Felodipine

Oral doses of 240 mg/kg and 264 mg/kg in male and female mice, respectively, and 2390 mg/kg and 2250 mg/kg in male and female rats, respectively, caused significant lethality.

In a suicide attempt, one patient took 150 mg felodipine together with 15 tablets each of atenolol and spironolactone and 20 tablets of nitrazepam. The patient's blood pressure and heart rate were normal on admission to hospital; he subsequently recovered without significant sequelae.

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly bradycardia.

If severe hypotension occurs, symptomatic treatment should be instituted. The patient should be placed supine with the legs elevated. The administration of intravenous fluids may be useful to treat hypotension due to overdosage with calcium antagonists. In case of accompanying bradycardia, atropine (0.5–1 mg) should be administered intravenously. Sympathomimetic drugs may also be given if the physician feels they are warranted.

It has not been established whether felodipine can be removed from the circulation by hemodialysis.

To obtain up-to-date information about the treatment of overdose, consult your Regional Poison-Control Center. Telephone numbers of certified poison-control centers are listed in the Physicians' Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient.

Patients should be instructed to take PLENDIL whole and not to crush or chew the tablets. They should be told that mild gingival hyperplasia (gum swelling) has been reported. Good dental hygiene decreases its incidence and severity.

NOTE: As with many other drugs, certain advice to patients being treated with PLENDIL is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

• Angina
• Calcium Channel Blockers (CCBs)
• Congestive Heart Failure (CHF) Symptoms, Stages, and Prognosis

Absorption

Bioavailability

Almost completely absorbed following oral administration but undergoes extensive first-pass metabolism.1

Systemic bioavailability of felodipine is approximately 20%.1

Onset

Antihypertensive effect evident within 2–5 hours.1

Duration

During chronic administration, substantial BP control lasts for 24 hours, with trough reductions in DBP approximately 40–50% of peak reductions.1

Food

High-fat or high-carbohydrate meal increases peak plasma concentrations but does not affect extent of absorption.1 A light meal (e.g., orange juice, toast, and cereal) does not alter felodipine pharmacokinetics.1

Distribution

Extent

Crosses the blood-brain barrier.51

Crosses the placenta in animals.1

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Metabolized in the liver by CYP3A4.1

None of the 6 metabolites identified to date has substantial vasodilating activity.1

Elimination Route

Eliminated as metabolites, mainly in urine and to a lesser extent in feces.1

Half-life

Mean terminal half-life is approximately 11–16 hours following administration as an immediate-release formulation.1

Special Populations

Hepatic impairment: Clearance is decreased to about 60% of that observed in young healthy individuals.1

Geriatric patients: Felodipine clearance is decreased to about 45% of that observed in young healthy individuals.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Felodipine is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Felodipine is a calcium channel blocker. It works by affecting the movement of calcium into the cells of the heart and blood vessels. Felodipine relaxes blood vessels and increases the supply of blood and oxygen to the heart, which reduces the workload.

felodipine is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits to make sure felodipine is working properly and to check for unwanted effects.

Low blood pressure (hypotension) may occur while taking felodipine. Check with your doctor right away if you have the following symptoms: blurred vision; confusion; severe dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly; sweating; or unusual tiredness or weakness.

felodipine may cause fluid retention (edema) in some patients. Tell your doctor right away if you have bloating or swelling of the face, arms, hands, lower legs, or feet; tingling of the hands or feet; or unusual weight gain or weight loss.

Redness, swelling, or bleeding of the gums may occur while taking felodipine. Brushing and flossing your teeth carefully and regularly, and massaging your gums may help prevent this. Check with your doctor or dentist if you have any questions about how to take care of your teeth and gums, or if you notice any redness, swelling, or bleeding of your gums.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloating or swelling of face, arms, hands, lower legs, or feet
• rapid weight gain
• tingling of hands or feet
• unusual weight gain or loss

• Body aches or pain
• chills
• cough
• difficulty in breathing
• ear congestion
• fever
• headache
• loss of voice
• nasal congestion
• runny nose
• sneezing
• sore throat
• unusual tiredness or weakness

• Blurred vision
• chest pain, tightness, or heaviness
• confusion
• congestion
• cough producing mucus
• diarrhea
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• fast, slow, or irregular heartbeat
• general feeling of discomfort or illness
• hoarseness
• joint pain
• large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• muscle aches and pains
• nausea
• pain or discomfort in arms, jaw, back, or neck
• pale skin
• shivering
• shortness of breath
• sweating
• swelling or puffiness of face
• tender or swollen glands in neck
• trouble in swallowing
• trouble sleeping
• troubled breathing with exertion
• unusual bleeding or bruising
• voice changes
• wheezing

Get emergency help immediately if any of the following symptoms of overdose occur:

• Feeling of warmth
• redness of the face, neck, arms and occasionally, upper chest

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• constipation
• heartburn
• indigestion
• lack or loss of strength
• skin rash
• stomach discomfort, upset, or pain

• Bleeding gums
• irritation in mouth
• redness and swelling of gums

• Bloated or full feeling
• bloody nose
• burning while urinating
• decreased interest in sexual intercourse
• difficult or painful urination
• difficulty in moving
• discouragement
• disturbed color perception
• double vision
• dry mouth
• excess air or gas in stomach or intestines
• feeling sad or empty
• fear or nervousness
• frequent strong or increased urge to urinate
• halos around lights
• hives or welts
• inability to have or keep an erection
• increased need to urinate
• increased volume of pale or dilute urine
• irritability
• itching
• loss in sexual ability, desire, drive, or performance
• loss of interest or pleasure
• muscle cramps or stiffness
• night blindness
• overbright appearance of lights
• pain or tenderness around eyes and cheekbones
• passing gas
• passing urine more often
• redness of skin
• sleepiness or unusual drowsiness
• sleeplessness
• sores, welting, or blisters
• swelling of the breasts or breast soreness in both females and males
• swollen joints
• tiredness
• trouble concentrating
• tunnel vision
• unable to sleep

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to treat high blood pressure.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• A fast heartbeat.
• Very bad dizziness or passing out.
• Chest pain that is new or worse.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.

Felodipine is a calcium antagonist (calcium channel blocker). Felodipine is a dihydropyridine derivative that is chemically described as ± ethyl methyl 4-(2, 3-dichlorophenyl)-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedicarboxylate. Its empirical formula is C18H19Cl2NO4 and its structural formula is:

Felodipine, USP is a light yellow to yellow, crystalline powder with a molecular weight of 384.26. It is insoluble in water and is freely soluble in acetone and in methanol; very slightly soluble in heptane. Felodipine is a racemic mixture.

Felodipine extended-release tablets, USP provide extended release of Felodipine. They are available as tablets containing 2.5 mg, 5 mg or 10 mg of Felodipine, USP for oral administration. Inactive ingredients are: polyoxyl 40 hydrogenated castor oil, magnesium aluminum silicate, hypromellose 2208, lactose monohydrate, hydroxypropyl cellulose, sodium stearyl fumarate, hypromellose 2910 5cP, titanium dioxide and PEG 400. The 2.5 mg tablet strength also contains Iron oxide yellow, D&C yellow #10 aluminum lake and the 5 mg tablet strength also contains Iron oxide yellow.

USP dissolution test pending.

Felodipine Extended-Release Tablets, USP are available containing 2.5 mg, 5 mg or 10 mg of Felodipine, USP.

The 2.5 mg tablet is a yellow colored, circular shaped, biconvex, film coated tablet de-bossed with 'I31' on one side and plain on other side.

They are available as follows:

NDC 23155-048-01

bottles of 100 tablets

The 5 mg tablet is a light yellow colored, circular shaped, biconvex, film coated tablet de-bossed with 'I32' on one side and plain on other side.

They are available as follows:

NDC 23155-049-01

bottles of 100 tablets

The 10 mg tablet is a white colored, circular shaped, biconvex, film coated tablet de-bossed with 'I33' on one side and plain on other side.

They are available as follows:

NDC 23155-050-01

bottles of 100 tablets

Storage:

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Manufactured for:

Heritage Pharmaceuticals Inc .

Eatontown, NJ 077241.

866.901.DRUG (3784)

Made in India.

Issued 11/16

Felodipine Extended-Release Tablets USP , 2.5 mg

100 count bottle

Felodipine Extended-Release Tablets USP, 5 mg

100 count bottle

Felodipine Extended-Release Tablets USP, 10 mg

100 count bottle

• Antihypertensive
• Calcium Channel Blocker
• Calcium Channel Blocker, Dihydropyridine

Antihypertensive: 2 to 5 hours

Time to Peak

2.5 to 5 hours

Swallow tablet whole; tablet should not be divided, crushed, or chewed. May be administered without food or with a small meal that is low in fat and carbohydrates.

Concerns related to adverse effects:

• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers; reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease especially in the absence of concurrent beta-blockade.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition.

• Peripheral edema: The most common side effect is peripheral edema (dose dependent); occurs within 2 to 3 weeks of starting therapy.

Disease-related concerns:

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

• Heart failure: The ACCF/AHA heart failure guidelines recommend to avoid use in patients with heart failure (HF) due to lack of benefit and/or worse outcomes with calcium channel blockers in general (Yancy, 2013).

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

• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.

Special populations:

• Elderly: Initiate at a lower dose in the elderly.

Dosage forms specific issues:

• Lactose: May contain lactose; if necessary, consider alternative agents in patients intolerant of lactose.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.