Enalapril Co 20/12.5 Biotech 20 mg, 12.5 mg Tablets

Enalapril Co 20/12,5 Biotech is indicated for the treatment of hypertension in patients where fixed combination therapy is considered more appropriate than monotherapy.

Posology
Hypertension
The usual dosage is 1 tablet, administered once daily. If necessary, the dosage may be increased to a maximum of 2 tablets, administered once daily.
Special populations
Dosage in Renal insufficiency
Thiazides, including hydrochlorothiazide as contained in Enalapril Co 20/12,5 Biotech may not be appropriate diuretics for use in patients with renal impairment and are ineffective at creatinine clearance values of 30 ml/min or below (i.e., moderate or severe renal insufficiency). Enalapril Co 20/12,5 Biotech is not to be used as initial therapy in any patient with renal insufficiency. In patients with renal clearance of > 30 and < 80 ml/min, Enalapril Co 20/12,5 Biotech may be used but only after titration of the individual components.
Paediatric population
Safety and effectiveness in children have not been established.
Method of administration
Oral use.

• Hypersensitivity to enalapril, hydrochlorothiazide, other sulphonamide derived medicines or to any of the excipients of Enalapril Co 20/12,5 Biotech (see section 6.1).
• Severe renal impairment (creatinine clearance u2264 30 ml/min).
• Anuria.
• A history of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines.
• Hereditary or idiopathic angioedema.
• Hypertrophic obstructive, cardiomyopathy (HOCM).
• Pregnancy and lactation (see section 4.6).
• Severe hepatic impairment.
• Bilateral renal artery stenosis.
• Renal artery stenosis in patients with a single kidney.
• Aortic stenosis.
• Concomitant use of Enalapril Co 20/12,5 Biotech with potassium sparing diuretics such as spironolactone, triamterene, amiloride (see section 4.5).
• Porphyria.
• Lithium therapy: Concomitant administration with Enalapril Co 20/12,5 Biotech may lead to toxic blood concentrations of lithium (see section 4.5).
• The concomitant use of Enalapril Co 20/12,5 Biotech with aliskiren-containing medicines is contraindicated (see section 4.4).
• Patients with Addisonu2019s disease.
• Concomitant use with fluoroquinolones in patients with moderate to severe renal impairment (creatinine clearance u2264 30 ml/min) and in elderly patients (see section 4.5).
• Combination with sacubitril/valsartan due to increased risk of angioedema. Do not administer Enalapril Co 20/12,5 Biotech within 36 hours of switching to or from sacubitril/valsartan, a medicine containing a neprilysin inhibitor (see sections 4.4 and 4.5).
• Patients with a history of previous and/or current basal cell carcinoma and/or squamous cell carcinomas of the skin and lip.

Hypotension and Electrolyte Fluid Imbalance
Symptomatic hypotension is seen in uncomplicated hypertensive patients. In hypertensive patients receiving Enalapril Co 20/12,5 Biotech, symptomatic hypotension may occur following the initial dose; this is more likely to occur if the patient has been volume depleted, e.g., by diuretic therapy, dietary salt restriction, diarrhoea or vomiting (see sections 4.5 and 4.8). Previous diuretic therapy should be discontinued for 2-3 days prior to initiation of treatment with Enalapril Co 20/12,5 Biotech. Regular determination of serum electrolytes should be performed at appropriate intervals in such patients. Special attention should be paid to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident. In hypertensive 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 Co 20/12,5 Biotech 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. Thiazides (including hydrochlorothiazide) can cause fluid or electrolyte imbalance (hypokalaemia, hyponatraemia, and hypochloremic alkalosis). Warning signs of fluid or electrolyte imbalance are xerostomia, thirst, weakness, lethargy, somnolence, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Should a woman become pregnant while receiving Enalapril Co 20/12,5 Biotech, the treatment must be stopped promptly and switched to a different class of antihypertensive medicine. Should a woman contemplate pregnancy, the doctor should institute alternative medication (see section 4.6).

Although hypokalaemia may develop during use of thiazide diuretics, concurrent therapy with enalapril may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greatest in patients with cirrhosis of the liver, in patients experiencing brisk diuresis, in patients with inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or ACTH (see section 4.5). Hyponatraemia may occur in oedematous patients in hot weather. Chloride deficit is generally mild and does not usually require treatment. Thiazides may have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia. 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 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 heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with Enalapril Co 20/12,5 Biotech. 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 Co 20/12,5 Biotech, may be necessary.

Renal Function Impairment
Renal failure has been reported in association with enalapril and has been observed 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. If this occurs, therapy with Enalapril Co 20/12,5 Biotech should be discontinued. This situation should raise the possibility of underlying renal artery stenosis. Thiazides may not be appropriate diuretics for use in patients with renal impairment and are ineffective at creatinine clearance values of 30 ml/min or below (i.e., moderate or severe renal insufficiency) (see section 4.2). Enalapril Co 20/12,5 Biotech should not be administered to patients with renal insufficiency (creatinine clearance 30 ml/min) until titration of the individual components, enalapril and hydrochlorothiazide, have shown the need for the doses present in this combination formulation (see section 4.2).

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.

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

Aortic Stenosis/Hypertrophic Cardiomyopathy
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.

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 Enalapril Co 20/12,5 Biotech. 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.

Haemodialysis Patients
The use of enalapril is not indicated in patients requiring dialysis for renal failure. 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 medicine.

Kidney Transplantation
There is no experience regarding the administration of enalapril in patients with a recent kidney transplantation. Treatment with enalapril as contained in Enalapril Co 20/12,5 Biotech is therefore not recommended.

Hepatic failure
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 Enalapril Co 20/12,5 Biotech who develop jaundice or marked elevations of hepatic enzymes should discontinue the Enalapril Co 20/12,5 Biotech and receive appropriate medical follow-up. Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

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 as contained in Enalapril Co 20/12,5 Biotech 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.

Hyperkalaemia
The combination of enalapril and a low-dose diuretic cannot exclude the possibility of a hyperkalaemia occurring. 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, inter-current 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 medicine 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 medicine 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, dysrhythmias. If concomitant use of enalapril and any of the above-mentioned medicines is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium (see section 4.5).

Hypersensitivity/Angioedema
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including enalapril maleate. This may occur at any time during treatment. In such cases, Enalapril Co 20/12,5 Biotech 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. 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 adrenaline (epinephrine) solution 1:1 000 (0,3 ml to 0,5 ml) and/or measures to ensure a patent airway, should be administered promptly. Patients of black ethnicity receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to white patient. However, in general it appears that black patients have an increased risk for angioedema. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see section 4.3). Patients receiving coadministration 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 Enalapril Co 20/12,5 Biotech 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). In patients receiving thiazides, sensitivity reactions may occur with or without a history of allergy and bronchial asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.

Anaphylactoid Reactions during Hymenoptera Desensitisation
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
Patients receiving ACE inhibitors during low density lipoprotein (LDL)-apheresis with dextran sulfate have experienced life-threatening anaphylactic reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.

Cough
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.

Surgery/Anaesthesia
Enalapril blocks angiotensin II formation and therefore impairs the ability of patients undergoing major surgery or anaesthesia with medicines that produce hypotension to compensate via the renin-angiotensin system. Hypotension which occurs due to this mechanism can be corrected by volume expansion (see section 4.5).

Ethnic Differences
Enalapril is apparently less effective in lowering blood pressure in black patients than in non-black patients, possibly because of a higher prevalence of low-renin states in the black hypertensive population.

Metabolic and Endocrine Effects
Thiazide therapy, including treatment with hydrochlorothiazide, may impair glucose tolerance. Dosage adjustment of antidiabetic medicines, including insulin, may be required (see section 4.4). Diabetic patients treated with oral antidiabetic medicines 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).

Enalapril Maleate - Hydrochlorothiazide
Dual blockade of the renin - angiotensin - aldosterone system (RAAS)
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 medicine (see sections 4.3, 4.4 and 5.1).
Other Antihypertensive medicines
Concomitant use of these medicines may increase the hypotensive effects of enalapril and hydrochlorothiazide. Concomitant use with nitroglycerin and other nitrates, or other vasodilators, may further reduce blood pressure.
Fluoroquinolones
Concomitant use of fluoroquinolones and ACE inhibitors/Angiotensin receptor blockers may precipitate acute kidney injury. The mechanism of the possible interaction between the different classes of medicines, over and above different mechanisms of kidney damage, is unknown (see section 4.3).
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 due to reduced renal clearance and enhance the risk of lithium toxicity with ACE inhibitors. Use of Enalapril Co 20/12,5 Biotech with lithium is contraindicated with Enalapril Co 20/12,5 Biotech (see section 4.3).

Allopurinol
The concurrent use of ACE inhibitors, such as enalapril, as in Enalapril Co 20/12,5 Biotech, and allopurinol might increase the risk of neutropenia/agranulocytosis and serious infection especially in renal impairment (section 4.3 and 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 medicine. Therefore, the antihypertensive effect of angiotensin II receptor antagonists, ACE inhibitors or diuretics may be attenuated by NSAIDs including selective COX-2 inhibitors. The coadministration of NSAIDs (including COX-2 inhibitors) and angiotensin II receptor antagonists or ACE inhibitors as in Enalapril Co 20/12,5 Biotech exert an additive effect on the increase in serum potassium and may result in a deterioration of renal function. These effects are usually reversible. 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.

Enalapril Maleate
Potassium - sparing Diuretics, Potassium Supplements, or other medicine 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 medicine 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 medicines 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 sections 4.2 and 4.4). The hypotensive effects can be reduced by discontinuation of the diuretic or by increasing volume or salt intake.

Tricyclic Antidepressants/Antipsychotics/Anaesthetics
Concomitant use of certain anaesthetic medicines, tricyclic antidepressants and antipsychotics with Enalapril Co 20/12,5 Biotech may result in further reduction of blood pressure (see section 4.4).

Gold
Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported 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 Enalapril Co 20/12,5 Biotech 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.

Women of child - bearing potential
Patients planning pregnancy should be changed to alternative antihypertensive treatments. When pregnancy is diagnosed, treatment with Enalapril Co 20/12,5 Biotech should be stopped immediately, and, if appropriate, alternative therapy should be started.
Pregnancy
Enalapril Co 20/12,5 Biotech is contraindicated during pregnancy. Pregnant women should be informed of the potential hazards to the foetus and must not take Enalapril Co 20/12,5 Biotech during pregnancy (see section 4.3). Foetal exposure to ACE inhibitors during the first trimester of pregnancy has been reported to be associated with an increased risk of malformations of the cardiovascular (atrial and/or ventricular septal defect, pulmonic stenosis, patent ductus arteriosus) and central nervous system (microcephaly spins bifida) and of kidney malformations. Enalapril Co 20/12,5 Biotech passes through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. Oligohydramnios as well as hypotension, oliguria and anuria in new-borns, have been reported after administration of ACE inhibitors [as contained in Enalapril Co 20/12,5 Biotech] during the second and third trimester. Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur.
Breastfeeding
Enalapril Co 20/12,5 Biotech is contraindicated during breastfeeding. Both enalapril and thiazides, including hydrochlorothiazide, as in Enalapril Co 20/12,5 Biotech, appear in human milk. If use of Enalapril Co 20/12,5 Biotech is deemed essential, the patient should stop breastfeeding. Hydrochlorothiazide in high doses causing intense diuresis can inhibit the milk production.
Fertility
There are no data on fertility.

When driving vehicles or operating machines it should be taken into account that dizziness or weariness may occur (see section 4.8).

a. Summary of the safety profile
The most common side effects reported were headache and cough.
b. Tabulated list of adverse reactions
The following undesirable side effects have been reported for enalapril maleate:
System organ class
Frequent
Less frequent
Frequency unknown
Blood and lymphatic system disorders
Anaemia (including aplastic and haemolytic), neutropenia, decreases in haemoglobin, decreases in haematocrit, thrombocytopenia, agranulocytosis, bone marrow depression, pancytopenia, lymphadenopathy,
Immune system disorders
Hypersensitivity/ angio - oedema of the face, extremities, lips, tongue, glottis and/or larynx
Autoimmune diseases
Endocrine disorders
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Metabolism and nutrition disorders
Hypoglycaemia (see section 4.4), anorexia Gout
Psychiatric disorder
Depression
Confusion
Nervous system disorders
Dizziness, headache,
Somnolence, paraesthesia,
syncope, taste alterations
vertigo, nervousness, insomnia, dream abnormality, sleep disorders
Eye disorders
Blurred vision
Ear and labyrinth disorders
Tinnitus
Cardiac disorders
Chest pain, rhythm disturbances, angina pectoris, tachycardia Palpitations, myocardial infarction or cerebrovascular accident*, possibly secondary to excessive hypotension in high risk patients (see section 4.4)
Vascular disorders
Hypotension (including orthostatic hypotension) Flushing, orthostatic hypotension, Raynaud's phenomenon
Respiratory, thoracic, and mediastinal disorders
Cough, dyspnoea Rhinorrhoea, sore throat and hoarseness, bronchospasm/asthma, pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilia, pneumonia
Gastrointestinal disorders
Nausea, diarrhoea, abdominal pain Ileus, pancreatitis, vomiting, dyspepsia, constipation, gastric irritations, dry mouth, peptic ulcer, stomatitis/aphthous ulcerations, glossitis, intestinal angioedema, flatulence
Hepatobiliary disorders
Hepatic failure, hepatitis u2013 either hepatocellular or cholestatic, hepatitis including necrosis, cholestasis (including jaundice)
Skin and subcutaneous tissue disorders
Rash, Diaphoresis, pruritus, urticaria, alopecia, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, erythroderma, pemphigus A symptom complex has been reported which may include some or all of the following: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, a positive ANA, elevated ESR, eosinophilia, and leucocytosis. Rash, photosensitivity or other dermatologic manifestations may occur.
Musculoskeletal, connective tissue, and bone disorder
Muscle cramps Arthralgia
Renal and urinary disorder
Renal dysfunction, renal failure, proteinuria Oliguria
Reproductive system and breast disorders
Impotence, gynecomastia
General disorder and administration site conditions
Asthenia, fatigue Malaise, fever
Investigations
Hyperkalaemia, increases in serum creatinine Increases in blood urea, hyponatraemia, elevations of liver enzymes, elevations of serum bilirubin
The following undesirable side effects have been reported for hydrochlorothiazide:
System organ class
Frequent
Less frequent
Frequency unknown
Infections and infestations
Sialoadenitis
Neoplasm benign, malignant and unspecified (including cysts and polyps)
Non - melanoma skin cancer (Basal cell carcinoma and squamous cell carcinoma
Blood and lymphatic system disorders
A plastic anaemia, haemolytic anaemia, bone marrow depression, leukopenia, neutropenia, agranulocytosis, thrombocytopenia
Immune system disorders
Hypersensitivity, allergy, anaphylactic reactions
Endocrine disorders
Loss of diabetic control
Metabolism and nutrition disorders
Electrolyte imbalance (including hyponatraemia), volume depletion Anorexia, loss of appetite, hypercholesterolaemia, hyperglycaemia
Psychiatric disorders
Restlessness
Nervous system disorders
Light-headedness
Eye disorders
Xanthopsia, acute myopia, acute angle-closure glaucoma, transient blurred vision
Vascular disorders
Necrotizing angiitis (vasculitis)
Respiratory, thoracic, and mediastinal disorders
Respiratory distress (including pneumonitis and pulmonary oedema)
Gastrointestinal disorders
Pancreatitis, stomach upset Anorexia, gastric irritation
Hepatobiliary disorders
Hepatocellular jaundice, cholestatic jaundice
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus like reactions (or reactivation of lupus erythematosus), photosensitivity reactions, cutaneous vasculitis, toxic epidermal necrolysis Urticaria, purpura
Musculoskeletal, connective tissue, and bone disorder
Weakness, muscle spasm
Renal and urinary disorder
Interstitial nephritis, renal dysfunction, glycosuria
General disorders
Fever
Investigations
Increase in triglycerides
The following undesirable side effects have been reported for Enalapril Co 20/12,5 Biotech:
System organ class
Frequent
Less frequent
Frequency unknown
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non - melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma)
Blood and lymphatic system disorders
Decreases in haemoglobin, decreases in haematocrit, thrombocytopenia, agranulocytosis, decrease in platelets, decrease in white cell count, anaemia (including aplastic and haemolytic), neutropenia, bone marrow depression, leukopenia, pancytopenia, lymphadenopathy, autoimmune diseases
Immune system disorders
Hypersensitivity / angioedema of the face, extremities, lips, tongue, glottis and/or larynx
Endocrine disorders
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Metabolism and nutrition disorders
Hyperglycaemia, hypokalaemia, increase in cholesterol, increase in triglycerides Hyperuricaemia, gout, hyponatraemia, hypoglycaemia, anorexia
Psychiatric disorder
Insomnia
Nervous system disorders
Dizziness, headache, paraesthesia, depression, taste alteration Nervousness, somnolence, vertigo, paresis (due to hypokalaemia), confusion, dream abnormality, sleep disorders
Eye disorders
Blurred vision Choroidal effusion
Ear and labyrinth disorders
Tinnitus
Cardiac disorders
Chest pain, palpitations, tachycardia, rhythm disturbances, angina pectoris Flushing, myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients. Raynaudu2019s phenomenon
Vascular disorders
Hypotension (including orthostatic hypotension), syncope Non-orthostatic hypotension
Respiratory, thoracic, and mediastinal disorders
Cough, dyspnoea Rhinorrhoea, sore throat and hoarseness, bronchospasm /asthma, pulmonary infiltrates, respiratory distress (including pneumonitis and pulmonary oedema), rhinitis, allergic alveolitis /eosinophilic pneumonia
Gastrointestinal disorders
Nausea, diarrhoea, vomiting Dyspepsia, abdominal pain, constipation, flatulence, dry mouth, pancreatitis, ileus, gastric irritations, peptic ulcer, stomatitis, aphthous ulcerations, glossitis, intestinal angioedema
Hepatic failure, hepatic necrosis (may be fatal), hepatitis u2013 either hepatocellular or cholestatic,
Skin and subcutaneous tissue disorders
Rash, diaphoresis, pruritus, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis, purpura, cutaneous lupus erythematosus, erythroderma, pemphigus urticaria, alopecia A symptom complex has been reported which may include some or all of the following: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, a positive ANA, elevated ESR, eosinophilia, and leucocytosis. Rash, photosensitivity or other dermatologic manifestations may occur.
Musculoskeletal, connective tissue, and bone disorder
Muscle cramps Arthralgia
Renal and urinary disorder
Renal dysfunction, renal failure, proteinuria, oliguria
Reproductive system and breast disorders
Decreased libido, impotence Gynaecomastia
General disorder and administration site conditions
Asthenia, fatigue Fever, malaise
Investigations
Increases in blood urea, increase in serum creatinine, elevations of liver enzymes, elevations of serum bilirubin, hyperkalaemia.

No specific information is available on the treatment of overdosage with Enalapril Co 20/12,5 Biotech. Treatment is symptomatic and supportive. Therapy with Enalapril Co 20/12,5 Biotech should be discontinued and the patient observed closely. Suggested measures include induction of emesis, administration of activated charcoal, and administration of a laxative if ingestion is recent, and correction of dehydration, electrolyte imbalance and hypotension by established procedures, introduced within 2 hours of ingestion. Enalapril maleate 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. 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 ingestion is recent, take measures aimed at eliminating enalapril maleate (e.g., emesis, administration of absorbents, and sodium sulfate). If available, angiotensin II infusion and/or intravenous catecholamines may be beneficial. 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. Hydrochlorothiazide The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalaemia may accentuate cardiac dysrhythmias.