S-amlodipine

Uses

S-Amlodipine is calcium channel blocker and may be used alone or in combination with other antihypertensive agents for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
Pediatric Use: S-Amlodipine (1.25 to 2.5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years. The effect of S-Amlodipine on blood pressure in patients less than 6 years of age is not known.

Geriatric Use: Clinical studies of 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 amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required

S-amlodipine is also used to associated treatment for these conditions: High Blood Pressure (Hypertension)

How S-amlodipine works

S-amlodipine blocks the transmembrane influx of calcium through L-type calcium channels into the vascular and cardiac smooth muscles resulting in vasodilation and a subsequent decrease in blood pressure. S-amlodipine inhibits calcium influx in vascular smooth muscle to a greater degree than in cardiac muscle, leading to decreased peripheral vascular resistance and lowered blood pressure. In vitro studies have shown a negative inotropic effect but this is unlikely to be clinically relevant.

Dosage

S-amlodipine dosage

Adults: The usual initial antihypertensive oral dose of S-Amlodipine is 2.5 mg once daily, and the maximum dose is 5 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 1.25 mg once daily and this dose may be used when adding S-Amlodipine to other antihypertensive therapy. Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently.

Children: The effective antihypertensive oral dose in pediatric patients ages 6-17 years is 1.25 mg to 2.5 mg once daily. Doses in excess of 2.5 mg daily have not been studied in pediatric patients.

Side Effects

Most common adverse reactions to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1.0% are fatigue, nausea, abdominal pain and somnolence.

Toxicity

Patients experiencing an overdose may present with hypotension and reflex tachycardia. Treat overdose with cardiac and respiratory monitoring, frequent blood pressure measurement, elevation of extremities to treat hypotension, and possible administration of vasopressors. Hemodialysis is not expected to be useful as levamlodipine is highly protein bound.

Precaution

Hypotension: Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.

Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.

Patients with Hepatic Failure: Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.

Interaction

Impact of Other Drugs on Amlodipine-

• CYP3A Inhibitors: Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment 
• CYP3A Inducers: No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.
• Sildenafil: Monitor for hypotension when sildenafil is coadministered with amlodipine.

• Simvastatin: Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
• Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate

Food Interaction

• Take with or without food. Co-administration with food does not affect bioavailability.

S-amlodipine Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

S-amlodipine multivitamins interaction

[Moderate] Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium.

Calcium chloride has been used to manage acute severe verapamil toxicity.

Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

S-amlodipine Drug Interaction

Moderate: zolpidem, aspirin, aspirin / butalbital / caffeine, calcium carbonate, calcium / vitamin d, multivitamin with minerals, calcium / vitamin d, cyclobenzaprine, atorvastatin, metoprololUnknown: allopurinol, ubiquinone, venlafaxine, omega-3 polyunsaturated fatty acids, levothyroxine, levothyroxine, pregabalin, psyllium, acetylcysteine, semaglutide

Volume of Distribution

The volume of distribution of levamlodipine is similar to amlodipine. The volume of distribution of amlodipine is 21L/kg.

Elimination Route

Oral levamlodipine has a T_max of 6-12h and a bioavailability of 64-90%. Absorption of levamlodipine is not significantly affected by food.

20mg or oral s-amlodipine besylate reaches a C_max of 6.13±1.29ng/mL with a T_max of 8.4±3.6h and an AUC of 351±72h*ng/mL. 20mg or oral s-amlodipine maleate reaches a C_max of 5.07±1.09ng/mL with a T_max of 10.7±3.4h and an AUC of 330±88h*ng/mL.

Half Life

S-amlodipine has a half life of 30-50h.

Clearance

The oral clearance of S-amlodipine besylate is 6.9±1.6mL/min/kg and the oral clearance of S-amlodipine maleate is 7.3±2.1mL/min/kg.

Elimination Route

S-amlodipine is 60% eliminated in urine with 10% eliminated as the unmetabolized drug.

Pregnancy & Breastfeeding use

The limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy.

Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine on milk production.

Contraindication

S-Amlodipine is contraindicated in patients with known sensitivity to amlodipine.

Acute Overdose

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. Single oral doses of amlodipine equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m² basis) caused a marked peripheral vasodilation and hypotension.

If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.

Storage Condition

Store bottles at 20°C to 25°C.

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