Amlodipine

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

Amlodipine is a Dihydropyridine Calcium antagonist that inhibits the transmembrane influx of Calcium ions into cardiac and vascular smooth muscle. It has greater affinity towards vascular smooth muscle than on cardiac muscle. Amlodipine is peripheral vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and thereby reduces blood pressure. Amlodipine reduces tone, decreases coronary vasoreactivity and lowers cardiac oxygen demand by reducing after load.

General pharmacodynamic effects

Amlodipine has a strong affinity for cell membranes, modulating calcium influx by inhibiting selected membrane calcium channels. This drug's unique binding properties allow for its long-acting action and less frequent dosing regimen , .

Hemodynamic effects

Trade Name Amlodipine
Availability Prescription only
Generic Amlodipine
Amlodipine Other Names Amlodipine, Amlodipino, Amlodipinum
Related Drugs aspirin, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, propranolol, Xarelto, spironolactone
Weight 5mg, 10mg,
Type Tablet Medlife Pure Generics, + Atenolol Tablet Medlife Pure Generics, Tablet, Oral Tablet, Oral, Caplet
Formula C20H25ClN2O5
Weight Average: 408.876
Monoisotopic: 408.145199627
Protein binding

About 98% , .

Groups Approved
Therapeutic Class Calcium-channel blockers
Manufacturer Medlife, Tulip Lab Pvt Ltd, Essential Drugs Company Ltd, Kent Pharma Uk Ltd, Hexpharm, Bernofarm, Soho, Mutifa, Pharos, Ifars, Puspa Pharma, Indofarma, Phapros, Medikon, Harbat Farma, Errita Pharma, Sejahtera Lestari Farma, Tempo Scan Pasific, Pertiwi Agung, Yarindo, Otto, Erlimpex, Novell, Pratapa Nirmala, Nufarindo, Rama Emerald, First Medifarma, Dexa Medica, Promedrahardjo, Imedco Farma, Zenith, Pfizer, Mulia Farma Suci, Infion, Pyridam Farma, Futamed, Tropica Mas, Sampharindo Perdana, Rama Emerald Multi Sukses, Kimia Farma, Mahakam Beta Farma, Berlico Mulia Farma, Guardian Pharmatama, Interbat, Combiphar, Nulab, Imfarmind, Scott Edil Pharam Ltd, Baroque Pharmaceuticals Pvt Ltd, Celogen Generics Pvt Ltd, Ratnamani Healthcare Pvt Ltd, Alpa Laboratories Pvt Ltd, Ocean Healthcare Pvt Limited, Cambridge Health Care Limited
Available Country India, Bangladesh, United Kingdom, United States, Netherlands, Indonesia, Nigeria
Last Updated: September 19, 2023 at 7:00 am
Amlodipine
Amlodipine

Uses

Patients with mild to moderate hypertension (alone or in combination with other antihypertensives).

The treatment of chronic stable and vasospastic angina.

Raynaud\'s disease.

Amlodipine is also used to associated treatment for these conditions: Anginal Pain, Cardiovascular Events, Chronic Stable Angina Pectoris, Coronary Artery Disease (CAD), High Blood Pressure (Hypertension), Homozygous Familial Hypercholesterolemia, Hypertension,Essential, Mixed Dyslipidemias, Primary Hypercholesterolemia, Vasospastic Angina

How Amlodipine works

Mechanism of action on blood pressure

Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells . Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure .

Mechanism of action in angina

The exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:

Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements .

Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking .

Dosage

Amlodipine dosage

For treatment of both hypertension and angina pectoris, the usual initial dose is 5 mg once daily. If the desired therapeutic effect cannot be achieved within 2-4 weeks, the dose may be increased to a maximum dose of 10 mg once daily. Amlodipine 10 mg once daily provides symptomatic improvement in patients with Raynaud's disease.

Use in children: Use of Amlodipine in children (under 12 years of age) is not recommended.

Side Effects

Amlodipine is generally well tolerated. The most commonly observed side effects are headache, peripheral oedema, palpitations, flushing, dizziness, nausea, abdominal pain.

Toxicity

Acute oral toxicity (LD50): 37 mg/kg (mouse) .

Overdose

An overdose of amlodipine could result in a high degree of peripheral vasodilatation with a possibility of reflex tachycardia. Significant and prolonged hypotension leading to shock and fatal outcomes have been reported .

Carcinogenesis, mutagenesis, impairment of fertility

Rats and mice treated with amlodipine maleate in the diet on a long-term basis for up to 2 years demonstrated no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was comparable to the maximum recommended human dose of 10 mg amlodipine per day. For the rat, the highest dose was measured to be about twice the maximum recommended human dose .

Mutagenicity studies using amlodipine maleate showed no drug-related gene or chromosomal effects .

There was no impact on the fertility of rats given oral amlodipine maleate (males for 64 days and females for 14 days before mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose) .

Use in pregnancy

The safety of amlodipine in human pregnancy or lactation has not been proven. Amlodipine is therefore considered a pregnancy category C drug . Use amlodipine only if the potential benefit justifies the potential risk .

Use in nursing

Discontinue when administering amlodipine .

Precaution

Hypotension: Since the vasodilUse in renal failure

Although Amlodipine is excreted primarily via kidney, mild renal impairment does not appear to have an effect on the plasma concentrations. Severe renal impairment may however require a dosage reduction. Amlodipine is not dialyzable.

Use in patients with impaired hepatic function

Amlodipine half-life is prolonged in patient with impaired hepatic function. Amlodipine should therefore be administered at lower (5mg) initial dose in these patients.

Use in heart failure

An increased number of pulmonary oedema has been reported.atation induced by Amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration of Amlodipine. Nonetheless, caution should be exercised when administering the drug with any other peripheral vasodilator particularly in patients with severe aortic stenosis.

Cardiac failure: Patients with heart failure should be treated with caution. Calcium channel blockers, including Amlodipine, should be usedwith caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.

Beta blocker withdrawal: Amlodipine gives no protection against the danger of abrupt beta blocker withdrawal; any such withdrawal should be gradualreduction of the dose of beta blocker.

Hepatic failure: The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function. Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Slow dose titration and careful monitoring may be required in patients with severe hepatic impairment.

Interaction

Use of Amlodipine together with thiazide diuretics or angiotensin-converting-enzyme inhibitors in the treatment of hypertension is additive. There are no hazardous interaction of Amlodipine with Digoxin, Cimetidine, Warfarin and food.

Food Interaction

  • Avoid grapefruit products.
  • Avoid natural licorice.
  • Take with or without food. The absorption is unaffected by food.

[Minor] The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine.

The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

Data have been conflicting and the clinical significance is unknown.

Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

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.

Volume of Distribution

21 L/kg , .

Elimination Route

Amlodipine absorbed slowly and almost completely from the gastrointestinal tract. Peak plasma concentrations are achieved 6-12 hours after oral administration. The estimated bioavailability of amlodipine is 64-90%. Steady-state plasma amlodipine levels are achieved after 7-8 days of consecutive daily dosing. Absorption is not affected by food .

Half Life

The terminal elimination half-life of about 30–50 hours .

Plasma elimination half-life is 56 hours in patients with impaired hepatic function, titrate slowly when administering this drug to patients with severe hepatic impairment .

Clearance

Total body clearance (CL) has been calculated as 7 ± 1.3 ml/min/kg (0.42 ± 0.078 L/ h/kg) in healthy volunteers , .

Elderly patients show a reduced clearance of amlodipine with an AUC (area under the curve) increase of about 40–60%, and a lower initial dose may be required .

Elimination Route

Elimination from the plasma occurs in a biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7-8 days of consecutive daily dosing . Amlodipine is 10% excreted as unchanged drug in the urine. Amlodipine can be initiated at normal doses in patients diagnosed with renal failure , .

Pregnancy & Breastfeeding use

Pregnancy: Safety in pregnancy has not been established.

Lactation: It is not known whether Amlodipine is excreted in breast milk. It is advised to stop breastfeeding during treatment with Amlodipine.

Contraindication

Amlodipine is contraindicated in patients with-

  • Hypersensitivity to amlodipine, dihydropyridine derivatives or any of the excipients
  • Shock (including cardiogenic shock)
  • Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis)
  • Unstable angina
  • Hemodynamically unstable heart failure after acute myocardial infarction (during the first 28 days)
  • Severe hypotension

Special Warning

Children with hypertension from 6 years to 17 years of age: 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in pediatric patients.

Children under 6 years old:  The effect of amlodipine on blood pressure in patients less than 6 years of age is not known.

Elderly: Amlodipine used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.

Renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.

Hepatic impairment: Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautions and should start at the lower end of the dosing range. The pharmacokinetics of Amlodipine have not been studied in severe hepatic impairment. Amlodipine should be initiated at the lowest dose (2.5 mg once daily) and titrated slowly in patients with severe hepatic impairment.

Acute Overdose

There is no well documented experience with Amlodipine overdosage. In case of clinically significant hypotension due to Amlodipine over dosage, calls for active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output. Since Amlodipine is highly protein-bound, dialysis is unlikely to be of benefit.

Storage Condition

Keep out of the reach of children. Store below 30° C. Keep in the original package in a cool & dry place in order to protect from light and moisture.

Innovators Monograph

You find simplified version here Amlodipine

Amlodipine contains Amlodipine see full prescribing information from innovator Amlodipine Monograph, Amlodipine MSDS, Amlodipine FDA label

FAQ

What is Amlodipine used for?

Amlodipine is a medicine used to treat high blood pressure (hypertension).Amlodipine is also used to prevent chest pain caused by heart disease. 

How safe is Amlodipine?

Amlodipine is generally a safe and effective drug, but it may cause side effects in some people.

How does Amlodipine work?

Amlodipine works in high blood pressure by relaxing and widening blood vessels.

What are the common side effects of Amlodipine?

The most common side effects include headache, flushing, feeling tired and swollen ankles.

Is Amlodipine safe during pregnancy?

early pregnancy does not appear to be associated with an increased rate of fetal malformations compared with other antihypertensive medications or maternal hypertension without treatment.

Is Amlodipine safe during breastfeeding?

Amlodipine use of Amlodipine during breastfeeding has not caused any adverse effects in breastfed infants. If Amlodipine is required by the mother, it is not a reason to discontinue breastfeeding.

Can I drink alcohol with Amlodipine?

Yes, you can drink alcohol with Amlodipine.But drinking alcohol can increase the blood pressure-lowering effect of Amlodipine, which can make you feel sleepy, dizzy or bring on a headache. If this happens to you, it's best to stop drinking alcohol while you're taking Amlodipine.

Can I drive after taking Amlodipine ?

If the tablets make you feel sick, dizzy or tired, or give you a headache, do not drive or use machines and contact your doctor immediately.

When is the best time to take Amlodipine?

It does not matter what time of day you take Amlodipine morning or evening, but it is best to take it at the same time every day,

How long does Amlodipine take to work?

Amlodipine starts to work on the day you start taking it, but it may take a couple of weeks for full effect. If you're taking Amlodipine for high blood pressure, you may not have any symptoms.

How long does Amlodipine stay in my system?

Amlodipine will stay in your system for about 10 days after your last dose.

Can I take Amlodipine for a long time?

Amlodipine is generally safe to take for a long time. In fact, it works best when you take it for a long time.

Can Amlodipine cause kidney damage?

Amlodipine should not cause kidney damage and in fact are used to treat high blood pressure and slow the progression of chronic kidney disease.

When should I stop taking Amlodipine?

If you have been using Amlodipine regularly for several weeks, do not suddenly stop using it.

Is Amlodipine bad for my liver?

Liver injury due to Amlodipine have not been reported.

Does Amlodipine affect heart rate?

Amlodipine has little or no effect on your heart rate.

Can Amlodipine cause depression?

Mood changes such as depression or anxiety may occurs.

Can Amlodipine cause a cough?

No, you probably won't have a cough when taking Amlodipine.

What happens if I overdose of Amlodipine?

If you take too much Amlodipine by accident, contact your doctor or go to your nearest hospital straight away. An overdose of Amlodipine can cause dizziness and sleepiness.

What happens if I miss a dose of Amlodipine?

If you forget to take a dose of Amlodipine, take it as soon as you remember that day and then carry on as normal. If you forget to take the dose for the whole day, skip the missed dose and carry on as normal the next day. Do not take a double dose to make up for a forgotten one.

*** Taking medicines without doctor's advice can cause long-term problems.
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