Felodip (Tablets) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Klocke Pharma-Service, GmbH (Germany)

Quality Control Release

Merckle, GmbH (Germany)

Contact Information

TEVA (Israel)

ATC Code

C08CA02 (Felodipine)

Active Substance

Felodipine (Rec.INN registered by WHO)

Dosage Forms

	Felodip	Extended-release film-coated tablets, 2.5 mg: 30, 60, or 100 pcs.
		Extended-release film-coated tablets, 5 mg: 30, 60, or 100 pcs.
		Extended-release film-coated tablets, 10 mg: 30, 60, or 100 pcs.

Dosage Form, Packaging, and Composition

Extended-release film-coated tablets yellow, round, biconvex, engraved with “2.5” on one side, odorless; the cross-section of the tablet reveals a core from white to almost white.

Excipients : lactose monohydrate – 25.2 mg, microcrystalline cellulose (type Avicel PH101) – 51.75 mg, hypromellose (Methocel E50LV) – 110 mg, povidone (type K-25) – 7.35 mg, propyl gallate – 0.067 mg, microcrystalline cellulose (type Emcocel 90M) – 8 mg, colloidal silicon dioxide – 1.3 mg, magnesium stearate – 0.833 mg.

Film coating composition hypromellose (type Pharmacoat 606) – 6.149 mg, iron oxide yellow dye (E172) – 0.192 mg, titanium dioxide (E171) – 0.954 mg, talc – 0.93 mg, propylene glycol – 1.074 mg.

10 pcs. – blisters (3) – cardboard packs^×.
10 pcs. – blisters (6) – cardboard packs^×.
10 pcs. – blisters (10) – cardboard packs^×.

Extended-release film-coated tablets light pink, round, biconvex, engraved with “5” on one side, odorless; the cross-section of the tablet reveals a core from white to almost white.

Excipients : lactose monohydrate – 23.95 mg, microcrystalline cellulose (type Avicel PH101) – 50.5 mg, hypromellose (Methocel E50LV) – 110 mg, povidone (type K-25) – 7.35 mg, propyl gallate – 0.067 mg, microcrystalline cellulose (type Emcocel 90M) – 8 mg, colloidal silicon dioxide – 1.3 mg, magnesium stearate – 0.833 mg.

Film coating composition hypromellose (type Pharmacoat 606) – 6.666 mg, iron oxide red dye (E172) – 0.019 mg, iron oxide yellow dye (E172) – 0.007 mg, titanium dioxide (E171) – 0.435 mg, talc – 1.008 mg, propylene glycol – 1.165 mg.

10 pcs. – blisters (3) – cardboard packs^×.
10 pcs. – blisters (6) – cardboard packs^×.
10 pcs. – blisters (10) – cardboard packs^×.

Extended-release film-coated tablets red-brown, round, biconvex, engraved with “10” on one side, odorless; the cross-section of the tablet reveals a core from white to almost white.

Excipients : lactose monohydrate – 21.45 mg, microcrystalline cellulose (type Avicel PH101) – 48 mg, hypromellose (Methocel E50LV) – 110 mg, povidone (type K-25) – 7.35 mg, propyl gallate – 0.067 mg, microcrystalline cellulose (type Emcocel 90M) – 8 mg, colloidal silicon dioxide – 1.3 mg, magnesium stearate – 0.833 mg.

Film coating composition hypromellose (type Pharmacoat 606) – 6.572 mg, iron oxide red dye (E172) – 0.081 mg, iron oxide yellow dye (E172) – 0.044 mg, titanium dioxide (E171) – 0.467 mg, talc – 0.992 mg, propylene glycol – 1.144 mg.

10 pcs. – blisters (3) – cardboard packs^×.
10 pcs. – blisters (6) – cardboard packs^×.
10 pcs. – blisters (10) – cardboard packs^×.

^× protective transparent perforated stickers may additionally be applied.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

Slow calcium channel blocker, a dihydropyridine derivative. It has antihypertensive and antianginal effects.

It reduces blood pressure by decreasing total peripheral vascular resistance. It has a dose-dependent anti-ischemic effect. It reduces myocardial infarction size and protects against reperfusion complications.

It has virtually no negative inotropic effect and minimal effect on the conduction system.

Pharmacokinetics

Absorption and Distribution

The slow release of felodipine from the coated tablets prolongs the absorption phase and provides a uniform plasma concentration of felodipine over 24 hours. Felodipine is almost completely absorbed from the gastrointestinal tract. The bioavailability of the drug is independent of the dose within the therapeutic range and is approximately 15%.

Binding to plasma proteins, primarily albumin, is 99%.

It penetrates the blood-brain barrier and the placental barrier and is excreted in breast milk.

No accumulation of felodipine occurs with long-term use.

Metabolism and Excretion

Felodipine is almost completely metabolized in the liver to form inactive metabolites.

The T_1/2 of felodipine is 25 hours. It is excreted as metabolites: about 70% of the administered dose is excreted in the urine, the remainder in the feces. Less than 0.5% of the dose is excreted unchanged in the urine.

Pharmacokinetics in Special Patient Groups

In elderly individuals and patients with impaired liver function, the plasma concentration of felodipine is higher than in young patients.

The pharmacokinetic parameters of felodipine do not change in patients with impaired renal function, including those undergoing hemodialysis.

Indications

• arterial hypertension (as monotherapy or in combination with other antihypertensive agents, such as beta-blockers, diuretics, or ACE inhibitors);
• stable angina pectoris (as monotherapy or in combination with beta-blockers).

ICD codes

Dosage Regimen

The drug is taken orally in the morning before meals or after a light breakfast. The film-coated tablets should not be chewed, divided, or crushed.

Arterial Hypertension

Adults (including elderly patients)

The dose is always determined individually.

Treatment starts with a dose of 5 mg once daily. If necessary, the dose can be increased; the usual maintenance dose is 5-10 mg once daily. To determine the individual dose, it is best to use tablets containing 2.5 mg of felodipine.

In elderly patients or patients with impaired liver function, the recommended initial dose is 2.5 mg once daily.

Stable Angina Pectoris

Adults

The dose is always determined individually.

Treatment starts with a dose of 5 mg once daily; if necessary, the dose can be increased to 10 mg once daily. The maximum daily dose is 20 mg once daily.

The drug Felodip can be used in combination with beta-blockers, ACE inhibitors, or diuretics.

Combination therapy usually enhances the antihypertensive effect of the drug. The development of arterial hypotension should be prevented.

In patients with severe liver dysfunction, the therapeutic dose should be reduced.

In patients with impaired renal function, the pharmacokinetics of the drug do not change significantly.

Adverse Reactions

As with other slow calcium channel blockers, the drug Felodip may cause facial flushing, headache, palpitations, dizziness, and increased fatigue. These reactions are reversible and most often occur at the beginning of treatment or when increasing the dose of the drug. Also, depending on the dose, peripheral edema may appear, which is a consequence of precapillary vasodilation. Patients with gum inflammation or periodontitis may experience mild gum swelling. This can be prevented by maintaining good oral hygiene.

The frequency of adverse effects is classified according to WHO recommendations: very common (≥10%); common (≥1%, <10%); uncommon (≥0.1%, <1%); rare (≥0.01%, <0.1%); very rare, including isolated cases (<0.01%).

Immune system disorders very rare – hypersensitivity reaction, angioedema.

Nervous system disorders common – headache; uncommon – dizziness, paresthesia; rare – syncope.

Cardiac and vascular disorders very common – peripheral edema; common – flushing; rare – tachycardia, palpitations.

Gastrointestinal disorders uncommon – nausea, abdominal pain; rare – vomiting; very rare – gingival hyperplasia, gingivitis.

Hepatobiliary disorders very rare – increased activity of liver transaminases.

Skin and subcutaneous tissue disorders uncommon – rash, pruritus; rare – urticaria; very rare – photosensitivity reaction, leukocytoclastic vasculitis.

Musculoskeletal and connective tissue disorders rare – arthralgia, myalgia.

Renal and urinary disorders very rare – pollakiuria.

General disorders uncommon – fatigue; rare – sexual dysfunction.

Contraindications

• Hypersensitivity to felodipine or other components of the drug;
• Decompensated heart failure;
• Acute myocardial infarction;
• Unstable angina pectoris;
• Hemodynamically significant heart valve stenosis;
• Dynamic obstruction of the cardiac outflow tract;
• Lactose intolerance, lactase deficiency, or glucose-galactose malabsorption (the drug contains lactose);
• Pregnancy;
• Breastfeeding period (due to insufficient experience of use);
• Age under 18 years (efficacy and safety have not been established);

With caution

Hepatic and/or renal impairment, elderly patients over 65 years of age.

Use in Pregnancy and Lactation

Felodip is contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

For patients with impaired liver function, the initial dose is 2.5 mg/day. In patients with severe liver impairment, the dose of the drug should be reduced.

Use with caution in hepatic insufficiency.

Use in Renal Impairment

The pharmacokinetic parameters of felodipine do not change in patients with impaired renal function, including those undergoing hemodialysis.

Use with caution in renal insufficiency.

Pediatric Use

Contraindication: children and adolescents under 18 years of age (efficacy and safety have not been established).

Geriatric Use

For elderly patients, the initial dose is 2.5 mg/day.

Special Precautions

Felodip (like other vasodilators) can, in rare cases, cause significant arterial hypotension, which in predisposed patients may lead to myocardial ischemia.

Currently, there are no data on the advisability of using the drug for the secondary prevention of myocardial infarction.

Felodip is effective and well tolerated by patients, regardless of gender and age, as well as by patients with bronchial asthma and other lung diseases, with impaired renal function, diabetes mellitus, gout, with hyperlipidemia, Raynaud’s syndrome, and after lung transplantation.

Felodip does not affect plasma glucose concentration or lipid profile.

Effect on ability to drive vehicles and operate machinery

Patients who experience weakness and dizziness during treatment with Felodip should refrain from driving vehicles and engaging in activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms excessive decrease in blood pressure, bradycardia.

Treatment symptomatic therapy. In case of excessive decrease in blood pressure, the patient should be placed in a horizontal position with a low headboard. For bradycardia – intravenous administration of atropine at a dose of 0.5-1 mg. If necessary, to increase circulating blood volume – infusions of dextrose (glucose) solution, sodium chloride, or dextran. Drugs with a predominant effect on alpha-adrenergic receptors are prescribed if the above measures are ineffective.

Drug Interactions

With simultaneous use with felodipine, the plasma concentration of digoxin increases; however, no change in the dosing regimen of Felodip is required.

With simultaneous use with cytochrome P450 inhibitors (including cimetidine, erythromycin, itraconazole, ketoconazole), the metabolism of felodipine in the liver slows down, leading to an increase in its plasma concentration.

With simultaneous use with inducers of liver microsomal enzymes (including phenytoin, carbamazepine, rifampicin, barbiturates), the plasma concentration of felodipine decreases.

NSAIDs do not weaken the antihypertensive effect of felodipine.

The high degree of binding of felodipine to plasma proteins does not affect the binding of free fractions of other drugs (including warfarin).

Beta-blockers, verapamil, tricyclic antidepressants, and diuretics enhance the antihypertensive effect of felodipine.

Felodip should not be used simultaneously with grapefruit juice due to the flavonoid it contains, which increases the bioavailability of felodipine.

Storage Conditions

The drug should be stored out of the reach of children, in the original packaging (blister in a carton), at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 4 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.