Felodipine - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Felodipine is a medication used for the treatment of hypertension or high blood pressure or hypertension. It is available as an extended-release oral tablet. It binds to the calcium channels and blocks their action, especially in the smooth muscles. This binding prevents calcium influx into the cells, which causes contraction. Thus, Felodipine prevents the contraction of smooth muscles, which results in high blood pressure. The U.S. Food and Drug Administration (FDA) approved the use of Felodipine for hypertension in 1998. The off-label use of the drug includes the treatment of angina or chest pain. The use of Felodipine should not be suddenly withdrawn as it may result in adverse events. The common side effects of the drug include indigestion, headache, flushing, sudden decrease in blood pressure, etc.

How Does Felodipine Work?

Felodipine is a calcium-channel blocker. Calcium channels cause the entry of calcium into the cells. When the calcium concentration in the cells increases, it causes contraction. Now, when the calcium channels are blocked in the blood vessels, this contraction does not occur; rather, they are relaxed. Hence, it is used to treat hypertension by dilating the blood vessels, thereby reducing the pressure. In short, it impedes the voltage-dependent calcium ion currents in the smooth muscles of the blood vessels.

Dosage:

• The starting dose of Felodipine is 2.5 mg. The dose is then titrated by the doctor based on the response to the therapy.

• The tablets are to be administered either with a light meal or without food.

• Felodipine tablets should not be crushed or chewed but swallowed as a whole.

• The tablets should be used only as directed by the physician for patients with liver diseases and those above the age of 65.

Warnings and Precautions:

• Peripheral Edema: It is a condition characterized by the swelling of legs caused by fluid retention. Felodipine has been reported to cause peripheral edema in adult and elderly patients taking the drug. This adverse effect of the drug is to be closely monitored after the therapy with the drug begins.

• Hypotension: A decrease in blood pressure can happen due to the dilatory effect of Felodipine on the blood vessels. It is considered an exaggerated response to the pharmacology of the drug. Patients have also reported fainting due to a sudden decline in blood pressure. The doctor will advise the necessary steps to be taken if the patient counters this effect.

• Heart Failure: Felodipine requires cautious use in patients with heart failure, as the safety and efficacy of the drug are not yet established in such patients. It is particularly if the patient is on concomitant therapy with the drugs belonging to the class of beta-blockers (Propranolol, Metoprolol, Atenolol, etc.). Felodipine can also precipitate an increased heart rate (tachycardia) and result in angina (chest pain) as a rebound mechanism to counter the decrease in blood pressure.

• Patients With Liver Diseases: It is observed that the concentration of Felodipine in the plasma is higher in patients with impaired liver function and attains the drug response with a smaller dose. Hence, the drug is started only at the lowest dose, which is then adjusted based on monitoring results of the blood pressure levels.

For Patients

What Is Hypertension?

Hypertension, also known as high blood pressure, is a condition in which the force of the blood against the walls of the arteries is high, which may eventually cause health problems, such as heart disease. Blood pressure is determined by the amount of blood the heart pumps out and the quantity of resistance to blood flow in the arteries.

The more blood the heart pumps and the narrow arteries, the higher the blood pressure. Hypertension usually has no symptoms, so it may be unnoticed for a long time. That is why it is important to get blood pressure checked regularly. If untreated, hypertension can damage your heart, brain, kidneys, and other body parts. Treatment for hypertension includes lifestyle changes, such as eating a healthy diet and exercising regularly, and medications.

Learn More About Felodipine:

When and Why to Take Felodipine?

Felodipine is a prescription medication used for the treatment of hypertension. In case of any doubts or queries concerning drug use, talk with the doctor or pharmacist immediately. Speak with the doctor or pharmacist if the patient experiences a stronger or weaker effect than being informed.

How Effective Is Felodipine?

Studies have shown that there is a significant reduction in the blood pressure of 24/16 mmHg after six-week therapy in patients treated with Felodipine.

What Are the Things to Inform The Doctor Before Taking Felodipine?

It is important to let the doctor know of any of the following conditions; if present, before taking Felodipine:

• If the patient has a known history of allergy to Felodipine or any other medications belonging to the calcium-channel blocker class.

• If the patient is pregnant or intends to get pregnant. The physician should be notified immediately if the patient becomes pregnant while using this medication.

• If the patient is breastfeeding.

• If the patient has any other heart-related conditions other than high blood pressure or angina.

• Has recently suffered from a heart attack.

• If chest pain lasts for more than 15 minutes and the pain is radiating.

How Is Felodipine Given?

• Always take this medication exactly as directed by the doctor. If unsure, consult the doctor.

• The general frequency and time of administering the drug are once daily in the morning.

• Felodipine should be administered either before or after a light meal low in fat and carbohydrates.

• In case of any queries, talk to the pharmacist or the doctor.

Things to Do After Starting Felodipine:

Immediately seek medical help if the following are experienced after taking the medication:

• Hypersensitivity and Allergic Reactions: Symptoms may include swollen cheeks, lips, mouth, tongue, or throat, as well as elevated lumps on the skin (weals).

• Inflammation: Some mild gum growth is observed when a patient develops gingivitis (inflammation of the base of the teeth) or periodontitis (inflammation of the gum). Careful dental hygiene can prevent or stop enlargement.

What Are the Side Effects of Felodipine?

Most side effects will be experienced at the beginning of treatment or following a dose increase. If such reactions occur, they typically last a short time and resolve with time. But let the doctor know if any of the symptoms you notice worsen over time. The list of side effects of Felodipine are as follows:

• Swelling of ankles.

• Headache.

• Low blood pressure.

• Swelling.

• Flushing.

• Irregular heartbeats.

• Palpitations.

• Nausea.

• Abdominal pain.

• Burning or prickling sensation.

• Rash or itching.

• Fatigue.

• Dizziness.

The rarer side effects include

• Fainting.

• Joint pain.

• Vomiting.

• Muscular pain.

• Nettle rash (red, round, and itchy rashes on the skin).

• Sexual dysfunction.

Get in communication with the doctor, pharmacist, or nurse if any of these effects are experienced. This covers any potential adverse effects that aren't included in the list. By doing so, one can contribute to the knowledge of the safety of the drug.

What Should Be Done if a Dose Is Missed?

If a dose is missed, take it as soon as it is remembered and continue with the normal dosing regimen. However, if it is almost time for the next dose, skip the previous one and continue as scheduled. Avoid taking double doses to make up for a missed dose. In case of queries, contact the pharmacist or the doctor.

What Should Be Done to Treat Felodipine Overdose?

Avoid taking the tablet more than the advised dosage. Only take the number of tablets the doctor specified on the pharmacy label. Inform the doctor immediately if an overdose happens, or visit the local accident and emergency department.

How to Store Felodipine?

• Store Felodipine at room temperature between 15 to 30 degrees Celsius.

• Keep the tablets away from children and pets.

• The disposal of medications in wastewater or household waste is not recommended. Check how to dispose of expired medicines, according to a pharmacist. These actions will aid in keeping the environment safe.

Avoid Self-Medication:

Avoid taking this drug without a prescription, do not recommend it to others, and do not take it on someone else's advice. Different people react to medications differently, and some may even react worse. Make a list of all the prescriptions and non-prescription that are being taken whenever consulting a doctor, and take the medication only as instructed by a qualified healthcare professional.

For Doctors

Indication:

Felodipine is indicated for the treatment of hypertension and angina pectoris.

Mechanism of Action:

• Felodipine is classified as a 1,4-dihydropyridine calcium channel blocker (CCB) with a long half-life. Maintaining voltage-gated L-type calcium channels in their inactive conformation primarily affects vascular smooth muscle cells.

• Felodipine reduces calcium-dependent myocyte contraction and vasoconstriction by preventing the inflow of calcium into smooth muscle cells.

• It also competes with the mineralocorticoid receptor for binding, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and prevents calcium influx through voltage-gated T-type calcium channels.

Dosing:

Dosing Considerations:

• Renal Impairment: No specific dosing adjustment is required.

• Geriatrics: Therapy is to be commenced with 2.5 mg and adjusted to effect.

Pharmacodynamics:

Despite Felodipine's ability to bind to numerous endogenous molecules, it is still believed that the majority of its vasodilatory effects are caused by the blockage of voltage-gated L-type calcium channels. Felodipine binds directly to closed calcium channels, just like other DHP CCBs, maintaining their inactive conformation. Inactive channels are more common in smooth muscle cells because arterial smooth muscle depolarizations last longer than cardiac muscle depolarizations. The channel's alpha-1 subunit's alternative splicing increases the arterial selectivity of Felodipine. It has no impact on cardiac myocytes and conduction cells at therapeutic sub-toxic dosages.

Pharmacokinetics:

The pharmacokinetic parameters of Felodipine are as follows:

• Absorption:

Felodipine is fully absorbed from the gastrointestinal tract but only has a 15 % systemic availability due to significant first-pass metabolism through the portal circulation. Food has little impact on bioavailability.

• Distribution:

Felodipine is 99 % bound to plasma proteins, particularly albumin, and it has a volume of distribution of 10L/kg.

• Metabolism:

Felodipine is primarily metabolized by the hepatic cytochrome P450 3A4 enzymes. Six metabolites have been found, and none of them have any discernible vasodilatory effects.

• Excretion:

Due to a decrease in urine excretion, there are larger amounts of the metabolites in the plasma, although they remain inactive. Studies on animals have shown that Felodipine passes both the placenta and the blood-brain barrier.

Half-Life:

The half-life of Felodipine is 8.5 to 19.7 hours for healthy volunteers, 17.5 to 21.5 hours for hypertension patients, and 19.1 to 35.9 hours for geriatric patients.

Active Ingredient:

The active ingredient in Felodipine tablets is Felodipine.

Inactive Ingredient:

The inactive ingredients in Felodipine tablets are:

• Hydroxypropyl cellulose.

• Sodium stearyl fumarate.

• Titanium dioxide.

• Lactose.

• FD and C blue 2.

• Yellow iron oxide.

Toxicity:

Felodipine overdose may cause reflex tachycardia, peripheral vasodilation, and hypotension. However, a severe case can result in bradycardia and extreme hypotension, both of which are life-threatening. The danger of overdosing rises in the elderly, people with liver disease, and when beta-blockers and Felodipine are taken together. Lightheadedness, syncope, changed mental status, and shock brought on by severe hypotension are all possible overdose symptoms.

• Management of Mild to Moderate Toxicity: Patients may have mild hypotension, which may manifest as dizziness or syncope. Reflex tachycardia may develop as well as angina pectoris.

• Management of Severe Toxicity: This can cause severe circulatory collapse and hypotension, resulting in cardiogenic shock and end-organ dysfunction, including lethargy, syncope, bowel ischemia, renal failure, bradycardia, metabolic acidosis, and death. Hyperglycemia generally develops in patients with severe poisoning.

What Are the Drug Warnings and Precautions?

Cardiovascular:

• When used with a beta-blocker, use with extreme caution in individuals who have heart failure or compromised ventricular function.

• Significant hypotension and syncope are possible side effects. Reflex tachycardia brought on by hypotension may cause angina pectoris in those who are vulnerable to it.

• Mild peripheral edema that is dose- and age-dependent has been documented, often two to three weeks after therapy begins.

Hepatic:

• Patients with liver impairment may have elevated Felodipine plasma concentrations; dosage adjustment and close monitoring are recommended.

Contraindications:

• Hepatic Failure: Failure of the liver to metabolize Felodipine causes patients with this condition to have increased plasma concentrations of the drug.

• Syncope: Dihydropyridine calcium channel antagonists should not be administered to patients with severe hypotension because they could exacerbate the situation and lead to syncope.

• Acute Coronary Syndrome: Felodipine significantly reduces blood vessel constriction, which causes reflex tachycardia, which raises the demand for oxygen in the heart muscle and worsens myocardial ischemia.

• Pregnancy: Felodipine has been proven to have teratogenic effects during pregnancy and breastfeeding, including the ossification of the terminal phalanges and digital abnormalities. It was formerly an FDA category C pregnancy medication.

Monitoring:

• Reduction in anginal pain may indicate efficacy.

• A drop in blood pressure (BP) could signify effectiveness. BP response should be monitored carefully in patients with stage 2 hypertension and a BP of 160/100 mmHg or higher. BP response should be monitored at monthly intervals until control is achieved in patients starting or adjusting antihypertensive medication and every 3 to 6 months in patients who have met BP goals.

• Consider at baseline in patients starting therapy: hypertension, fasting blood sugar, serum creatinine with estimated GFR (glomerular filtration rate), serum potassium, sodium, and calcium, or a comprehensive metabolic panel.

• When starting treatment, patients should take into account their baseline lipid profile, complete blood count, hypertension, and urine results.

• Consider baseline ECG (electrocardiogram) and hypertension in patients starting treatment.

• For orthostatic hypotension and other negative effects at regular intervals (e.g., older or with postural symptoms).

• Compliance with therapy.

Drug Interactions:

Felodipine is metabolized by CYP3A4 inhibitors. The plasma levels of Felodipine may increase several-fold when CYP3A4 inhibitors are also administered. This could be because of increased bioavailability or decreased metabolism. These elevated concentrations could have more potent consequences (lower blood pressure and increased heart rate).

The major drug-drug interactions of Felodipine are as listed:

Contraindicated:

• Itraconazole.

• Ketoconazole.

• Levoketoconazole.

Interactions:

• Atazanavir.

• Belzutifan.

• Carbamazepine.

• Ceritinib.

• Clarithromycin.

• Clopidogrel.

• Conivaptan.

• Cyclosporine.

• Dantrolene.

• Digoxin.

• Doxorubicin.

• Droperidol.

• Duvelisib.

• Epirubicin.

• Fedratinib.

• Fexinidazole.

• Fosnetupitant.

• Idelalisib.

• Ivosidenib.

• Lacosamide.

• Larotrectinib.

• Lefamulin.

• Lorlatinib.

• Lumacaftor.

• Mibefradil.

• Morphine.

• Netupitant.

• Nilotinib.

• Pacritinib.

• Pixantrone.

• St John's Wort.

• Moderate

• Amprenavir.

• Dalfopristin.

• Fluconazole.

• Indinavir.

• Magnesium.

• Nelfinavir.

• Oxcarbazepine.

• Phenobarbital.

• Quinupristin.

• Rifapentine.

With Alcohol: Avoid using alcohol while on therapy with Felodipine as it may worsen the side effects of the drug.

With Food: Grapefruit juice - Consuming large amounts of grapefruit or juice results in serious side effects while taking Felodipine.

Other Specifications:

Felodipine in Patients with Hepatic Impairment:

Felodipine use is not advised in patients with hepatic impairment. Since the liver metabolizes Felodipine, patients with liver disease have greater plasma concentrations of the drug. If necessary, 2.5 mg of the medication is started once a day. These individuals' blood pressure needs to be closely monitored during dose adjustment.

Felodipine in Pregnant Women:

Felodipine has been demonstrated to have teratogenic effects in animal experiments, including digital abnormalities and ossification of terminal phalanges. Felodipine used to be a category C medication for pregnancy. Guidelines from the American College of Obstetricians and Gynecologists state that Felodipine is the preferred calcium channel blocker when using them during pregnancy.

Felodipine in Lactating Women:

There is no clinical data available on using Felodipine while nursing. The presence of Felodipine in human milk is unknown. Alternative therapies are preferred to control hypertension since Felodipine has the potential to cause major adverse reactions in infants.

Felodipine in Pediatric Patients:

Felodipine is not FDA-approved for treating pediatric hypertension, although the American Academy of Pediatrics recommends a 2.5 mg dose for patients older than six years of age.

Felodipine in Geriatric Patients:

It is advised to start people over 65 years old on a low dose of Felodipine (2.5 mg). They should closely monitor their blood pressure when changing the medication's dosage.

Felodipine in Patients With Renal Impairment:

Felodipine is safe for use in patients with renal impairment.