Inopan

InnoPran XL Extended Release Capsules

InnoPran XL is a nonselective, beta-adrenergic receptor-blocking agent designed for oral administration. It is available in 80-mg and 120-mg extended release capsules, each containing sustained-release beads coated with dual membranes to retard the release of propranolol hydrochloride for several hours after ingestion, followed by sustained release.

The active ingredient, propranolol hydrochloride, is chemically described as 1-(Isopropylamino)-3-(1-naphthyloxy)-2-propanol hydrochloride. It is a stable, white crystalline solid that is readily soluble in water and ethanol. Each capsule includes sugar spheres, ethylcellulose, povidone, hypromellose phthalate, diethyl phthalate, hypromellose, polyethylene glycol, gelatin, titanium dioxide, and black iron oxide. The 120-mg capsules also contain yellow iron oxide.

Clinical Pharmacology:

Propranolol is a nonselective beta-adrenergic receptor-blocking agent with no other autonomic nervous system activity. It specifically competes with beta-adrenergic receptor-stimulating agents for available receptor sites, thereby decreasing chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation.

Administration:

A single-dose, food-effect study showed that a high-fat meal increased the lag time from 3 to 5 hours and the time to reach the maximum concentration from 11.5 to 15.4 hours, but had no effect on the AUC. Following multiple-dose administration under fasting conditions, the steady-state lag time was between 4 and 5 hours, with peak plasma concentrations reached approximately 12 to 14 hours after dosing. Trough levels were achieved 24 to 27 hours after dosing and persisted for 3 to 5 hours after the next dose. The elimination half-life of propranolol was approximately 8 hours.

Pharmacokinetics:

The plasma levels of propranolol showed dose-proportional increases after single and multiple administrations of 80-, 120-, and 160-mg of InnoPran XL. Gender studies showed that females had about 49% higher mean AUC and 16% higher mean Cmax compared to males. The mean elimination half-life was longer in females than in males (11 hours versus 7.5 hours).

Indications and Usage:

InnoPran XL is indicated in the management of hypertension and may be used alone or in combination with other antihypertensive agents.

Contraindications:

Propranolol is contraindicated in cardiogenic shock, sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place. It is also contraindicated in bronchial asthma and in patients with known hypersensitivity to propranolol hydrochloride.

Important Safety Information:

InnoPran XL should be used with caution in patients with renal insufficiency, as the pharmacokinetics have not been evaluated in such patients. The antihypertensive effects of InnoPran XL were seen in the elderly (?65 years old) and men and women, but there were too few non-white patients to assess efficacy in these groups.