Midodrine

●  Brand Names: Orvaten, ProAmatine, Amatine (Canada)

●  Indication: Orthostatic hypotension (low blood pressure) and off-label use for POTS.

●  Contraindications: Heart disease, hyperthyroidism, adrenal tumor, kidney disease, elevated blood pressure while laying down. Drug interactions with the following and should be used with caution or clinician direction: Adderall/amphetamine, SNRIs (Cymbalta/duloxetine), Metoprolol, Florinef.

●  Mechanism of Action: Midodrine is an alpha-1 agonist, classified as a vasoconstrictor. Unlike stimulant medications, it is not believed to have direct effects on the central nervous system. The primary action of midodrine is to constrict blood vessels, which helps reduce blood pooling in the abdomen and legs, redistributing blood into the central circulation where it is needed. This mechanism increases vascular tone and raises blood pressure.

●  Side Effects: Common side effects: high blood pressure when lying down (in 15-20% of cases; dangerously high blood pressure could present as severe headache, ear pounding, blurred vision, anxiety, chest pain, or seizures), itching (pruritus) in 10-15%, a pins-and- needles sensation in 5-10%, and urinary urgency or a feeling of a full bladder in 5%. Note: tingling sensations on the scalp and the hair on the arms and neck standing on end. These are indications that the medication is effective and do not require discontinuation. Adolescents and young adults with NMH and POTS are unlikely to experience the same level of high blood pressure as older individuals with orthostatic hypotension (whose average age is around 50-60 years), but this should still be monitored.

●  Dosage: A conservative starting dose of midodrine is 2.5 mg three times daily to ensure it is well tolerated. The first dose should be taken upon waking in the morning, followed by another dose 4 hours later, and then a third dose 4 hours after that with last dose 3-4 hours before bed (e.g., 8 AM, 12 PM, 4 PM). A typical dosing progression example is as follows: 2.5 mg three times a day for 2-7 days, 5.0 mg three times a day for 2-7 days, 7.5 mg three times a day for 2-7 days, 10.0 mg three times a day.

  • If there is significant improvement at a lower dose, it may be advisable to maintain that dose for a longer period rather than gradually increasing to the maximum 10 mg three times daily. It is not always necessary to escalate the dose to 10 mg three times a day. Since the drug's effects typically last about 3-4 hours, dosing intervals may need to be adjusted once the medication's beneficial effects are apparent. In some cases, patients may benefit from doses up to 15 mg per dose.

  • As a general guideline, midodrine and stimulant medications should not be prescribed together, as the combination can lead to excessive increases in blood pressure. Typically, stimulant medications are discontinued before starting midodrine.

  • To help reduce the risk of supine hypertension, it is recommended to elevate the head of the bed by 30 degrees and avoid taking midodrine close to bedtime.

● Reproductive and Pregnancy Consideration: Theoretical concern that it could cause uterine arterial constriction, potentially leading to intrauterine growth restriction. However, there is limited human data available regarding the use of midodrine during pregnancy or lactation, and its safety in these situations has not been well established. As such, caution is advised when considering midodrine in pregnant or breastfeeding individuals.

Citations

Bradshaw, M. J., & Edwards, R. T. M. (1986). Postural hypotension—pathophysiology and management. QJM: An International Journal of Medicine, 60(5), 643-657. https://doi.org/10.1093/oxfordjournals.qjmed.a068022

Glatter, K. A., Tuteja, D., Chiamvimonvat, N., et al. (2005). Pregnancy in postural orthostatic tachycardia syndrome. Pacing and Clinical Electrophysiology, 28(6), 591-593. https://doi.org/10.1111/j.1540- 8159.2005.50026.x

McTavish, D., & Goa, K. L. (1989). Midodrine. Drugs, 38(6), 757-777. https://doi.org/10.2165/00003495-198938050-00004

Midodrine Hydrochloride [Prescribing information]. (2020, June). Upsher-Smith Laboratories, LLC. Maple Grove, MN.

Raj, S. R., Guzman, J. C., Harvey, P., et al. (2020). Canadian Cardiovascular Society position statement on postural orthostatic tachycardia syndrome (POTS) and related disorders of chronic orthostatic intolerance. Canadian Journal of Cardiology, 36(3), 357-372. https://doi.org/10.1016/j.cjca.2019.12.024

Shire US Inc. (2002, February). ProAmatine® (midodrine hydrochloride) tablets prescribing information. Florence, KY.