Vasodip Combo

/ Dexcel

The recommended dose is 1 tablet taken once daily at least 15 minutes before a meal. Treatment should be preferably administered in the morning. This product should not be administered with grapefruit juice.
Elderly patients: The dose should depend on the patient’s renal function (see “Use in renal impairment”).
Children and adolescents under 18 years of age: Since there is no clinical experience in patients under 18 years of age, use in children and adolescents is not currently recommended.
Use in renal impairment:  This drug is contraindicated in patients with severe renal dysfunction (creatinine clearance < 30 ml/min) or in patients undergoing haemodialysis. Particular caution is needed when initiating treatment in patients with mild to moderate renal dysfunction.
Use in hepatic impairment: It is contraindicated in severe hepatic dysfunction. Particular caution is needed when initiating treatment in patients with mild to moderate hepatic dysfunction.

Vasodip Combo 10: Treatment of essential hypertension in patients whose blood pressure is not adequately controlled by lercanidipine monotherapy.
Vasodip Combo 20: Treatment of essential hypertension in patients whose blood pressure is not adequately controlled by enalapril monotherapy.

– Hypersensitivity to a therapeutically active constituent (enalapril or lercanidipine), to any ACE-inhibitor or dihydropyridine calcium channel blocker or to any other constituent of this medicinal product.
– History of angioedema associated with ACE-inhibitor therapy.
– Hereditary or idiopathic angioedema.
– Association with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR<60ml/min/1.73m2).
– Second and third trimesters of pregnancy.
– Left ventricular outflow obstruction, including aortic stenosis.
– Untreated congestive heart failure.
– Unstable angina pectoris.
– Within 1 month of a myocardial infarction.
– Severe renal impairment (creatinine clearance < 30 ml/min), including patients undergoing haemodialysis.
– Severe hepatic impairment.
– Co-administration with: strong CYP 3A4 inhibitors, ciclosporin, grapefruit juice

Symptomatic hypotension is rarely seen in uncomplicated hypertensive patients. In hypertensive patients receiving enalapril, symptomatic hypotension is more likely to occur if the patient has been volume-depleted e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting. 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, hyponatremia 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 and/or diuretic is adjusted. Similar considerations may apply 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.
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 systematic blood pressure may occur with enalapril. 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 may be necessary.
Sick sinus syndrome: Particular caution is recommended in the use of lercanidipine in patients with sick-sinus syndrome (without a pacemaker).
Left ventricular dysfunction and ischaemic heart disease: Although haemodynamic controlled studies revealed no impairment of ventricular function, caution must be exercised when treating patients with left ventricular dysfunction with calcium channel blockers.  It has been suggested that patients with ischaemic heart disease show an elevated cardiovascular risk under treatment with some short-acting dihydropyridines.  Although lercanidipine is long-acting, caution is advised in these patients. In rare cases, some dihydropyridines can cause precordial pain or angina pectoris.  Very rarely, patients with pre-existing angina pectoris may experience increased frequency, duration or severity of these attacks.  Isolated cases of myocardial infarction may be observed.
Use in renal impairment: Particular caution is required with enalapril when initiating treatment in patients with mild to moderate renal impairment. Routine monitoring of serum potassium and creatinine under enalapril treatment is part of the normal medical care of these patients. Reports of renal failure associated with the use of enalapril have been made especially in patients with severe heart failure or underlying renal disease, including renal artery stenosis.  If diagnosed promptly and treated appropriately, renal failure under enalapril treatment 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.
Renovascular hypertension: Patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney are particularly at risk of developing hypotension or renal insufficiency under ACE-inhibitor therapy. 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 and cautious titration and monitoring renal function.
Kidney transplantation: There is no experience in the use of lercanidipine or enalapril in patients who have recently undergone renal transplantation. Therefore treatment of these patients with Vasodip Combo is not recommended.
Hepatic failure: The antihypertensive effect of lercanidipine can be potentiated in patients with hepatic dysfunction. 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 elevation 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 on ACE-inhibitors. Neutropenia is rare in patients with normal renal function and without particular risk factors.  Enalapril should be used with extreme caution in patients with collagen vascular disease, those under treatment with immunosuppressants, allopurinol, procainamide or if several of these risk factors are present, especially in pre-existing impairment of renal function.  Severe infections occurred in some of these patients that in few cases did not respond to intensive antibiotic treatment.  If enalapril is used in such patients, regular monitoring of leucocytes is advised and patients should be instructed to report any signs of infection to their doctor.
Hypersensitivity/angioneurotic oedema: Angioneurotic oedema with involvement of the face, extremities, lips, tongue, glottis and/or larynx, has been reported in patients treated with ACE-inhibitors, including enalapril. It may occur at any time during treatment. In such cases, enalapril must be stopped immediately. The patient is to be carefully monitored in order to ensure that the symptoms have fully resolved before discharge from the hospital. 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. When the tongue, glottis or larynx are affected and are likely to cause airway obstruction, appropriate treatment must be instituted promptly (e.g. subcutaneous administration of adrenalin 1:1000) (0.3 ml to 0.5 ml) and/or measures to ensure a patent airway. A higher incidence of angioedema on ACE-inhibitors has been reported in black patients, when compared to non-black patients. Patients with a history of angioedema not triggered by an ACE-inhibitor can be at a higher risk of developing angioedema if they are to receive an ACE-inhibitor.Anaphylactoid reactions during desensitisation with insect venoms: Life-threatening anaphylactoid reactions have occurred rarely during desensitisation therapy against insect venoms and concurrent use of an ACE-inhibitor. These reactions can be avoided by temporarily discontinuing the ACE-inhibitor prior to each desensitisation.
Anaphylactoid reactions during LDL apheresis: Life-threatening anaphylactoid reactions have occurred rarely during a low density lipoprotein (LDL)-apheresis with dextran sulfate and concurrent use of an ACE-inhibitor.  These reactions can be avoided by temporarily discontinuing the ACE-inhibitor prior to each apheresis. 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.
Cough: Cough has been reported in connection with the use of ACE-inhibitors.  Typically, the cough is non-productive, persistent and subsides after discontinuation of the therapy.  A cough induced by ACE-inhibitor should also be considered in the differential diagnosis of cough.
Surgery/anaesthesia: In patients undergoing major surgery or anaesthesia with agents that reduce blood pressure, enalapril inhibits the formation of angiotensin II, that would otherwise occur due to a compensatory secretion of renin. If hypotension develops as a result of this mechanism, it can be corrected by volume expansion.
Hyperkalaemia: An increase in serum potassium has been observed in some patients on ACE-inhibitors including enalapril.  Risk factors for hyperkalaemia are: 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 as well as concurrent treatment with other drugs that can lead to an increase in serum potassium values (e.g. heparin). The use of potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes particularly in patients with impaired renal function may lead to a significant increase in serum potassium. 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.
Lithium: The combination of lithium and enalapril is generally not recommended.
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.  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.
Inducers of CYP3A4: CYP3A4 inducers such as anticonvulsants (e.g. phenytoin, carbamazepine) and rifampicin can reduce serum levels of lercanidipine so that the efficacy of the drug can be lower than expected.
Ethnic differences: As with other ACE-inhibitors, enalapril is apparently less effective in lowering blood pressure in black patients than in non-blacks, possibly because plasma renin levels are often lower in the black hypertensive population.
Pregnancy: This drug is not recommended during pregnancy. ACE-inhibitors, like enalapril, should not be initiated during pregnancy. 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.  The use of lercanidipine is also not recommended during pregnancy or in women planning to become pregnant.
Lactation: The use of Vasodip Combo is not recommended during lactation.
Pediatric use: The safety and efficacy of this association has not been demonstrated in children.
Alcohol: Alcohol should be avoided because it may potentiate the effect of vasodilator antihypertensives.
Lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take it.
For full details see prescribing information.

The safety of this drug  has been evaluated in five double-blind controlled clinical studies and in two long term open-label extension phases. In total, 1,141 patients have received Vasodip Combo at a dose of 10 mg/10 mg, 20 mg/10 mg and 20 mg/20 mg. The undesirable effects observed with combination therapy have been similar to those already observed with one or the other of the constituents given alone. The most commonly reported adverse reactions during treatment with this drug were cough (4.03%), dizziness (1.67%) and headache (1.67%).
Additional information on the individual components: Lercanidipine alone: The adverse drug reactions most commonly reported in controlled clinical trials were headache, dizziness, edema peripheral, tachycardia, palpitations and flushing, with each occurring in less than 1% of patients.
Enalapril alone: Among the adverse drug reactions reported for enalapril are:
Nervous system and psychiatric disorders: Common: depression, headache.
Eye disorders: Very common: vision blurred.
Cardiac and vascular disorders: Very common: dizziness. Common: hypotension (including orthostatic hypotension), syncope, rhythm disturbances, angina pectoris, tachycardia, chest pain
Respiratory, thoracic and mediastinal disorders: Very common: cough, Common: dyspnea.
Gastrointestinal disorders: Very common: nausea, Common: diarrhea, abdominal pain, dysgeusia.
Skin and subcutaneous tissue disorders: Common: Rash, hypersensitivity/angioneurotic edema: angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx have been reported.
General disorders and administration site conditions: Very common: asthenia, Common: zatigue.
Investigations: Common: blood potassium increased, blood creatinine increased.

The antihypertensive effect of it could be potentiated by other blood-pressure lowering drugs such as diuretics, beta blocker, alpha-blocker and other substances. In addition, the following interactions have been observed with one or other constituents of the combined product:
Lercanidipine: Contraindicated combinations: Inhibitors of CYP3A4 : Since lercanidipine is metabolised by the enzyme CYP3A4, simultaneously administered inhibitors and inducers of CYP3A4 may interact with the metabolism and excretion of lercanidipine. The combination of lercanidipine and strong inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) is contraindicated. An interaction study with ketoconazole, a strong inhibitor of CYP3A4, showed a marked rise in plasma levels of lercanidipine (a 15-fold increase in area under the drug concentration-time curve [AUC] and an 8-fold increase in C_max of the eutomer S-lercanidipine).
Ciclosporin: Ciclosporin and lercanidipine must not be used together. Increased plasma concentrations of both drugs have been observed following concurrent administration. A study in healthy young volunteers showed no changes in plasma lercanidipine levels when ciclosporin was taken 3 hours after ingestion of lercanidipine, but the AUC of ciclosporin rose by 27%. Co-medication of lercanidipine with ciclosporin caused a 3-fold rise in plasma lercanidipine levels and a 21% increase in AUC of ciclosporin.
Grapefruit juice: Lercanidipine should not be taken with grapefruit juice. As with other dihydropyridines, the metabolism of lercanidipine can be inhibited by the ingestion of grapefruit juice, resulting in a rise in the systemic availability of lercanidipine and increased hypotensive effect.
Combinations requiring precautions for use: Alcohol: Alcohol should be avoided since it may potentiate the effect of vasodilator antihypertensives.
Substrates of CYP3A4: Caution is required on the co-prescribing of lercanidipine with other substrates of CYP3A4 such as terfenadine, astemizole, Class III antiarrhythmics, e.g. amiodarone, quinidine.
Inducers of CYP3A4: Concurrent use of lercanidipine with CYP3A4 inducers such as anticonvulsants (e.g. phenytoin, carbamazepine) and rifampicin should be approached with caution, because the antihypertensive effect of lercanidipine can be reduced.  Blood pressure must therefore be monitored more frequently than usual.
Digoxin: Co-administration of 20 mg lercanidipine in patients chronically treated with ß-methyldigoxin showed no evidence of pharmacokinetic interaction. Healthy volunteers treated with digoxin after administration of 20 mg lercanidipine showed a mean increase in digoxin C_max of 33%, whereas neither AUC nor renal clearance were significantly altered. Patients on concomitant treatment with digoxin should be closely monitored for clinical signs of digoxin toxicity.
Combinations to be taken into account: Midazolam: In elderly volunteers the concurrent administration of oral midazolam 20 mg enhanced the absorption of lercanidipine (by about 40%) and decreased its rate of absorption (t_max was delayed from 1.75 to 3 hours).  No changes in midazolam concentrations occurred.
Metoprolol: When lercanidipine was co-administered with metoprolol – a ß-blocker predominantly eliminated by the liver – the bioavailability of metoprolol was unchanged, whereas the bioavailability of lercanidipine was reduced by 50%. This effect may be due to the reduction in hepatic blood flow caused by ß-blockers and hence might also occur with other preparations of this class of drug. Nevertheless, lercanidipine can be safely used at the same time as blockers of b-adrenergic receptors.
Cimetidine: Concomitant administration of cimetidine 800 mg daily does not cause significant modifications in plasma levels of lercanidipine, but caution is required at higher doses since the bioavailability of lercanidipine, and therefore its hypotensive effect may be increased.
Fluoxetine: An interaction study with fluoxetine (an inhibitor of CYP2D6 and CYP3A4), conducted in healthy volunteers aged 65 ± 7 years (mean ± s.d.), showed no clinically relevant modification of the pharmacokinetics of lercanidipine.
Simvastatin: When a 20 mg dose of lercanidipine was repeatedly co-administered with 40 mg of simvastatin, the AUC of lercanidipine was not significantly modified, whereas the AUC of simvastatin increased by 56% and that of its principal active metabolite, ß-hydroxyacid by 28%. It is unlikely that such changes are of clinical relevance. No interaction is expected if lercanidipine is administered in the morning and simvastatin in the evening, as indicated for such a drug.
Warfarin: Co-administration of 20 mg lercanidipine to fasted healthy volunteers did not alter the pharmacokinetics of warfarin.
Pediatric population: Interaction studies have only been performed in adults.
Enalapril maleate
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): Clinical trial data has 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.
Potassium-sparing diuretics and potassium supplements: ACE-inhibitors attenuate diuretic-induced potassium loss. Potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes may lead to significant increases in serum potassium. If concomitant use is indicated because of demonstrated hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.
Lithium: Reversible increases in serum lithium concentrations and toxic effects have been reported during concomitant administration of lithium with ACE-inhibitors. Concomitant use of thiazide diuretics may increase serum lithium concentrations and hence enhance the risk of lithium toxicity with ACE-inhibitors. Use of enalapril with lithium is therefore not recommended, but if the combination is necessary, serum lithium levels must be carefully monitored.
Antidiabetics: Epidemiological studies have suggested that concomitant administration of ACE-inhibitors and antidiabetic drugs (insulin, oral antidiabetics) may cause an increased blood glucose-lowering effect, with risk of hypoglycaemia. These cases are apparently more likely to occur in the first weeks of combined treatment and in patients with renal impairment.
Diuretics (thiazide or loop diuretics): Prior treatment with high-dose diuretics may result in volume depletion and a risk of hypotension when initiating treatment with enalapril. The hypotensive effects can be reduced by discontinuation of the diuretic, by increasing volume or giving salt, or by initiating therapy with a low dose of enalapril.
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 others 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.
Tricyclic antidepressants/neuroleptics/anaesthetics/narcotics: Concomitant use of certain anaesthetic agents, tricyclic antidepressants and neuroleptics with ACE-inhibitors may lead to a further reduction in blood pressure.
Other antihypertensives: Concomitant use of other antihypertensives may increase the hypotensive effects of enalapril. Concomitant use of nitroglycerine and other nitrates or other vasodilators may further reduce blood pressure.
Sympathomimetics: Sympathomimetics may reduce the antihypertensive effects of ACE-inhibitors.
Acetylsalicylic acid, thrombolytics and β-blockers: Enalapril can be safely administered concomitantly with acetyl salicylic acid (at cardiologic doses), thrombolytics and β-blockers.
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.
For full details see prescribing information.

Pregnancy: For enalapril The use of ACE inhibitors (enalapril) is not recommended during the first trimester of pregnancy. The use of ACE inhibitors (enalapril) is contra-indicated during the second and third trimesters of pregnancy.
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). Maternal oligohydramnios, presumably representing decreased fetal renal function, has occurred and may result in limb contractures, craniofacial deformations and hypoplastic lung development. Should exposure to ACE inhibitor 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.
For lercanidipine: Animal studies with lercanidipine have not shown teratogenic effects, but these have been observed with other dihydropyridine compounds. No clinical data on exposed pregnancies are available for lercanidipine, Therefore its use is not recommended during pregnancy or in women with childbearing potential unless effective contraception is used.
For enalapril and lercanidipine in association: There are no or limited amount of data from the use of enalapril maleate/lercanidipine HCl in pregnant women. Animal studies are insufficient with respect to reproductive toxicity.  It should not be used in the second and third trimester of pregnancy. It is not recommended in the first trimester of pregnancy and in women of childbearing potential not using contraception.
Lactation: For enalapril: Limited pharmacokinetic data demonstrate very low concentrations in breast milk. Although these concentrations seem to be clinically irrelevant, the use of it in breastfeeding 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 the case of an older infant, the use of this drug a breast-feeding mother may be considered if this treatment is necessary for the mother and the child is observed for any adverse effect.
For lercanidipine: The excretion of lercanidipine in human milk is unknown.  For enalapril and lercanidipine in association consequently, the use of it, is not recommended during lactation.
Fertility: Reversible biochemical changes in the head of spermatozoa which can impair fecundation have been reported in some patients treated by channel blockers. In cases where repeated in-vitro fertilization is unsuccessful and where another explanation cannot be found, the possibility of calcium channel blockers as the cause should be considered.

In the post-marketing experience, some cases of intentional overdose requiring hospitalization were reported with administration of enalapril/lercanidipine at doses from 100 up to 1000 mg each. The reported symptoms (blood pressure systolic decreased, bradycardia, restlessness, somnolence and flank pain) could also be due to the concomitant administration of high doses of other drugs (e.g. beta-blockers).
Symptoms of overdose with enalapril and lercanidipine alone: The most prominent features of overdose reported with enalapril to date are marked hypotension (beginning some six hours after ingestion of the tablets), concomitant with blockade of the renin-angiotensin system, and stupor. Symptoms associated with overdose 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 300 mg and 440 mg of enalapril respectively. As with other dihydropyridines, overdose with lercanidipine might be expected to cause excessive peripheral vasodilatation with marked hypotension and reflex tachycardia.
Treatment of cases of overdose with enalapril and lercanidipine alone: The recommended treatment of overdose with enalapril is intravenous infusion of saline solution. If hypotension occurs, the patients should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. If the tablets were ingested recently, measures to eliminate enalapril maleate should be taken (e.g. vomiting, gastric lavage, administration of absorbents or sodium sulfate). Enalaprilat can be removed from the circulation by haemodialysis. Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine should be continuously monitored.  With lercanidipine, in the case of severe hypotension, bradycardia and unconsciousness, cardiovascular support can be helpful, with intravenous atropine to counteract the bradycardia. In view of the prolonged pharmacological action of lercanidipine, the cardiovascular status of patients who have taken an overdose must be monitored for at least 24 hours. There is no information about the value of dialysis. Since the drug is highly lipophilic, it is very unlikely that plasma levels will be indicative of the duration of the risk phase. Dialysis may not be effective.