Lisinopril Dihydrate Tablet 5 mg, each tablet contains : Lisinopril dihydrate equivalent to Lisinopril 5 mg.
Lisinopril Dihydrate with Lisinopril dihydrate (equivalent to Lisinopril) as active ingredient is available in 5 mg and 10 mg tablets.
Hypertension : Lisinopril Dihydrate is indicated in the treatment of essential hypertension and renovascular hypertension. Lisinopril Dihydrate may be used alone or concomitantly with other classes of antihypertensive agents.
Congestive heart failure : Lisinopril Dihydrate is indicated in the management of congestive heart failure as an adjunctive treatment with diuretics and where appropriate, Digitalis.
Acute myocardial infarction : Lisinopril Dihydrate is indicated for the treatment of haemodynamically stable patients within 24 hours of an acute myocardial infraction, to prevent the subsequent development of left ventricular dysfunction or heart failure and to improve survival. Patients should receive, as appropriate, the standard recommended treatment such as thrombolytics, Aspirin and β-blocker.
DOSAGE AND ADMINISTRATIONS :
Lisinopril Dihydrate should be administered orally in a single daily dose. As with all other medication taken once daily, Lisinopril Dihydrate should be taken at approximately the same time each day. Since absorption of Lisinopril Dihydrate tablets is not affected by food, the tablets may be administered before, during or after meals.
Dosage should be adjusted according to blood pressure response.
In patients with essential hypertension the usual recommended starting dose is 10 mg. The usual effective maintenance dosage is 20 mg administered in a single daily dose. In general if the desired therapeutic effect cannot be achieved in a period of 2 – 4 weeks on a certain dose level, the dose can be further increased. The maximum dose used in long-term was 80 mg/day.
A lower starting dose is required in the presence of renal impairment, in patients in whom diuretic therapy cannot be discontinued, patients who are volume and/or salt-depleted for any reason and in patients with renovascular hypertension.
Symptomatic hypotension may occur following initiation of therapy with Lisinopril Dihydrate; this is more likely in patients who are being treated currently with diuretics. Caution is recommended, therefore, since these patients may be volume and/or salt depleted.
The diuretic should be discontinued 2 – 3 days before beginning therapy with Lisinopril Dihydrate (see WARNINGS AND PRECAUTIONS). In hypertensive patients in whom the diuretic cannot be discontinued, therapy with Lisinopril Dihydrate should be initiated with a 5 mg dose. The subsequent dosage of Lisinopril Dihydrate should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed.
Dosage adjustment in renal impairment
Dosage in patients with renal impairment should be based on creatinine clearance, as outlined in Table 1 below.
|< 10 (including patients on dialysis)
10 – 30
31 – 80
2.5 – 5
5 – 10
* Dosage and/or frequency of administration should be adjusted depending on the blood pressure response.
The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.
Some patients with renovascular hypertension, especially those with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, may develop an exaggerated response to the first dose of Lisinopril Dihydrate. Therefore, a lower starting dose of 2.5 or 5 mg is recommended. Thereafter, the dosage may be adjusted according to the blood pressure response.
Congestive heart failure
As adjunctive therapy with diuretics and where appropriate, Digitalis, Lisinopril Dihydrate may be initiated with a starting dose of 2.5 mg once a day. The doses were adjusted at 4 weeks intervals in patients requiring an additional therapeutic effect. Dose adjustment should be based on the clinical response of individual patients. The usual effective dosage range is 5 – 20 mg/day administered in a single daily 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, if possible, prior to therapy with Lisinopril Dihydrate. The effect of starting dose of Lisinopril Dihydrate on blood pressure should be monitored carefully.
Acute myocardial infarction
Treatment with Lisinopril Dihydrate may be started within 24 hours of the onset of symptoms. The first dose of Lisinopril Dihydrate 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) when treatment is started or during the first 3 days after the infarct should be given a lower dose 2.5 mg orally (see WARNINGS AND PRECAUTIONS). If hypotension occur (systolic blood pressure ≤ 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 < 90 mmHg for more than 1 hour) Lisinopril Dihydrate should be withdrawn.
Dosing should continue for 6 weeks. Patients who develop symptoms of heart failure should continue with Lisinopril Dihydrate (see DOSAGE AND ADMINISTRATIONS for congestive heart failure).
Lisinopril Dihydrate is compatible with intravenous or transdermal Glyceryl trinitrate.
Safety and effectiveness of Lisinopril Dihydrate in children have not been established.
There was no age related change in the efficacy or safety profile of the drug. When advanced age is associated with decrease in renal function, however, the guidelines set out in table 1 should be used to determine the starting dose of Lisinopril Dihydrate. Thereafter, The dosage should be adjusted according to the blood pressure response.
Limited data are available for overdose in humans. Symptoms associated with overdosage of ACE inhibitors may include hypotension, circulatory shock, electrolyte disturbance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.
The recommended treatment of overdose is intravenous infusion of Normal saline solution. If hypotension occurs the patient should be placed in the shock position. If available, treatment with angiotensin II and/or intravenous catecholamines may also be considered. If ingestion is recent, take measures aimed at eliminating Lisinopril (e.g., emesis, gastric lavage administration of absorbents and sodium sulphate). Lisinopril may be removed from the general circulation by haemodialysis (see WARNINGS AND PRECAUTIONS). Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored frequently.
Hypersensitivity to Lisinopril, to any of the excipients or any other angiotensin-converting enzyme (ACE) inhibitor.
History of angioedema associated with previous angiotensin-converting enzyme (ACE) inhibitor therapy.
Hereditary or idiopathic angioedema.
Pregnancy (see pregnancy and lactation).
Combination with Aliskiren-containing medicines in patients with diabetes mellitus (type I or II) or with moderate to severe renal impairment (GFR < 60 ml/minute/1.73 m2).
WARNINGS AND PRECAUTIONS :
Symptomatic hypotension is seen rarely in uncomplicated hypersensitive patients. In hypersensitive patients receiving Lisinopril hypotension is most likely to occur if the patient has been volume-depleted e.g., by diuretic therapy, dietary salt restriction, dialysis, diarrhoea, vomiting or has severe renin-dependent hypertension (see DRUG INTERACTIONS and ADVERSE REACTIONS). In patients with congestive heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatremia or functional renal impairment. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjusment should be closely monitored. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an IV infusion of Normal saline. A transient hypotensive response is not a contra-indication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.
In some patients with congestive heart failure who have normal or low blood pressure additional lowering of systemic blood pressure may occur with Lisinopril. This effect is anticipated and is not usually a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose or discontinuation of Lisinopril may be necessary.
Hypotension in acute myocardial infarction
Treatment with Lisinopril must not be initiated in acute myocardial infarction patients who are at risk of further serious haemodynamic deterioration after treatment with a vasodilator. These are patients with systolic blood pressure of 100 mmHg or lower or cardiogenic shock. During the first 3 days following the infarction, the dose should be reduced if the systolic blood pressure is 120 mmHg or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if systolic blood pressure is 100 mmHg or lower. If hypotension persists (systolic blood pressure < 90 mmHg for more than 1 hour) then Lisinopril should be withdrawn.
Dual blockade of the renin-angiotensin-aldosteron system (RAAS) with Aliskiren-containing medicines
Dual blockade of the renin-angiotensin-aldosteron system by combining Lisinopril with Aliskiren is not recommended since there is an increased risk of hypotension, hyperkalaemia and changes in renal function. The use of Lisinopril with Aliskiren is contraindicated in patients with diabetes mellitus (type I or II) or moderate to severe renal impairment (GFR < 60 ml/minute/1.73m2) (see CONTRAINDICATION).
Aortic and mitral valve stenosis/hypertrophic cardiomyopathy
As with other ACE inhibitors, Lisinopril should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy.
Renal function impairment
In cases of renal impairment (creatinine clearance < 80 ml/minute), the initial Lisinopril dosage should be adjusted according to the patient’s creatinine clearance (see Table 1 in DOSAGE AND ADMINISTRATIONS) and then as a function of the patient’s response to treatment. Routine monitoring of potassium and creatinine is part of normal medical practice for these patients.
In patients with heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.
In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney who have been treated with ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen. This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor to the above, they should be discontinued and renal function should be monitored during the first weeks of Lisinopril therapy.
Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when Lisinopril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or Lisinopril may be required.
In acute myocardial infarction, treatment with Lisinopril should not be initiated in patients with evidence of renal dysfunction, defined as serum creatinine concentration exceeding 177 micromol/l and or proteinuria exceeding 500 mg/24 hours. If renal dysfunction develops during treatment with Lisinopril (serum creatinine concentration exceeding 265 micromol/l or a doubling from the pre-treatment value) then the physician should consider withdrawal of Lisinopril.
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported uncommonly in patients treated with ACE inhibitors, including Lisinopril. This may occur at any time during therapy. In such cases, Lisinopril should be discontinued promptly and appropriate treatment and monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patients. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient.
Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. Patients with involvement of the tongue, glottis or larynx, are likely to experience airway obstruction, especially those with a history of airway surgery. In such cases emergency therapy should be administered promptly. This may include the administration of adrenaline and/or the maintenance of a patent airway. The patient should be under close medical supervision until complete and sustained resolution of symptoms has occured.
Angiotensin converting enzyme inhibitors cause a higher rate of angioedema in black patients than in non-black patients.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see CONTRAINDICATIONS).
Anaphylactoid reactions in haemodialysis patients
Anaphylactoid reactions have been reported in patients undergoing certain haemodialysis procedures (e.g., with the high flux membrane AN 69) and treated concomitantly with an ACE inhibitor. In these patients consideration should be given to using a different type of dialysis membrane or different class of antihypertensive agent.
Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis
Rarely, patients receiving ACE inhibitors during low-density lipoproteins (LDL) apheresis with Dextran sulphate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.
Patients receiving ACE inhibitors during desensitisation treatment (e.g., hymenoptera venom) have sustained anaphylactoid reactions. In the same patients, these reactions have been avoided when ACE inhibitors were temporarily withheld but they have reappeared upon inadvertent re-administration of the medicinal product.
Very rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving Lisinopril who develop jaundice or marked elevations of hepatic enzymes should discontinue Lisinopril and receive appropriate medical follow-up.
Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia occurs rarely. Neutropenia and agranulocytosis are reversible after discontinuation of the ACE inhibitor. Lisinopril should be used with extreme caution in patients with collagen vascular disease, immunosuppresant therapy, treatment with Allopurinol or Procainamide or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Some of these patients developed serious infection, which in a few instances did not respond to intensive antibiotic therapy. If Lisinopril is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.
ACE inhibitors cause a higher rate of angiodema in black patients than in non-black patients. As with other ACE inhibitors, Lisinopril may be less effective in lowering blood pressure in black patients than in non-blacks, possibly because of a higher prevalence of low-renin states in the black hypertensive population.
Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor induced cough should be considered as part of the differential diagnosis of cough.
In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, Lisinopril 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.
Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including Lisinopril. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, diabetes mellitus or those using concomitant potassium-sparing diuretics, potassium supplements or potassium containing salt substitutes or those patients taking other drugs associated with increases in serum potassium (e.g., Heparin). If concomitant use of the above-mentioned agents is deemed appropriate, regular monitoring serum potassium is recommended (see DRUG INTERACTIONS).
In diabetic patients treated with oral antidiabetic agents or Insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor (see DRUG INTERACTIONS).
The combination of Lithium and Lisinoprilis generally not recommended (see DRUG INTERACTIONS).
Lisinopril should not be used during the first trimester of pregnancy. Lisinopril is contraindicated in the second and third trimesters of pregnancy (see CONTRAINDICATIONS). Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitors therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is detected, ACE inhibitors treatment should discontinue as soon as possible and if appropriate, alternative therapy should be started.
Exposure to ACE inhibitors therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see PHARMACOLOGY).
Should exposure to Lisinopril have occured from the second trimester of pregnancy, an ultrasound check of renal function and the skull is recommended.
Infants should be closely observed for hypotension, oliguria and hyperkalaemia. Lisinopril which crosses the placenta, has been removed from the neonatal circulation by peritoneal dialysis with some clinical benefit and theoretically may be removed by exchanged transfusion.
Because no information is available regarding the use of Lisinopril during breast-feeding, Lisinopril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Effects on the ability to drive or operate machinery
When driving vehicles or operating machines it should be taken into account that occasionally dizziness or tiredness may occur.
DRUG INTERACTIONS :
Concomitant use of these agents may increase the hypotensive effects of Lisinopril. Concomitant use with Glyceryl trinitrate and other nitrates or other vasodilators, may further reduce blood pressure. The combination of Lisinopril with Aliskiren-containing medicines should be avoided (see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS).
When a diuretic is added to the therapy of a patient receiving Lisinopril the antihypertensive effect is usually additive.
Patients already on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally 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 (see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATIONS).
Potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutes
Although in clinical trials, serum potassium usually remained within normal limits, hyperkalaemia did occur in some patients. Risk factors for the development of hyperkalaemia include renal insufficiency, diabetes mellitus and concomitant use of potassium-sparing diuretics (e.g., Spironolactone, Triamterene or Amiloride), potassium supplements or potassium-containing salt substitutes. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutes, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium. If Lisinopril is given with a potassium-losing diuretic, diuretic-induced hypokalaemia may be ameliorated.
Reversible increases in serum Lithium concentrations and toxicity have been reported during concomitant administration of Lithium with ACE inhibitors. Concomitant use of Thiazide diuretics may increase the risk of Lithium toxicity and enhance the already increased Lithium toxicity with ACE inhibitors. Use of Lisinopril with Lithium is not recommended, but if the combination proves necessary, careful monitoring of serum Lithium levels should be performed (see WARNINGS AND PRECAUTIONS).
Non steroidal anti-inflammatory drugs (NSAIDs) including Acetylsalicylic acid ≥ 3 g/day
When ACE-inhibitors are administered simultaneously with non-steroidal anti-inflamatory drugs (i.e., Acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs), attenuation of the antihypersensitive effect may occur. Concomitant use of ACE-inhibitors and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure and an increase in serum potassium, especially in patients with poor pre-existing renal function. These effects are usually reversible. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically thereafter.
Nitritoid reactions (symptoms of vasodilatation including flushing, nausea, dizziness and hypotension, which can be very severe) following injectable gold (for example, Sodium aurothiomalate) are reported more frequently in patients receiving ACE inhibitor therapy.
Concomitant use of certain anaesthetic medicinal products, tricyclic antidepressants and antipsychotics with ACE inhibitors may result in further reduction blood pressure (see WARNINGS AND PRECAUTIONS).
Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.
Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicines (Insulins, oral hypoglycaemic agents) may cause an increased blood glucose lowering effect with risk of hypoglycaemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.
Acetylsalicylic acid, thrombolytics, β-blockers, nitrates
Lisinopril may be used concomitantly with Acetylsalicylic acid (at cardiologic doses), thrombolytics, β-blockers and/or nitrates.
ADVERSE REACTIONS :
Blood and the lymphatic system disorders :
Rare : Decrease in haemoglobin, decrease in haematocrit.
Very rare : Bone marrow depression, anaemia, thrombocytopenia, leucopenia, neutropenia, agranulocytosis (see WARNINGS AND PRECAUTIONS), haemolytic anaemia, lymphadenopathy, autoimmune disease.
Endocrine disorders :
Rare : Inappropriate antidiuretic hormone secretion.
Metabolism and nutrition disorders :
Very rare : Hypoglycaemia.
Nervous system and psychiatric disorders :
Common : Dizziness, headache, depressive symptoms in hypertensive patient.
Uncommon : Mood alterations, depressive symptoms in CHF patient paraesthesia, vertigo, taste disturbance, sleep disturbances, hallucinations.
Rare : Mental confusion, olfactory disturbance.
Cardiac and vascular disorders :
Common : Orthostatic effects (including hypotension), syncope (in CHF patient).
Uncommon : Myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients (see WARNINGS AND PRECAUTIONS), palpitations, tachycardia, Raynaud’s phenomenon, syncope in hypertensive patient.
Respiratory, thoracic and mediastinal disorders :
Common : Cough.
Uncommon : Rhinitis.
Very rare : Bronchospasm, sinusitis, allergic alveolitis/eosinophilic pneumonia.
Gastrointestinal disorders :
Common : Diarrhoea, vomiting.
Uncommon : Nausea, abdominal pain and indigestion.
Rare : Dry mouth.
Very rare : Pancreatitis, intestinal angioedema, hepatitis-either hepatocellular or cholestatic, jaundice and hepatic failure (see WARNINGS AND PRECAUTIONS).
Skin and subcutaneous tissue disorders :
Uncommon : Rash, pruritus hypersensitivity/angioneurotic oedema : Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx.
Rare : Urticaria, alopecia, psoriasis.
Very rare : Diaphoresis, pemphigus, toxic epidermal necrolysis, Steven-Johnson syndrome, erythema multiforme cutaneous pseudolymphoma.
A symptom complex has been reported which may include one or more of the following :
Fever, vasculitis, myalgia, arthralgia/arthritis, a positive antinuclear antibodies (ANA), elevated red blood cell sedimentation rate (ESR), eosinophilia and leucocytosis, rash, photosensitivity or other dermatological manifestations may occur.
Renal and urinary disorders :
Common : Renal dysfunction.
Rare : Uraemia, acute renal failure.
Very rare : Oligouria/anuria.
Reproductive system and breast disorders :
Uncommon : Impotence.
Rare : Gynaecomastia.
General disorders and administration site condition :
Uncommon : Fatigue, asthenia.
Uncommon : Increases in blood urea, increases in serum creatinine, increases in liver enzymes, hyperkalaemia.
Rare : Increases in serum bilirubin, hyponatraemia.
Lisinopril Dihydrate Tablet 5 mg Box, 10 strips @ 10 tablets
Reg. No. GKL2002363610A1
STORE BELOW 30ºC
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
Sidoarjo – Indonesia