Lacibloc

4 mg: Lacidipine 4 mg film-coated tablet appears as white to off-white film-coated tablet, oval-shaped, biconvex, with break line on one side and plain on the other side.
Each film-coated tablet contains: Lacidipine 4 mg.
6 mg: Lacidipine (Lacibloc) 6 mg appears as white to off-white film coated tablet, oval shaped, plain on one side and bisected on the other side.
Each film-coated tablet contains: Lacidipine 6 mg.
The main use of calcium-channel blockers is in the management of angina pectoris and hypertension; some are also employed in cardiac arrhythmias.
Calcium-channel blockers, also known as calcium antagonists, calcium-entry blockers, and slow-channel blockers inhibit the cellular influx of calcium which is responsible for maintenance of the plateau phase of the action potential. Thus calcium-channel blockers primarily affect tissues in which depolarization is dependent upon calcium rather than sodium influx, and these include vascular smooth muscle, myocardial cells, and cells within the sino-atrial (SA) and atrioventricular (AV) nodes. The main actions of the calcium-channel blockers include dilation of coronary and peripheral arteries and arterioles with little or no effect on venous tone, negative inotropic action, reduction of heart rate, and slowing of AV conduction. However, the effects of individual drugs, and therefore their uses, are modified by their selectivity of action at different tissue sites and by baroreceptor reflexes.

Calcium Channel Blocker (Dihydropyridine derivative).
Pharmacology: Pharmacodynamics: Lacidipine is a specific and potent calcium antagonist, with a predominantly selectivity for calcium channels in the vascular smooth muscle.
Its main action is to dilate peripheral arterioles, reducing peripheral vascular resistance and lowering blood pressure.
Pharmacokinetics: 4 mg: Absorption: Lacidipine is rapidly but poorly absorbed from the gastrointestinal tract following oral dosing and undergoes extensive first-pass metabolism in the liver. Absolute bioavailability averages about 10%. Peak plasma concentrations are reached between 30 and 150 min.
Metabolism: There are four principal metabolites which possess little, if any pharmacodynamic activity. The drug is eliminated primarily by hepatic metabolism (involving P450 CYP3A4). There is no evidence that Lacidipine causes either induction or inhibition of hepatic enzymes.
Elimination: Approximately 70% of the administered dose is eliminated as metabolites in the faeces and the remainder as metabolites in the urine.
The average terminal half-life of lacidipine ranges from between 13 and 19 h at steady state.
6 mg: Lacidipine is rapidly but poorly absorbed from the gastrointestinal tract following oral administration and undergoes extensive first-pass metabolism; the bioavailability has been reported to be 2 to 9%, or 18.5% (range 4 to 52%) using a more sensitive assay method. It is more than 95% bound to plasma proteins. Lacidipine is eliminated by metabolism in the liver and metabolites are excreted mainly by the biliary route. About 70% of an oral dose is eliminated in the faeces, the remainder in the urine. The average steady-state terminal elimination half-life of lacidipine is 13 to 19 hours.

4 mg: As a treatment of hypertension either alone or in combination with other antihypertensive agents, e.g. beta-blockers, diuretics, and ACE inhibitors.
6 mg: Lacidipine is used in the treatment of hypertension.

4 mg: The initial dosage is 2 mg once daily. It should be taken at the same time each day, preferably in the morning, with or without food.
The treatment of hypertension should be adapted to the severity of the condition, and according to individual response.
The dose may be increased to 4 mg and if necessary to 6 mg after adequate time has been allowed for the full pharmacological effect to occur. In practice this should not be less than three to four weeks, unless the clinical condition requires a more rapid upward titration.
Treatment may be continued indefinitely.
Hepatic impairment: No dose modification is required in patients with mild or moderate hepatic impairment. Insufficient data are available to make a recommendation for patients with severe hepatic impairment.
Renal impairment: As Lacidipine is not excreted by the kidneys the dose does not require modification in patients with renal impairment.
Children: No experience has been gained with lacidipine in children.
Elderly: No dose modification is required.
6 mg: The usual initial dose is 2 mg daily by mouth increased if necessary after 3 to 4 weeks or more to 4 mg daily; a further increase in dose to 6 mg daily may be necessary in some patients or as prescribed by the physician.

There have been no recorded cases of Lacidipine overdosage. The most likely problem would be prolonged peripheral vasodilation associated with hypotension and tachycardia. Bradycardia or prolonged AV conduction could theoretically occur. There is no specific antidote. Standard general measures for monitoring cardiac function and appropriate supportive and therapeutic measures should be used.

Hypersensitivity to any component of the preparation.
As with other dihydropyridines, Lacidipine is contraindicated in patients with severe aortic stenosis.

4 mg: As with other calcium antagonists, lacidipine should be used with caution in patients with poor cardiac reserve.
As with other dihydropyridine calcium antagonists lacidipine should be used with care in patients with unstable angina pectoris.
Lacidipine should be used with caution in patients with impaired liver function because antihypertensive effect may be increased. There is no evidence that lacidipine impairs glucose tolerance or alters diabetic control.
6 mg: Lacidipine should be used with caution in patients with hypotension, in patients whose cardiac reserved are poor, and in those with heart failure since deterioration of heart failure has been noted. Lacidipine should not be used in cardiogenic shock, in patients who have recently suffered a myocardial infarction, or in acute unstable angina. Lacidipine should not be used to treat an angina attack in chronic stable angina. In patients with severe aortic stenosis, Lacidipine may increase the risk of developing heart failure. Sudden withdrawal of Lacidipine might be associated with an exacerbation of angina. The dose may be needed to be reduced in patients with hepatic impairment.
In specialized studies, Lacidipine has been shown not to affect the spontaneous function of the SA node or to cause prolonged conduction within the AV nodes. However, the theoretical potential for a calcium antagonist to affect the activity of the SA and AV nodes should be noted, and therefore Lacidipine (Lacibloc) should be used with caution in patients with pre-existing abnormalities in the activity of the SA and AV nodes. As has been reported with other dihydropyridine calcium channel antagonists, Lacidipine (Lacibloc) should be used with caution in patients with congenital or documented acquired QT prolongation.
Lacidipine (Lacibloc) should also be used with caution in patients treated concomitantly with medications known to prolong the QT interval such as, class I and III antiarrhythmics, tricyclic antidepressants, some antipsychotics, antibiotics (e.g. erythromycin) and some antihistamines (e.g. terfenadine).

There are no data on the safety of Lacidipine in human pregnancy.
Animal studies have shown no teratogenic effects or growth impairment.
Lacidipine should only be used in pregnancy when the potential benefits for the mother outweigh the possibility of adverse effects in the fetus or neonate.
The possibility that Lacidipine can cause relaxation of the uterine muscle at term should be considered.
Milk transfer studies in animals have shown that lacidipine (or its metabolites) are likely to be excreted into breast milk.
Lacidipine should only be used during lactation when the potential benefits for the mother outweigh the possibility of adverse effects in the foetus or neonate.

4 mg: Lacidipine is usually well tolerated. Some individuals may experience minor side-effects which are related to its known pharmacological action of peripheral vasodilation. Such effects are usually transient and usually disappear with continued administration of lacidipine at the same dosage.
Psychiatric disorders: Very rare: Depression.
Nervous system disorders: Common: Headache, dizziness.
Very rare: Tremor.
Cardiac disorders: Common: Palpitation, tachycardia.
Uncommon: Aggravation of underlying angina, syncope, hypotension.
As with other dihydropyridines aggravation of underlying angina has been reported in a small number of individuals, especially at the start of treatment. This is more likely in patients with symptomatic ischaemic heart disease.
Vascular disorders: Common: Flushing.
Gastrointestinal disorders: Common: Stomach discomfort, nausea.
Uncommon: Gingival hyperplasia.
Skin and subcutaneous tissue disorders: Common: Skin rash (including erythema and itching).
Rare: Angioedema, urticaria.
Renal and urinary disorder: Common: Polyuria.
General disorders and administration site conditions: Common: Asthenia, oedema.
Investigations: Common: Reversible increase in alkaline phosphatase (clinically significant increases are uncommon).
6 mg: The most common adverse effects of Lacidipine are associated with its vasolidator action and often diminish on continued therapy. They include dizziness, flushing, headache, hypotension, peripheral edema, tachycardia and palpitations.
Nausea and other gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain and mental depression have also occured. A paradoxical increase in ischaemic chest pain may occur at the start of the treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischaemia or transient blindness.
As with other dihydropyridines, aggravation of underlying angina has been reported in a small number of individuals, especially at the start of treatment. This is more likely in patients with symptomatic ischaemic heart disease.

Lacidipine is highly protein bound (more than 95%) to albumin and alpha-1-glycoprotein.
As with other dihydropyridines, Lacidipine should not be taken with grapefruit juice as bioavailability may be altered.
In clinical studies in patients with a renal transplant treated with cyclosporin, Lacidipine reversed the decrease in renal plasma flow and glomerular filtration rate induced by cyclosporin.
4 mg: Co-administration of lacidipine with other agents recognised to have a hypotensive effect, including anti-hypertensive agents, (e.g. diuretics, beta-blockers, or ACE inhibitors), may have an additive hypotensive effect. However, no problems have been identified in studies with common antihyperspecific interaction tensive agents (e.g. beta-blockers and diuretics) or with digoxin, tolbutamide or warfarin. The plasma level of lacidipine may be increased by simultaneous administration of cimetidine.
Lacidipine is known to be metabolised by cytochrome CYP3A4 and, therefore, significant inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lacidipine.
6 mg: Lacidipine may enhance the antihypertensive effects of other antihypertensive drugs such as beta blockers although the combination is generally well tolerated. Enhanced antihypertensive effects may also be seen with concomitant used of drugs such as aldesleukin and antipsychotics that cause hypotension. Lacidipine may modify insulin and glucose responses and therefore diabetic patients may need to adjust their antidiabetic treatment when receiving Lacidipine. Lacidipine is extensively metabolized in the liver by the cytochrome P-450 enzyme system, and interactions may occur other drugs, such as quinidine, sharing the same metabolic pathway, and with enzyme inducers, such as carbamazepine, phenytoin, and rifampicin, and enzyme inhibitors, such as cimetidine and erythromycin.

Store at temperatures not exceeding 30°C.
4 mg: Protect from light and moisture.

Calcium Antagonists

C08CA09 - lacidipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.

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