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Tedavide kullanılır:
Militian Inessa Mesropovna tarafından tıbbi olarak gözden geçirilmiştir, Eczane Son güncelleme: 24.03.2022
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Aynı bileşenlere sahip en iyi 20 ilaç:
Hipertansiyon
Lisinopril Cinfa, yetişkin hastalarda ve 6 yaş ve üstü pediatrik hastalarda hipertansiyon tedavisi için düşük kan basıncına endikedir. Kan basıncının düşürülmesi, öncelikle felç ve miyokard enfarktüsü gibi ölümcül ve ölümcül olmayan kardiyovasküler olay riskini azaltır. Bu faydalar, çok çeşitli farmakolojik sınıflardan gelen antihipertansif ilaçların kontrollü çalışmalarında görülmüştür.
Yüksek tansiyonun kontrolü, uygun olduğu şekilde, lipit kontrolü, diyabet yönetimi, antitrombotik tedavi, sigarayı bırakma, egzersiz ve sınırlı sodyum alımı dahil olmak üzere kapsamlı kardiyovasküler risk yönetiminin bir parçası olmalıdır. Birçok hastada kan basıncı hedeflerine ulaşmak için 1'den fazla ilaç gerekecektir. Hedefler ve yönetim hakkında özel tavsiyeler için, Ulusal Yüksek Tansiyon Eğitim Programı'nın Yüksek Tansiyonun Önlenmesi, Tespiti, Değerlendirilmesi ve Tedavisi Ortak Ulusal Komitesi (JNC) gibi yayınlanmış kılavuzlara bakınız.
Kardiyovasküler morbidite ve mortaliteyi azaltmak için randomize kontrollü çalışmalarda çeşitli farmakolojik sınıflardan ve farklı etki mekanizmalarına sahip çok sayıda antihipertansif ilaç gösterilmiştir, ve bunun kan basıncını düşürdüğü sonucuna varılabilir, ve ilaçların başka bir farmakolojik özelliği değil, bu faydalardan büyük ölçüde sorumludur. En büyük ve en tutarlı kardiyovasküler sonuç yararı inme riskinde bir azalma olmuştur, ancak miyokard enfarktüsü ve kardiyovasküler mortalitede de düzenli olarak azalma görülmüştür.
Yüksek sistolik veya diyastolik basınç artmış kardiyovasküler riske neden olur ve mmHg başına mutlak risk artışı daha yüksek kan basınçlarında daha fazladır, böylece şiddetli hipertansiyonun mütevazı azalmaları bile önemli fayda sağlayabilir. Kan basıncının düşürülmesinden kaynaklanan göreceli risk azalması, değişen mutlak risk taşıyan popülasyonlarda benzerdir, bu nedenle hipertansiyonlarından bağımsız olarak daha yüksek risk altında olan hastalarda mutlak fayda daha fazladır (Örneğin, diyabet veya hiperlipidemili hastalar) ve bu tür hastaların daha düşük bir kan basıncı hedefine daha agresif tedaviden faydalanmaları beklenir.
Bazı antihipertansif ilaçların Siyah hastalarda daha küçük kan basıncı etkileri (monoterapi olarak) vardır ve birçok antihipertansif ilacın ek onaylanmış endikasyonları ve etkileri vardır (ör.anjina, kalp yetmezliği veya diyabetik böbrek hastalığı üzerine). Bu düşünceler terapi seçimine rehberlik edebilir.
Lisinopril Cinfa tek başına veya diğer antihipertansif ajanlarla uygulanabilir.
Kalp yetmezliği
Lisinopril Cinfa'nın sistolik kalp yetmezliği belirtilerini ve semptomlarını azalttığı belirtilmektedir.
Akut Miyokard İnfarktüsünde Ölüm Oranının Azaltılması
Lisinopril Cinfa, akut miyokard enfarktüsünden sonraki 24 saat içinde hemodinamik olarak stabil hastaların tedavisinde mortalitenin azaltılması için endikedir. Hastalar, uygun şekilde, trombolitik, aspirin ve beta-blokerler gibi önerilen standart tedavileri almalıdır.
Hipertansiyon
Lisinopril Cinfa, yetişkin hastalarda ve 6 yaş ve üstü pediatrik hastalarda hipertansiyon tedavisi için düşük kan basıncına endikedir. Kan basıncının düşürülmesi, öncelikle felç ve miyokard enfarktüsü gibi ölümcül ve ölümcül olmayan kardiyovasküler olay riskini azaltır. Bu faydalar, çok çeşitli farmakolojik sınıflardan gelen antihipertansif ilaçların kontrollü çalışmalarında görülmüştür.
Yüksek tansiyonun kontrolü, uygun olduğu şekilde, lipit kontrolü, diyabet yönetimi, antitrombotik tedavi, sigarayı bırakma, egzersiz ve sınırlı sodyum alımı dahil olmak üzere kapsamlı kardiyovasküler risk yönetiminin bir parçası olmalıdır. Birçok hastada kan basıncı hedeflerine ulaşmak için 1'den fazla ilaç gerekecektir. Hedefler ve yönetim hakkında özel tavsiyeler için, Ulusal Yüksek Tansiyon Eğitim Programı'nın Yüksek Tansiyonun Önlenmesi, Tespiti, Değerlendirilmesi ve Tedavisi Ortak Ulusal Komitesi (JNC) gibi yayınlanmış kılavuzlara bakın.
Çok sayıda antihipertansif ilaç, çeşitli farmakolojik sınıflardan ve farklı etki mekanizmalarına sahiptir, kardiyovasküler morbidite ve mortaliteyi azaltmak için randomize kontrollü çalışmalarda gösterilmiştir, ve bunun kan basıncını düşürdüğü sonucuna varılabilir, ve ilaçların başka bir farmakolojik özelliği değil, bu faydalardan büyük ölçüde sorumludur. En büyük ve en tutarlı kardiyovasküler sonuç yararı inme riskinde bir azalma olmuştur, ancak miyokard enfarktüsü ve kardiyovasküler mortalitede de düzenli olarak azalma görülmüştür.
Yüksek sistolik veya diyastolik basınç artmış kardiyovasküler riske neden olur ve mmHg başına mutlak risk artışı daha yüksek kan basınçlarında daha fazladır, böylece şiddetli hipertansiyonun mütevazı azalmaları bile önemli fayda sağlayabilir. Kan basıncının düşürülmesinden kaynaklanan göreceli risk azalması, değişen mutlak risk taşıyan popülasyonlarda benzerdir, bu nedenle hipertansiyonlarından bağımsız olarak daha yüksek risk altında olan hastalarda mutlak fayda daha fazladır (Örneğin, diyabet veya hiperlipidemili hastalar) ve bu tür hastaların daha düşük bir kan basıncı hedefine daha agresif tedaviden faydalanmaları beklenir.
Bazı antihipertansif ilaçların siyah hastalarda daha küçük kan basıncı etkileri (monoterapi olarak) vardır ve birçok antihipertansif ilacın ek onaylanmış endikasyonları ve etkileri vardır (ör.anjina, kalp yetmezliği veya diyabetik böbrek hastalığı üzerine). Bu düşünceler terapi seçimine rehberlik edebilir.
Lisinopril Cinfa tek başına veya diğer antihipertansif ajanlarla uygulanabilir.
Kalp yetmezliği
Lisinopril Cinfa'nın diüretiklere ve dijitallere yeterince yanıt vermeyen hastalarda kalp yetmezliği belirtilerini ve semptomlarını azalttığı belirtilmektedir.
Akut Miyokard Enfarktüsü
Lisinopril Cinfa, akut miyokard enfarktüsünden sonraki 24 saat içinde hemodinamik olarak stabil hastaların tedavisinde mortalitenin azaltılması için endikedir. Hastalar, uygun şekilde, trombolitik, aspirin ve beta-blokerler gibi önerilen standart tedavileri almalıdır.
Hypertension
Adults
Initial Therapy in adults: The recommended initial dose is 10 mg taken orally once a day. Adjust dosage as needed according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg per day have been used but do not appear to give greater effect.
Use With Diuretics In Adults
If blood pressure is not controlled with Lisinopril Cinfa alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of Lisinopril Cinfa.
The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day.
Pediatric Patients 6 Years Of Age And Older With Hypertension
For pediatric patients with glomerular filtration rate > 30 mL/min/1.73m², the recommended starting dose is 0.07 mg per kg (up to 5 mg total) taken orally once daily. Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients.
Lisinopril Cinfa is not recommended in pediatric patients less than 6 years of age or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m².
Heart Failure
The recommended starting dose for Lisinopril Cinfa, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg taken orally once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.
Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension. The appearance of hypotension after the initial dose of Lisinopril Cinfa does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.
Reduction Of Mortality In Acute Myocardial Infarction
Initiation
In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give Lisinopril Cinfa 5 mg orally, followed by 5 mg after 24 hours, and then 10 mg once daily. Dosing should continue for at least six weeks. In patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mmHg) during the first 3 days after the infarct initiate therapy with 2.5 mg once daily and titrate up based on tolerability.
Maintenance
The usual maintenance dose is 10 mg once daily. If hypotension (systolic blood pressure ≤ 100 mmHg) occurs during maintenance treatment, give 5 mg once daily with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) Lisinopril Cinfa should be withdrawn.
Dose In Patients With Renal Impairment
No dose adjustment of Lisinopril Cinfa is required in patients with creatinine clearance > 30 mL/min.
In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of Lisinopril Cinfa to half of the usual recommended dose, i.e., hypertension, 5 mg once daily; systolic heart failure, 2.5 mg once daily and acute myocardial infarction, 2.5 mg once daily. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily.
Hypertension
Initial therapy in adults: The recommended initial dose is 10 mg once a day. Adjust dosage according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give a greater effect.
Use With Diuretics In Adults
If blood pressure is not controlled with Lisinopril Cinfa alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide 12.5 mg).
The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day.
Pediatric Patients 6 Years Of Age And Older With Hypertension
For pediatric patients with glomerular filtration rate >30 mL/min/1.73 m2, the recommended starting dose is 0.07 mg/kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg/kg (up to 40 mg) once daily. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients.
Lisinopril Cinfa is not recommended in pediatric patients <6 years or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2.
Heart Failure
The recommended starting dose for Lisinopril Cinfa, when used with diuretics and (usually) digitalis as adjunctive therapy is 5 mg once daily. The recommended starting dose in these patients with hyponatremia (serum sodium <130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.
Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension. The appearance of hypotension after the initial dose of Lisinopril Cinfa does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.
Acute Myocardial Infarction
In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give Lisinopril Cinfa 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for at least 6 weeks.
Initiate therapy with 2.5 mg in patients with a low systolic blood pressure (100-120 mmHg) during the first 3 days after the infarct. If hypotension occurs (systolic blood pressure ≤100 mmHg) consider doses of 2.5 or 5 mg. If prolonged hypotension occurs (systolic blood pressure <90 mmHg for more than 1 hour) discontinue Lisinopril Cinfa.
Dose In Patients With Renal Impairment
No dose adjustment of Lisinopril Cinfa is required in patients with creatinine clearance >30 mL/min. In patients with creatinine clearance 10-30 mL/min, reduce the initial dose of Lisinopril Cinfa to half of the usual recommended dose (i.e., hypertension, 5 mg; heart failure or acute MI, 2.5 mg). For patients on hemodialysis or creatinine clearance <10 mL/min, the recommended initial dose is 2.5 mg once daily.
Preparation Of Suspension
To make 200 mL of a suspension at 1.0 mg/mL, add 10 mL of Purified Water USP to a polyethylene terephthalate (PET) bottle containing ten 20-mg tablets of Lisinopril Cinfa and shake for at least one minute.
Add 30 mL of Sodium Citrate and Citric Acid Oral Solution or Cytra-2 diluent and 160 mL of Ora-Sweet SF™ to the concentrate in the PET bottle and gently shake for several seconds to disperse the ingredients. The suspension should be stored at or below 25°C (77°F) and can be stored for up to four weeks. Shake the suspension before each use.
Lisinopril Cinfa, aşağıdaki hastalarda kontrendikedir
- anjiyotensin dönüştürücü enzim inhibitörü ile önceki tedaviye bağlı anjiyoödem veya aşırı duyarlılık öyküsü
- kalıtsal veya idiyopatik anjiyoödem
Diyabetli hastalarda aliskireni Lisinopril Cinfa ile birlikte uygulamayın.
Lisinopril Cinfa, bir neprilizin inhibitörü (örn., sakubitril). Bir neprilizin inhibitörü olan sakubitril / valsartan'a geçtikten sonra 36 saat içinde Lisinopril Cinfa uygulamayın.
Lisinopril Cinfa, aşağıdaki hastalarda kontrendikedir
- anjiyotensin dönüştürücü enzim inhibitörü ile önceki tedaviye bağlı anjiyoödem veya aşırı duyarlılık öyküsü
- kalıtsal veya idiyopatik anjiyoödem.
Diyabetli hastalarda aliskireni Lisinopril Cinfa ile birlikte uygulamayın. Lisinopril Cinfa, bir neprilizin inhibitörü (örn., sakubitril). Neprilizin inhibitörü içeren bir ürün olan sakubitril / valsartan'a geçtikten sonra 36 saat içinde Lisinopril Cinfa uygulamayın.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Fetal Toxicity
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Lisinopril Cinfa as soon as possible.
Angioedema And Anaphylactoid Reactions
Angioedema
Head and Neck Angioedema
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including lisinopril, at any time during treatment. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Lisinopril Cinfa should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients.
Patients receiving coadministration of an ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema.
Intestinal Angioedema
Intestinal angioedema has occurred in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.
Anaphylactoid Reactions
Anaphylactoid Reactions During Desensitization
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.
Anaphylactoid Reactions During Dialysis
Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Impaired Renal Function
Monitor renal function periodically in patients treated with Lisinopril Cinfa. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the reninangiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on Lisinopril Cinfa. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Lisinopril Cinfa.
Hypotension
Lisinopril Cinfa can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology.
In these patients, Lisinopril Cinfa should be started under very close medical supervision and such patients should be followed closely for the first two weeks of treatment and whenever the dose of Lisinopril Cinfa and/or diuretic is increased. Avoid use of Lisinopril Cinfa in patients who are hemodynamically unstable after acute MI.
Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy.
Surgery/Anesthesia
In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Lisinopril Cinfa may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
Hyperkalemia
Serum potassium should be monitored periodically in patients receiving Lisinopril Cinfa. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes.
Hepatic Failure
ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical treatment.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
There was no evidence of a tumorigenic effect when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg per kg per day (about 56 or 9 times* the maximum recommended daily human dose, based on body weight and body surface area, respectively). There was no evidence of carcinogenicity when lisinopril was administered for 92 weeks to (male and female) mice at doses up to 135 mg per kg per day (about 84 times* the maximum recommended daily human dose). This dose was 6.8 times the maximum human dose based on body surface area in mice.
Lisinopril was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. It was also negative in a forward mutation assay using Chinese hamster lung cells. Lisinopril did not produce single strand DNA breaks in an in vitro alkaline elution rat hepatocyte assay. In addition, lisinopril did not produce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.
There were no adverse effects on reproductive performance in male and female rats treated with up to 300 mg per kg per day of lisinopril. This dose is 188 times and 30 times the maximum human dose when based on mg/kg and mg/m², respectively.
Studies in rats indicate that lisinopril crosses the blood brain barrier poorly. Multiple doses of lisinopril in rats do not result in accumulation in any tissues. Milk of lactating rats contains radioactivity following administration of 14C lisinopril. By whole body autoradiography, radioactivity was found in the placenta following administration of labeled drug to pregnant rats, but none was found in the fetuses.
*Calculations assume a human weight of 50 kg and human body surface area of 1.62m².
Use In Specific Populations
Pregnancy
Risk Summary
Lisinopril Cinfa can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue Lisinopril Cinfa as soon as possible.
The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.
Fetal/Neonatal Adverse Reactions
Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.
Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Lisinopril Cinfa for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Lisinopril Cinfa, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.
Lactation
Risk Summary
No data are available regarding the presence of lisinopril in human milk or the effects of lisinopril on the breastfed infant or on milk production. Lisinopril is present in rat milk. Because of the potential for severe adverse reactions in the breastfed infant, advise women not to breastfeed during treatment with Lisinopril Cinfa.
Pediatric Use
Antihypertensive effects and safety of lisinopril have been established in pediatric patients aged 6 to 16 years. No relevant differences between the adverse reaction profile for pediatric patients and adult patients were identified.
Safety and effectiveness of lisinopril have not been established in pediatric patients under the age 6 or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m².
Neonates With A History Of In Utero Exposure To Lisinopril Cinfa
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
Geriatric Use
No dosage adjustment with Lisinopril Cinfa is necessary in elderly patients. In a clinical study of lisinopril in patients with myocardial infarctions (GISSI-3 Trial), 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over. In this study, 4.8 % of patients aged 75 years and older discontinued lisinopril treatment because of renal dysfunction vs. 1.3% of patients younger than 75 years. No other differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Race
ACE inhibitors, including Lisinopril Cinfa, have an effect on blood pressure that is less in Black patients than in non-Blacks.
Renal Impairment
Dose adjustment of Lisinopril Cinfa is required in patients undergoing hemodialysis or whose creatinine clearance is ≤ 30 mL/min. No dose adjustment of Lisinopril Cinfa is required in patients with creatinine clearance > 30 mL/min.
WARNINGS
Included as part of the "PRECAUTIONS" Section
PRECAUTIONS
Fetal Toxicity
Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Lisinopril Cinfa as soon as possible.
Angioedema And Anaphylactoid Reactions
Angioedema
Head and Neck Angioedema
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including Lisinopril Cinfa, at any time during treatment. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Lisinopril Cinfa should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients.
Patients receiving concomitant ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.
Patients receiving concomitant ACE inhibitor and neprilysin inhibitor therapy may be at increased risk for angioedema.
Intestinal Angioedema
Intestinal angioedema has occurred in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.
Anaphylactoid Reactions
Anaphylactoid Reactions During Desensitization
Two patients undergoing desensitizing treatment with Hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.
Anaphylactoid Reactions During Dialysis
Sudden and potentially life-threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Impaired Renal Function
Monitor renal function periodically in patients treated with Lisinopril Cinfa. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on Lisinopril Cinfa. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Lisinopril Cinfa.
Hypotension
Lisinopril Cinfa can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology.
In these patients, start Lisinopril Cinfa under medical supervision and follow such patients for the first two weeks of treatment and whenever the dose of Lisinopril Cinfa and/or diuretic is increased. Avoid use of Lisinopril Cinfa in patients who are hemodynamically unstable after acute MI.
Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy.
Surgery/Anesthesia
In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Lisinopril Cinfa may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
Hyperkalemia
Monitor serum potassium periodically in patients receiving Lisinopril Cinfa. Drugs that inhibit the reninangiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes.
Hepatic Failure
ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical treatment.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
There was no evidence of a tumorigenic effect when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg per kg per day or for 92 weeks to male and female mice at doses up to 135 mg per kg per day. These doses are 10 times and 7 times, respectively, the MRHDD when compared on a body surface area basis.
Lisinopril was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. It was also negative in a forward mutation assay using Chinese hamster lung cells. Lisinopril did not produce single strand DNA breaks in an in vitro alkaline elution rat hepatocyte assay. In addition, lisinopril did not produce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.
There were no adverse effects on reproductive performance in male and female rats treated with up to 300 mg/kg/day of lisinopril (33 times the MRHDD when compared on a body surface area basis).
Studies in rats indicate that lisinopril crosses the blood brain barrier poorly. Multiple doses of lisinopril in rats do not result in accumulation in any tissues. Milk of lactating rats contains radioactivity following administration of 14C lisinopril. By whole body autoradiography, radioactivity was found in the placenta following administration of labeled drug to pregnant rats, but none was found in the fetuses.
Use In Specific Populations
Pregnancy
Pregnancy Category D
In the unusual case that there is no appropriate alternative therapy to drugs affecting the reninangiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Lisinopril Cinfa, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Lisinopril Cinfa for hypotension, oliguria, and hyperkalemia.
Nursing Mothers
Milk of lactating rats contains radioactivity following administration of 14C lisinopril. It is not known whether this drug is secreted in human milk. Because many drugs are secreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ACE inhibitors, discontinue nursing or discontinue Lisinopril Cinfa.
Pediatric Use
Antihypertensive effects and safety of Lisinopril Cinfa have been established in pediatric patients aged 6 to 16 years. No relevant differences between the adverse reaction profile for pediatric patients and adult patients were identified.
Safety and effectiveness of Lisinopril Cinfa have not been established in pediatric patients under the age of 6 or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2.
Neonates With A History Of In Utero Exposure To Lisinopril Cinfa
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion.
Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
Geriatric Use
No dosage adjustment with Lisinopril Cinfa is necessary in elderly patients. In a clinical study of Lisinopril Cinfa in patients with myocardial infarctions (GISSI-3 Trial) 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over. In this study, 4.8% of patients aged 75 years and older discontinued Lisinopril Cinfa treatment because of renal dysfunction vs. 1.3% of patients younger than 75 years. No other differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Race
ACE inhibitors, including Lisinopril Cinfa, have an effect on blood pressure that is less in Black patients than in non-Blacks.
Renal Impairment
Dose adjustment of Lisinopril Cinfa is required in patients undergoing hemodialysis or whose creatinine clearance is ≤30 mL/min. No dose adjustment of Lisinopril Cinfa is required in patients with creatinine clearance >30 mL/min.
Klinik Araştırmalar Deneyimi
Klinik araştırmalar çok çeşitli koşullar altında yapıldığından, bir ilacın klinik çalışmalarında gözlenen advers reaksiyon oranları, başka bir ilacın klinik çalışmalarındaki oranlarla doğrudan karşılaştırılamaz ve uygulamada gözlemlenen oranları yansıtmayabilir.
Hipertansiyon
Lisinopril ile tedavi edilen hipertansiyonu olan hastalarda yapılan klinik çalışmalarda, lisinopril hastalarının% 5.7'si advers reaksiyonlarla kesilmiştir.
Sadece lisinopril ile aşağıdaki advers reaksiyonlar (lisinoprilde plaseboya göre% 2 daha fazla olaylar) gözlenmiştir: baş ağrısı (% 3.8), baş dönmesi (% 3.5) ve öksürük (% 2.5).
Kalp yetmezliği
Dört yıla kadar lisinopril ile tedavi edilen sistolik kalp yetmezliği olan hastalarda,% 11'i advers reaksiyonlarla tedaviyi bıraktı. Kalp yetmezliği olan hastalarda yapılan kontrollü çalışmalarda, 12 hafta boyunca plasebo ile tedavi edilen hastaların% 7.7'sine kıyasla, 12 hafta boyunca lisinopril ile tedavi edilen hastaların% 8.1'inde tedavi kesildi.
Lisinopril ile aşağıdaki advers reaksiyonlar (lisinopril üzerinde plaseboya göre% 2 daha büyük olaylar) gözlenmiştir: hipotansiyon (% 3.8) ve göğüs ağrısı (% 2.1).
Kalp yetmezliği olan hastalarda yapılan iki dozlu ATLAS çalışmasında, advers reaksiyonlara bağlı geri çekilme, toplam kesilme sayısında (% 17-18) veya nadir spesifik reaksiyonlarda (<% 1) düşük ve yüksek doz grupları arasında farklı değildi. . Çoğunlukla ACE inhibisyonu ile ilişkili olan aşağıdaki advers reaksiyonlar, yüksek doz grubunda daha yaygın olarak bildirilmiştir:
Tablo 1: Dozla İlgili Advers İlaç Reaksiyonları: ATLAS çalışması
Yüksek doz (N = 1568) | Düşük Doz (N = 1596) | |
Baş dönmesi | % 19 | % 12 |
Hipotansiyon | % 11 | 7% |
Kreatinin arttı | % 10 | 7% |
Hiperkalemi | 6% | 4% |
Senkop | 7% | 5% |
Akut Miyokard Enfarktüsü
Lisinopril ile tedavi edilen hastalarda, lisinopril almayan hastalara kıyasla daha yüksek hipotansiyon insidansı (% 5.3) ve böbrek fonksiyon bozukluğu (% 1.3) vardı. Kontrollü klinik çalışmalarda lisinopril ile tedavi edilen hipertansiyon veya kalp yetmezliği olan hastaların% 1 veya daha yükseklerinde meydana gelen ve etiketlemenin diğer bölümlerinde yer almayan diğer klinik advers reaksiyonlar aşağıda listelenmiştir:
Bir bütün olarak vücut : Yorgunluk, asteni, ortostatik etkiler.
Sindirim: Pankreatit, kabızlık, şişkinlik, ağız kuruluğu, ishal.
Hematolojik: Nadir kemik iliği depresyonu, hemolitik anemi, lökopeni / nötropeni ve trombositopeni vakaları.
Endokrin: Diyabetes mellitus, uygun olmayan antidiyüretik hormon salgısı.
Metabolik: Gut. Cilt: Ürtiker, alopesi, ışığa duyarlılık, eritem, kızarma, terleme, kutanöz psödolenfom, toksik epidermal nekroliz, Stevens -Johnson sendromu ve kaşıntı.
Özel Duyular: Görme kaybı, diplopi, bulanık görme, kulak çınlaması, fotofobi, tat bozuklukları, koku alma bozukluğu.
Ürogenital: İktidarsızlık.
Çeşitli: Pozitif ANA, artmış eritrosit sedimantasyon hızı, artralji / artrit, kas ağrısı, ateş, vaskülit, eozinofili, lökositoz, parestezi ve vertigo içeren bir semptom kompleksi bildirilmiştir. Döküntü, ışığa duyarlılık veya diğer dermatolojik belirtiler tek başına veya bu semptomlarla kombinasyon halinde ortaya çıkabilir.
Klinik Laboratuvar Test Bulguları
Serum Potasyum
Klinik çalışmalarda hipertansiyon ve kalp yetmezliği olan lisinopril ile tedavi edilen hastaların sırasıyla% 2.2 ve% 4.8'inde hiperkalemi (5.7 mEq / L'den büyük serum potasyum) meydana geldi.
Kreatinin, Kan Üre Azot
Sadece lisinopril ile tedavi edilen hipertansiyonu olan hastaların yaklaşık% 2'sinde, tedavinin kesilmesiyle geri dönüşümlü olarak kan üre azotu ve serum kreatinininde küçük artışlar gözlenmiştir. Arttırmalar, eşlik eden diüretik alan hastalarda ve renal arter darlığı olan hastalarda daha yaygındı. Eşzamanlı diüretik tedavisi sırasında kalp yetmezliği olan hastaların% 11.6'sında kan üre azotu ve serum kreatinininde geri dönüşümlü küçük artışlar gözlenmiştir. Diüretik dozu azaldığında bu anormallikler sıklıkla düzeldi.
Lisinopril ile tedavi edilen GISSI-3 çalışmasında akut miyokard enfarktüsü olan hastalar, hastanede ve altı haftada (kreatinin konsantrasyonunu 3 mg / dL'nin üzerine çıkaran) böbrek fonksiyon bozukluğu insidansına (% 2.4'e karşı% 1.1) sahipti. başlangıç serum kreatinin konsantrasyonunun iki katına çıkarılması veya daha fazlası).
Hemoglobin ve Hematokrit
Hemoglobin ve hematokritte küçük düşüşler (ortalama yaklaşık% 0.4 g ve% 1.3 azalma) lisinopril ile tedavi edilen hastalarda sık sık meydana geldi, ancak başka bir anemi nedeni olmayan hastalarda nadiren klinik öneme sahipti. Klinik çalışmalarda, hastaların% 0.1'inden azı anemi nedeniyle tedaviyi bıraktı.
Pazarlama Sonrası Deneyim
Etiketlemenin diğer bölümlerinde bulunmayan lisinopril'in onay sonrası kullanımı sırasında aşağıdaki advers reaksiyonlar tanımlanmıştır. Bu reaksiyonlar, belirsiz büyüklükteki bir popülasyondan gönüllü olarak bildirildiğinden, sıklıklarını güvenilir bir şekilde tahmin etmek veya ilaca maruz kalma ile nedensel bir ilişki kurmak her zaman mümkün değildir.
Diğer reaksiyonlar şunları içerir:
Metabolizma ve Beslenme Bozuklukları
Hiponatremi, oral antidiyabetik ajanlar veya insülin kullanan diyabetik hastalarda hipoglisemi vakaları.
Sinir Sistemi ve Psikiyatrik Bozukluklar
Ruh hali değişiklikleri (depresif belirtiler dahil), zihinsel karışıklık, halüsinasyonlar
Deri ve Deri Altı Doku Bozuklukları
Sedef hastalığı
Klinik Araştırmalar Deneyimi
Klinik araştırmalar çok çeşitli koşullar altında yapıldığından, bir ilacın klinik çalışmalarında gözlenen advers reaksiyon oranları, başka bir ilacın klinik çalışmalarındaki oranlarla doğrudan karşılaştırılamaz ve uygulamada gözlemlenen oranları yansıtmayabilir.
Hipertansiyon
Lisinopril Cinfa'da plaseboya göre% 2 daha fazla olaylar) aşağıdaki advers reaksiyonlar gözlendi: baş ağrısı (% 5.7'ye karşı% 1.9), baş dönmesi (% 5.4'e karşı% 1.9), öksürük (% 3.5'e karşı% 1.0) .
Kalp yetmezliği
Kalp yetmezliği olan hastalarda yapılan kontrollü çalışmalarda, 12 hafta boyunca Lisinopril Cinfa ile tedavi edilen hastaların% 8.1'inde tedavi kesildi, 12 hafta boyunca plasebo ile tedavi edilen hastaların% 7.7'si.
Lisinopril Cinfa'da plaseboya kıyasla aşağıdaki advers reaksiyonlar (Lisinopril Cinfa'da plaseboya göre% 2 daha fazla olaylar) gözlendi: hipotansiyon (% 4.4'e karşı% 0.6), göğüs ağrısı (% 3.4'e karşı% 1.3).
Kalp yetmezliği olan hastalarda yapılan ATLAS çalışmasında, advers reaksiyonların geri çekilmesi düşük ve yüksek doz gruplarında benzerdi. Çoğunlukla ACE inhibisyonu ile ilişkili olan aşağıdaki advers reaksiyonlar, yüksek doz grubunda daha yaygın olarak bildirilmiştir:
Tablo 1: Dozla İlgili Advers İlaç Reaksiyonları: ATLAS çalışması
Yüksek doz (N = 1568) | Düşük Doz (N = 1596) | |
Baş dönmesi | % 19 | % 12 |
Hipotansiyon | % 11 | 7% |
Kreatinin arttı | % 10 | 7% |
Hiperkalemi | 6% | 4% |
Senkop | 7% | 5% |
Akut Miyokard Enfarktüsü
Lisinopril Cinfa ile tedavi edilen GISSI-3 çalışmasındaki hastalar, Lisinopril Cinfa almayan hastalara kıyasla daha yüksek hipotansiyon (% 9.0'a karşı% 3.7) ve böbrek fonksiyon bozukluğu (% 2.4'e karşı% 1.1) insidansına sahipti.
Kontrollü klinik çalışmalarda Lisinopril Cinfa ile tedavi edilen hipertansiyon veya kalp yetmezliği olan hastaların% 1 veya daha fazlasında meydana gelen ve etiketlemenin diğer bölümlerinde yer almayan diğer klinik advers reaksiyonlar aşağıda listelenmiştir:
Bir bütün olarak vücut : Yorgunluk, asteni, ortostatik etkiler.
Sindirim: Pankreatit, kabızlık, şişkinlik, ağız kuruluğu, ishal.
Hematolojik: Nadir kemik iliği depresyonu, hemolitik anemi, lökopeni / nötropeni ve trombositopeni vakaları.
Endokrin: Diyabetes mellitus, uygun olmayan antidiyüretik hormon salgısı.
Metabolik: Gut
Cilt: Ürtiker, alopesi, ışığa duyarlılık, eritem, kızarma, terleme, kutanöz psödolenfom, toksik epidermal nekroliz, Stevens. Johnson sendromu ve kaşıntı.
Özel Duyular: Görme kaybı, diplopi, bulanık görme, kulak çınlaması, fotofobi, tat bozuklukları, koku alma bozuklukları.
Ürogenital: İktidarsızlık
Çeşitli: Pozitif ANA, artmış eritrosit sedimantasyon hızı, artralji / artrit, kas ağrısı, ateş, vaskülit, eozinofili, lökositoz, parestezi ve vertigo içeren bir semptom kompleksi bildirilmiştir. Döküntü, ışığa duyarlılık veya diğer dermatolojik belirtiler tek başına veya bu semptomlarla kombinasyon halinde ortaya çıkabilir.
Klinik Laboratuvar Test Bulguları
Serum Potasyum: Klinik çalışmalarda hipertansiyon ve kalp yetmezliği olan Lisinopril Cinfa ile tedavi edilen hastaların sırasıyla% 2.2 ve% 4.8'inde hiperkalemi (serum potasyum> 5.7 mEq / L) meydana geldi.
Kreatinin, Kan Üre Azot
Sadece Lisinopril Cinfa ile tedavi edilen hipertansiyonu olan hastaların yaklaşık% 2'sinde, tedavinin kesilmesiyle geri dönüşümlü olarak kan üre azotu ve serum kreatinininde küçük artışlar gözlenmiştir. Arttırmalar, eşlik eden diüretik alan hastalarda ve renal arter darlığı olan hastalarda daha yaygındı. Eşzamanlı diüretik tedavisi sırasında kalp yetmezliği olan hastaların% 11.6'sında kan üre azotu ve serum kreatinininde geri dönüşümlü küçük artışlar gözlenmiştir. Diüretik dozu azaldığında bu anormallikler sıklıkla düzeldi.
Lisinopril Cinfa ile tedavi edilen GISSI-3 çalışmasında akut miyokard enfarktüsü olan hastalar, hastanede ve 6 haftada (kreatinin konsantrasyonunu 3 mg / dL'nin üzerine çıkaran) böbrek fonksiyon bozukluğu insidansına (% 2.4'e karşı% 1.1) sahipti. veya başlangıç serum kreatinin konsantrasyonunun iki katına çıkarılması veya daha fazlası).
Hemoglobin ve Hematokrit
Lisinopril Cinfa ile tedavi edilen hastalarda hemoglobin (ortalama 0.4 mg / dL) ve hematokritte (ortalama% 1.3) küçük düşüşler meydana geldi, ancak başka bir anemi nedeni olmayan hastalarda nadiren klinik öneme sahipti. Klinik çalışmalarda, hastaların% 0.1'inden azı anemi tedavisini bıraktı.
Karaciğer Enzimleri Nadiren, karaciğer enzimleri ve / veya serum bilirubin yükselmeleri meydana gelmiştir.
Pazarlama Sonrası Deneyim
Etiketlemenin diğer bölümlerinde bulunmayan lisinopril'in onay sonrası kullanımı sırasında aşağıdaki advers reaksiyonlar tanımlanmıştır. Bu reaksiyonlar, belirsiz büyüklükteki bir popülasyondan gönüllü olarak bildirildiğinden, sıklıklarını güvenilir bir şekilde tahmin etmek veya ilaca maruz kalma ile nedensel bir ilişki kurmak her zaman mümkün değildir. Diğer reaksiyonlar şunları içerir:
Metabolizma ve Beslenme Bozuklukları
Hiponatremi, oral antidiyabetik ajanlar veya insülin kullanan diyabetik hastalarda hipoglisemi vakaları
Sinir Sistemi ve Psikiyatrik Bozukluklar
Ruh hali değişiklikleri (depresif belirtiler dahil), zihinsel karışıklık
20 g / kg'lık tek bir oral dozun ardından sıçanlarda ölümcüllük görülmedi ve aynı dozu alan 20 fareden birinde ölüm meydana geldi. Doz aşımının en olası tezahürü, olağan tedavinin normal salin çözeltisinin intravenöz infüzyonu olacağı hipotansiyon olacaktır.
Lisinopril hemodiyaliz ile uzaklaştırılabilir.
20 g / kg'lık tek bir oral dozun ardından, sıçanlarda ölümcüllük görülmedi ve aynı dozu alan 20 fareden birinde ölüm meydana geldi. Doz aşımının en olası tezahürü, olağan tedavinin normal salin çözeltisinin intravenöz infüzyonu olacağı hipotansiyon olacaktır.
Lisinopril hemodiyaliz ile uzaklaştırılabilir.
Hypertension
Adult Patients
Administration of lisinopril to patients with hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is usually not observed although it can occur and should be anticipated in volume and/or salt-depleted patients. When given together with thiazide-type diuretics, the blood pressure lowering effects of the two drugs are approximately additive.
In most patients studied, onset of antihypertensive activity was seen at one hour after oral administration of an individual dose of lisinopril, with peak reduction of blood pressure achieved by 6 hours. Although an antihypertensive effect was observed 24 hours after dosing with recommended single daily doses, the effect was more consistent and the mean effect was considerably larger in some studies with doses of 20 mg or more than with lower doses; however, at all doses studied, the mean antihypertensive effect was substantially smaller 24 hours after dosing than it was 6 hours after dosing.
The antihypertensive effects of lisinopril are maintained during long-term therapy. Abrupt withdrawal of lisinopril has not been associated with a rapid increase in blood pressure, or a significant increase in blood pressure compared to pretreatment levels.
Non-Steroidal Anti-Inflammatory Agents
In a study in 36 patients with mild to moderate hypertension where the antihypertensive effects of lisinopril alone were compared lisinopril given concomitantly with indomethacin, the use of indomethacin was associated with a reduced effect, although the difference between the two regimens was not significant.
Hypertension
Adult Patients
Administration of Lisinopril Cinfa to patients with hypertension results in a reduction of supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is usually not observed although it can occur and should be anticipated in volume and/or salt-depleted patients. When given together with thiazidetype diuretics, the blood pressure lowering effects of the two drugs are approximately additive.
In most patients studied, onset of antihypertensive activity was seen at one hour after oral administration of an individual dose of Lisinopril Cinfa, with peak reduction of blood pressure achieved by 6 hours. Although an antihypertensive effect was observed 24 hours after dosing with recommended single daily doses, the effect was more consistent and the mean effect was considerably larger in some studies with doses of 20 mg or more than with lower doses. However, at all doses studied, the mean antihypertensive effect was substantially smaller 24 hours after dosing than it was 6 hours after dosing.
The antihypertensive effects of Lisinopril Cinfa are maintained during long-term therapy. Abrupt withdrawal of Lisinopril Cinfa has not been associated with a rapid increase in blood pressure or a significant increase in blood pressure compared to pretreatment levels.
Adult Patients
Lisinopril Cinfa is bioequivalent to lisinopril tablets under fasted and fed conditions.
Following oral administration of lisinopril tablets, peak serum concentrations of lisinopril occur within about 7 hours, although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. Food does not alter the bioavailability of lisinopril tablets. Declining serum concentrations exhibit a prolonged terminal phase, which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose. Upon multiple dosing, lisinopril exhibits an effective half-life of 12 hours.
Lisinopril does not appear to be bound to other serum proteins. Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine. Based on urinary recovery, the mean extent of absorption of lisinopril is approximately 25%, with large intersubject variability (6-60%) at all doses tested (5-80 mg). The absolute bioavailability of lisinopril is reduced to 16% in patients with stable NYHA Class II-IV congestive heart failure, and the volume of distribution appears to be slightly smaller than that in normal subjects. The oral bioavailability of lisinopril in patients with acute myocardial infarction is similar to that in healthy volunteers.
Impaired renal function decreases elimination of lisinopril, which is excreted principally through the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 mL/min. Above this glomerular filtration rate, the elimination half-life is little changed. With greater impairment, however, peak and trough lisinopril levels increase, time to peak concentration increases and time to attain steady state is prolonged. Lisinopril can be removed by hemodialysis.
Pediatric Patients
The pharmacokinetics of lisinopril were studied in 29 pediatric hypertensive patients between 6 years and 16 years with glomerular filtration rate > 30 mL/min/1.73 m². After doses of 0.1 to 0.2 mg per kg, steady state peak plasma concentrations of lisinopril occurred within 6 hours and the extent of absorption based on urinary recovery was about 28%. These values are similar to those obtained previously in adults. The typical value of lisinopril oral clearance (systemic clearance/absolute bioavailability) in a child weighing 30 kg is 10 L/h, which increases in proportion to renal function.
Adult Patients
Following oral administration of Lisinopril Cinfa, peak serum concentrations of lisinopril occur within about 7 hours, although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. Declining serum concentrations exhibit a prolonged terminal phase which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose. Upon multiple dosing, lisinopril exhibits an effective half-life of 12 hours.
Lisinopril does not appear to be bound to other serum proteins. Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine. Based on urinary recovery, the mean extent of absorption of lisinopril is approximately 25 percent, with large inter-subject variability (6-60 percent) at all doses tested (5-80 mg). Lisinopril absorption is not influenced by the presence of food in the gastrointestinal tract. The absolute bioavailability of lisinopril is reduced to about 16 percent in patients with stable NYHA Class II-IV congestive heart failure, and the volume of distribution appears to be slightly smaller than that in normal subjects.
The oral bioavailability of lisinopril in patients with acute myocardial infarction is similar to that in healthy volunteers.
Impaired renal function decreases elimination of lisinopril, which is excreted principally through the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 mL/min. Above this glomerular filtration rate, the elimination half-life is little changed. With greater impairment, however, peak and trough lisinopril levels increase, time to peak concentration increases and time to attain steady state is prolonged. Older patients, on average, have (approximately doubled) higher blood levels and area under the plasma concentration time curve (AUC) than younger patients. Lisinopril can be removed by hemodialysis.
Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly. Multiple doses of lisinopril in rats do not result in accumulation in any tissues. Milk of lactating rats contains radioactivity following administration of 14C lisinopril. By whole body autoradiography, radioactivity was found in the placenta following administration of labeled drug to pregnant rats, but none was found in the fetuses.
Pediatric Patients
The pharmacokinetics of lisinopril were studied in 29 pediatric hypertensive patients between 6 years and 16 years with glomerular filtration rate >30 mL/min/1.73 m2. After doses of 0.1 to 0.2 mg/kg, steady state peak plasma concentrations of lisinopril occurred within 6 hours and the extent of absorption based on urinary recovery was about 28%. These values are similar to those obtained previously in adults. The typical value of lisinopril oral clearance (systemic clearance/absolute bioavailability) in a child weighing 30 kg is 10 L/h, which increases in proportion to renal function.
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