Change to section

Details of change

4.1. Therapeutic Indications

Changed:

‘‘For use in the treatment of idiopathic orthostatic hypotension (Shy-Drager and Bradbury-Eggleston Syndromes).’’

to

‘’ For use in the treatment of severe orthostatic hypotension due to dysfunction of the autonomic nervous system when corrective factors have been ruled out.’’

4.2. Posology and Method of Administration

Changed:

‘’Adults and adolescents:’’

to

‘’Adults:’’

‘’Children:’’

to

‘’Paediatric population:’’

Added:

Patients with renal impairment:

No specific studies have been performed addressing a possible dose-reduction in patients with renal impairment. Midodrine is contraindicated in patients with acute renal disease and severe renal impairment (see 4.3).

Patients with hepatic impairment:

No specific studies have been performed in this patient population.

4.3. Contraindications

Added:

•Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

•Hypertrophy of the prostate gland with residual urine volume increased

•Proliferative diabetic retinopathy

•Obliterative or spastic vessel disease (e.g. cerebrovascular occlusions and spasms)

Deleted:

•Any urinary outflow obstructive disorder or known hypersensitivity to any component of the product.  It is also contraindicated in patients with

4.5.  Interaction with other medicinal products and other forms of interaction

Formatting/ Change:

Interaction with other medicinal products and other forms of interaction

to

Interactions with Other medicaments and Other Forms of Interaction

Added:

Midodrine is an inhibitor of Cytochrome P450 CYP2D6 and may therefore affect the metabolism of other drugs metabolised by this isoenzyme (e.g. perphenazine, amiodaorone, metoclopramide). This may lead to increased systemic exposure and increased effects of these drugs.

Deleted/ Added:

The concomitant use of midodrine with vasoconstrictor, sympathomimetic pressor agents e.g. decongestants, some appetite suppressants and other drugs which cause hypertension such as reserpine, guanethidine, methyldopa, tricyclic antidepressants, antihistamines, thyroid hormones, MAO-inhibitors including over-the-counter remedies should be avoided as this may cause excessive hypertension.

Deleted:

Atropine

Midodrine may enhance or potentiate the blood-pressure raising effect of atropine.

4.6. Pregnancy and Lactation

Changed:

Pregnancy

There is no evidence of safety of midodrine hydrochloride in human pregnancy nor is there evidence from animal work that it is free from hazard. Avoid in pregnancy unless the possible clinical benefits clearly outweigh the potential hazards.

to

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). Midon is not recommended during pregnancy and in women of childbearing potential not using contraception. Any woman becoming pregnant during treatment should be withdrawn from the treatment immediately upon established pregnancy.

4.8. Undesirable Effects

Added:

Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000), very rare (<1/10,000); Not known (cannot be estimated from the available data).

Deleted:

Side effects include:

Added:

Psychiatric disorders

Uncommon:  Sleep disorders, insomnia.

Not known: Anxiety, confusional state

Eye disorders

Rare: Visual disturbance

Not known: Increased tear production.

Gastrointestinal disorders

Common: Nausea, dyspepsia, vomiting, stomatitis.

Uncommon: Abdominal pain.

Not known: Diarrhoea

Skin and subcutaneous tissue disorders

Very common: Piloerection.

Common:  Chills, skin rash, pruritus (mainly of the scalp), flushing.

Deleted:

[Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1,000), very rare (<1/10,000)]

Other reported symptoms include increased tear production.

Added:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is 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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9. Overdose

Added:

Overdosage of midodrine produces piloerection, sensation of coldness, an urgent desire to empty the bladder, hypertension and bradycardia. 

These effects can be counteracted by induced emesis and administration of alpha -sympatholytic drugs. 

10. DATE OF REVISION OF THE TEXT

Changed to:

11^th March 2015

Change to section

Details of change

4.1. Therapeutic Indications

Changed:

‘‘For use in the treatment of idiopathic orthostatic hypotension (Shy-Drager and Bradbury-Eggleston Syndromes).’’

to

‘’ For use in the treatment of severe orthostatic hypotension due to dysfunction of the autonomic nervous system when corrective factors have been ruled out.’’

4.2. Posology and Method of Administration

Changed:

‘’Adults and adolescents:’’

to

‘’Adults:’’

‘’Children:’’

to

‘’Paediatric population:’’

Added:

Patients with renal impairment:

No specific studies have been performed addressing a possible dose-reduction in patients with renal impairment. Midodrine is contraindicated in patients with acute renal disease and severe renal impairment (see 4.3).

Patients with hepatic impairment:

No specific studies have been performed in this patient population.

4.3. Contraindications

Added:

•Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

•Hypertrophy of the prostate gland with residual urine volume increased

•Proliferative diabetic retinopathy

•Obliterative or spastic vessel disease (e.g. cerebrovascular occlusions and spasms)

Deleted:

•Any urinary outflow obstructive disorder or known hypersensitivity to any component of the product.  It is also contraindicated in patients with

4.5.  Interaction with other medicinal products and other forms of interaction

Formatting/ Change:

Interaction with other medicinal products and other forms of interaction

to

Interactions with Other medicaments and Other Forms of Interaction

Added:

Midodrine is an inhibitor of Cytochrome P450 CYP2D6 and may therefore affect the metabolism of other drugs metabolised by this isoenzyme (e.g. perphenazine, amiodaorone, metoclopramide). This may lead to increased systemic exposure and increased effects of these drugs.

Deleted/ Added:

The concomitant use of midodrine with vasoconstrictor, sympathomimetic pressor agents e.g. decongestants, some appetite suppressants and other drugs which cause hypertension such as reserpine, guanethidine, methyldopa, tricyclic antidepressants, antihistamines, thyroid hormones, MAO-inhibitors including over-the-counter remedies should be avoided as this may cause excessive hypertension.

Deleted:

Atropine

Midodrine may enhance or potentiate the blood-pressure raising effect of atropine.

4.6. Pregnancy and Lactation

Changed:

Pregnancy

There is no evidence of safety of midodrine hydrochloride in human pregnancy nor is there evidence from animal work that it is free from hazard. Avoid in pregnancy unless the possible clinical benefits clearly outweigh the potential hazards.

to

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). Midon is not recommended during pregnancy and in women of childbearing potential not using contraception. Any woman becoming pregnant during treatment should be withdrawn from the treatment immediately upon established pregnancy.

4.8. Undesirable Effects

Added:

Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000), very rare (<1/10,000); Not known (cannot be estimated from the available data).

Deleted:

Side effects include:

Added:

Psychiatric disorders

Uncommon:  Sleep disorders, insomnia.

Not known: Anxiety, confusional state

Eye disorders

Rare: Visual disturbance

Not known: Increased tear production.

Gastrointestinal disorders

Common: Nausea, dyspepsia, vomiting, stomatitis.

Uncommon: Abdominal pain.

Not known: Diarrhoea

Skin and subcutaneous tissue disorders

Very common: Piloerection.

Common:  Chills, skin rash, pruritus (mainly of the scalp), flushing.

Deleted:

[Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1,000), very rare (<1/10,000)]

Other reported symptoms include increased tear production.

Added:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is 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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9. Overdose

Added:

Overdosage of midodrine produces piloerection, sensation of coldness, an urgent desire to empty the bladder, hypertension and bradycardia. 

These effects can be counteracted by induced emesis and administration of alpha -sympatholytic drugs. 

10. DATE OF REVISION OF THE TEXT

Changed to:

11^th March 2015