Lisinopril

 
Pregnancy Categories C (first trimester) and D (second and third trimesters).  See WARNINGS, Fetal/Neonatal Morbidity and Mortality .

 
Milk of lactating rats contains radioactivity following administration of ¹⁴C lisinopril. It is not known whether this drug is excreted in human milk.  Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ACE inhibitors, a decision should be made whether to discontinue nursing or discontinue lisinopril, taking into account the importance of the drug to the mother.

 
Antihypertensive effects of lisinopril have been established in hypertensive pediatric patients aged 6 to 16 years.
 
There are no data on the effect of lisinopril on blood pressure in pediatric patients under the age 6 or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m². (See  CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism and Pharmacodynamics and Clinical Effects , and DOSAGE AND ADMINISTRATION .)

Clinical studies of lisinopril 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 other drug therapy.
 
In the ATLAS trial of lisinopril in patients with congestive heart failure, 1,596 (50%) were 65 and over, while 437 (14%) were 75 and over.  In a clinical study of lisinopril in patients with myocardial infarctions 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over.  In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients, and other reported clinical experiences has not identified differences in responses between the elderly and younger patients (see CLINICAL PHARMACOLOGY – Pharmacodynamics and Clinical Effects – Heart Failure and CLINICAL PHARMACOLOGY – Pharmacodynamics and Clinical Effects – Acute Myocardial Infarction ).
 
Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
 
Pharmacokinetic studies indicate that maximum blood levels and area under the plasma concentration time curve (AUC) are doubled in older patients (see CLINICAL PHARMACOLOGY – Pharmacokinetics and Metabolism ).
 
This drug 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, congestive heart failure, or myocardial infarction should always include assessment of renal function (see DOSAGE AND ADMINISTRATION ).

 
Following a single oral dose of 20 g/kg no lethality occurred in rats, and death occurred in one of 20 mice receiving the same dose.  The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution.
 
Lisinopril can be removed by hemodialysis. (See WARNINGS, Anaphylactoid Reactions During Membrane Exposure .)

 
Lisinopril is an oral long-acting angiotensin converting enzyme inhibitor.  Lisinopril, a synthetic peptide derivative, is chemically described as (S)-1-[N² -(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its empirical formula is C₂₁H₃₁N₃O₅.2H₂O and its structural formula is:


[image: MM1]
 
Lisinopril is a white to off-white, crystalline powder, with a molecular weight of 441.53. It is soluble in water and sparingly soluble in methanol and practically insoluble in ethanol.
 
Lisinopril is supplied as 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, and 40 mg tablets for oral administration.
 
Inactive Ingredients:  

2.5 mg tablets – dibasic calcium phosphate, magnesium stearate, mannitol, starch and pregelatinized starch.
 
5 mg tablets – dibasic calcium phosphate, magnesium stearate, mannitol, starch, pregelatinized starch and ferric oxide red.
 
10, 20, 30, and 40 mg tablets - dibasic calcium phosphate, magnesium stearate, mannitol, starch, pregelatinized starch and ferric oxide yellow.

[image: MM2]

 

2.5 mg Tablets – White to off-white, round shaped, biconvex, uncoated tablets, debossed with ‘A’ on one side and ‘20’ on the other side.

 

5 mg Tablets – Light red colored, round shaped, biconvex, uncoated tablets, debossed with ‘A’ on one side and on other side with ‘2&1’ on either side of score line.

10 mg Tablets – Light yellow colored, round shaped, biconvex, uncoated tablets, debossed with ‘A’ on one side and on other side with ‘22’.

20 mg Tablets – Light yellow colored, capsule shaped, biconvex, uncoated tablets, debossed with ‘A’ on one side and on other side with ‘23’.

 

30 mg Tablets – Light yellow colored, round shaped, uncoated tablets, debossed with ‘A’ on one side and on other side with ‘24’.

They are supplied by State of Florida DOH Central Pharmacy as follows:

NDC	Strength	Quantity/Form	Color	Source Prod. Code
53808-0700-1	10 mg	30 Tablets in a Blister Pack	Light	65862-039
53808-0617-1	20 mg	30 Tablets in a Blister Pack	Light	65862-040

Storage
 
Store at controlled room temperature, 20°-25°C (68°-77°F) [see USP ]. Protect from moisture, freezing and excessive heat.
 
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
 
¶ Registered trademark of Hospal Ltd.
  
Manufactured for:
Aurobindo Pharma USA, Inc
2400 Route 130 North
Dayton, NJ 08810
 
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 072, India.

And Repackaged By:

State of Florida DOH Central Pharmacy
104-2 Hamilton Park Drive
Tallahassee, FL 32304
United States