Efonta T

Efonta T Uses, Dosage, Side Effects, Food Interaction and all others data.

Efonidipine is a calcium channel blocker of the dihydropyridine class, commercialized by Shionogi & Co. (Japan). Initially, it was marketed in 1995 under the trade name, Landel. The drug has been shown to block T-type in addition to L-type calcium channels . It has also been studied in atherosclerosis and acute renal failure . This drug is also known as NZ-105, and several studies have been done on its pharmacokinetics in animals .

Dihydropyridines (DHPs), act mainly on L-type calcium channels, essentially causing reflex tachycardia, which negatively affects cardiac function. This leads to a decrease in blood pressure and an increase in heart rate. Efonidipine acts on both L-type and T-type calcium channels. Because inhibition of T-type calcium channels in the sinoatrial (SA node) node attenuate reflex tachycardia, this drug favorably affects cardiac pacing. The effect of efonidipine on heart rate deserves special recognition with regard to reflex tachycardia, due to its unique effects in relation to other drugs in its class .

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.

There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has a much greater affinity ( > 3,000 fold) for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure.

Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1 receptor subtype. It has the highest affinity for the AT1 receptor among commercially available ARBS and has minimal affinity for the AT2 receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.

Efonta T
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Efonta T
Generic	Efonidipine + Telmisartan
Weight	20mg
Type	Tablet
Therapeutic Class
Manufacturer	Ajanta Pharma Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

For the treatment of hypertension.

Telmisartan is an angiotensin II receptor blocker (ARB) used for treatment of hypertension and Cardiovascular (CV) risk reduction in patients who are used for ACE inhibitors.

Efonta T is also used to associated treatment for these conditions: Cardiovascular Events, Diabetic Nephropathy, Heart Failure, High Blood Pressure (Hypertension)

How Efonta T works

This drug inhibits the L-type and T-type calcium channels, thereby leading to vasodilation and decreased automaticity of the heart. Efonidipine exerts negative chronotropic effects, decreasing heart rate. Acting on SA node cells by inhibiting T-type calcium channel activity, Efonidipine prolongs the late phase-4 depolarization of the sinoatrial node action potential, decreasing heart rate. This is associated with decreased myocardial oxygen demand and increases of blood flow to the coronary arteries and thereby attenuates myocardial ischemia. Efonidipine increases glomerular filtration rate (GFR) without increasing intra-glomerular pressure and filtration fraction . This increase leads to the prevention of renal damage that is normally associated with hypertension.

Efonidipine increases the rate of renal sodium excretion via the suppression of aldosterone synthesis and aldosterone secretion from the adrenal glands. Aldosterone-induced renal parenchymal fibrosis is said to be suppressed by efonidipine .

L-type calcium channel blockers, such as efonidipine, preferentially dilate afferent arterioles in the kidney, whereas both L-/T-type and L-/N-type calcium channel blockers potently dilate both afferent and efferent arterioles. The distinct actions of calcium channel blockers on the renal microcirculation are demonstrated by changes in glomerular capillary pressure and subsequent renal injury: L-type calcium channel blockers favor an increase in glomerular capillary pressure, whereas L-/T-type and L-/N-type CCBs alleviate glomerular hypertension. This supports the theory that L-Type/T-type calcium channel blockers may be of benefit in renal hypertension . Efonidipine is a long-acting medication due to a low dissociation constant .

Recent studies suggest that efonidipine reduces plasma aldosterone levels in patients on regular hemodialysis, which is of additional benefit to the cardiovascular protection by antihypertensive therapy with efonidipine in patients with end-stage renal disease .

Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT₁-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Studies also suggest that telmisartan is a partial agonist of PPARγ, which is an established target for antidiabetic drugs. This suggests that telmisartan can improve carbohydrate and lipid metabolism, as well as control insulin resistance without causing the side effects that are associated with full PPARγ activators.

Dosage

Efonta T dosage

Hypertension: Dosage must be individualized. The usual starting dose of Telmisartan tablets is 40 mg once a day. Blood pressure response is dose-related over the range of 20 to 80 mg

Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. When additional blood pressure reduction beyond that achieved with 80 mg Telmisartan is required, adiuretic may be added.

No initial dosage adjustment is necessary for elderly patients or patients with renal impairment, including those on hemodialysis. Patients ondialysismay develop orthostatic hypotension; their blood pressure should be closely monitored.

Cardiovascular Risk Reduction: The recommended dose of Telmisartan tablets is 80 mg once a day and can be administered with or without food. It is not known whether doses lower than 80 mg of telmisartan are effective in reducing the risk of cardiovascular morbidity and mortality.

When initiating Telmisartan therapy for cardiovascular risk reduction, monitoring of blood pressure is recommended, and if appropriate, adjustment of medications that lower blood pressure may be necessary.

Telmisartan tablets may be administered with other antihypertensive agents with or without food.

Side Effects

Most people tolerate telmisartan well. Side effects are usually minor and either require no treatment or can easily be treated by physician. The most common telmisartan side effects include-Upper respiratory infection such as the common cold or flu up to 7 percent of people, Back pain up to 3 percent of people, Diarrhea up to 3 percent of people, Inflammation of the sinuses up to 3 percent of people.

Toxicity

Ld50: >5 g/kg in rats, orally . Some common adverse effects include hot flashes, flushing of the face, and headache. Elevation in serum total cholesterol, ALT (SGPT), AST (SGOT) and BUN may also occur. Frequent urination, pedal edema, increased triglycerides have been found to occur in less than 0.1% of patients .

Intravenous LD₅₀ in rats is 150-200 mg/kg in males and 200 to 250 mg/kg in females. Acute oral toxicity is low: no deaths and no changes occurred in rats or dogs at 2000 mg/kg, the highest dose tested. Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.

Precaution

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Telmisartan may potentially cause extreme low blood pressure or a decrease in kidney function. Hyperkalemia may occur in patients on ARBs, particularly in patients with advanced renal impairment, heart failure, on renal replacement therapy or on potassium supplements, potassium-sparing diuretics, potassium containing salt substitutes or other drugs that increase potassium levels.

Interaction

When certain medicines are taken together, there is a possibility of developing drug interactions. With Telmisartan, drugs such as potassium supplements or potassium-sparing diuretics may cause an interaction. When Telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in through concentration (20%) where observed. Therefore, monitor digoxin levels when initiating, adjusting and discontinuing Telmisartan for the purpose of keeping the digoxin level within the therapeutic range. NSAID use may lead to increase risk of renal impairment and loss of antihypertensive effect. Monitor renal function periodically in patients receiving Telmisartan and NSAID therapy.

Volume of Distribution

500 L

Elimination Route

The metabolism of efonidipine was studied in rats. The absorption ratio of radioactivity estimated from the sum of biliary and urinary excretions was found to be approximately 62% . The radioactivity was high in the gastrointestinal tract and liver, followed by the adrenal glands , suggesting high rates of metabolism in these regions.

The unchanged drug in the plasma accounted for 47.7% of radioactivity at 2hr after ingestion, demonstrating a lower first-pass effect in comparison with other drugs in the same class. In plasma, major metabolites of NZ-105 were: N-debenzylated compound (DBZ), N-dephenylated compound (DPH), oxidative deaminated compound (AL), AL-corresponding pyridine compound (ALP), unknown metabolite M-1 and M-25. NZ-105 was metabolized by N-debenzylation, N-dephenylation, oxidative deamination, ester hydrolysis and oxidation of 1, 4-dihydropyridine ring to its corresponding pyridine .

Absolute bioavailability depends on dosage. Food slightly decreases the bioavailability (a decrease of about 6% is seen when the 40-mg dose is administered with food).

Half Life

The peak plasma concentration is attained at approximately 1.5 to 3.67 hours after ingestion. The half-life is measured to be about 4 hours .

Bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours.

Clearance

>800 mL/min

Elimination Route

Efonidipine is also referred to as NZ-105 and has been found to be mainly eliminated by the biliary system .

Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).

Pregnancy & Breastfeeding use

Telmisartan has been assigned to pregnancy categories C (use during first trimester) by the FDA. When pregnancy is detected or expected, Telmisartan should be discontinued as soon as possible. The use of drugs that act directly on the RAA system during the second and third trimesters has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. There are no data on the excretion of Telmisartan into human milk, due to the potential for serious adverse effects in the nursing infant, a decision should be made to discontinue nursing or discontinue the drug.

Contraindication

Telmisartan is contraindicated in conditions like Pregnancy, Adjunct in treatment of opioid dependence, Dry or painful cough. Telmisartan is also contraindicated in patients with known hypersensitivity to telmisartan.

Special Warning

Renal Impairment: Severe impairment or on haemodialysis: Initially, 20 mg once daily.

Hepatic Impairment: Mild to moderate: Max: 40 mg once daily. Severe: Contraindicated.

Acute Overdose

Symptoms: Hypotension, bradycardia, tachycardia, dizziness, acute renal failure and elevated serum creatinine.

Management: Supportive and symptomatic treatment. Induction of emesis and/or gastric lavage. Activated charcoal may be useful. Salt and volume replacement should be given immediately if hypotension occurs and place patient in supine position.