VASODRINE

What it is

VASODRINE contains midodrine hydrochloride and is available in tablet strengths of 2.5 mg and 5 mg. Midodrine is a rapidly absorbed prodrug of the pharmacologically active constituent desglymidodrine, which is a sympathomimetic agent with a direct and selective effect on peripheral α1-adrenergic receptors. This α1-stimulative effect induces vasoconstriction of the venous system, causing a reduction in venous pooling.

Approved indications

— Severe symptomatic orthostatic hypotension due to autonomic dysfunction in adults when exacerbating factors have been addressed and other forms of treatment remain inadequate.

Dosing overview

The initial dose is 2.5 mg three times a day. Depending on the results of supine and standing blood pressure recordings, this dose may be increased weekly up to a dose of 10 mg three times a day. This is the usual maintenance dosage, however twice daily dosing may be appropriate for some patients. The maximum recommended dose should not exceed 30 mg daily. The last daily dose should be taken at least 4 hours before bedtime in order to prevent supine hypertension. Initiation of midodrine should be undertaken under close medical supervision in a controlled clinical setting by a specialist with expertise in the treatment of severe orthostatic hypotension.

Key safety warnings

VASODRINE should only be used in patients whose lives are considerably impaired despite standard clinical care including non-pharmacologic treatment, plasma volume expansion and lifestyle alterations. Clinical benefits of midodrine, principally improved ability to carry out activities of daily life, have not been verified. The number needed to harm for supine hypertension was 8 (95% CI 3–27). Regular monitoring of supine and standing blood pressure is necessary due to the risk of hypertension in the supine position. Patients should be told to report symptoms of supine hypertension immediately such as chest pain, palpitations, shortness of breath, headache and blurred vision. Slowing of the heart rate may occur after midodrine administration due to vagal reflex. Caution is advised when midodrine is used concomitantly with cardiac glycosides and other agents that directly or indirectly reduce heart rate. Patients should be monitored for signs or symptoms suggesting bradycardia. A few cases of Torsades de pointes, arrhythmia and ventricular arrhythmias have been reported in post-marketing surveillance databases. Caution is advised when using midodrine in patients who experience bradycardia, patients with congenital QT prolongation, patients taking antiarrhythmic medications or patients taking any other medications which prolong the QT interval.

Contraindications

VASODRINE is contraindicated in hypersensitivity to the active substance or excipients; severe organic heart disease (such as bradycardia, heart attack, congestive heart failure, cardiac conduction disturbances or aortic aneurysm); hypertension; obliterative blood vessel disease, cerebrovascular occlusions and vessel spasms; acute kidney disease; acute nephritis; severe renal impairment (creatinine clearance less than 30 ml/min); serious prostate disorder or hypertrophy of the prostate gland with residual urine volume increased; urinary retention; proliferative diabetic retinopathy; phaeochromocytoma; hyperthyroidism or thyrotoxicosis; narrow angle glaucoma; and vasovagal hypotension.

PBS listing

No information about PBS listing is available in the provided sources.

Regulatory history

VASODRINE received TGA approval on 4 December 2019. VASODRINE midodrine hydrochloride 2.5 mg and 5 mg immediate release tablets were first listed on the ARTG on 18 December 2019. The TGA evaluated VASODRINE as a new chemical entity via a literature-based submission, noting its mechanism as a selective α1-receptor agonist that increases arterial blood pressure, and considered its established international use for over 20 years in treating orthostatic hypotension.