Therapeutic Use Midodrine is an alpha adrenergic agonist. It therefore acts to increase blood pressure through peripheral vasoconstriction, and this mode of action provides particular increase in standing blood pressure, and hence a reduction in postural drop in blood pressure. It tends to increase systolic more than diastolic blood pressure. It is actually a pro-drug, and is metabolised to the active metabolite desglymidodrine. It is licensed in a number of countries in the EU and in the US, but is not currently licensed in the UK. Relevant details have been taken from the Eire SPC (http://www.medicines.ie/medicine/6209/SPC/Midon+Tablets+2.5mg/) Cautions Avoid in pregnancy unless patient benefits clearly outweigh patient hazards Contra-indications Contraindications: - hypertension, severe organic heart disease, thyrotoxicosis, phaeochromocytoma, acute nephritis, severe renal impairment (creatinine clearance <30ml/min), urinary retention, narrow angle glaucoma or known hypersensitivity to any component of the product. Dosage and administration The usual starting dose is 2.5 mg twice daily. The dose should be increased slowly until an optimal response is obtained. Most patients are controlled at 20-30 mg daily given in divided doses, three to four hours apart. Doses in excess of 30 mg daily are to be prescribed by the specialist only. The last dose should be taken at least four hours before bedtime to reduce the risk of supine hypertension. Great caution should be exercised in patients with mild to moderate renal insufficiency (Creatinine clearance between 30 and 90 ml/min). When the dose has been stabilised over 2 reviews, and the GP informed with a month’s notice of handing over (to allow any discussion between GP and specialist), the patient can be handed over to Primary care prescribing. Side-effects
CVS: Palpitations, tachycardia, reflex bradycardia, arrhythmias and supine hypertension
GI disorders: nausea/dyspepsia, vomiting
CNS: headache, restlessness, excitability, irritability, light-headedness or dizziness
Skin: Piloerection, chills, parasthesia, rash, pruritus (mostly scalp) and flushing
Other reported symptoms include increased tear production
The management of postural hypotension A step-wise approach is generally recommended. Full assessment should enable a diagnosis of the likely cause of postural hypotension – whether drug-related, secondary to systemic disease such as anaemia or dehydration, or related to autonomic neuropathy. Treatment steps can then be summarised:
1. Review medication, and stop, or reduce dose of possible offending medications, with
2. Prescribe graduated compression stockings (NOT TEDS) – and consider practical
assistance to enable their usage. Some situations will preclude their use – peripheral vascular disease, or inability to apply the stockings daily.
3. Review progress after a reasonable period (several weeks), and consider further drug
4. Prescribe fludrocortisone if it is considered that this will not induce heart failure, starting
5. Titrate fludrocortisone slowly over several weeks until either the desired effect has been
achieved or maximum dose of 300mcg reached.
6. Where fludrocortisone cannot be prescribed, or has proved ineffective, then midodrine
should be considered at an initial dose of 2.5mg two to three times daily.
7. Titrate midodrine to a usual maximum dose of 10mg three times per day. Midodrine should
only be continued if symptoms of hypotension have been significantly reduced.
Drug interactions The hypertensive effect may be enhanced by guanethidine, atropine, antihistamines, thyroid hormones, methyldopa or tricyclic antidepressants. Effect may be antagonised by alpha blockers. An exaggerated response to this drug may be expected in those patients who have received MAOIs within the previous 14 days and in patients receiving other sympathomimetic agents e.g. decongestants and some appetite suppressants. May intensify bradycardia produced by beta-blockers, digoxin (or other glycosides) or psychopharmaceutical drugs. Increased risk of glaucoma/increased intraocular pressure in combination with mineralcorticoids or glucocorticoids (e.g. fludrocortisone). Monitoring The major difficulty with midodrine is that it will increase supine blood pressure, as well as reducing postural drop, and hence it is difficult to use where supine blood pressure is already on the high side. It is essential to monitor supine and sitting blood pressures during the use of the drug. Where supine blood pressure rises above 160mmHg, dose of midodrine should be reduced. If this results in a return of symptoms, then a review in secondary care is indicated. Electrolyte monitoring on midodrine is not essential, although may be indicated for other reasons in these patients. It is essential to monitor blood pressure, and a minimum of every 3 months is suggested. Rising supine blood pressure is a reason to reduce or stop the midodrine. Where a patient remains free of symptoms and free of an excessive drop in blood pressure on standing, attempts should be made to withdraw the drug stepwise. Aspects of care for which the hospital is responsible • To initiate midodrine therapy having followed an approach consistent with that described above.
This means that midodrine is an unusual prescription where other approaches have failed to resolve the problem.
• To monitor in out-patients and adjust dosage accordingly, and review the balance of efficacy with
• To write to the GP requesting shared care at least 1 month before this will be required to
commence and inform the GP of the existence of the shared care guideline on the Intranet and/or provide a copy directly. The letter must include the pre-treatment blood pressure reading.
• To perform ongoing reviews of the patients’ treatment when requested by the GP and advise on
treatment withdrawal when it is no longer considered appropriate.
Aspects of care for which the GP is responsible • After agreeing to accept shared care, to prescribe midodrine on an ongoing basis. • Monitor patient for adverse effects and control of symptoms and refer to the hospital specialist
• Monitoring blood pressure every 3 months, and referring to the hospital specialist where standing blood pressure rises consistently by more than 20 mm Hg, or where symptoms of orthostatic hypotension return. To perform the primary care monitoring test as described above and adjust doses as directed.
Aspects of care for which the patient is responsible To ensure they have a clear understanding of their treatment.
To request future supplies when needed, store the medication appropriately and take as directed.
To report adverse effects or worsening symptoms to their GP. Patients should report symptoms of supine hypertension immediately such as cardiac awareness (palpitations, chest pain and shortness of breath), headache, blurred vision etc, and the patient should be advised to discontinue the medication immediately Cost 12 months treatment at 10mg twice daily is approximately £423, but this may vary depending on supplier because as it is currently unlicensed, it is classed as a “special item” which may incur various extra charges. Availability of back-up advice and support Hospital number: 08454 222222 Reviewed by Dr Arnold Deering June 2010 Consultants: Gloucester
Gloucester 08454 226108 (Mon to Fri, 9 – 5.30pm) Cheltenham 08454 223030 (Mon to Fri, 9 – 5.30pm)
This Shared Care Guideline has been agreed by Medicines Management Interface Group (MMIG, formerly
CF2M) in collaboration with the Medicines Information Service at Gloucestershire Royal Hospital and above consultant(s). The information contained in this guideline is issued on the understanding that it is the best available from the resources at our disposal on the date of issue. Further information may be obtained from the specialist or your local medicines information centre. This guideline does not contain a complete list of indications, precautions, warnings etc. For further information please refer to the Eire product Summary of Product Characteristics for full details. This can be found at http://www.medicines.ie/ (NB product not licensed in UK) This guideline can be found in an electronic format at the NHS Gloucestershire ‘Traffic Light’ system prescribing website http://nww.glospct.nhs.uk/C11/Specialist%20Drug%20Traffic%20Light/default.aspx . ▼ Suspected ADRs associated with Blank Triangle drugs should be reported via the CSM Yellow Card Scheme. ▼
Jean-Louis Nandrino a,b , Fabrice Leroy a,b and Laurent Pezard b,c,d (a) UPRES “Temps, ´emotion et cognition”, Universit´e Lille 3(c) Neurosciences Cognitives et Imagerie c´er´ebrale LENA-CNRS UPR 640(d) Institut de Psychologie, Universit´e Paris 5Address for correspondance: L. Pezard, LENA-CNRS UPR 640, 47 Bd del’Hˆopital, 75651 Paris cedex 13. France. The development of the ma