Medication: Midodrine

Midodrine is a drug that can be used to treat people with disorders of the autonomic nervous system which include low blood pressure, neuro-cardiogenic or vasovagal syncope (fainting) and postural tachycardia syndrome. It is usually used only after other measures have been ineffective in controlling symptoms (e.g. high fluid intake, additional salt in some patients, counter manoeuvres, small frequent meals, gentle exercise, compression clothing- as appropriate).

Midodrine hydrochloride is the generic (chemical) name, but some manufacturers use their own brand names for the same drug, which include Bramox, Gutron, ProAmatine and Orvaten. It comes in 2.5, 5, or 10mg tablets.

In 2015, Bramox became licenced for use in adults with severe orthostatic hypotension (low blood pressure on standing up) in the UK. It is not yet licenced for use in PoTS or in children. Bramox is also available in 2.5, 5mg and 10mg tablets.

How does midodrine work?

Midodrine works by causing blood vessels to narrow, thereby increasing blood pressure. Indirectly, it may also reduce heart rate.

Midodrine starts to work around an hour after swallowing it and levels of the drug in the bloodstream fall significantly after about 3 hours so that it no longer works effectively. This explains why you take the tablet several times a day so you don’t lose the effect between tablets.

The brain has a protective mechanism that stops some drugs from entering and very little midodrine crosses this blood-brain barrier. It is removed from the body by the kidneys within 24 hours.

How do I take midodrine?

As its effect is short-lived, midodrine needs to be taken frequently throughout the day. It works best if the first dose is taken an hour or so before getting out of bed, then at 3 to 4 hourly intervals throughout the day. The last dose should ​NOT​ be taken within 4 hours before going to bed. If necessary, your doctor may instruct you to gradually increase the amount to a maximum total dose of 30mg in 24 hours. Midodrine can be taken with or without food.

What are the risks of taking midodrine?

The main risk of taking midodrine is ‘supine hypertension’. This is excessively high blood pressure on lying down. One advantage of midodrine is that it only works for a short time. Not taking it within 4 hours of going to bed reduces the risk of supine hypertension

Supine hypertension does not usually cause symptoms but rarely people may experience chest pain, unexpected headache or blurred vision. If you develop these symptoms, you should stop midodrine and inform the prescribing doctor. Elevating the head of your bed may reduce the risk of supine hypertension.

In addition, midodrine should not be continued if it causes high or unstable daytime blood pressure.

Who should not take midodrine?

Midodrine should not be prescribed in patients with the following conditions:

• Severe heart disease
• Unusually slow heart rate
• Hypertension
• Conditions that cause blockage, narrowing or spasm of the arteries in the heart or limbs
• Some prostate gland problems causing difficulties with urination
• Urinary retention
• Phaeochromocytoma
• Acute or severe kidney disease
• Overactive thyroid
• Some types of diabetic eye disease
• Narrow-angle glaucoma
• Allergy to midodrine or any of the other ingredients in the tablet
• Pregnancy

In women who are pregnant Midodrine can cross the placenta, and we don’t know what effect it could have on the baby.

Use of Midodrine has not been studied in children and it should only be used in people under the age of 18 following the recommendation of a specialist paediatrician who is very experienced in its use.

If you have severe disturbance of your autonomic nervous system, midodrine could make the fall in your blood pressure when you stand worsen. Your doctor should monitor your blood pressure when you are lying down and standing and may stop midodrine if this happens.

If you have abnormal kidney or liver function, you might not be able to take midodrine. Your doctor should check this with a blood test before you start and should check your kidney and liver function after starting it and on a regular basis (eg once a year).

If you are taking any drugs that affect your heart rate, midodrine may make your heart rate too slow. Your doctor should check all the other medicines you are taking before you start midodrine and will monitor you as necessary.

• Goosebumps
• itching of the scalp
• burning on urinating.

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• Pins and needles
• itching
• increased blood pressure when lying down
• headache
• nausea (feeling sick)
• heartburn
• inflammation of the lining of the mouth
• flushing
• rash
• chills
• difficulty urinating or emptying your bladder.

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• Sleep disturbances
• insomnia
• restlessness
• excitability
• irritability
• slowed heart rate
• urge to urinate.

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• Palpitations
• rapid heartbeat
• abnormal liver blood test.

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Side effects that we don’t know how many people experience, but are probably quite rare:
abdominal pain, being sick (vomiting), diarrhoea, anxiety, confusion.

Possible side effects that are currently being monitored by the regulators and manufacturers:
Chest pain, inflammation of the heart muscle.

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Interactions with other medicines

Midodrine should be used with caution in combination with the following drugs:

Digoxin, beta blockers (e.g. bisoprolol, atenolol, propranolol), other drugs that reduce the heart rate, steroids (prednisolone, fludrocortisone), alpha adrenergic receptor stimulators (phenylephrine, methoxamine), tricyclic antidepressants, antihistamines (including ones you can buy without prescription for hay fever), thyroid hormones, MAO inhibitors, dihydroergotamine, rauwolfia alkaloid medicines (eg reserpine), other drugs that narrow blood vessels or stimulate the central nervous system.

Midodrine should not be given to people taking alpha blockers (phentolamine, prazosin).

Some medications can cause higher levels of midodrine in your bloodstream and therefore more side effects. Examples include medication to protect against malaria (even if you have taken them in the previous year), antidepressants, or drugs to help you stop smoking. It is important you tell your doctor and pharmacist if you are taking these medications when midodrine is prescribed for you.

Midodrine may affect the breakdown of other medications within the body. You therefore need to tell your doctor or pharmacist if you are taking antidepressants, beta blockers or drugs to treat abnormal heart rates as you may need to be more closely monitored.

Is midodrine safe to take in pregnancy?

The effects of midodrine in the unborn baby are unknown as there have been no studies investigating the use of midodrine in pregnancy; however, midodrine is known to cross the placenta and into the baby’s bloodstream. Midodrine is not generally recommended in pregnancy and but is occasionally used with extreme caution and only upon the advice of a specialist during pregnancy and breastfeeding.

Monitoring midodrine treatment

Blood pressure checks and a kidney function blood test should be carried out before midodrine is started. Blood pressure and heart rate should be monitored during treatment with midodrine. It is especially important to have your blood pressure checked after lying down.

What does ‘unlicensed’ mean?

Midodrine has marketing authorisation in the UK, USA and some other European countries for the treatment of symptomatic postural hypotension due to disorders of the autonomic nervous system only. It is not licensed for any other condition and is therefore unlicensed (or ‘off licence’) for use in PoTS.

How do I obtain midodrine?

As midodrine is unlicensed in the UK for PoTS, it is usually recommended by a hospital doctor with experience in using this drug. Midodrine may be obtained in the following ways:

• Now that it has a license in the UK for postural hypotension, some GPs may also be willing to prescribe it in PoTS. This is more likely to happen if the patient’s hospital consultant provides a ‘Shared care Agreement’ (a document which provides advice to the GP about how to prescribe, side effects, monitoring and how to contact the hospital team if there are problems).
• Some hospital consultants will prescribe the midodrine and it is dispensed by the hospital pharmacy. Other hospital consultants will issue an FP10, which is the green NHS prescription that can be dispensed by your local community pharmacy.
• Midodrine is usually obtained on an NHS prescription. If it is prescribed during a private consultation with a consultant, they will issue a private prescription (and the patient will have to pay the full cost of the drug, which can be expensive).
• A private consultant may write to an NHS doctor asking if they would be willing to issue an NHS prescription (in which case the patient will pay only the cost of an NHS prescription, or nothing if they are entitled to free prescriptions).

How to store midodrine

Midodrine should be stored out of reach of children and used before its expiry date.

It should be kept in its original packaging to protect it from light.

If your doctor prescribes Midodrine for you, you should read the patient information leaflet that is issued with the medication for more detailed information.

NICE Evidence Summary Oct 2015