The P-I-E-N-O Parkinsn's List Drug Database
felodipine / AgonTM ,PlendilTM
BLOOD PRESSURE:
Description: Felodipine is an oral calcium-channel blocker used in the treatment of hypertension. It is a member of the dihydropyridine class and is a potent peripheral vasodilator similar to nifedipine, isradipine, and amlodipine. Felodipine has greater selectivity for vascular smooth muscle relative to myocardial muscle than does nifedipine. Felodipine was approved by the FDA in July 1991 for the treatment of hypertension.
Mechanism of Action: Similar to other calcium-channel antagonists, felodipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged. Felodipine inhibits this influx possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The resultant decrease in intracellular calcium inhibits the contractile processes of the smooth muscle cells, resulting in dilation of coronary and systemic arteries. These effects elicit an increased oxygen delivery to the myocardial tissue, a decreased total peripheral resistance, a decreased systemic blood pressure, and a decreased afterload.
Felodipine has no effect on atrioventricular (AV) or sinoatrial nodal conduction. Negative inotropic effects rarely are noted clinically, presumably due to a reflex increase in heart rate in response to felodipine's vasodilatory activity. Felodipine therapy usually does not affect cardiovascular parameters in patients with normal ventricular function, but patients with decreased left ventricular function can experience an increase in ejection fraction and a decrease in left ventricular filling pressures. Reduced afterload and reduced myocardial wall tension lead to reduced myocardial oxygen demand, which now seems to best explain the benefit of felodipine and other dihydropyridines in the treatment of angina. Felodipine causes vasodilation in coronary, skeletal, and cerebral vasculature. Pharmacokinetics: Felodipine is rapidly absorbed following an oral dose but undergoes extensive first-pass metabolism, resulting in a bioavailability of approximately 13-16%. Peak serum levels of felodipine occur 2.5-5 hours following administration. Felodipine's onset of action occurs within 2-5 hours. The drug is highly protein-bound (99%). The drug's effects during pregnancy have not been adequately studied in humans, but fetal anomalies have occurred in animal models. It is not known whether the drug is distributed into breast milk.
Hepatic metabolism of felodipine is complete and results in inactive compounds that are excreted in the urine (70%) and feces (10%). Elimination half-life is roughly 11-16 hours, and duration of action allows for once-daily dosing. In contrast to other calcium-channel blockers, dose reduction is not required in patients with renal impairment.
CONTRAINDICATIONS/PRECAUTIONS: Felodipine's effects during pregnancy have not been adequately studied in humans, but fetal anomalies have occurred in animal models. Felodipine is an FDA pregnancy category C drug. It is not known if felodipine is excreted in breast milk.
Felodipine decreases peripheral resistance and can worsen hypotension. Felodipine should not be used in patients with systolic blood pressures of less than 90 mm Hg (i.e., severe hypotension). Felodipine should be used with caution in patients with mild to moderate hypotension. Blood pressure should be monitored carefully in all patients receiving felodipine.
Risk-benefit should be assessed when considering the use of felodipine in patients with bradycardia, heart failure, acute myocardial infarction with pulmonary congestion, or cardiogenic shock because the potential inotropic effects of the drug can worsen these conditions.
Hepatic dysfunction can reduce the clearance of felodipine by approximately 60%. Felodipine should be used cautiously or in lower doses in patients with hepatic disease. Renal impairment does not change felodipine concentrations, but accumulation of inactive metabolites may occur. The elderly can experience a delayed clearance of felodipine and can be at greater risk for accumulation and toxicity.
DRUG INTERACTIONS: Serum digoxin concentrations can be increased by concomitant administration of felodipine. This effect is believed to be due to decreased renal and nonrenal clearance of digoxin induced by felodipine. Although some reports show no effect on digoxin, plasma levels of digoxin should be monitored carefully when felodipine is administered to patients receiving digoxin. Adding digoxin to felodipine would not seem to be as much of a problem.
The concomitant use of calcium-channel blockers and ›-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, bradycardia, cardiac conduction abnormalities, and congestive heart failure can occur, so patients should be monitored carefully. Felodipine has been shown to increase metoprolol area-under-the-curve. Alpha-adrenergic blocking agents and felodipine have been used concomitantly without adverse effect.
Administration of cimetidine, an HA-receptor antagonist, can inhibit the cytochrome P-450 mixed-function oxidase system, thereby increasing the plasma levels of felodipine if the drugs are given simultaneously. Dosages of felodipine should be reduced accordingly. Calcium-channel blocker metabolism does not appear to be affected by ranitidine or famotidine.
In a small number of epileptic patients taking either carbamazepine, phenobarbital, or phenytoin, felodipine area-under-the-curve and plasma concentrations were significantly lower than in matched, non-epileptic controls. It is thought that these anticonvulsants markedly enhance the hepatic metabolism of felodipine. Higher doses of felodipine may be necessary in epileptic patients receiving any of these anticonvulsants. In addition, although no data are available, it is likely that felodipine may be affected by other hepatic enzyme inducers such as rifabutin or rifampin.
ADVERSE REACTIONS: The majority of the adverse effects reported during felodipine administration are due to the vasodilatory actions of the drug and include flushing, weakness, syncope, hypotension, peripheral edema, sinus tachycardia, dizziness, and lightheadedness. Headache is reported more frequently during isradipine, felodipine, and nifedipine therapy than with other calcium-channel blockers.
Felodipine-induced peripheral edema occurs during therapy but is probably related to vasodilation of arterioles rather than to left ventricular dysfunction.
Additional adverse effects reported less frequently during felodipine administration include muscle cramping, dyspnea, nausea/vomiting, heartburn, diarrhea, cough, wheezing, sleep disturbances, visual disturbances, asthenia, paresthesia, arthralgia, musculoskeletal problems, and constipation. Difficulty breathing, chest congestion, angina, chills, and sexual dysfunction also have been reported.
PATIENT INFORMATION:
What do felodipine extended-release tablets do?
Felodipine (PlendilTM ) is a calcium-channel blocker. It affects the amount of calcium found in your heart and muscle cells. This results in relaxation of blood vessels, which can reduce the amount of work the heart has to do. Felodipine reduces high blood pressure (hypertension). It is not a cure. Generic felodipine extended-release tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take felodipine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take felodipine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets whole with a drink of water, do not crush or chew. Take your doses at regular intervals. Do not take your medicine more often then directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children.
Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with felodipine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking felodipine?
Serious side effects with felodipine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with felodipine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take felodipine?
Check your blood pressure and pulse rate regularly; this is important while you are taking felodipine. Ask your doctor what your blood pressure and pulse rate should be and when you should contact him or her.
You may feel dizzy or lightheaded. Do not drive, use machinery, or do anything that needs mental alertness until you know how felodipine affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Avoid alcoholic drinks; they can make you more dizzy, increase flushing and rapid heartbeats.
Felodipine can cause dental problems for some patients. Clean and floss your teeth carefully and regularly. Check with your dentist if your gums get swollen or inflamed and have the dentist clean your teeth regularly.
If you are going to have surgery, tell your doctor or dentist that you are taking felodipine.
Do not suddenly stop taking felodipine. Ask your doctor how to gradually reduce the dose.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature below 30C (86F). Keep container tightly closed. Protect from light. Throw away any unused medicine after the expiration date.
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