS
General
Blood Pressure: Because Ломир СРО® (isradipine) decreases peripheral resistance, like other calcium blockers Ломир СРО® (isradipine) may occasionally produce symptomatic hypotension. However, symptoms like syncope and severe dizziness have rarely been reported in hypertensive patients administered Ломир СРО® (isradipine), particularly at the initial recommended doses (see DOSAGE AND ADMINISTRATION).
Use in Patients with Congestive Heart Failure: Although acute hemodynamic studies in patients with congestive heart failure have shown that immediate-release DynaCirc® (isradipine) reduced afterload without impairing myocardial contractility, it has a negative inotropic effect at high doses in vitro and possibly in some patients. Caution should be exercised when using Ломир СРО® (isradipine) in congestive heart failure patients, particularly in combination with a beta-blocker.
Peripheral Edema: Peripheral edema, when it occurs, is usually mild to moderate in severity. It is a localized phenomenon thought to be associated with vasodilation of arterioles and other small blood vessels,and not due to left ventricular dysfunction or generalized fluid retention. Peripheral edema is dose-related with an incidence ranging from approximately 9% at 5 mg; 13% at 10 mg; 16% at 15 mg; and 36% at the highest dose studied (20 mg once-daily). With patients whose hypertension is complicated by congestive heart failure, care should be taken to differentiate this edema from the effects of decreasing left ventricular function. Although the frequency of edema is correlated with dose, no Ломир СРО® (isradipine) treated patients discontinued the short-term (6 weeks or less), placebo-controlled hypertension studies as a result of edema. Less than 5% of Ломир СРО® (isradipine) treated patients in long-term studies discontinued due to edema.
Other: As with any other non-deformable material, caution should be used when administering Ломир СРО® (isradipine) in patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic).There have been reports of obstructive symptoms in patients with known strictures associated with ingestion of other GITS products.
Carcinogenesis, Mutagenesis,Impairment of Fertility
Treatment of male rats for 2 years with 2.5, 12.5, or 62.5 mg/kg/day isradipine admixed with the diet (approximately 6, 31, and 156 times the maximum recommended daily dose based on a 50 kg man) resulted in dose dependent increases in the incidence of benign Leydig cell tumors and testicular hyperplasia relative to untreated control animals. These findings, which were replicated in a subsequent experiment, may have been indirectly related to an effect of isradipine on circulating gonadotropin levels in the rats; a comparable endocrine effect was not evident in male patients receiving therapeutic doses of the drug on a chronic basis. Treatment of mice for two years with 2.5, 15, or 80 mg/kg/day isradipine in the diet (approximately 6,38,and 200 times the maximum recommended dose based on a 50 kg man) showed no evidence of oncogenicity. There was no evidence of mutagenic potential based on the results of a battery of mutagenic tests.No effect on fertility was observed in male and female rats treated with up to 60 mg/kg/day isradipine.
Pregnancy
Pregnancy Category C: Isradipine was administered orally to rats and rabbits during organogenesis. Treatment of pregnant rats with doses of 6, 20, or 60 mg/kg/day produced a significant reduction in maternal weight gain during treatment with the highest dose (150 times the maximum recommended human daily dose) but with no lasting effects on the mother or the offspring.Treatment ofpregnant rabbits with doses of 1,3,or 10mg/kg/day (2.5,7.5,and 25 times the maximum recommended human daily dose) produced decrements in maternal body weight gain and increased fetal resorption at the two higher doses.There was no evidence of embryotoxicity at doses which were not maternotoxic and no evidence of teratogenicity at any dose tested.In a peri/postnatal administration study in rats,reduced maternal body weight gain during late pregnancy at oral doses of 20 and 60 mg/kg/day isradipine was associated with reduced birth weights and decreased peri and postnatal pup survival.
There are no adequate and well controlled studies in pregnant women. The use of Ломир СРО® (isradipine) during pregnancy should only be considered if the potential benefit outweighs potential risks.
Nursing Mothers
It is not known whether DynaCirc® (isradipine) is excreted in human milk.Because many drugs are excreted in human milk,and because of the potential for adverse effects of DynaCirc® (isradipine) on nursing infants,a decision should be made as to whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness have not been established in children.
Geriatric Use
Clinical studies of Ломир СРО® (isradipine) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Elderly patients have deceased clearance of DynaCirc® (isradipine) with a higher average AUC and Cmax (see Pharmacokinetics and Metabolism).The larger extent of bioavailability may be a result of a reduced clearance and/or reduced first-pass metabolism of the drug. In general, dose selection for an elderly patient should be cautious,reflecting the greater frequency of decreased hepatic, renal,or cardiac function,and of concomitant disease or other drug therapy (see DOSAGE AND ADMINISTRATION).
In a controlled clinical trial with Ломир СРО® (isradipine), dose-related edema occurred at an incidence of approximately 9% at 5 mg; 13% at 10 mg; 16% at 15 mg; and 36% at the highest dose studied (20 mg), was mild to moderate in severity,and was not related to age or gender.
The incidences of elicited or volunteered adverse reactions (excluding non-drug related) in the following tables are based on 6-week multicenter, placebo-controlled, double-blind hypertension studies. Less than 1% of Ломир СРО® (isradipine) or placebo-treated patients discontinued from these studies due to adverse reactions.
The most common adverse experiences ( ≥ 1.0%) reported with Ломир СРО® (isradipine) in a dose-response study are shown in the following table.There were no discontinuations of patients treated with Ломир СРО® (isradipine) in this study due to these common side effects.
Most Frequently Reported Newly-Occurring Adverse Reactions in Dose-Response Study
| Adverse Reactions (Excluding Non-Drug Related) | Ломир СРО® (isradipine) | ||||
| 5 mg (N=79) | 10 mg (N=79) | 15 mg (N=82) | 20 mg (N=78) | Placebo Group (N=83) | |
| Headache | 13.9% | 12.7% | 18.3% | 10.3% | 15.7% |
| Edema | 8.9% | 12.7% | 15.9% | 35.9% | 3.6% |
| Dizziness | 5.1% | 6.3% | 3.7% | 6.4% | 2.4% |
| Constipation | 3.8% | 1.3% | 1.2% | 2.6% | 0.0% |
| Fatigue | 2.5% | 7.6% | 3.7% | 3.8% | 2.4% |
| Flushing | 2.5% | 3.8% | 1.2% | 1.3% | 1.2% |
| Abdominal Discomfort | 1.3% | 5.1% | 3.7% | 5.1% | 1.2% |
| Rash | 1.3% | 1.3% | 0.0% | 2.6% | 0.0% |
The table below shows elicited or volunteered adverse experiences for Ломир СРО® (isradipine) treated patients in two 6-week, placebo-controlled, multicenter studies, at doses from 5-20 mg, and considered by the investigator to be at least possibly drug related.The results for Ломир СРО® (isradipine) treated patients are presented for all doses pooled together (reported by at least 1.0% of active drug treated patients).The incidence of adverse reactions are listed below:
| Adverse Reactions (Excluding Non-Drug Related) | Treatment Group | |
| Ломир СРО®(isradipine) (N=422) | Placebo (N=186) | |
| Edema | 15.2% | 2.2% |
| Headache | 13.0% | 12.4% |
| Dizziness | 4.7% | 2.7% |
| Fatigue | 4.3% | 2.2% |
| Abdominal Discomfort | 2.8% | 0.5% |
| Flushing | 1.9% | 0.5% |
| Constipation | 1.7% | 0.0% |
| Palpitations | 1.2% | 0.0% |
| Nausea | 1.2% | 1.6% |
| Abdominal Distention | 1.2% | 0.0% |
The following adverse experiences were reported in 0.5%-1.0% or less of Ломир СРО® (isradipine) or immediate-release DynaCirc® (isradipine) treated patients in hypertensive studies,or were noted in postmarketing experience with immediate-release DynaCirc® (isradipine) Capsules. More serious events are shown in italics. The relationship of these adverse experiences to isradipine administration is uncertain.
SKIN:Pruritus, urticaria, angioedema.
MUSCULOSKELETAL: Backache/pain, joint pain,neck pain/sore/stiff,legs ache/pain,cramps of legs/feet.
RESPIRATORY: Dyspnea, nasal congestion,cough.
CARDIOVASCULAR: Epistaxis,tachycardia,chest pain,shortness of breath,hypotension, syncope,atrial or ventricular fibrillation,myocardial infarction,heart failure.
GASTROINTESTINAL:Diarrhea,vomiting,appetite increased or decreased.
UROGENITAL: Pollakiuria,impotence,dysuria,nocturia.
CENTRAL NERVOUS: Drowsiness, insomnia, lethargy,nervousness, libido decrease/frigidity,impotence, depression, paresthesia (which includes numbness and tingling), transient ischemic attack,stroke.
AUTONOMIC: Dry mouth,hyperhidrosis,visual disturbance.
MISCELLANEOUS: Weight gain, throat discomfort, drug fever, leukopenia, elevated liver function tests.
No gastrointestinal bleeding has been reported in clinical trials with Ломир СРО® (isradipine) Controlled Release Tablets.
In a long-term (one-year) Ломир СРО® (isradipine) open-label, hypertension trial, the adverse events reported were generally the same as those seen in the short-term placebo-controlled studies. About 6% of Ломир СРО® (isradipine) treated patients discontinued the long-term trial due to adverse reactions.
With immediate-release DynaCirc® (isradipine) Capsules, most of the adverse experiences were transient, mild, and related to vasodilatory effects.The following table shows the most common adverse events reported in U.S.clinical tri-als for immediate-release DynaCirc® (isradipine) Capsules, volunteered or elicited, and considered by the investigator to be at least possibly drug related.
| Adverse Experience | DynaCirc® (isradipine) | Placebo (N=297) % | ActiveControls* (N=414) % | |||
| All Doses | 2.5 mg b.i.d. | 5 mg b.i.d.† | 10 mg b.i.d.†† | |||
| Headache | 13.7 | 12.6 | 10.7 | 22.0 | 14.1 | 9.4 |
| Dizziness | 7.3 | 8.0 | 5.3 | 3.4 | 4.4 | 8.2 |
| Edema | 7.2 | 3.5 | 8.7 | 8.5 | 3.0 | 2.9 |
| Palpitations | 4.0 | 1.0 | 4.7 | 5.1 | 1.4 | 1.5 |
| Fatigue | 3.9 | 2.5 | 2.0 | 8.5 | 0.3 | 6.3 |
| Flushing | 2.6 | 3.0 | 2.0 | 5.1 | 0.0 | 1.2 |
| Chest Pain | 2.4 | 2.5 | 2.7 | 1.7 | 2.4 | 2.9 |
| Nausea | 1.8 | 1.0 | 2.7 | 5.1 | 1.7 | 3.1 |
| Dyspnea | 1.8 | 0.5 | 2.7 | 3.4 | 1.0 | 2.2 |
| Abdominal Discomfort | 1.7 | 0.0 | 3.3 | 1.7 | 1.7 | 3.9 |
| Tachycardia | 1.5 | 1.0 | 1.3 | 3.4 | 0.3 | 0.5 |
| Rash | 1.5 | 1.5 | 2.0 | 1.7 | 0.3 | 0.7 |
| Pollakiuria | 1.5 | 2.0 | 1.3 | 3.4 | 0.0 | <1.0 |
| Weakness | 1.2 | 0.0 | 0.7 | 0.0 | 0.0 | 1.2 |
| Vomiting | 1.1 | 1.0 | 1.3 | 0.0 | 0.3 | 0.2 |
| Diarrhea | 1.1 | 0.0 | 2.7 | 3.4 | 2.0 | 1.9 |
| †Initial dose of 2.5 mg b.i.d.followed by maintenance dose of 5.0 mg b.i.d. ††Initial dose of 2.5 mg b.i.d.followed by sequential titration to 5.0 mg b.i.d.,7.5 mg b.i.d.,and maintenance dose of 10.0 mg b.i.d. *Propranolol,prazosin,hydrochlorothiazide,enalapril,captopril. |
In open-label,long-term studies of up to two years in duration with immediate-release DynaCirc® (isradipine) Capsules, the adverse experiences reported were generally the same as those reported in the short-term controlled trials. The overall frequencies of these adverse events were slightly higher in the long-term than in the controlled studies, but in the controlled studies most adverse reactions were mild and transient.
Хотя нет хорошо документированного опыта передозировки DynaCirc® (израдипин), имеющиеся данные свидетельствуют о том, что, как и в случае с другими дигидропиридинами, грубая передозировка приведет к чрезмерной периферической вазодилатации с последующей выраженной и, вероятно, длительной системной гипотензией. Клинически значимая передозировка гипотонии требует активной сердечно-сосудистой поддержки, включая мониторинг сердечной и дыхательной функции, повышение нижних конечностей и внимание к объему циркулирующей жидкости и выходу мочи. Вазоконстриктор (такой как адреналин, норэпинефрин или левартенол) может быть полезен для восстановления тонуса сосудов и артериального давления при условии, что нет никаких противопоказаний к его применению. Поскольку ирадипин сильно связан с белком, диализ вряд ли будет полезен.
Значительная летальность наблюдалась у мышей, получавших пероральные дозы более 200 мг / кг, и кроликов, получавших около 50 мг / кг израдипина. Крысы переносили дозы более 2000 мг / кг без влияния на выживаемость.
