Trisopril® Lisinopril Tablets USP 5mg
Pharmacological action, Pharmacokinetics, Indications, Contraindications, Warnings, Dosage and direction for use, Side effects and special precautions, Interactions, Known symptoms of overdose and particulars of its treatment, Storage, Presentation, NAFDAC Registration number, Product owner, Licence owner and Manufacturer of Trisopril Tablet Medicine for Hypertension.
Each uncoated tablet contains:
Lisinopril USP eq. to Anhydrous Lisinopril 5.0mg
Lisinopril is a peptidyl dipeptidase inhibitor. It inhibits the angiotensin converting enzyme (ACE) that catalyses the conversion of angiotensin I to the vasoconstrictor peptide angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased concentrations of angiotensin II which results in decreased vasopressor activity and reduced aldosterone secretion. The latter decrease may result in an increase in serum potassium concentration. While the mechanism through which lisinopril lowers blood pressure is believed to be primary suppression of the renin-angiotensin-aldosterone system, lisinopril is also antihypertensive in patients with low-renin hypertension. ACE is identical to kininase II, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodilatory peptide, play a role in the therapeutic effects of lisinopril remains to be elucidated.
Peak serum concentration occurred within 6 to 8 hours, although there was a trend to a small delay in time taken to reach peak plasma concentrations in acute myocardial infarction patients. Upon multiple dosing, lisinopril exhibits an effective half-life of accumulation of 12.6 hours. The extent of absorption of lisinopril was approximately 25%, with interpatient variability (6- 60%) a) at all doses tested (5-80mg). 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. Lisinopril is excreted unchanged in the urine. Impaired renal function decreases elimination of lisinopril, which is excreted via the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30mL/min. Older patients have higher blood levels and higher values for the area under the plasma concentration time curve than younger patients. Lisinopril can be removed by dialysis.
Lisinopril is indicated in the treatment of mild to moderate hypertension. It may be used alone or concomitantly with other classes of antihypertensive agents. Lisinopril is indicated in the management of congestive heart failure as an adjunctive treatment with diuretics and, where appropriate, digitalis. Lisinopril is indicated for the treatment of haemodynamically stable patients, within 24 hours after acute myocardial infarction, to prevent the subsequent development of left ventricular dysfunction or heart failure and to improve survival. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blocker. Administration is by the oral route.
The safety of lisinopril has not been established in breastfeeding mothers. Lisinopril is contraindicated in patients who are hypersensitive to any components of the product and in patients with a history of angioneurotic oedema relating to previous treatment with angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angiodema. Lisinopril should not be given to patients with aortic stenosis or hypertrophic cardiomyopathy.
Should a woman become pregnant while receiving an ACE-inhibitor, the treatment must be stopped promptly and switched to a different medicine. Should a woman contemplate pregnancy, the doctor should institute alternative medication.
ACE-inhibitors can cause foetal and neonatal morbidity when administered to pregnant women during the 2nd and 3rd trimesters. ACE-inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. Oligohydramnios, which may result in limb contractures, cranofacial deformities and hypoplastic lung development, as well as hypotension, renal failure, hyperkalaemia, oliguria and anuria in new-borns have been reported after administration of ACE-inhibitors in the second and third trimesters. Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur. The adverse effects to the embryo and foetus do not appear to have resulted from intra-uterine ACE-inhibitor exposure limited to the first trimester. Infants whose mothers have taken lisinopril should be closely observed for hypertension, oliguria and hyperkalaemia. Lisinopril crosses the human placenta. Limited experience indicates that peritoneal dialysis may be of some benefit in the clearance of lisinopril from the neonatal circulation. Lisinopril can theoretically be removed from the neonatal circulation by exchange transfusion.
DOSAGE AND DIRECTIONS FOR USE
Absorption of lisinopril tablets is not affected by food, and tablets may be administered before, during or after meals. Lisinopril should be administered in a single daily dose. Lisinopril should be taken at approximately the same time each day.
Mild to Moderate Hypertension: The recommended starting dose is 10mg. The usual effective maintenance dosage is 20 mg administered in a single daily dose. Dosage should be adjusted according to blood pressure response. A maximum dose of 40 mg a day in hypertension is recommended. If the desired therapeutic effect cannot be achieved in a period of 2 to 4 weeks on a certain dose level, the dose can further be increased.
Diuretic-Treated Patients: Symptomatic hypotension may occur following initiation of therapy with lisinopril; this is more likely in patients who are being treated currently with diuretics. Caution is recommended in all patients who may be vulome-and/or salt-depleted. The diuretic should be discontinued 2 to 3 days before beginning therapy with lisinopril. In hypertensive patients in whom the diuretic cannot be discontinued, therapy with lisinopril should be initiated with a 5 mg dose. The subsequent dosage of lisinopril should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed.
Dosage Adjustment In Renal Impairment: A lower dose is required in the presence of renal impairment, in patients to whom diuretic therapy cannot be discontinued and in patients who are volume-and/or salt-depleted for any reason. Safety has not been established in patients with creatinine clearance below 30 mL/min. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 20 mg daily.
Renovascular Hypertension: Special care to be exercised in some patients with renovascular hypertension because of the possibility of exaggerated response. The dosage should he lowered to 2,5 mg or 5 mg and the patient should be monitored.
Congestive Heart Failure: In patients not adequately controlled by digitalis and/or diuretics, lisinopril may be added in a starting dose of 2,5 mg once a day. This may be increased at 4 week intervals in patients requiring an additional therapeutic effect.
Dose adjustment should be based on the clinical response of the individual patients. The usual effective dosage range is 5 to 20mg per day administered in a single dose. Patients at high risk of symptomatic hypotension, e.g. patients with salt-depletion with or without hyponatraemia, patients with hypovolaemia or patients who have been receiving vigorous diuretic therapy, should have these conditions corrected, prior to therapy with lisinopril. The effect of the starting dosage of lisinopril on blood pressure should be monitored carefully.
Acute Myocardial Infarction: Treatment with lisinopril may be started within 24 hours of the onset of symptoms. The first dose of lisinopril is 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily thereafter. Patients with a low systolic blood pressure (120 mmHg or less) should be given a lower dose – 2,5 mg orally (see Special precautions). If hypotension occurs (systolic blood pressure less than or equal to 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2,5 mg if needed. If prolonged hypotension occurs (systolic blood pressure less than 90 mmHg for more than 1 hour), lisinopril should be withdrawn. Dosing should continue for 6 weeks. The benefit appears to be greatest in patients with large myocardial infarctions and evidence of impaired left ventricular function. Patients who develop symptons of heart failure should continue with lisinopril. Lisinopril is compatible with intravenous or transdermal glycerol trinitrate.
Pediatric Use: Safety and effectiveness of lisinopril in children has not been established.
Use in the elderly: there are no age-related changes in the efficacy or safety profile of the agent. When advanced age is associated with a decrease in renal function, however, the guidelines set out in the dose should be used to determine the starting dose of lisinopril. Thereafter, the dosage should be adjusted according to the blood pressure response.
SIDE EFFECTS AND SPECIAL-PRECAUTIONS
The following side-effects may occur more frequently: Dizziness, headache, diarrhea, fatigue, nausea and cough. Orthostatic effects (including hypotension), rash, fatigue.
Bone marrow depression, manifest as anaemia, and/or leucopenia and/or thrombocytopenia have also been reported. Agranulocytosis has been reported.
Diuretics: When a diuretic is added to the therapy of a patient receiving lisinopril, the antihypertensive effect is addictive. Patients already on diuretics and especially those, in whom diuretics therapy was recently instituted, amy experience an excessive reduction of blood pressure when lisinopril is added. The possibility of symptomatic hypotension with lisinopril can be minimized by discontinuing the diuretic prior to initiation of treatment with lisinopril.
Other Agents: Indomethacin may diminish the antihypertensive efficacy of concomitant-administered lisinopril. In some patients with compromised renal function who are being treated with non-steroidal anti-inflammatory drugs (NSAIDS), the co-administration of lisinopril may result in further deterioration in renal function. Lisinopril has been used concomitantly with nitrates without evidence of clinically significant adverse interactions. Lithium elimination may be reduced. Therefore the lithium levels of serum should be carefully compared if lithium salts are to be administered.
Serum Potassium: Serum potassium tends to rise but usually remains within normal limits, however hyperkalaemia may occur. Risk factors for the development of hyperkalaemia include renal insufficiency, diabetes mellitus and concomitant use of potassium-containing salt substitutes. The use of potassium supplements, potassium sparing diuretics or potassium-containing salt sunstitutes, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium. If concomitant use of lisinopril and any of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring serum potassium.
Serum Lithium: the lithium elimination may be reduced. Therefore the lithium levels of serum should be carefully compared if lithium salts are to be administered.
KNOWN SYMPTOMS OF OVERDOSE AND PARTICULARS OF ITS TREATMENT
The symptoms of overdosage may include severe hypotension, electrolyte disturbances and renal failure. Treatment is symptomatic and supportive.
Store in a cool and dry place. Protected from light.
Keep all medicines away from children.
3 blisters of 10 tablets in a carton.
NAFDAC Reg. No.: A4-6801
Baroque Pharmaceuticals Pvt. Ltd.,
Anand, Gujarat, India.
Manufactured under license from
Novopharm Formulations (P) Ltd.,
105, Rajmandir, 62 Alkapuri Society,
R. C. Dutt Road, Vadodara 390007,
Tricare Pharma Limited
6 Yusuf Oyero Street, Off Demurin
Street, Ketu, Lagos, Nigeria