Midodrine

This guidance is aimed for primary and secondary care clinicians involved in the management of patients with:

  • Inappropriate sinus tachycardia (IST)
  • Postural orthostatic tachycardia syndrome (POTS)
  • Severe orthostatic hypotension due to autonomic dysfunction

Introduction

Midodrine is a pro-drug which is converted to the active metabolite, desglymidodrine, an alpha adrenergic agonist. This causes peripheral arterial and venous constriction, producing an increase in vascular tone and blood pressure (BP).

At present there are no approved medicines for the treatment of POTS or IST and therefore in these circumstances, midodrine is prescribed for an unlicensed indication. Treatments must be tailored to each patient, taking into account the cause of their syndrome and their symptoms, since the same medicines can have very different effects on different individuals.

In line with the guidance from the General Medical Council (GMC), it is the responsibility of the prescriber to determine the clinical need of the patient and the suitability of using midodrine outside of its authorised indication.

This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.

Treatment Options for Midodrine (in SWL)

Severe orthostatic hypotension due to autonomic dysfunction

  • Licensed indication (Bramox® brand) – when corrective factors have been ruled out and other forms of treatment are inadequate.

Postural orthostatic tachycardia syndrome (POTS) and inappropriate sinus tachycardia (IST) (unlicensed indication)

Following failure of simple methods to control symptoms (fluid, exercise, and compression clothing). Midodrine is suitable for patients with low blood pressure associated with symptoms of POTS such as palpitations, hypotension associated with dizziness, light-headedness and near syncope, dyspnoea, hyperventilation, low exercise tolerance, fatigue, insomnia, and anxiety.

Note for all indications: Midodrine is AMBER 3. Refer to section below on transfer of prescribing responsibility.

Midodrine for unlicensed indications

  • Treatment must be initiated by a specialist, after careful evaluation of the overall balance of the patient’s expected benefits and risks.
  • The initiating clinician / organisation is responsible for ensuring the patient is provided with a structured support process (including availability of contact numbers for specialist nurses), follow-up and the supply of midodrine for the first three months of treatment or until the dose is stable. During this time, efforts should be made to reinforce adherence and address any adverse effects.

Transfer of prescribing responsibility to patient’s GP

Midodrine is AMBER 3 prescribing status.

Following the initial 3-month period and when the patient is on a stable dose of midodrine, prescribing responsibility may be considered for transfer to the patient’s own GP, when the consultant and the GP are in agreement that the patient’s condition is stable or predictable. Transfer of prescribing responsibility should be followed, and the midodrine transfer of care document to be completed and forwarded to the GP to ensure seamless care.

Contraindications

For full details refer to (BNF) or Summary of Product Characteristics (SPC):

  • Hypersensitivity to the active substance or to any of the excipients
  • Severe organic heart disease (such as bradycardia, heart attack, congestive heart failure, cardiac conduction disturbances or aortic aneurysm)
  • Serious obliterative blood vessel disease, cerebrovascular occlusions, and vessel spasms
  • Hypertension
  • Serious prostate disorders
  • Urinary retention
  • Severe renal impairment (CrCl  less than 30ml/min) or acute kidney disease
  • Proliferative diabetic retinopathy
  • Pheochromocytoma
  • Hyperthyroidism/ thyrotoxicosis
  • Narrow angle glaucoma
  • Pregnancy or women of childbearing potential not using contraception measures
  • Breastfeeding
  • or contraindications for use with other medicines, refer to Drug Interactions

Cautions

For full details refer to BNF or Summary of Product Characteristics SPC

  • Severe orthostatic hypotension with supine hypertension
  • Severe disturbances of the autonomic nervous system
  • Atherosclerotic disease especially with symptoms of intestinal angina or claudication of the legs
  • Hepatic impairment – due to lack of clinical data
  • Mild to moderate renal impairment (CrCl 30 to 89ml/min) – due to lack of clinical data close monitoring is recommended
  • For cautions for use with other medication – see Drug Interactions

Dosing

Severe orthostatic hypotension due to autonomic dysfunction

  • The initial recommended dose is 2.5mg three times a day with or without food.
  • Depending on the supine and standing blood pressure readings, the dose may be increased weekly to achieve optimal control of symptoms, to a maximum dose of 10mg three times a day.

POTS or IST

  • The initial recommended dose is 2.5mg three times a day with or without food, titrated at intervals of more than 3 days until optimal response in obtained.
  • The normal recommended maximum dose is 30mg daily. Doses in excess of 40mg daily are not recommended. Upon escalating the dosage, the supine and standing blood pressure should be closely monitored. Most patients are controlled at or below 30mg/day given in 3 or 4 divided doses, but midodrine can be given up to six times daily if required to give adequate control of symptoms.
  • The last daily dose should be taken at least 4 hours before bedtime to reduce the risk of supine hypertension.
  • There is limited data on dosing in elderly patients and SPC recommends cautious dose titration.
  • There are no specific studies that have focused on a possible dose reduction in patients with renal impairment. Midodrine is contra-indicated in severe renal dysfunction (CrCl  less than 30ml/min) and acute renal failure.

Monitoring

  • Midodrine can increase supine blood pressure as well as result in a postural blood pressure drop. Regular monitoring of supine, standing and sitting blood pressure (for 2 to 3 minutes) is required, usually every 3 months or more frequently if recommended by the specialist and if symptoms recur. Increases in supine blood pressure will require a dose reduction or cessation of therapy – seek specialist advice.
  • Renal (creatinine clearance) and liver function should be monitored before starting treatment with midodrine then at least annually throughout therapy, or more frequently if clinically indicated.

Side effects

For full details refer to BNF or Summary of Product Characteristics SPC

Supine hypertension is a common side effect and can be a dose dependent effect. Patients should be told to monitor and report the following symptoms immediately: cardiac awareness (chest pain, palpitations, and shortness of breath), headache and blurred vision. To prevent supine hypertension, patients should be advised to take their last daily dose at least 4 hours before bedtime. The risk of supine hypertension occurring at night can also be reduced by elevating the head. Reduction in the midodrine dose may help control supine hypertension, but if it does not resolve, then midodrine must be stopped.

The most frequent and very common side effects include piloerection, pruritus (mainly of the scalp), paraesthesia, headache, nausea, dyspepsia, stomatitis, dysuria, urinary disorders, chills, flushing and/or rash.

Drug Interactions

For full details refer to BNF or Summary of Product Characteristics SPC

  • Sympathomimetics and other vasoconstrictive substances (e.g. reserpine, guanethidine, tricyclic antidepressants, antihistamines, thyroid hormones, and MAO-inhibitors)
    • Concomitant use should be avoided as these can cause a pronounced increase in blood pressure.
  • Alpha-adrenergic antagonists (e.g. prazosin and phentolamine)
    • Concomitant use should be avoided as these can antagonise the effects of midodrine.
  • Cardiac glycosides (e.g. digoxin and digitoxin)
    • Concomitant use is not recommended as the heart rate reducing effect may be potentiated and heart block can occur
  • Drugs that directly or indirectly reduce heart rate
    • Caution is advised. Monitor heart rate and check for signs and symptoms of bradycardia as midodrine can potentiate bradycardia
  • Corticosteroids
    • Concomitant use can potentiate or enhance corticosteroids hypertensive effects.
  • Mineralocorticoids or glucocorticoids (e.g. fludrocortisone)
    • Concomitant use may increase risk of glaucoma or increase intraocular pressure and should be carefully monitored.
  • Drugs metabolised by CYP2D6 enzyme (e.g. promethazine)
    • Concomitant use can reduce their clearance and enhance their effect.

Roles and responsibilities

Initiating clinician or organisation

  • To initiate midodrine in line with local guidance; notify GP that midodrine has been prescribed using the notification of initiation document.
  • To ensure patient has consented to treatment and, where appropriate, is aware the use is for an unlicensed indication.
  • To provide counselling to improve adherence and address any adverse effects (including advice on dosage, frequency and the risks and benefits of treatment).
  • As part of self-monitoring, patient should be recommended to use BP monitors approved by the British and Irish Hypertension Society (BIHS) and provided with appropriate training on how to measure their blood pressure.
  • Perform baseline monitoring tests: Blood pressure (supine, sitting and standing), baseline renal (creatinine clearance) and liver function.
  • Supply midodrine for at least the first 3 months of therapy and/ or until the patient is on a stable dose. (Amber 3 prescribing status)
  • Following the initial three months of treatment and when the dose is stable, transfer prescribing responsibility to the GP using the midodrine transfer of care document.
  • Provide the GP with relevant specialist contact information should further assistance be required during working hours.
  • To review patient at the request of GP should any problems arise (side-effects / lack of efficacy).
  • Provide the patient with contact information for specialist nurse advice during normal working hours.
  • To review therapy at least annually and communicate promptly with the GP if treatment is changed.

Patient’s own GP

  • To ensure use of midodrine is in line with local guidance.
  • To agree to take over prescribing responsibility when the patient is stable on therapy (at least 3 months after initiation and in line with the midodrine transfer of care guidance).
  • To provide on-going prescriptions for midodrine after 3 months and once prescribed a stable dose.
  • To monitor blood pressure every 3 months (Note: patient’s home blood pressure readings can be considered – if using validated and approved blood pressure monitors and are competent in measuring blood pressure).
  • Seek advice from the specialist if blood pressure rises consistently more than 20mmHg or where symptoms of orthostatic hypotension return.
  • Review renal (creatinine clearance) and liver function at least annually, more frequently if clinically indicated.
  • To monitor the patient for adverse effects and control of symptoms.
  • To report and seek advice regarding any concerns, for example: side-effects, co-morbidities, pregnancy, or lack of efficacy to the specialist team.
  • To advise the specialist if non-adherence is suspected.
  • To refer back to the specialist if the patient’s condition deteriorates or treatment fails.
  • To stop treatment on the advice of the specialist or immediately if an urgent need to stop treatment arises

Note: A combination treatment with midodrine and ivabradine is prescribed in a few patients for treatment of POTS and/or IST

References

  1. Summary of Product Characteristics, Bramox® 2.5mg tablets. Updated Apr 2022. Accessed: 15/10/2025
  2. NICE Evidence Summary: Orthostatic hypotension due to autonomic dysfunction: midodrine [ESNM61] October 2015. Accessed: 12/08/2025
  3. Ross AJ, Ocon AJ, Medow MS et al. A double-blind placebo-controlled cross-over study of the vascular effects of midodrine in neuropathic compared with hyperadrenergic postural tachycardia syndrome. Clinical Science 2014;126(4):289-96
  4. Ross AJ; Ocon AJ; Medow MS; Stewart JM. Therapies for postural tachycardia syndrome in children Zhonghua er ke za zhi. Chinese journal of paediatrics, 2011;49(6):428-432),
  5. Zhang FW.; Liao Y.; Li XY; et al. Effect of selective alpha1 receptor agonist in the treatment of children with postural orthostatic tachycardia syndrome. Chinese journal of paediatrics, 2008;46(9):688-691
  6. Chen L.; DU J.B.; Jin H.F.; et al. Midodrine hydrochloride is effective in the treatment of children with postural orthostatic tachycardia syndrome. Circuion 2011;75(4);927-931)
  7. Chen L; Wang L; Sun J; et al. Outcomes in adolescents with postural orthostatic tachycardia syndrome treated with midodrine and betablockers. Pacing and Clinical Electrophysiology 2009; 32(2):234-238
  8. Lai CC.; Fischer PR.; Brands CK.; et al. Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia. Circulation 1997;96:575–80

V1.1 – Approved by SWL Integrated Medicines Committee (IMOC) December 2025