Felodipine

Felodipine(中文:非洛地平) is a dihydropyridine calcium-channel blocker. It is used in the management of hypertension and angina.

Pronunciation

Felodipine extended-release 2.5mg

Generic Name:	Felodipine
Brand Name:	PLENDIL
Class:	Cardiovascular Drug
Subclass:	Dihydropyridine Calcium-channel Blocker, CCB
Legal Classification:	P1S1S3

Drug Names

Generic Name 藥物化學名稱	HA Code 藥物代碼	Legal Classification法律藥物分類	Brand Name 品牌名稱
Felodipine Extended-Release Tablet 2.5mg	FELO03	P1S1S3	PLENDIL TABLET
Felodipine Extended-Release Tablet 5mg	FELO01	P1S1S3	PLENDIL TABLET

Mechanism of Action

Felodipine relaxes and widens blood vessels. It does this by blocking calcium going into muscles in the heart and blood vessels. Muscles need calcium to contract, so when you block the calcium, it makes the muscle cells relax. This lowers your blood pressure and makes it easier for your heart to pump blood around your body.

In angina, felodipine works by improving the blood and oxygen supply to your heart. Angina is chest pain that comes on when not enough blood gets to the muscles of the heart. This usually happens because the arteries going to the heart become hardened and narrowed.

Route of Administration

Felodipine is given orally in an extended release formulation once daily.

Dosage

Agina

• BY MOUTH
• Adult: 5 mg daily, increased if necessary to 10 mg daily.

Hypertension

• BY MOUTH
• Adult: 5 mg daily, usual maintenance 5 – 10 mg once daily.

Elderly:initially 2.5 mg daily, to be taken in the morning; usual maintenance 5 – 10 mg once daily.

Side Effects

The following definitions of frequencies are used:

Very common ≥ 1/10

Common ≥ 1/100 to < 1/10

Uncommon ≥ 1/1,000 to < 1/100

Rare ≥ 1/10,000 to < 1/1,000

Very rare < 1/10,000

System Organ Class	Frequency	Adverse reactions
Nervous system disorder	Common	Headache
Cardiac disorders	UnCommon	Tachycardia, palpitations
Vascular disorders	Common	Flushing
Gastro-intestinal disorders	UnCommon	Abdominal pain, nausea, constipation
	Very rare	Gum hyperplasia
General disorders	Common	Peripheral oedema

Pharmacokinetics

Absorption

Felodipine is administered as extended-release tablets, from which it is completely absorbed in the gastrointestinal tract. The extended-release tablets produce a prolonged absorption phase of felodipine. This results in even felodipine plasma concentrations within the therapeutic range for 24 hours. Maximum blood plasma levels (tmax) are achieved with the prolonged-release form after 3 to 5 hours. The rate but not the extent of absorption of felodipine is increased when taken simultaneously with food with a high fat content.

Distribution

Felodipine is about 99% bound to plasma protein (albumin).

Metabolism

Felodipine is extensively metabolized in the liver by cytochrome P450 3A4 (CYP3A4) and all identified metabolites are inactive. Felodipine is a high clearance medicinal product with an average blood clearance of 1200 ml/min. There is no significant accumulation during long-term treatment.

Elimination

The half-life of felodipine in the elimination phase is approximately 25 hours and steady state is reached after 5 days.

How long does felodipine take to work?

Following administration of felodipine, a reduction in blood pressure generally occurs within 2 to 5 hours. During chronic administration, substantial blood pressure control lasts for 24 hours.

Drug Management

Drug Interaction:

Felodipine is metabolized in the liver by cytochrome P450 3A4 (CYP3A4). Concomitant administration of substances which interfere with CYP3A4 enzyme system may affect plasma concentrations of felodipine.

Interactions leading to increased plasma concentration of felodipine

CYP3A4 enzyme inhibitors have been shown to cause an increase in felodipine plasma concentrations. In case of clinically significant adverse events due to elevated felodipine exposure when combined with strong CYP3A4 inhibitors, adjustment of felodipine dose and/or discontinuation of the CYP3A4 inhibitor should be considered.

Examples:

- Cimetidine

- Erythromycin

- Itraconazole

- Ketoconazole

- Anti HIV/protease inhibitors (e.g. ritonavir)

- Certain flavonoids present in grapefruit juice

Felodipine tablets should not be taken together with grapefruit juice.

Interactions leading to decreased plasma concentration of felodipine

Enzyme inducers of the cytochrome P450 3A4 system have been shown to cause a decrease in plasma concentrations of felodipine. In case of lack of efficacy due to decreased felodipine exposure when combined with potent inducers of CYP3A4, adjustment of felodipine dose and/or discontinuation of the CYP3A4 inducer should be considered.

Examples:

- Phenytoin

- Carbamazepine

- Rifampicin

- Barbiturates

- Hypericum perforatum (Saint John's wort)

Additional interactions

Tacrolimus: Felodipine may increase the concentration of tacrolimus. When used together, the tacrolimus serum concentration should be followed and the tacrolimus dose may need to be adjusted.

Caution:

Predisposition to tachycardia

Contraindication:

Cardiac outflow obstruction

• Significant cardiac valvular obstruction (e.g. aortic stenosis)
• Uncontrolled heart failure
• Unstable angina
• Within 1 month of myocardial infarction

Pregnancy: avoid

FAQ

How should I take the tablet?

You will usually take felodipine once a day in the morning.

It is best to take it on an empty stomach or after a light meal.

What should I avoid while taking?

Avoid eating grapefruit or drinking grapefruit juice while taking amlodipine. Grapefruit juice can increase felodipine in your body and make side effects worse, such as flushing or getting headaches.

What happen if I miss a dose?

If you forgot to take a dose and you take felodipine once a day – take it take it as soon as you remember unless it is less than 12 hours until your next dose. In this case leave out the missed dose and take your next dose at the usual time. Never take 2 doses to make up for a forgotten one.