Efnocar 10 Tablet

Efonidipine Hydrochloride Ethanolate Tablets 10 mg / 20 mg / 40 mg

EFNOCAR-10

Each film coated tablet contains:

Efonidipine Hydrochloride Ethanolate 10 mg

Excipients q.s.

Colour: Titanium Dioxide IP

EFNOCAR-20

Each film coated tablet contains:

Efonidipine Hydrochloride Ethanolate 20 mg

Excipients q.s.

Colour: Titanium Dioxide IP

EFNOCAR-40

Each film coated tablet contains:

Efonidipine Hydrochloride Ethanolate 40 mg

Excipients q.s.

Colour: Titanium Dioxide IP

Film coated tablet

10/ 20/40 mg

4.1 Therapeutic Indication

Efonidipine is indicated for the management of

• Essential hypertension and renal parenchymal hypertension
• Angina

4.2 Posology and method of administration

Adults

• Essential hypertension and renal parenchymal hypertension: 20-40 mg orally once daily. A dose of up to 80 mg/day has been reported to be safe and effective in clinical trials.
• Angina: 40 mg/day.

Elderly

Efonidipine should be started with a low dose (20mg/day) and the patient's condition should be monitored. The dose should be halved in case the patient is intolerant to the higher dose.

In Children

Efonidipine is not recommended in infants and children as safety is not established in this group of patients.

4.3 Contraindications

• In patients with known hypersensitivity to Efonidipine or any other component of the formulation
• In pregnant women

4.4 Special warnings and precautions for use

• Should be administered with caution in patients with hepatic impairment.
• Should be administered with caution in patients with low BP and/or sinus node dysfunction.
• The drug should be withdrawn gradually to prevent rebound hypertension or worsening of angina.
• Administration of the drug may cause hypotension. Under such circumstances appropriate measures should be taken to either reduce the dose or withdraw the drug.
• Should not be taken with grapefruit juice as there may be excessive lowering of blood pressure.
• Dizziness may occur while taking antihypertensive agents. Hence, working on aerial platform, working with dangerous machinery and/or driving should be avoided.
• To be sold by retail on the prescription of Cardiologist / Nephrologist / Endocrinologist and Specialist in General / Internal medicine / Critical Care medicine only.

4.5 Drugs interactions

Concomitant administration of other antihypertensive agent/s may enhance the antihypertensive effect of efonidipine.

• Administration of calcium channel blockers (CCBs) with Cimetidine may cause elevated levels of CCBs.
• Increased levels of CCBs observed when taken concomitantly with grapefruit juice which may result in excessive lowering of blood pressure.
• Efonidipine when taken along with Tacrolimus may cause increased blood levels of Tacrolimus.

4.6 Use in special populations

Pregnancy

Efonidipine should not be administered in pregnant women.

Nursing Mothers

Efonidipine should not be administered in lactating women.

4.7 Effects on ability to drive and use machines

If patients taking Efonidipine suffer from dizziness, headache, fatigue or nausea the ability to react may be impaired. Caution is recommended especially at the start of treatment.

4.8 Undesirable effects

The common side effects are hot flushes, palpitations, facial flushing and headache. In addition, elevation in serum total cholesterol, ALT (SGPT), AST (SGOT) and BUN may occur.

Tabulated list of adverse reactions

,!--

Reporting of suspected adverse reactions

-->

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. Healthcare professionals are asked to report any suspected adverse reactions via email to:medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

4.9 Overdose

In humans, experience with intentional overdose is limited. The stomach should be emptied by aspiration and gastric lavage if the patient reports immediately or up to two hours after overdosage.

Clinically significant hypotension due to Efonidipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade.

5.1 Mechanism of Action

Efonidipine, a new generation dihydropyridine (DHP) calcium channel blocker, inhibits both L-type and T-type calcium channels.

5.2 Pharmacodynamic properties

• Efonidipine exhibits antihypertensive effect through vasodilatation by blocking L-type and T-type calcium channels.
• Efonidipine has a negative chronotropic effect. Working on sino atrial node cells by inhibiting T-type calcium channel activation, Efonidipine prolongs the late phase-4 depolarization of the sino atrial node action potential and suppresses an elevated HR. The negative chronotropic effect of Efonidipine decreases heart rate, myocardial oxygen demand and increases coronary blood flow.
• Efonidipine increases coronary blood flow by blocking L & T-type calcium channels and attenuates myocardial ischaemia.
• By reducing synthesis and secretion of aldosterone, Efonidipine prevents hypertrophy and remodeling of cardiac myocytes.
• Efonidipine increases glomerular filtration rate without increasing intra-glomerular pressure and filtration fraction. This prevents hypertension induced renal damage.
• Efonidipine prevents Rho-kinase and NF-kB induced renal parenchymal fibrosis and provides long term renal protection.
• Efonidipine suppresses renin secretion from the Juxta Glomerular apparatus in the kidneys. •Efonidipine enhances sodium excretion from the kidneys by suppressing aldosterone synthesis and secretion from the adrenal glands. Aldosterone induced renal parenchymal fibrosis is suppressed by Efonidipine. •Efonidipine prevents NF-kB induced hypertrophy and inflammation in the renal vasculature and protects the kidneys.
• Efonidipine protects against endothelial dysfunction due to its anti-oxidant activity and by restoring nitric oxide bioavailability.
• Efonidipine has anti-atherogenic activity and protects the blood vessels from atherosclerosis.
• Efonidipine lowers blood pressure in cerebral resistance vessels and prevents hypertension induced brain damage.

5.3 Pharmacokinetic properties

Absorption

Peak plasma concentration is achieved in about 1.5 to 3.67 hours after administration. The bioavailability of Efonidipine is ~25% and half-life is approximately 4 hours.

Efonidipine 40mg when administered to healthy volunteers under fasting conditions shows the following pharmacokinetic profile:

The dissociation constant of Efonidipine from dihydropyridine receptors is very low (0.0042/min/nM), signifying very slow dissociation from the receptors. This explains the long duration of action of Efonidipine.

Metabolism

Efonidipine is primarily metabolized in the liver. The important metabolites are N-dephenylated Efonidipine (DPH), deaminated Efonidipine (AL) and N-debenzylated Efonidipine (DBZ). DBZ and DPH exhibit activity as calcium antagonists. The vasodilating properties of DBZ and DPH were about two-thirds and one-third respectively than that of the parent compound. Results suggest that the majority of the pharmacological effect after oral dosing of Efonidipine hydrochloride in man is due to unchanged compound and its metabolites make a small contribution to the pharmacological effect.

Elimination

Biliary route is the main pathway of excretion. No significant amount of unchanged drug is excreted in urine. In the urine collected for 24 h after an oral dosing, 1.1% of the dose was excreted as deaminated Efonidipine, and 0.5% as a pyridine analogue of deaminated Efonidipine.

6.1 Animal Toxicology or Pharmacology

The acute toxicology of efonidipine was studied in male and female mice, rats, and dogs following oral or intravenous administration. The intravenous LD, values in male mice and rats were 77 and 51 mg/kg, respectively. The oral LD, values for efonidipine in mice, rats, and dogs were higher than 1,500 mag. The signs of toxicity observed in mice and rats were depression of spontaneous movement, hypothermia, sedation, piloerection, lying, gasping, and clonic convulsion. The dogs developed mild diarrhea, soft stools, or a temporary decrease in food consumption.

A 13-week oral subacute toxicity study of efonidipine was performed in male or female rats and dogs. Increases in water consumption and urine volume were observed in male and female rats receiving efonidipine at 300 mg/kg/day. Urinalysis revealed a high concentration of Na+ and C1- in the rats receiving 100 or 300 mg/kg/day. Organ weight measurement revealed an increase in liver and heart weight in male animals receiving 10 mg/kg/day or more and in female animals receiving 30 mg/kg/day or more.

Thus, in this study, the noneffective dose level was 3 mg/kg/day in rats. The effects observed at 300 or 100 mg/kg/day in groups of male or female dogs included reversible hyperemia of the sclera. Pathological examination revealed a dose-induced increase in the absolute and relative heart weight in female dogs treated with the drug at 100 mg/kg/day or more. Thus, the maximum noneffective dose of efonidipine in dogs of either sex was estimated to be around 30 mg/kg/day.

An oral chronic toxicity study of efonidipine was carried out in rats and dogs. Efonidipine was administered to rats at a daily dose of 1.5, 7, or 30 mg/kg for one year.

Organ weight measurement revealed an increase or a tendency of increase in heart weight in male or female rats receiving 30 mg/kg/day. A decreased thyroid weight in the males and an elevated liver weight in the females were found in the 30 mg/kg/day group.

Therefore, the noneffective estimated oral dose of efonidipine in rats was 7 mg/kg/day. Efonidipine in a gelatin capsule containing 2.0, 6.5, or 20 mg/kg/day was administered to dogs once daily for one year. The estimated effective dose was ca 20 mg/kg/day and the noneffective dose was ca 6.5 mg/kg/day

Efonidipine is a novel dihydropyridine calcium channel blocker having anti-hypertensive and anti-anginal properties.

Chemical name: (±) -2 - [benzyl (phenyl) amino] ethyl 1, 4-dihydro-2 ,6-dimethyl- 5-(5,5-dimethyl-2-oxo-1 ,3,2-dioxaphosphorinan-2-yl) -4 - (3-nitrophenyl) -3-pyridinecarboxylate hydrochloride ethanol.

Molecular formula: C34H38 N3O7P • HCl •C2H6O

Molecular mass: 714.18 g/mol

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on pack

8.3 Packaging information

10 Blister strips of 10 tablets each

8.4 Storage and handing instructions

• Store below 25°C. Protected from light & moisture.
• Keep out of reach of children.

Efnocar is a type of medicine known as a calcium channel blocker (CCB). It is used to treat high blood pressure (hypertension) and a type of chest pain called angina. It can be used by itself or with other medicines to treat these conditions. Do not use Efnocar if you are allergic to efonidipine (the active ingredient in Efnocar), or to the inactive ingredients.

Tell your doctor about any prescription and non-prescription medicines you are taking, including natural or herbal remedies. Tell your doctor if you:

• ever had heart disease
• ever had liver problems
• are pregnant, or plan to become pregnant.
• are breast-feeding. Do not breast-feed while taking Efnocar.

You can stop breast-feeding or take a different medicine.

It may be easier to take your dose if you do it at the same time every day, such as with breakfast or dinner, or at bedtime.

While you are taking Efnocar do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor.

09/10/2024