Generic name: felodipine

Brand name: Plendil

Manufacturer: AstraZeneca

Plendil is a long-acting calcium channel blocker used to treat high blood pressure and angina (chest pain). Plendil belongs to a class of drugs known as calcium channel blockers. It works by relaxing blood vessels so that blood can flow more easily. Plendil is available in generic form.

Pharmacokinetics

Plendil is absorbed rapidly and extensively from the gastrointestinal tract following oral administration. The bioavailability of Plendil is approximately 60%. Peak plasma concentrations of felodipine are achieved within 2-4 hours after an oral dose. The mean apparent volume of distribution is 21 L/kg. Plasma protein binding of felodipine is about 94% and is independent of concentration over the therapeutic range.

The elimination half-life of Plendil is 12 hours. Felodipine is mainly metabolized by CYP3A4 to an active metabolite, norfelodipine, which has pharmacologic activity similar to that of the parent compound. Both compounds are excreted in the urine, with felodipine accounting for 10% of the dose and norfelodipine accounting for 60%.

Indications

Plendil is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including Plendil.

Plendil is also indicated for the treatment of chronic stable angina.

Contraindications

Plendil is contraindicated in patients with known hypersensitivity to this product or any of its ingredients. Plendil is also contraindicated in patients with severe hypotension (systolic blood pressure <90 mmHg) or cardiogenic shock.

Warnings and Precautions

Hypotension: Plendil may cause symptomatic hypotension, which is more likely to occur in patients who are volume- or salt depleted as a result of treatment with high diuretic doses, dietary salt restriction, dialysis, diarrhea, or vomiting. Symptomatic hypotension is also more likely to occur in patients with left ventricular outflow obstruction (e.g., aortic stenosis and hypertrophic obstructive cardiomyopathy), and in patients receiving concomitant antihypertensive therapy. In these patients, Plendil should be initiated under close medical supervision with careful monitoring of blood pressure. If hypotension occurs, the patient should be placed in a supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further Plendil treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

Angina: In clinical trials with Plendil for the treatment of angina, there were reports of worsening angina and acute myocardial infarction. These events occurred early in therapy (within 1 month) and mostly in patients with preexisting unstable angina or severe congestive heart failure. Therefore, caution is advised when Plendil is administered to patients with unstable angina or congestive heart failure.

Coadministration with CYP3A4 Inhibitors: Coadministration of Plendil with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, grapefruit juice) increases the plasma concentrations of felodipine and may result in hypotension, tachycardia, and flushing. Therefore, caution is advised when Plendil is coadministered with strong CYP3A4 inhibitors. If necessary, the dosage of Plendil should be reduced.

Coadministration with CYP3A4 Inducers: Coadministration of Plendil with strong CYP3A4 inducers (e.g., rifampin, St. John’s wort) decreases the plasma concentrations of felodipine and may result in increased blood pressure. Therefore, caution is advised when Plendil is coadministered with strong CYP3A4 inducers. If necessary, the dosage of Plendil should be increased.

Renal Impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment. In patients with severe renal impairment (creatinine clearance <30 mL/min), the maximum recommended dose is 5 mg once daily.

Hepatic Impairment: No dose adjustment is necessary for patients with mild hepatic impairment. In patients with moderate hepatic impairment, the maximum recommended dose is 10 mg once daily. Plendil has not been studied in patients with severe hepatic impairment and should therefore be used with caution in these patients.

Pediatric Use: Safety and effectiveness of Plendil in pediatric patients have not been established.

Geriatric Use: Clinical studies of Plendil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Side Effects

The most common side effects of Plendil are headache, dizziness, fatigue, and peripheral edema. These side effects usually are mild and resolve with continued treatment.

Serious side effects have been reported with Plendil, including hypotension, worsening angina, and acute myocardial infarction. These events occurred early in therapy (within 1 month) and mostly in patients with preexisting unstable angina or severe congestive heart failure. Therefore, caution is advised when Plendil is administered to patients with unstable angina or congestive heart failure.

Dosage and Administration

The recommended starting dose of Plendil is 5 mg once daily. The dosage may be increased to a maximum recommended dose of 10 mg once daily, based on blood pressure response.

Patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min) do not require a dose adjustment. In patients with severe renal impairment (creatinine clearance <30 mL/min), the maximum recommended dose is 5 mg once daily.

No dose adjustment is necessary for patients with mild hepatic impairment. In patients with moderate hepatic impairment, the maximum recommended dose is 10 mg once daily. Plendil has not been studied in patients with severe hepatic impairment and should therefore be used with caution in these patients

Overdose

There is limited information on the Plendil overdose in humans. The most common signs and symptoms reported following Plendil overdose are hypotension and bradycardia. In case of Plendil overdose, treatment should be symptomatic and supportive. There is no specific antidote for Plendil overdose.

Storage

Plendil should be stored at room temperature, 20°C to 25°C (68°F to 77°F).