S-Amlodipine

S-Amlodipine is an antihypertensive agent belonging to the Calcium Channel Blocker class.

S-Amlodipine is a Calcium Channel Blocker used to treat Hypertension and Angina.

S-Amlodipine is absorbed slowly and almost entirely from the gastrointestinal tract. Peak plasma concentrations are achieved 6-12 hours after oral administration. The estimated bioavailability of S-Amlodipine is 64-90%. Steady-state plasma S-Amlodipine levels are achieved after 7-8 days of consecutive daily dosing. Absorption is not affected by food. The plasma protein binding of S-Amlodipine is approximately 93%. S-Amlodipine is heavily (approximately 90%) converted to inactive metabolites via hepatic breakdown, with 10% of the parent compound and 60% of the metabolites found excreted in the urine.

S-Amlodipine shows common side effects swelling of the hands, feet, ankles, or lower legs, headache, upset stomach, nausea, stomach pain, dizziness or light-headedness, drowsiness, excessive tiredness, flushing, etc.

S-Amlodipine is available in the form of Oral Tablets, Oral solutions, and Oral Suspension.

S-Amlodipine is available in India, China, Korea, Russia, Ukraine.

S-Amlodipine, a dihydropyridine Ca channel blocker, is the pharmacologically active antihypertensive isomer of Amlodipine. It reduces peripheral vascular resistance and blood pressure by directly inhibiting Ca transmembrane ion influx into vascular smooth muscles and, to a lesser extent, into cardiac muscle cells.

The Duration of Action for S-Amlodipine in the body is 30-50h.

The Tmax was found within 6-12 hours following the administration of S-Amlodipine.

S-Amlodipine is available in the form of an Oral Tablet.

S-Amlodipine tablet taken orally, Usually once a day with or without food.

S-Amlodipine is a medicine that is used in the treatment of hypertension (high blood pressure) and angina pectoris (chest pain due to insufficient blood flow to the heart). This medicine works by relaxing the blood vessels, which makes the blood flow easily, thus lowering the blood pressure. This will reduce your risk of heart attack (blockage of heart muscles due to the formation of plaques) or a stroke (brain damage that occurs when the blood flow to a part of the brain is reduced or interrupted) by making it easier for your heart to pump blood around your body.

S-Amlodipine is a Calcium Channel Blocker used to treat Hypertension and Angina.

S-Amlodipine is approved for use in the following clinical indications

• Hypertension

Hypertension (high blood pressure) can cause damage to the blood vessels that leads to heart problems, kidney problems, stroke, and medical conditions. S-Amlodipine is used in the treatment of hypertension. It reduces the increased blood pressure and improves blood flow.

• Angina pectoris

Angina pectoris is a heart condition characterized by chest pain. It occurs when the heart muscle does not get enough blood as required. The symptoms include squeezing, pressure, heaviness, tightness, or pain in the chest. S-Amlodipine is used in the prevention of angina pectoris.

Hypertension

Indicated as monotherapy or in combination with other antihypertensive agents for hypertension

Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarction.

Initial: 2.5 mg PO qDay; may increase to up to 5 mg PO qDay

Small, fragile, or elderly patients, or patients with hepatic insufficiency, may be started on 1.25 mg qDay, and this dose may be used when added to other antihypertensive therapy

Adjust dosage according to blood pressure goals

In general, wait 7-14 days between titration steps; titrate more rapidly, if clinically warranted, provided the patient is assessed frequently

S-Amlodipine is available in various strengths as 1.25mg, 2.5mg, 5mg.

S-Amlodipine is available in the form of Oral Tablet.

• Dosage Adjustment in Hepatic impairment Patient

Hypertension:

Initial: 1.25 mg once daily; titrate slowly in patients with severe hepatic impairment.

Avoid grapefruit juice while taking S-Amlodipine .

S-Amlodipine is contraindicated in patients with known sensitivity towards Amlodipine.

Concerns related to adverse effects:

• Hypotension: Symptomatic hypotension can occur; acute hypotension upon initiation is unlikely due to the gradual onset of action. BP must be lowered at a rate appropriate for the patient's clinical condition.

Disease-related concerns:

• Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may cause hypotension or reduce coronary perfusion, resulting in ischemia.

• Heart failure: Calcium channel blockers should be avoided whenever possible in patients with heart failure with reduced ejection fraction (AHA/ACC/HFSA [Heidenreich 2022]).

• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose; titrate slowly in patients with severe hepatic impairment.

It is not known whether S-Amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while S-Amlodipine is administered.

Pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Avoid grapefruit juice while taking S-Amlodipine .

Common Adverse effects

• Peripheral edema, Flushing, palpitations, Pruritus, skin rash, Abdominal pain, nausea, Male sexual disorder, Asthenia, dizziness, drowsiness, Muscle cramps, Dyspnea.

Rare Adverse effects

• Peripheral ischemia, sinus tachycardia, syncope, vasculitis, Diaphoresis, erythema multiforme, Hot flash, hyperglycemia, weight gain, weight loss, Anorexia, constipation, dysphagia, flatulence, gingival hyperplasia, pancreatitis, vomiting, xerostomia, Difficulty in micturition, female sexual disorder, nocturia, urinary frequency, Leukopenia, purpuric disease, thrombocytopenia, Angioedema, hypersensitivity reaction, Abnormal dreams, anxiety, depersonalization, depression, hypoesthesia, insomnia, malaise, pain, paresthesia, peripheral neuropathy, rigors, tremor, vertigo, Arthralgia, back pain, myalgia, osteoarthritis, Conjunctivitis, diplopia, eye pain, Tinnitus, Epistaxis.

May increase serum concentrations with moderate and strong CYP3A4 inhibitors. It may increase the serum levels of simvastatin, lovastatin, and immunosuppressants (e.g. ciclosporin, tacrolimus).

The common side effects of S-Amlodipine include the following

Common

● Swelling of the hands, feet, ankles, or lower legs, headache, upset stomach, nausea, stomach pain, dizziness or light-headedness, drowsiness, excessive tiredness, flushing.

Rare

● More frequent or more severe chest pain, rapid, pounding, or irregular heartbeat, fainting.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. S-Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with S-Amlodipine maleate at doses up to 10 mg S-Amlodipine /kg/day (respectively, 8 times and 23 times the maximum recommended human dose of 10 mg on a mg/m² basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving S-Amlodipine maleate at a dose equivalent to 10 mg S-Amlodipine /kg/day for 14 days before mating and throughout mating and gestation. S-Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose.

• Nursing Mothers

It is not known whether S-Amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while S-Amlodipine is administered.

• Pediatric Use

Effect of S-Amlodipine on blood pressure in patients less than 6 years of age is not known.

• Geriatric Use

Clinical studies of S-Amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of S-Amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required.

Symptoms:

May be related to racemic Amlodipine including excessive peripheral vasodilation, marked hypotension, reflex tachycardia.

Management:

In case of large overdose, monitor cardiac and respiratory function and perform gastric lavage. Monitor blood pressure. For hypotension, initiate CV support including elevation of extremities and administration of fluids. Consider administration of vasopressors (e.g. phenylephrine) in case hypotension remains unresponsive.

Pharmacodynamic

S-Amlodipine inhibits L-type calcium channels in vascular smooth muscle, reducing peripheral vascular resistance and blood pressure. It is given once daily in doses of 1.25-2.5mg in children and 2.5-5mg in adults. Patients should be counselled regarding the risk of symptomatic hypotension, worsening angina, and myocardial infarction.

Pharmacokinetics

• Absorption: Bioavailability: 64-90%. Time to peak plasma concentration: 6-12 hours.
• Distribution: Plasma protein binding: Approx 93%.
• Metabolism: Extensively metabolised in the liver (approx 90%) to form inactive metabolites.
• Excretion: Via urine (10% as unchanged drug, 60% as metabolites). Elimination half-life: Approx 14.62-68.88 hours.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf
• https://www.uptodate.com/contents/S-Amlodipine -drug-information
• https://go.drugbank.com/drugs/DB00381
• https://www.drugs.com/S-Amlodipine .html
• https://medlineplus.gov/druginfo/meds/a692044.html
• https://reference.medscape.com/drug/katerzia-norvasc-S-Amlodipine -342372
• https://www.rxlist.com/consumer_S-Amlodipine _norvasc/drugs-condition.htm