PROAMATINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROAMATINE (PROAMATINE).
Midodrine is a prodrug that is converted to desglymidodrine, an alpha1-adrenergic receptor agonist. It causes vasoconstriction and increases peripheral vascular resistance, leading to an increase in blood pressure.
| Metabolism | Hepatic metabolism via hydrolysis to the active metabolite desglymidodrine; further metabolism via glucuronidation. |
| Excretion | Primarily renal excretion of unchanged drug; approximately 40-80% of an administered dose is excreted unchanged in urine. Minor biliary/fecal excretion accounts for less than 5%. |
| Half-life | Terminal elimination half-life is approximately 0.4 hours (range 0.2-0.7 hours). Clinically, due to rapid elimination, repeated dosing every 3-4 hours is required to maintain therapeutic effect. |
| Protein binding | Approximately 20-25% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution is about 0.2-0.4 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 50-70% due to extensive first-pass metabolism in the gut wall. |
| Onset of Action | Oral: onset within 15-30 minutes after administration. Intravenous: onset within 1-2 minutes. |
| Duration of Action | Oral: lasts approximately 2-3 hours. Intravenous: lasts approximately 10-15 minutes. Clinical note: duration is short, necessitating frequent dosing or continuous infusion for sustained effect. |
10 mg orally three times daily, with doses given in the morning, at midday, and in the late afternoon to avoid nighttime supine hypertension.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-59 mL/min: 5 mg orally three times daily; for GFR <30 mL/min: 2.5 mg orally three times daily or avoid use. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh class C) and consider dose reduction. |
| Pediatric use | Safety and efficacy not established; use not recommended in pediatric patients. |
| Geriatric use | Start at 5 mg orally three times daily; monitor for supine hypertension and orthostatic hypotension; use lowest effective dose. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROAMATINE (PROAMATINE).
| Breastfeeding | Unknown if midodrine or desglymidodrine is excreted in human milk. Due to potential for serious adverse reactions in nursing infants, such as hypertension and bradycardia, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Limited data. No adequate studies in pregnant women. In animal studies, midodrine (active metabolite) showed no teratogenicity at doses up to 7 times the maximum recommended human dose. However, uterine contractions may be induced due to alpha-adrenergic effects, posing risk of placental insufficiency and fetal hypoxia, especially in third trimester. Use only if potential benefit justifies risk. |
■ FDA Black Box Warning
Not applicable; no FDA boxed warning.
| Serious Effects |
["Severe hypertension","Supine hypertension (systolic >180 mm Hg or diastolic >115 mm Hg)","Acute renal failure or severe renal impairment","Pheochromocytoma","Thyrotoxicosis","Urinary retention due to mechanical obstruction"]
| Precautions | ["Supine hypertension (monitor supine blood pressure; avoid dosing close to bedtime)","Bradycardia (especially in patients with pre-existing cardiac conduction abnormalities)","Renal impairment (reduce dose or avoid if creatinine clearance <30 mL/min)","Urinary retention (use with caution in patients with prostatic hypertrophy or bladder obstruction)"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate frequently. Assess uterine activity and fetal heart rate if used near term. Monitor for signs of placental insufficiency. Consider fetal ultrasound for growth assessment if prolonged use. |
| Fertility Effects | No specific studies on fertility effects in humans. In animal studies, no impairment of fertility was observed. |