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Amlodipine with Lisinopril

Indications

Amlodipine+Lisinopril is indicated in the treatment of mild to moderate hypertension. It is also indicated in hypertension not responding to monotherapy with ACE inhibitors or calcium antagonists. It may also be substituted for the titrated doses of the individual components.

Dosage and Administration

The usual initial dosage is one tablet (amlodpine 5mg+Lisinopril 5mg) daily. If blood pressure control is inadequate after a week or two, the dose may be increased to two tablets daily.
The dosage, however, should be individualized.

Contraindications

Hypersensitivity to either component, history of angioedema related to previous treatment with an ACE inhibitor and in patients with hereditary or idiopathic angioedema

Warnings and Precautions

Pregnancy
When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible. In a published retrospective epidemiological study, infants whose mother had taken an ACE inhibitor drug during the first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function. If oligohydramnios is observed, lisinopril should be discontinued unless it is considered lifesaving for the mother. Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment. Hence, the combination is contraindicated in pregnancy.

Lactation
It is not known whether lisinopril or amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while the combination is administered.

Pediatric Use
Safety and effectiveness of combination in children < 6 years of age have not been established.

Geriatric Use
Clinical studies of amlodipine and lisinopril monotherapy in patients with hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience in this population has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient
should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.

Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40-60% and a lower initial dose may be required.

Pharmacokinetic studies indicate that maximum blood levels and area under plasma concentration curve (AUC) are doubled in elderly patients treated with lisinopril. Lisinopril is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Evaluation of patients with hypertension should always include assessment of renal function.

Aggravation of Angina
Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy, or at the time of dosage increase.

Congestive Heart Failure
In general, calcium channel blockers should be used with caution in patients with heart failure. Placebo-controlled trials of amlodipine in patients with New York Heart Association (NYHA) Class III or IV heart failure showed no overall adverse effect on survival or cardiac morbidity. In NYHA Class II/III heart failure patients, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or left ventricular ejection fraction.

Renal Impairment
Amlodipine+Lisinopril should be used with caution in patients with severe renal disease. As a consequence of inhibition of the RAAS, changes in renal function may be anticipated in susceptible individuals. In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur, which is usually reversible. When such patients are treated with Amlodipine+Lisinopril, renal function should be monitored during the first few weeks of therapy. Evaluation of patients with hypertension should always include assessment of renal function.

Hepatic Impairment
Caution should be exercised when administering combination in patients with severe liver damage because of prolongation of the elimination half-life of amlodipine.

Drug Interactions

Diuretics: Patients on diuretics may occasionally experience an excessive reduction of blood pressure after initiation of therapy with this combination. The possibility of hypotensive effects can be minimized by either discontinuing the combination or increasing the salt intake prior to initiation of treatment.

Agents Increasing Serum Potassium: Lisinopril attenuates potassium loss caused by thiazide-type diuretics. If concomitant use of these agents is indicated, they should be used with caution, and with frequent monitoring of serum potassium.

Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium.

The combination and lithium should be co-administered with caution, and frequent monitoring of serum lithium levels is recommended.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): In some patients with compromised renal function who are being treated with NSAIDs, the coadministration of lisinopril may result in a further deterioration of renal function.

These effects are usually reversible. NSAIDs blunt the antihypertensive effect of ACE inhibitors, including lisinopril, and this should be given consideration in patients taking NSAIDs concomitantly with the combination. Indomethacin may reduce the antihypertensive efficacy of lisinopril.

Side effects

The combination of amlodipine and lisinopril is well tolerated. Angioneurotic edema has been reported with ACE inhibitors. In such cases, the combination should be discontinued immediately. Other side effects include nausea, headache, dizziness, cough, diarrhea, fatigue, rash, edema, flushing, palpitations, and asthenia.

Overdosage

The most likely manifestation of overdosage of lisinopril would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Lisinopril can be removed by hemodialysis.

If massive overdose of amlodipine should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. As amlodipne is highly protein bound, hemodialysis is not likely to be of benefit.

 

Important Links

Ministry of Health & Family Welfare, Govt. of India

National Pharmaceutical Pricing Authority

Department of AYUSH

Department of Chemicals and Petrochemicals

Central Council for Research in Ayurvedic Sciences

Medical Council of India

Pharmacy Council of India

Nursing Council of India

Indian Pharmacist Association

Indian Medical Association

 



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