Midodrine Hydrochloride
Midodrine Hydrochloride Prescribing Information
Midodrine hydrochloride tablets, USP are indicated for the treatment of symptomatic orthostatic hypotension (OH). Because midodrine hydrochloride tablets, USP can cause marked elevation of supine blood pressure (BP > 200 mmHg systolic), it should be used in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations. The indication is based on midodrine hydrochloride tablets, USP effect on increases in 1-minute standing systolic blood pressure, a surrogate marker considered likely to correspond to a clinical benefit. At present, however, clinical benefits of midodrine hydrochloride tablets, USP principally improved ability to perform life activities, have not been established. Further clinical trials are underway to verify and describe the clinical benefits of midodrine hydrochloride tablets, USP.
After initiation of treatment, midodrine hydrochloride tablets, USP should be continued only for patients who report significant symptomatic improvement.
The recommended dose of midodrine hydrochloride tablets is 10 mg, 3 times daily. Dosing should take place during the daytime hours when the patient needs to be upright, pursuing the activities of daily living. A suggested dosing schedule of approximately 4-hour intervals is as follows: shortly before, or upon arising in the morning, midday and late afternoon (not later than 6 P.M.). Doses may be given in 3-hour intervals, if required, to control symptoms, but not more frequently. Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (about 45%) at this dose. In order to reduce the potential for supine hypertension during sleep, midodrine hydrochloride tablets should not be given after the evening meal or less than 4 hours before bedtime. Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established. Because of the risk of supine hypertension, midodrine hydrochloride tablets should be continued only in patients who appear to attain symptomatic improvement during initial treatment.
The supine and standing blood pressure should be monitored regularly, and the administration of midodrine hydrochloride tablets should be stopped if supine blood pressure increases excessively.
Because desglymidodrine is excreted renally, dosing in patients with abnormal renal function should be cautious; although this has not been systematically studied, it is recommended that treatment of these patients be initiated using 2.5 mg doses.
Dosing in children has not been adequately studied.
Blood levels of midodrine and desglymidodrine were similar when comparing levels in patients 65 or older vs. younger than 65 and when comparing males vs. females, suggesting dose modifications for these groups are not necessary.
Midodrine hydrochloride tablets are contraindicated in patients with severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine hydrochloride tablets should not be used in patients with persistent and excessive supine hypertension.
The most frequent adverse reactions seen in controlled trials were supine and sitting hypertension; paresthesia and pruritus, mainly of the scalp; goosebumps; chills; urinary urge; urinary retention and urinary frequency.
The frequency of these events in a 3-week placebo-controlled trial is shown in the following table:
Adverse Events | ||||
Placebo n = 88 | Midodrine n = 82 | |||
Event | # of reports | % of patients | # of reports | % of patients |
| Total # of reports | 22 | 77 | ||
| Paresthesia* | 4 | 4.5 | 15 | 18.3 |
| Piloerection | 0 | 0 | 11 | 13.4 |
| Dysuria† | 0 | 0 | 11 | 13.4 |
| Pruritus‡ | 2 | 2.3 | 10 | 12.2 |
| Supine hypertension § | 0 | 0 | 6 | 7.3 |
| Chills | 0 | 0 | 4 | 4.9 |
| Pains¶ | 0 | 0 | 4 | 4.9 |
| Rash | 1 | 1.1 | 2 | 2.4 |
* Includes hyperesthesia and scalp paresthesia
† Includes dysuria (1), increased urinary frequency (2), impaired urination (1), urinary retention (5), urinary urgency (2)
‡ Includes scalp pruritus
§ Includes patients who experienced an increase in supine hypertension
¶ Includes abdominal pain and pain increase
Less frequent adverse reactions were headache; feeling of pressure/fullness in the head; vasodilation/flushing face; confusion/thinking abnormality; dry mouth; nervousness/anxiety and rash. Other adverse reactions that occurred rarely were visual field defect; dizziness; skin hyperesthesia; insomnia; somnolence; erythema multiforme; canker sore; dry skin; dysuria; impaired urination; asthenia; backache; pyrosis; nausea; gastrointestinal distress; flatulence and leg cramps.
The most potentially serious adverse reaction associated with midodrine hydrochloride therapy is supine hypertension. The feelings of paresthesia, pruritus, piloerection and chills are pilomotor reactions associated with the action of midodrine on the alpha-adrenergic receptors of the hair follicles. Feelings of urinary urgency, retention and frequency are associated with the action of midodrine on the alpha-receptors of the bladder neck.
The risk of hypertension increases with concomitant administration of drugs that increase blood pressure (phenylephrine, pseudoephedrine, ephedrine, dihydroergotamine, thyroid hormones, or droxidopa). Avoid concomitant use of drugs that increase blood pressure. If concomitant use cannot be avoided, monitor blood pressure closely.
Avoid use of MAO inhibitors or linezolid with midodrine.
Midodrine hydrochloride has been used in patients concomitantly treated with salt-retaining steroid therapy (i.e., fludrocortisone acetate), with or without salt supplementation. The potential for supine hypertension should be carefully monitored in these patients and may be minimized by either reducing the dose of fludrocortisone acetate or decreasing the salt intake prior to initiation of treatment with midodrine hydrochloride. Alpha-adrenergic blocking agents, such as prazosin, terazosin, and doxazosin, can antagonize the effects of midodrine hydrochloride.
Midodrine hydrochloride is a vasopressor/antihypotensive. The chemical name for midodrine hydrochloride is acetamide, 2-amino-
Midodrine hydrochloride, USP is an odorless, white, crystalline powder. It is soluble in water and sparingly soluble in methanol and has a pKa of 7.8 (0.3% aqueous solution) and a pH of 3.5 to 5.5 (5% aqueous solution). It has a melting range of 200° to 203°C.
Each midodrine hydrochloride tablet, USP for oral administration contains 2.5 mg, 5 mg or 10 mg of midodrine hydrochloride, USP. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, microcrystalline cellulose, pregelatinized starch (maize) and stear-o-wet M (magnesium stearate and sodium lauryl sulphate).