GUTRON Tablets Ref.[8181] Active ingredients: Midodrine

Serious orthostatic hypotension

Regular monitoring of orthostatic blood pressure is necessary due to the risk of hypertension in the supine position, e.g. at night. If hypertension occurs in the supine position and does not respond to a reduction of the dosage, treatment with midodrine must be stopped.

The time of administration of the drug is important in this context: Avoid administration in the evenings. The risk of hypertension during the night is reduced by elevating the head.

Patients should be monitored for possible secondary events on hypertension. In patients suffering from serious disturbances of the autonomous nervous system, administration of midodrine may lead to a further reduction of blood pressure in the standing position. If this is the case, further treatment with midodrine should be stopped.

Caution must be observed in patients with atherosclerotic disease especially with symptoms of intestinal angina or claudication of the legs.

Caution is recommended in the case of patients with prostate disorders. Use of the drug may cause urinary retention.

It is advised always to monitor the blood pressure and renal function in patients before start of long-term treatment with midodrine.

Treatment with midodrine has not been studied in patients with liver impairment. It is therefore recommendable to evaluate the hepatic parameters before starting treatment with midodrine and on continuous basis.

The medicinal product should not be used in the paediatric age group until further data are available.

This medicinal product contains Sunset Yellow (E110) which may cause allergic reactions.

• Midodrine is an inhibitor of Cytochrome P450 CYP2D6 and may therefore affect the metabolism of other drugs metabolised by this isoenzyme (e.g. perphenazine, amiodorone, metoclopramide). This may lead to increased systemic exposure and increased effects of these drugs.
• Concomitant treatment with sympathomimeticsand other vasoconstrictive substances such as reserpine, guanethidine, tricyclic antidepressants, antihistamines, thyroid hormones and MAO-inhibitors including over-the-counter remedies should be avoided as a pronounced increase in blood pressure may occur. - The effect of midodrine is blocked by α-adrenergic blockers such as prazosine and phentolamine.
• Monitoring is recommended if midodrine is combined with other drugs that directly or indirectly reduce the heart rate.
• Simultaneous use of digitalis preparations is not recommended, since the bradycardia which occurs as a result of the use of midodrine is then potentiated and heart block may occur.
• Midodrine may enhance or potentiate the hypertensive effects of possible bloodpressure raising effect of corticosteroid preparations.

Pregnancy

There are no data from the use of midodrine in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Gutron is not recommended during pregnancy and in woman of childbearing potential not using contraception.

Breast-feeding

It is unknown whether midodrine is excreted in the breast milk. A risk to the suckling child cannot be excluded. Gutron should not be used during breast-feeding.

Negligible influence; however in case of dizziness or lightheadedness, care should be taken when driving vehicles or operating machinery.

Summary of safety profile

The most frequently occurring events associated with treatment include piloerection, dysuria and pruritus. Events of supine hypertension have been reported during treatment, the degree of which is dose dependent (see Section 4.4).

Tabulated list of adverse reactions

The following table presents the adverse drug reactions reported from clinical trials and from spontaneous reporting. The frequency groupings follow this convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).

Very common (≥1/10)
Common (≥1/100, < 1/10)
Uncommon (≥ 1/1000, < 1/100)
Rare (≥ 1/10,000, < 1/1000)
Not known

Psychiatric disorders

Uncommon: Sleep disorders Insomnia

Not known: Anxiety

Nervous system disorders

Common: Paraesthesia Paraesthesia of the scalp Headache

Uncommon: Restlessness Excitability Irritability

Cardiac disorders

Uncommon: Reflex bradycardia

Rare: Tachycardia Palpitations

Vascular disorders

Common: Supine hypertension (dose dependent effect)

Gastrointestinal disorders

Common: Nausea Heartburn Stomatitis

Not known: Abdominal pain Vomiting Diarrhoea

Hepatobiliary disorders

Rare: Hepatic function abnormal Raised liver enzymes

Skin and subcutaneous tissue disorders

Very common: Piloerection (goosebumps) Pruritus of the scalp

Common: Pruritus Chills, flushing, skin rash

Renal and urinary disorders

Very common: Dysuria

Common: Urinary retention

Uncommon: Urinary urgency

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.