Enalapril Maleate Tablets USP 10mg Taj Pharma

1. Name of the medicinal product

Enalapril Maleate Tablets USP 2.5mg Taj Pharma
Enalapril Maleate Tablets USP 5mg Taj Pharma
Enalapril Maleate Tablets USP 10mg Taj Pharma
Enalapril Maleate Tablets USP 20mg Taj Pharma

2. Qualitative and quantitative composition

a) Enalapril Maleate Tablets USP 2.5mg Taj Pharma
Each uncoated tablet contains:
Enalapril Maleate USP 2.5mg
Excipients: Q.S.

b) Enalapril Maleate Tablets USP 5mg Taj Pharma
Each uncoated tablet contains:
Enalapril Maleate USP 5mg
Excipients: Q.S.

c) Enalapril Maleate Tablets USP 10mg Taj Pharma
Each uncoated tablet contains:
Enalapril Maleate USP 10mg
Excipients: Q.S.

d) Enalapril Maleate Tablets USP 20mg Taj Pharma
Each uncoated tablet contains:
Enalapril Maleate USP 20mg
Excipients: Q.S.

Excipient: each tablet contains 154mg of lactose monohydrate.

Excipient(s) with known effect

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Uncoated Tablets.
Enalapril Maleate Taj Pharma tablets are available in 4 strengths (2.5mg, 5mg, 10mg and 20mg), Each looks like white round shaped tablet.

*The scoreline is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4. Clinical particulars

Therapeutic indications

• Treatment of Hypertension
• Treatment of Symptomatic Heart Failure
• Prevention of Symptomatic Heart Failure in patients with Asymptomatic Left Ventricular Dysfunction (ejection fraction ≤35%) (See section 5.1.)

Posology and method of administration

Posology

The absorption of Enalapril Maleate Taj Pharma Tablets is not affected by food.

The dose should be individualised according to patient profile (see section 4.4) and blood pressure response.

Paediatric Population

There is limited clinical trial experience of the use of Enalapril Maleate Taj Pharma in hypertensive paediatric patients (see sections 4.4, 5.1 and 5.2).

Hypertension

The initial dose is 5 to maximally 20mg, depending on the degree of hypertension and the condition of the patient (see below). Enalapril Maleate Taj Pharma is given once daily. In mild hypertension, the recommended initial dose is 5 to 10mg. Patients with a strongly activated renin-angiotensin-aldosterone system (e.g., renovascular hypertension, salt and/or volume depletion, cardiac decompensation, or severe hypertension) may experience an excessive blood pressure fall following the initial dose. A starting dose of 5mg or lower is recommended in such patients and the initiation of treatment should take place under medical supervision.

Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with enalapril. A starting dose of 5mg or lower is recommended in such patients. If possible, diuretic therapy should be discontinued for 2-3 days prior to initiation of therapy with Enalapril Maleate Taj Pharma. Renal function and serum potassium should be monitored.

The usual maintenance dose is 20mg daily. The maximum maintenance dose is 40mg daily.

Heart Failure/Asymptomatic Left Ventricular Dysfunction

In the management of symptomatic heart failure, Enalapril Maleate Taj Pharma is used in addition to diuretics and, where appropriate, digitalis or beta-blockers. The initial dose of Enalapril Maleate Taj Pharma in patients with symptomatic heart failure or asymptomatic left ventricular dysfunction is 2.5mg, and it should be administered under close medical supervision to determine the initial effect on the blood pressure. In the absence of, or after effective management of, symptomatic hypotension following initiation of therapy with Enalapril Maleate Taj Pharma in heart failure, the dose should be increased gradually to the usual maintenance dose of 20mg, given in a single dose or two divided doses, as tolerated by the patient. This dose titration is recommended to be performed over a 2 to 4 week period. The maximum dose is 40mg daily given in two divided doses.

Table 1: Suggested Dosage Titration of Enalapril Maleate Taj Pharma in Patients with Heart Failure/Asymptomatic Left Ventricular Dysfunction

* Special precautions should be followed in patients with impaired renal function or taking diuretics (see section 4.4).

Blood pressure and renal function should be monitored closely both before and after starting treatment with Enalapril Maleate Taj Pharma (see section 4.4) because hypotension and (more rarely) consequent renal failure have been reported. In patients treated with diuretics, the dose should be reduced if possible before beginning treatment with Enalapril Maleate Taj Pharma. The appearance of hypotension after the initial dose of Enalapril Maleate Taj Pharma does not imply that hypotension will recur during chronic therapy with Enalapril Maleate Taj Pharma and does not preclude continued use of the drug. Serum potassium and renal function also should be monitored.

Dosage in Renal Insufficiency

Generally, the intervals between the administration of enalapril should be prolonged and/or the dosage reduced.

Table 2: Dosage in Renal Insufficiency

*See section 4.4. Enalaprilat is dialysable. Dosage on nondialysis days should be adjusted depending on the blood pressure response.

Use in Elderly

The dose should be in line with the renal function of the elderly patient (see section 4.4).

Use in Paediatrics

For patients who can swallow tablets, the dose should be individualised according to patient profile and blood pressure response. The recommended initial dose is 2.5mg in patients 20 to <50 kg and 5mg in patients ≥50 kg. Enalapril Maleate Taj Pharma is given once daily. The dosage should be adjusted according to the needs of the patient to a maximum of 20mg daily in patients 20 to <50 kg and 40mg in patients ≥50 kg (see section 4.4).

Enalapril Maleate Taj Pharma is not recommended in neonates and in paediatric patients with glomerular filtration rate <30 ml/min/1.73 m², as no data are available.

Method of administration

Oral use.

• Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or any other ACE inhibitor.
• History of angioedema associated with previous ACE inhibitor therapy.
• Hereditary or idiopathic angioedema.
• Second and third trimesters of pregnancy (see sections 4.4 and 4.6).
• The concomitant use of Enalapril Maleate Taj Pharma with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m²) (see sections 4.5 and 5.1).
• Combination with sacubitril/valsartan due to the increased risk of angioedema. Do not administer Enalapril Maleate Taj Pharma within 36 hours of switching to or from sacubitril/valsartan, a product containing a neprilysin inhibitor. (See sections 4.4 and 4.5.)
  • Special warnings and precautions for use

Symptomatic Hypotension

Symptomatic hypotension is rarely seen in uncomplicated hypertensive patients. In hypertensive patients receiving Enalapril Maleate Taj Pharma, symptomatic hypotension is more likely to occur if the patient has been volume – depleted, e.g., by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting (see sections 4.5 and 4.8). In patients with 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, hyponatraemia or functional renal impairment. In these patients, therapy should be started under medical supervision and the patients should be followed closely whenever the dose of Enalapril Maleate Taj Pharma and/or diuretic is adjusted. Similar considerations may 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 intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.

In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with Enalapril Maleate Taj Pharma. This effect is anticipated, and usually is not a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose and/or discontinuation of the diuretic and/or Enalapril Maleate Taj Pharma may be necessary.

Aortic or Mitral Valve Stenosis/Hypertrophic Cardiomyopathy

As with all vasodilators, ACE inhibitors should be given with caution in patients with left ventricular valvular and outflow tract obstruction and avoided in cases of cardiogenic shock and haemodynamically significant obstruction.

Renal Function Impairment

In cases of renal impairment (creatinine clearance <80 ml/min) the initial enalapril dosage should be adjusted according to the patient’s creatinine clearance (see section 4.2) and then as a function of the patient’s response to treatment. Routine monitoring of potassium and creatinine are part of normal medical practice for these patients.

Renal failure has been reported in association with enalapril and has been mainly in patients with severe heart failure or underlying renal disease, including renal artery stenosis. If recognised promptly and treated appropriately, renal failure when associated with therapy with enalapril is usually reversible.

Some hypertensive patients, with no apparent pre-existing renal disease have developed increases in blood urea and creatinine when enalapril has been given concurrently with a diuretic. Dosage reduction of enalapril and/or discontinuation of the diuretic may be required. This situation should raise the possibility of underlying renal artery stenosis (see section 4.4, Renovascular hypertension).

Renovascular hypertension

There is an increased risk of hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with ACE inhibitors. Loss of renal function may occur with only mild changes in serum creatinine. In these patients, therapy should be initiated under close medical supervision with low doses, careful titration, and monitoring of renal function.

Kidney Transplantation

There is no experience regarding the administration of Enalapril Maleate Taj Pharma in patients with a recent kidney transplantation. Treatment with Enalapril Maleate Taj Pharma is therefore not recommended.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Neutropenia/Agranulocytosis

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. Enalapril should be used with extreme caution in patients with collagen vascular disease, immunosuppressant 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 infections which in a few instances did not respond to intensive antibiotic therapy. If enalapril 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.

Hypersensitivity/Angioneurotic Oedema

Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including Enalapril Maleate Taj Pharma. This may occur at any time during treatment. In such cases, Enalapril Maleate Taj Pharma should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patient. 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. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate therapy, which may include subcutaneous epinephrine solution 1:1000 (0.3 ml to 0.5 ml) and/or measures to ensure a patent airway, should be administered promptly.

Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-blacks.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also section 4.3).

Patients receiving co-administration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.

Patients receiving concomitant ACE inhibitor and neprilysin inhibitor therapy (e.g., sacubitril, racecadotril) may be at increased risk for angioedema (see section 4.5). The combination of enalapril with sacubitril/valsartan is contraindicated due to the increased risk of angioedema (see section 4.3). Sacubitril/valsartan must not be initiated until 36 hours after taking the last dose of enalapril therapy. If treatment with sacubitril/valsartan is stopped, enalapril therapy must not be initiated until 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5).

Anaphylactoid Reactions during Hymenoptera Desensitisation

Rarely, patients receiving ACE inhibitors during desensitisation with hymenoptera venom have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each desensitisation.

Anaphylactoid Reactions during LDL Apheresis

Rarely, patients receiving ACE inhibitors during low density lipoprotein (LDL)-apheresis with dextran sulfate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.

Haemodialysis Patients

Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes (e.g., 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 a different class of antihypertensive agent.

Hypoglycaemia

Diabetic patients treated with oral antidiabetic agents or insulin starting an ACE inhibitor should be told to closely monitor for hypoglycaemia, especially during the first month of combined use (see section 4.5).

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is nonproductive, persistent, and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Surgery/Anaesthesia

In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, enalapril blocks 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.

Hyperkalaemia

Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including enalapril. Risk factors for the development of hyperkalaemia include those with renal insufficiency, worsening of renal function, age (>70 years), diabetes mellitus, intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium supplements or potassium-containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium (e.g., heparin, trimethoprim-containing products such as cotrimoxazole). The use of potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, or other drugs that may increase serum potassium, particularly in patients with impaired renal function may lead to a significant increase in serum potassium. Hyperkalaemia can cause serious, sometimes fatal arrhythmias. If concomitant use of enalapril and any of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium (see section 4.5).

Lithium

The combination of lithium and enalapril is generally not recommended (see section 4.5).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia, and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Lactose

Enalapril Maleate Taj Pharma contains lactose and therefore should not be used by patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Enalapril Maleate Taj Pharma contains less than 200mg of lactose per tablet.

Paediatric population

There is limited efficacy and safety experience in hypertensive children >6 years old, but no experience in other indications. Limited pharmacokinetic data are available in children above 2 months of age (see also sections 4.2, 5.1 and 5.2). Enalapril Maleate Taj Pharma is not recommended in children in other indications than hypertension.

Enalapril Maleate Taj Pharma is not recommended in neonates and in paediatric patients with glomerular filtration rate <30 ml/min/1.73 m², as no data are available (see section 4.2).

Pregnancy

ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, 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 (see sections 4.3 and 4.6).

Ethnic differences

As with other angiotensin converting enzyme inhibitors, enalapril is apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of a higher prevalence of low-renin states in the black hypertensive population.

• Interaction with other medicinal products and other forms of interaction

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

Clinical trial data have shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1).

Potassium sparing diuretics, potassium supplements, or other drugs that may increase serum potassium

ACE inhibitors attenuate diuretic induced potassium loss. Potassium sparing diuretics (e.g., spironolactone, eplerenone, triamterene or amiloride), potassium supplements, potassium-containing salt substitutes, or other drugs that may increase serum potassium (e.g., heparin, trimethoprim-containing products such as cotrimoxazole) may lead to significant increases in serum potassium. If concomitant use of enalapril and any of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium (see section 4.4).

Diuretics (thiazide or loop diuretics)

Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with enalapril (see section 4.4). The hypotensive effects can be reduced by discontinuation of the diuretic, by increasing volume or salt intake or by initiating therapy with a low dose of enalapril.

Other antihypertensive agents

Concomitant use of these agents may increase the hypotensive effects of enalapril. Concomitant use with nitroglycerine and other nitrates, or other vasodilators, may further reduce blood pressure.

Lithium

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 further increase lithium levels and enhance the risk of lithium toxicity with ACE inhibitors. Use of enalapril with lithium is not recommended, but if the combination proves necessary, careful monitoring of serum lithium levels should be performed (see section 4.4).

Tricyclic antidepressants/Antipsychotics/Anaesthetics/Narcotics

Concomitant use of certain anaesthetic medicinal products, tricyclic antidepressants and antipsychotics with ACE inhibitors may result in further reduction of blood pressure (see section 4.4).

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 (COX-2) Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors may be attenuated by NSAIDs including selective COX-2 inhibitors.

The co-administration of NSAIDs (including COX-2 inhibitors) and angiotensin II receptor antagonists or ACE inhibitors exert an additive effect on the increase in serum potassium, and may result in a deterioration of renal function. These effects are usually reversible. Rarely, acute renal failure may occur, especially in patients with compromised renal function (such as the elderly or patients who are volume-depleted, including those on diuretic therapy). Therefore, the combination should be administered with caution in patients with compromised renal function. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically thereafter.

Gold

Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including enalapril.

Mammalian Target of Rapamycin (mTOR) Inhibitors

Patients taking concomitant mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see section 4.4).

Neprilysin Inhibitors

Patients receiving concomitant ACE inhibitor and neprilysin inhibitor therapy (e.g., sacubitril, racecadotril) may be at increased risk for angioedema (see section 4.4). The concomitant use of enalapril with sacubitril/valsartan is contraindicated, as the concomitant inhibition of neprilysin and ACE may increase the risk of angioedema. Sacubitril/valsartan must not be started until 36 hours after taking the last dose of enalapril therapy. Enalapril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan. (See sections 4.3 and 4.4.)

Sympathomimetics

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.

Antidiabetics

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 (see sections 4.4 and 4.8).

Alcohol

Alcohol enhances the hypotensive effect of ACE inhibitors.

Acetyl salicylic acid, thrombolytics and β-blockers

Enalapril can be safely administered concomitantly with acetyl salicylic acid (at cardiologic doses), thrombolytics and β-blockers.

Paediatric population

Interaction studies have only been performed in adults.

• Fertility, pregnancy and lactation

Pregnancy

ACE inhibitors:

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 inhibitor 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 diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.

Exposure to ACE inhibitor 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 section 5.3). Maternal oligohydramnios, presumably representing decreased foetal renal function, has occurred and may result in limb contractures, craniofacial deformations and hypoplastic lung development.

Should exposure to ACE inhibitors have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.

Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension (see sections 4.3 and 4.4).

Breast-feeding

Limited pharmacokinetic data demonstrate very low concentrations in breast milk (see section 5.2). Although these concentrations seem to be clinically irrelevant, the use of Enalapril Maleate Taj Pharma in breast-feeding is not recommended for preterm infants and for the first few weeks after delivery, because of the hypothetical risk of cardiovascular and renal effects and because there is not enough clinical experience. In case of an older infant, the use of Enalapril Maleate Taj Pharma in breast-feeding mother may be considered if this treatment is necessary for the mother and the child is observed for any adverse effect.

• Effects on ability to drive and use machines

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.

• Undesirable effects

The following undesirable effects have been reported for enalapril in clinical studies and in post-marketing experience:

Table 3. Undesirable effects of Enalapril Maleate Taj Pharma

* Incidence rates were comparable to those in the placebo and active control groups in the clinical trials.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

• Overdose

Limited data are available for overdosage in humans. The most prominent features of overdosage reported to date are marked hypotension, beginning some six hours after ingestion of tablets, concomitant with blockade of the renin-angiotensin system, and stupor. Symptoms associated with overdosage of ACE inhibitors may include circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300mg and 440mg of enalapril, respectively.

The recommended treatment of overdosage 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 infusion and/or intravenous catecholamines may also be considered. If ingestion is recent, take measures aimed at eliminating Enalapril Maleate Taj Pharma (e.g., emesis, gastric lavage, administration of absorbents, and sodium sulfate). Enalaprilat may be removed from the general circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.

5. Pharmacological properties
   • Pharmacodynamic properties

Pharmacotherapeutic group: Angiotensin converting enzyme inhibitors,

Enalapril Maleate Taj Pharma (Enalapril Maleate Taj Pharma) is the maleate salt of enalapril, a derivative of two amino-acids, L-alanine and L-proline. Angiotensin converting enzyme (ACE) is a peptidyl dipeptidase which catalyses the conversion of angiotensin I to the pressor substance angiotensin II. After absorption, enalapril is hydrolysed to enalaprilat, which inhibits ACE. Inhibition of ACE results in decreased plasma angiotensin II, which leads to increased plasma renin activity (due to removal of negative feedback of renin release), and decreased aldosterone secretion.

ACE is identical to kininase II. Thus Enalapril Maleate Taj Pharma may also block the degradation of bradykinin, a potent vasodepressor peptide. However, the role that this plays in the therapeutic effects of Enalapril Maleate Taj Pharma remains to be elucidated.

Mechanism of action

While the mechanism through which Enalapril Maleate Taj Pharma lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, Enalapril Maleate Taj Pharma is antihypertensive even in patients with low-renin hypertension.

Pharmacodynamic effects

Administration of Enalapril Maleate Taj Pharma to patients with hypertension results in a reduction of both supine and standing blood pressure without a significant increase in heart rate.

Symptomatic postural hypotension is infrequent. In some patients the development of optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of Enalapril Maleate Taj Pharma has not been associated with rapid increase in blood pressure.

Effective inhibition of ACE activity usually occurs 2 to 4 hours after oral administration of an individual dose of enalapril. Onset of antihypertensive activity was usually seen at one hour, with peak reduction of blood pressure achieved by 4 to 6 hours after administration. The duration of effect is dose-related. However, at recommended doses, antihypertensive and haemodynamic effects have been shown to be maintained for at least 24 hours.

In haemodynamic studies in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with an increase in cardiac output and little or no change in heart rate. Following administration of Enalapril Maleate Taj Pharma there was an increase in renal blood flow; glomerular filtration rate was unchanged. There was no evidence of sodium or water retention. However, in patients with low pretreatment glomerular filtration rates, the rates were usually increased.

In short term clinical studies in diabetic and nondiabetic patients with renal disease, decreases in albuminuria and urinary excretion of IgG and total urinary protein were seen after the administration of enalapril.

When given together with thiazide-type diuretics, the blood pressure-lowering effects of Enalapril Maleate Taj Pharma are at least additive. Enalapril Maleate Taj Pharma may reduce or prevent the development of thiazide-induced hypokalaemia.

In patients with heart failure on therapy with digitalis and diuretics, treatment with oral or injection Enalapril Maleate Taj Pharma was associated with decreases in peripheral resistance and blood pressure. Cardiac output increased, while heart rate (usually elevated in patients with heart failure) decreased. Pulmonary capillary wedge pressure was also reduced. Exercise tolerance and severity of heart failure, as measured by New York Heart Association criteria, improved. These actions continued during chronic therapy.

In patients with mild to moderate heart failure, enalapril retarded progressive cardiac dilatation/enlargement and failure, as evidenced by reduced left ventricular end diastolic and systolic volumes and improved ejection fraction.

Dual Blockade of the renin-angiotensin-aldosterone system (RAAS)

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor blocker.

ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.

ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the placebo group.

Clinical efficacy and safety

A multicentre, randomised, double-blind, placebo-controlled trial (SOLVD Prevention trial) examined a population with asymptomatic left ventricular dysfunction (LVEF<35%). 4,228 patients were randomised to receive either placebo (n=2,117) or enalapril (n=2,111). In the placebo group, 818 patients had heart failure or died (38.6%) as compared with 630 in the enalapril group (29.8%) (risk reduction: 29%; 95% CI; 21-36%; p<0.001). 518 patients in the placebo group (24.5%) and 434 in the enalapril group (20.6%) died or were hospitalised for new or worsening heart failure (risk reduction 20%; 95% CI; 9-30%; p<0.001).

A multicentre, randomised, double-blind, placebo-controlled trial (SOLVD Treatment trial) examined a population with symptomatic congestive heart failure due to systolic dysfunction (ejection fraction <35%). 2,569 patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n=1,284) or enalapril (n=1,285). There were 510 deaths in the placebo group (39.7%) as compared with 452 in the enalapril group (35.2%) (reduction in risk, 16%; 95% CI, 5-26%; p=0.0036). There were 461 cardiovascular deaths in the placebo group as compared with 399 in the enalapril group (risk reduction 18%, 95% CI, 6-28%, p<0.002), mainly due to a decrease of deaths due to progressive heart failure (251 in the placebo group vs 209 in the enalapril group, risk reduction 22%, 95% CI, 6-35%). Fewer patients died or were hospitalised for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26%; 95% CI, 18-34%; p<0.0001). Overall in SOLVD study, in patients with left ventricular dysfunction, Enalapril Maleate Taj Pharma reduced the risk of myocardial infarction by 23% (95% CI, 11-34%; p<0.001) and reduced the risk of hospitalisation for unstable angina pectoris by 20% (95% CI, 9-29%; p<0.001).

Paediatric population

There is limited experience of the use in hypertensive paediatric patients >6 years. In a clinical study involving 110 hypertensive paediatric patients 6 to 16 years of age with a body weight ≥20 kg and a glomerular filtration rate >30 ml/min/1.73 m², patients who weighed <50 kg received either 0.625, 2.5 or 20mg of enalapril daily and patients who weighed ≥50 kg received either 1.25, 5 or 40mg of enalapril daily. Enalapril administration once daily lowered trough blood pressure in a dose-dependent manner. The dose-dependent antihypertensive efficacy of enalapril was consistent across all subgroups (age, Tanner stage, gender, race). However, the lowest doses studied, 0.625mg and 1.25mg, corresponding to an average of 0.02mg/kg once daily, did not appear to offer consistent antihypertensive efficacy. The maximum dose studied was 0.58mg/kg (up to 40mg) once daily. The adverse experience profile for paediatric patients is not different from that seen in adult patients.

• Pharmacokinetic properties

Absorption

Oral enalapril is rapidly absorbed, with peak serum concentrations of enalapril occurring within one hour. Based on urinary recovery, the extent of absorption of enalapril from oral enalapril tablet is approximately 60%. The absorption of oral Enalapril Maleate Taj Pharma is not influenced by the presence of food in the gastrointestinal tract.

Following absorption, oral enalapril is rapidly and extensively hydrolysed to enalaprilat, a potent angiotensin converting enzyme inhibitor. Peak serum concentrations of enalaprilat occur about 4 hours after an oral dose of enalapril tablet. The effective half-life for accumulation of enalaprilat following multiple doses of oral enalapril is 11 hours. In subjects with normal renal function, steady-state serum concentrations of enalaprilat were reached after 4 days of treatment.

Distribution

Over the range of concentrations which are therapeutically relevant, enalaprilat binding to human plasma proteins does not exceed 60%.

Biotransformation

Except for conversion to enalaprilat, there is no evidence for significant metabolism of enalapril.

Elimination

Excretion of enalaprilat is primarily renal. The principal components in urine are enalaprilat, accounting for about 40% of the dose, and intact enalapril (about 20%).

Renal impairment

The exposure of enalapril and enalaprilat is increased in patients with renal insufficiency. In patients with mild to moderate renal insufficiency (creatinine clearance 40-60 ml/min) steady state AUC of enalaprilat was approximately two-fold higher than in patients with normal renal function after administration of 5mg once daily. In severe renal impairment (creatinine clearance ≤30 ml/min), AUC was increased approximately 8-fold. The effective half-life of enalaprilat following multiple doses of Enalapril Maleate Taj Pharma is prolonged at this level of renal insufficiency and time to steady state is delayed (see section 4.2). Enalaprilat may be removed from the general circulation by haemodialysis. The dialysis clearance is 62 ml/min.

Children and adolescents

A multiple dose pharmacokinetic study was conducted in 40 hypertensive male and female paediatric patients aged 2 months to ≤16 years following daily oral administration of 0.07 to 0.14mg/kg Enalapril Maleate Taj Pharma. There were no major differences in the pharmacokinetics of enalaprilat in children compared with historic data in adults. The data indicate an increase in AUC (normalised to dose per body weight) with increased age; however, an increase in AUC is not observed when data are normalised by body surface area. At steady state, the mean effective half-life for accumulation of enalaprilat was 14 hours.

Lactation

After a single 20mg oral dose in five postpartum women the average peak enalapril milk level was 1.7 µg/L (range 0.54 to 5.9 µg/L) at 4 to 6 hours after the dose. The average peak enalaprilat level was 1.7 µg/L (range 1.2 to 2.3 µg/L); peaks occurred at various times over the 24 hour period. Using the peak milk level data, the estimated maximum intake of an exclusively breastfed infant would be about 0.16% of the maternal weight-adjusted dosage.

A woman who had been taking oral enalapril 10mg daily for 11 months had peak enalapril milk levels of 2 µg/L 4 hours after a dose and peak enalaprilat levels of 0.75 µg/L about 9 hours after the dose. The total amount of enalapril and enalaprilat measured in milk during the 24 hour period was 1.44 µg/L and 0.63 µg/L of milk respectively.

Enalaprilat milk levels were undetectable (<0.2 µg/L) 4 hours after a single dose of enalapril 5mg in one mother and 10mg in two mothers; enalapril levels were not determined.

• Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. Reproductive toxicity studies suggest that enalapril has no effects on fertility and reproductive performance in rats, and is not teratogenic. In a study in which female rats were dosed prior to mating through gestation, an increased incidence of rat pup deaths occurred during lactation. The compound has been shown to cross the placenta and is secreted in milk. Angiotensin converting enzyme inhibitors, as a class, have been shown to be foetotoxic (causing injury and/or death to the foetus) when given in the second or third trimester.

6. Pharmaceutical particulars
   • List of excipients

Sodium hydrogen carbonate

Maize starch

Pregelatinised corn starch

Magnesium stearate

Lactose monohydrate

Iron oxide red – 10mg and 20mg tablets only

Iron oxide yellow – 20mg tablet only

• Incompatibilities

Not applicable.

• Shelf life

2 years.

• Special precautions for storage

Do not store above 25°C. Store in the original package in order to protect from moisture.

• Nature and contents of container

Enalapril Maleate Taj Pharma 2.5mg – All-aluminium blister packages containing 2, 11, 20, 28, 30, 40, 49 x 1, 50, or 100 tablets.

Enalapril Maleate Taj Pharma 5mg – All-aluminium blister packages containing 2, 14, 20, 28, 28 x 1, 30, 49 x 1, 50, 56, 60, 98, or 100 tablets.

Enalapril Maleate Taj Pharma 10mg – All-aluminium blister packages containing 28, 49 x 1, 30, 50, 98 or 100 tablets.

Enalapril Maleate Taj Pharma 20mg – All-aluminium blister packages containing 10, 14, 20, 28, 28 x 1, 30, 49 x 1, 50, 56, 60, 84, 90, 98, 100 or 500 tablets.

Maximum pack size for each strength of the Enalapril Maleate Taj Pharma is 100, 120, 240, 360 and 500 tablets.

Not all pack sizes may be marketed.

• Special precautions for disposal and other handling

No special requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Enalapril Maleate Tablets USP 10mg Taj Pharma

Package leaflet: Information for the user

Enalapril Maleate Taj Pharma

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Enalapril Maleate Taj Pharma is and what it is used for
2. What you need to know before you take Enalapril Maleate Taj Pharma
3. How to take Enalapril Maleate Taj Pharma
4. Possible side effects
5. How to store Enalapril Maleate Taj Pharma
6. Contents of the pack and other information

1. What Enalapril Maleate Taj Pharma is and what it is used for

Enalapril Maleate Taj Pharma contains an active substance called Enalapril Maleate Taj Pharma. This belongs to the group of medicines called ACE inhibitors (angiotensin converting enzyme inhibitors).

Enalapril Maleate Taj Pharma is used:

• to treat high blood pressure (hypertension)
• to treat heart failure (weakening of heart function). It can lower the need to go to hospital and can help some patients live longer
• to prevent the signs of heart failure. The signs include: shortness of breath, tiredness after light physical activity such as walking, or swelling of the ankles and feet.

This medicine works by widening your blood vessels. This lowers your blood pressure. The medicine usually starts to work within an hour, and the effect lasts for at least 24 hours. Some people will require several weeks of treatment until the best effect on your blood pressure is seen.

2. What you need to know before you take Enalapril Maleate Taj Pharma

Do not take Enalapril Maleate Taj Pharma

• if you are allergic to Enalapril Maleate Taj Pharma or any of the other ingredients of this medicine (listed in section 6)
• if you have ever had an allergic reaction to a type of medicine similar to this medicine called an ACE inhibitor
• if you have ever had swelling of your face, lips, mouth, tongue or throat which caused difficulty in swallowing or breathing (angioedema) when the reason why was not known or it was inherited
• if you have diabetes or impaired kidney function and you are treated with a blood pressure lowering medicine containing aliskiren
• if you are more than 3 months pregnant. (It is also better to avoid Enalapril Maleate Taj Pharma in early pregnancy – see Pregnancy section)
• if you are being treated with sacubitril/valsartan, a medicine for heart failure.

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking this medicine.

Warnings and precautions

Talk to your doctor or pharmacist before taking Enalapril Maleate Taj Pharma:

• if you have a heart problem
• if you have a condition involving the blood vessels in the brain
• if you have a blood problem such as low or lack of white blood cells (neutropenia/agranulocytosis), low blood platelet count (thrombocytopenia) or a decreased number of red blood cells (anaemia)
• if you have a liver problem
• if you have a kidney problem (including kidney transplantation). These may lead to higher levels of potassium in your blood which can be serious. Your doctor may need to adjust your dose of Enalapril Maleate Taj Pharma or monitor your blood level of potassium
• if you are having dialysis
• if you have been very sick (excessive vomiting) or had bad diarrhoea recently
• if you are on a salt-restricted diet, are taking potassium supplements, potassium-sparing agents, potassium-containing salt substitutes, or other drugs that may increase potassium in your blood (e.g., heparin [a medicine used to prevent blood clots], trimethoprim-containing products such as cotrimoxazole [medicines used to treat infections])
• if you are over 70 years of age
• if you have diabetes. You should monitor your blood for low blood glucose levels, especially during the first month of treatment. The level of potassium in your blood can also be higher
• if you have ever had an allergic reaction with swelling of the face, lips, tongue or throat with difficulty in swallowing or breathing. You should be aware that black patients are at increased risk of these types of reactions to ACE inhibitors
• if you have low blood pressure (you may notice this as faintness or dizziness, especially when standing)
• if you have collagen vascular disease (e.g., lupus erythematosus, rheumatoid arthritis or scleroderma), are on therapy that suppresses your immune system, are taking the drugs allopurinol or procainamide, or any combinations of these
• if you are taking an mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus: medicines used to treat certain types of cancer or to prevent the body’s immune system from rejecting a transplanted organ) or a medicine containing a neprilysin inhibitor such as sacubitril (available as fixed-dose combination with valsartan), used in patients with heart failure, and racecadotril, used in patients with acute diarrhoea. You may be at increased risk for an allergic reaction called angioedema.
• if you are taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor blocker (ARB) (also known as sartans – for example valsartan, telmisartan, irbesartan, etc.), in particular if you have diabetes-related kidney problems.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g., potassium) in your blood at regular intervals.

See also information under the heading “Do not take Enalapril Maleate Taj Pharma.”

You must tell your doctor if you think you are (or might become) pregnant. This medicine is not recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see Pregnancy section).

You should be aware that this medicine lowers the blood pressure in black patients less effectively than in non-black patients.

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking this medicine.

If you are about to have a procedure

If you are about to have any of the following, tell your doctor that you are taking Enalapril Maleate Taj Pharma:

• any surgery or receive anaesthetics (even at the dentist).
• a treatment to remove cholesterol from your blood called ‘LDL apheresis’.
• a desensitisation treatment, to lower the effect of an allergy to bee or wasp stings.

If any of the above applies to you, talk to your doctor or dentist before the procedure.

Other medicines and Enalapril Maleate Taj Pharma

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes herbal medicines. This is because Enalapril Maleate Taj Pharma can affect the way some medicines work. Also some other medicines can affect the way Enalapril Maleate Taj Pharma works. Your doctor may need to change your dose and/or to take other precautions.

In particular tell your doctor or pharmacist if you are taking any of the following medicines:

• an angiotensin II receptor blocker (ARB) or aliskiren (see also information under the headings “Do not take Enalapril Maleate Taj Pharma” and “Warnings and precautions”)
• other medicines to lower blood pressure, such as beta-blockers or water tablets (diuretics)
• medicines containing potassium (including dietary salt substitutes) or other drugs that may increase potassium in your blood (e.g., heparin [a medicine used to prevent blood clots], trimethoprim-containing products such as cotrimoxazole [medicines used to treat infections])
• medicines for diabetes (including oral antidiabetic medicines and insulin)
• lithium (a medicine used to treat a certain kind of depression)
• medicines for depression called ‘tricyclic antidepressants’
• medicines for mental problems called ‘antipsychotics’
• certain cough and cold medicines and weight reducing medicines which contain something called a ‘sympathomimetic agent’
• certain pain or arthritis medicines including gold therapy
• an mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus; medicines used to treat certain types of cancer or to prevent the body’s immune system from rejecting a transplanted organ). See also information under the heading “Warnings and precautions”
• a medicine containing a neprilysin inhibitor such as sacubitril (available as fixed-dose combination with valsartan) and racecadotril. The risk of angioedema (swelling of the face, lips, tongue or throat with difficulty in swallowing or breathing) may be increased. See also information under the headings “Do not take Enalapril Maleate Taj Pharma” and “Warnings and precautions”.
• non-steroidal anti-inflammatory drugs, including COX-2-inhibitors (medicines that reduce inflammation, and can be used to help relieve pain)
• aspirin (acetylsalicylic acid)
• medicines used to dissolve blood clots (thrombolytics)

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Enalapril Maleate Taj Pharma.

Enalapril Maleate Taj Pharma with food and drink

Enalapril Maleate Taj Pharma can be taken with or without food. Most people take Enalapril Maleate Taj Pharma with a drink of water.

Pregnancy and breast-feeding

Pregnancy

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Your doctor will normally advise you to stop taking Enalapril Maleate Taj Pharma before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Enalapril Maleate Taj Pharma. This medicine is not recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breast-feeding

Tell your doctor if you are breast-feeding or about to start breast-feeding. Breast-feeding newborn babies (first few weeks after birth), and especially premature babies, is not recommended whilst taking this medicine. In the case of an older baby your doctor should advise you on the benefits and risks of taking this medicine whilst breast-feeding, compared to other treatments.

Driving and using machines

You may feel dizzy or sleepy while taking this medicine. If this happens, do not drive or use any tools or machines.

Enalapril Maleate Taj Pharma contains lactose

Enalapril Maleate Taj Pharma contains lactose, which is a type of sugar. If you have been told by your doctor that you have intolerance to some sugars, talk to your doctor before taking this medicine.

3. How to take Enalapril Maleate Taj Pharma

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

• It is very important to continue taking this medicine for as long as your doctor prescribes it.
• Do not take more tablets than prescribed.
• The score line is only there to help you break the tablet if you have difficulty swallowing it whole.

High Blood Pressure

• The usual starting dose ranges from 5 to 20mg taken once a day.
• Some patients may need a lower starting dose.
• The usual long term dose is 20mg taken once a day.
• The maximal long term dose is 40mg taken once a day.

Heart Failure

• The usual starting dose is 2.5mg taken once a day.
• Your doctor will raise this amount step by step until the dose that is right for you has been achieved.
• The usual long term dose is 20mg each day, taken in one or two doses.
• The maximal long term dose is 40mg each day, divided in two doses.

Patients with kidney problems

Your dose of medicine will be changed depending on how well your kidneys are working:

• moderate kidney problems – 5mg to 10mg each day
• severe kidney problems – 2.5mg each day
• if you are having dialysis – 2.5mg each day. On days you are not having dialysis, your dose may be changed depending on how low your blood pressure is.

Elderly patients

Your dose will be decided by your doctor and will be based on how well your kidneys are working.

Use in children

Experience in the use of Enalapril Maleate Taj Pharma in children with high blood pressure is limited. If the child can swallow tablets, the dose will be worked out using the child’s weight and blood pressure. The usual starting doses are:

• between 20 kg and 50 kg – 2.5mg each day
• more than 50 kg – 5mg each day.

The dose can be changed according to the needs of the child:

• a maximum of 20mg daily can be used in children who are between 20 kg and 50 kg
• a maximum of 40mg daily can be used in children who are more than 50 kg.
• This medicine is not recommended in newborn babies (first few weeks after birth) and in children with kidney problems.

If you take more Enalapril Maleate Taj Pharma than you should

If you take more Enalapril Maleate Taj Pharma than you should, talk to your doctor or go to a hospital straight away. Take the medicine pack with you. The following effects may happen: feeling of light-headedness or dizziness. This is due to a sudden or excessive drop in blood pressure.

If you forget to take Enalapril Maleate Taj Pharma

• If you forget to take a tablet, skip the missed dose.
• Take the next dose as usual.
• Do not take a double dose to make up for a forgotten dose.

If you stop taking Enalapril Maleate Taj Pharma

Do not stop taking your medicine unless your doctor tells you to.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this medicine:

Stop taking Enalapril Maleate Taj Pharma and talk to a doctor straight away, if you notice any of the following:

• swelling of your face, lips, tongue or throat which may cause difficulty in breathing or swallowing
• swelling of your hands, feet or ankles
• if you develop a raised red skin rash (hives).

You should be aware that black patients are at increased risk of these types of reactions. If any of the above happen, stop taking Enalapril Maleate Taj Pharma and talk to a doctor straight away.

When you start taking this medicine you may feel faint or dizzy. If this happens, it will help to lie down. This is caused by your blood pressure lowering. It should improve as you continue to take the medicine. If you are worried, please talk to your doctor.

Other side effects include:

Very Common (may affect more than 1 in 10 people)

• feeling dizzy, weak or sick
• blurred vision

Common (may affect up to 1 in 10 people)

• light-headedness due to low blood pressure, changes in heart rhythm, fast heartbeat, angina or chest pain
• headache, depression, fainting (syncope), change in sense of taste
• shortness of breath
• diarrhoea, abdominal pain
• tiredness (fatigue)
• rash, allergic reactions with swelling of the face, lips, tongue or throat with difficulty in swallowing or breathing
• high levels of potassium in the blood, increased levels of creatinine in your blood (both are usually detected by a test).

Uncommon (may affect up to 1 in 100 people)

• flushing
• sudden fall in blood pressure
• fast or uneven heart beats (palpitations)
• heart attack (possibly due to very low blood pressure in certain high-risk patients, including those with blood flow problems of the heart or brain)
• stroke (possibly due to very low blood pressure in high-risk patients)
• anaemia (including aplastic and haemolytic)
• confusion, sleeplessness or sleepiness, nervousness
• feeling your skin prickling or being numb
• vertigo (spinning sensation)
• ringing in your ears (tinnitus)
• runny nose, sore throat or hoarseness
• asthma-associated tightness in chest
• slow movement of food through your intestine (ileus), inflammation of your pancreas
• being sick (vomiting), indigestion, constipation, anorexia
• irritated stomach (gastric irritations), dry mouth, ulcer
• muscle cramps
• impaired kidney function, kidney failure
• increased sweating
• itching or nettle rash
• hair loss
• generally feeling unwell (malaise), high temperature (fever)
• impotence
• high level of proteins in your urine (measured in a test)
• low level of blood sugar or sodium, high level of blood urea (all measured in a blood test).

Rare (may affect up to 1 in 1,000 people)

• ‘Raynaud’s phenomenon’ where your hands and feet may become very cold and white due to low blood flow
• changes in blood values such as a lower number of white and red blood cells, lower haemoglobin, lower number of blood platelets
• bone marrow depression
• swollen glands in neck, armpit or groin
• autoimmune diseases
• strange dreams or sleep problems
• accumulation of fluid or other substances in the lungs (as seen on X-rays)
• inflammation of your nose
• inflammation of the lungs causing difficulty breathing (pneumonia)
• inflammation of the cheeks, gums, tongue, lips, throat
• reduced amount of urine
• rash that looks like targets (erythema multiforme)
• ‘Stevens-Johnson syndrome’ and ‘toxic epidermal necrolysis’ (serious skin conditions where you have reddening and scaling of your skin, blistering or raw sores), exfoliative dermatitis/erythroderma (severe skin rash with flaking or peeling of the skin), pemphigus (small fluid-filled bumps on the skin)
• liver or gallbladder problems such as lower liver function, inflammation of your liver, jaundice (yellowing of the skin or eyes), high levels of liver enzymes or bilirubin (measured in a blood test)
• enlargement of breasts in males (gynaecomastia).

Very Rare (may affect up to 1 in 10,000 people)

• swelling in your intestine (intestinal angioedema).

Not known (frequency cannot be estimated from the available data)

• overproduction of antidiuretic hormone, which causes fluid retention, resulting in weakness, tiredness or confusion
• A symptom complex has been reported which may include some or all of the following: fever, inflammation of the blood vessels (serositis/vasculitis), muscle pain (myalgia/myositis), joint pain (arthralgia/arthritis). Rash, photosensitivity or other skin manifestations may occur.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

5. How to store Enalapril Maleate Taj Pharma

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and the carton after ‘EXP’. The expiry date refers to the last day of that month.

Do not store above 25°C. Store in the original package in order to protect from moisture.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enalapril Maleate Taj Pharma contains

• The active substance is Enalapril Maleate Taj Pharma (either 2.5mg, 5mg, 10mg, or 20mg).
• The other ingredients are Lactose Monohydrate, Sodium Hydrogen Carbonate, Maize Starch, Pregelatinised Starch, Magnesium Stearate. The 10mg Tablet Also Contains Iron Oxide Red And The 20mg Tablet Also Contains Iron Oxide Red And Iron Oxide Yellow.

What Enalapril Maleate Taj Pharma looks like and contents of the pack

Enalapril Maleate Taj Pharma tablets are available in 4 strengths which looks like white round shaped tablet.

*The scoreline is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Enalapril Maleate Taj Pharma is supplied in the following pack sizes:

Enalapril Maleate Taj Pharma 2.5mg – All-aluminium blister packages containing 2, 11, 20, 28, 30, 40, 49 x 1, 50, or 100 tablets.

Enalapril Maleate Taj Pharma 5mg – All-aluminium blister packages containing 2, 14, 20, 28, 28 x 1, 30, 49 x 1, 50, 56, 60, 98, or 100 tablets.

Enalapril Maleate Taj Pharma 10mg – All-aluminium blister packages containing 28, 49 x 1, 30, 50, 98 or 100 tablets.

Enalapril Maleate Taj Pharma 20mg – All-aluminium blister packages containing 10, 14, 20, 28, 28 x 1, 30, 49 x 1, 50, 56, 60, 84, 90, 98, 100 or 500 tablets.

Maximum pack size for each strength of the Enalapril Maleate Taj Pharma is 100, 120, 240, 360 and 500 tablets

Not all pack sizes may be marketed.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com