Lisinopril. Dosage, Side Effects, Interactions
Lisinopril is an active ingredient for the treatment of arterial hypertension (high blood pressure), heart failure (heart muscle weakness) and for the prophylaxis of cardiological diseases.
The active ingredient lisinopril has the following areas of application:
- heart failure
- Short-term treatment (6 weeks) of hemodynamically stable patients within 24 hours after an acute myocardial infarction
- Kidney complications in diabetes mellitus
- Treatment of kidney disease in hypertensive patients with type 2 diabetes mellitus and incipient nephropathy
The dose of lisinopril should be individualized according to the characteristics of each patient and depending on the blood pressure response.
How Lisinopril works
Like ramipril , captopril , enalapril, perindopril and zofenopril , lisinopril belongs to the class of ACE inhibitors . “ACE” ( angiotensin converting enzyme) is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II. Angiotensin II has both a direct and an indirect vasoconstrictive effect by releasing catecholamines from the adrenal medulla, facilitating norepinephrine release and increasing sympathetic tone. These factors all contribute to an increase in blood pressure. Furthermore, angiotensin II causes the release of aldosterone, also known as the “thirst hormone”, which is why ACE inhibition by enalapril also causes a weak diuretic effect.
- After oral administration of lisinopril, peak plasma levels are reached within approximately 7 hours
- absolute bioavailability is reduced by approximately 16% in patients with heart failure. The absorption of lisinopril is not affected by food
- Lisinopril is not metabolised and is excreted completely unchanged in the urine
- the clearance of lisinopril in healthy subjects is approximately 50 ml/min
- Lisinopril can be removed by dialysis
Dosage of Lisinopril
In general, the dose should be adjusted individually.
Lisinopril can be taken as monotherapy or in combination with antihypertensive drugs from other classes.
The recommended starting dose is 10 mg lisinopril. In patients with a strongly activated renin-angiotensin-aldosterone system, an initial dose of 2.5-5 mg is recommended, as a sharp drop in blood pressure can occur after taking the initial dose. In these patients, treatment should be initiated under medical supervision.
The recommended maintenance dose is 20 mg once a day. If the desired therapeutic effect cannot be achieved with a given dosage within a period of 2 to 4 weeks, the dosage should be increased. The maximum daily dose is 80 mg lisinopril.
Patients being treated with diuretics
Symptomatic hypotension is very likely to occur in patients treated concomitantly with diuretics . These patients may also be volume and/or salt depleted, so caution is advised. If possible, the diuretic therapy should be stopped 2 – 3 days before the administration of lisinopril. In patients in whom the diuretic cannot be discontinued, lisinopril 5 mg should be started. Renal function and serum potassium should be monitored. The subsequent maintenance dose must be individually adjusted, and the diuretic therapy can be resumed if necessary.
Impaired kidney function
In patients with impaired renal function, the dosage should be adjusted based on creatinine clearance. With a creatinine clearance of 31 – 80 ml/min the initial dose is 5 – 10 mg lisinopril, with 10 – 30 ml/min 2.5 – 5 mg lisinopril per day. For creatinine clearance below 10 ml/min including patients on dialysis, the starting dose is 2.5 mg, which can be increased in increments either until blood pressure is controlled or to a maximum of 40 mg daily.
Children and young people (6 – 16 years)
The initial dose should be determined by body weight and the maintenance dose should be adjusted individually. It should be noted that doses above 0.61 mg/kg or more than 40 mg have not been studied in children and adolescents. In patients weighing 20 to 50 kg, the recommended starting dose is 2.5 mg once a day, which can be individually adjusted in increments up to a maximum of 20 mg a day.
For children and adolescents weighing more than 50 kg, the starting dose is 5 mg once daily and should be adjusted up to a maximum of 40 mg lisinopril per day. In children with impaired renal function (GFR < 30 ml/min/1.73 m2), lisinopril should be given at a lower starting dose or with a longer dosing interval.
Lisinopril should be used in patients with symptomatic heart failure as adjunctive therapy to diuretics and, where appropriate, to digitalis or beta-blockers. The starting dose is 2.5 mg lisinopril once a day, which should be taken under medical supervision.
Dose increases should be in small increments of no more than 10 mg and the interval between dose increases should be at least 2 weeks. The maximum dose should not exceed 35 mg once a day.
Patients at risk of hypotension should be given e.g. B. the salt deficiency (with or without hyponatraemia) or the hypovolaemia should be corrected before therapy with lisinopril if possible. Renal function and serum potassium should be monitored.
Acute heart attack
The recommended standard therapy such as B. thrombolytics, acetylsalicylic acid and beta- blockers should be given to the patient as needed. Likewise, glyceryl trinitrate can be administered together with lisinopril.
Loading dose (during the first 3 days after the infarction)
Treatment with lisinopril can be started within 24 hours of the onset of symptoms provided that the systolic blood pressure is less than 100 mmHg. On the first and second day of therapy, the patients receive 5 mg lisinopril per day, the dose is increased to 10 mg from the third day. Patients with low systolic blood pressure (<120 mmHg) should start therapy with 2.5 mg lisinopril.
The initial dose should be adjusted according to creatinine clearance (< 80 ml/min) in patients with renal impairment.
The maintenance dose is 10 mg once a day. In patients with low systolic blood pressure (<100 mmHg), the daily maintenance dose can be reduced to 2.5-5 mg. Lisinopril should be discontinued if systolic blood pressure is less than 90 mmHg for more than one hour.
Treatment should be continued for 6 weeks and then the patient should be reassessed. Treatment with lisinopril is continued if patients develop symptoms of heart failure.
Kidney complications in diabetes mellitus
In hypertensive patients with type 2 diabetes mellitus and incipient nephropathy, the dosage is 10 mg once daily, increasing to 20 mg once daily if needed. The initial dose should be adjusted according to creatinine clearance (< 80 ml/min) in patients with renal impairment.
Children and young people
The use of lisinopril in children over 6 years of age is only recommended for the treatment of hypertension; there are no dosage recommendations for other indications. Lisinopril is not recommended in children under 6 years of age or in children with severe kidney damage.
Since advanced age is usually associated with reduced renal function, the initial dose should be adjusted according to creatinine clearance (< 80 ml/min).
Patients after kidney transplantation
The safety and efficacy in kidney transplant patients have not been established, therefore treatment with lisinopril is not recommended.
Type of application
Lisinopril should be taken orally once a day with or without food.
Side effects of Lisinopril
When used as directed and at low doses, ACE inhibitors such as lisinopril are considered to be well tolerated. Most side effects are associated with slowed breakdown and accumulation of bradykinin. This can cause the dry, hacking cough typical of ACE inhibitors. Respiratory tract infections, gastrointestinal complaints, visual disturbances, kidney dysfunction, skin rash, dizziness, taste disorders, headaches, nausea, bronchitis and fatigue have also been reported. In rare cases (frequency 0.1-0.2%) angioneurotic edema can occur.
- Diuretics : Additive antihypertensive effect.
- Lisinopril should not be taken together with potassium-sparing diuretics such as spironolactone , amiloride or triamteren : increase in potassium plasma levels is possible.
- Patients with kidney dysfunction or diabetics are particularly affected by the interaction of increased potassium plasma levels: If the potassium level increases, the effect of cardiac glycosides such as digitoxin or digoxin is weakened at the same time.
- Non-steroidal anti-inflammatory drugs such as ibuprofen , diclofenac , acetylsalicylic acid and naproxen : the antihypertensive effect of lisinopril is reduced. Blood pressure checks are therefore necessary with combined intake.
- Immunosuppressants such as allopurinol , glucocorticoids or procainamide : Increased risk of changes in the blood picture. If these combinations are unavoidable, blood counts should be checked regularly.
- Since ACE inhibitors promote the occurrence of allergic reactions, no hyposensitization (immunotherapy) should be carried out while they are being taken.
- Excretion of lithium can be delayed: Strong side effects possible due to increased plasma levels.
- If enalapril is combined with oral antidiabetics or insulin, regular blood sugar checks should be carried out due to an increased blood sugar-lowering effect.
- Injection of gold compounds (eg sodium aurothiomalate): Nitritoid reactions (symptoms of vasodilation such as flushing, nausea, dizziness and hypotension, which can be very severe) have been observed more frequently in patients receiving ACE inhibitor therapy
- Hypersensitivity to lisinopril or another angiotensin converting enzyme inhibitor (ACE inhibitor)
- angioneurotic edema associated with previous treatment with ACE inhibitors
- congenital or idiopathic angioneurotic edema
- second and third trimester of pregnancy
- Concomitant use with aliskiren -containing medicines is prohibited in patients with diabetes mellitus or renal impairment
The use of ACE inhibitors is not recommended during the first trimester of pregnancy as a small increased teratogenic risk cannot be excluded. The use of ACE inhibitors in the second and third trimester of pregnancy is contraindicated, as both foetotoxic and neonatal toxic effects can occur. Ultrasound studies of renal function and skull are recommended for exposure to ACE inhibitors from the second trimester of pregnancy. Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.
There is no information on the use of lisinopril during breast-feeding, therefore the use of lisinopril during breast-feeding is not recommended. Alternative antihypertensive therapy for use during lactation is preferable.
Driving and using machines
It should be taken into account that driving vehicles or using machines may occasionally cause dizziness or tiredness.
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