Last Updated on eMC 30-09-2016 View medicine  | Aspen Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:22-09-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
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Text in red = new text
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System Organ Class

Adverse event term

Frequency

Skin and subcutaneous tissue disorders

Rash (eczema, lichenoid eruption), toxic epidermal necrolysis, angioedema, urticaria

Not known

 

 

10 DATE OF REVISION OF THE TEXT

 

22/09/ 22/05 2016

Reasons for adding or updating:

  • Change to section 6.1 - List of excipients

Date of revision of text on the SPC:25-05-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

In section 6.1 List of excipients, the text has been amended. New text is shown below in red. Previous text is shown as strikethrough$0citric acid monohydrate$0anhydrous citric acid$0$0

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:06-11-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
Text strikethrough = deleted text

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

‘Aldomet’ Tablets 250 mg, contain methyldopa equivalent to 250 mg anhydrous methyldopa.

For a full list of excipients, see section 6.1.


4.2 Posology and method of administration

Posology

Use in adults:

Initial dosage: Usually 250 mg two or three times a day, for two days.

Adjustment: Usually adjusted at intervals of not less than two days, until an adequate response is obtained. The maximum recommended daily dosage is 3 g.

Many patients experience sedation for two or three days when therapy with ‘Aldomet’ is started or when the dose is increased. When increasing the dosage, therefore, it may be desirable to increase the evening dose first.

General considerations: Methyldopa is largely excreted by the kidney, and patients with impaired renal function may respond to smaller doses.

 Patients with renal impairment:

Methyldopa is largely excreted by the kidney, and patients with impaired renal function may respond to smaller doses.


Other antihypertensives:

Many patients experience sedation for two or three days when therapy with ‘Aldomet’ is started or when the dose is increased. When increasing the dosage, therefore, it may be desirable to increase the evening dose first.

 

Oral therapy - Adults: Initial dosage: Usually 250 mg two or three times a day, for two days.

 

Adjustment: Usually adjusted at intervals of not less than two days, until an adequate response is obtained. The maximum recommended daily dosage is 3g

Children Paediatric population:
Use in the elderlyOlder people:

Method of administration

 

Oral.

 

 

 

4.3 Contraindications

 

Aldomet’ is contra-indicated in patients with:

·       active hepatic disease, such as acute hepatitis and active cirrhosis

·       hypersensitivity to the active substance (including hepatic disorders associated with previous methyldopa therapy), or to any of the excipients listed in section 6.1

·       depression

·       on therapy with monoamine oxidase inhibitors (MAOIs)

·       with a catecholamine-secreting tumour such as phaeochromocytoma or paraganglioma

·       with porphyria.

 ‘Aldomet’ is not recommended for the treatment of phaeochromocytoma (see 4.4 ‘Special warnings and precautions for use’).



4.4 Special warnings and precautions for use

 

Some patients on continued therapy with methyldopa develop a positive Coombs test. From the reports of different investigators, the incidence averages between 10% and 20%. A positive Coombs test rarely develops in the first six months of therapy, and if it has not developed within 12 months, it is unlikely to do so later on continuing therapy. Development is also dose-related, the lowest incidence occurring in patients receiving 1 g or less

mof methyldopa per day. The test becomes negative usually within weeks or months of stopping methyldopa.

Prior knowledge of a positive Coombs reaction will aid in evaluating a cross-match for transfusion. If a patient with a positive Coombs reaction shows an incompatible minor cross-match, an indirect Coombs test should be performed. If this is negative, transfusion with blood compatible in the major cross-match may be carried out. If positive, the advisability of transfusion should be determined by a haematologist.

Reversible leukopenia, with primary effect on granulocytes has been reported rarely. The granulocyte count returned to normal on discontinuing therapy. Reversible thrombocytopenia has occurred rarely.

Occasionally, fever has occurred within the first three weeks of therapy, sometimes associated with eosinophilia or abnormalities in liver-function tests. Jaundice, with or without fever, may also occur. Its onset is usually within the first two or three months of therapy. In some patients the findings are consistent with those of cholestasis. Rare cases of fatal hepatic necrosis have been reported. Liver biopsy, performed in several patients with liver dysfunction, showed a microscopic focal necrosis compatible with drug hypersensitivity. Liver-function tests and a total and differential white blood-cell count are advisable before therapy and at intervals during the first six weeks to twelve weeks of therapy, or whenever an unexplained fever occurs.

 

 

As methyldopa fluoresces at the same wavelengths as catecholamines, spuriously high amounts of urinary catecholamines may be reported interfering with a diagnosis of catecholamine-secreting tumours such as phaeochromocytoma or paraganglioma.

It is important to recognise this phenomenon before a patient with a possible phaeochromocytoma is subjected to surgery. Methyldopa does not interfere with measurements of VMA (vanillylmandelic acid) by those methods which convert VMA to vanillin. Methyldopa is contraindicated for the treatment of patients with a catecholamine-secreting tumour such as phaeochromocytoma or paraganglioma.

 

4.4 Special warnings and precautions for use

 

Some patients on continued therapy with methyldopa develop a positive Coombs test. From the reports of different investigators, the incidence averages between 10% and 20%. A positive Coombs test rarely develops in the first six months of therapy, and if it has not developed within 12 months, it is unlikely to do so later on continuing therapy. Development is also dose-related, the lowest incidence occurring in patients receiving 1 g or less

mof methyldopa per day. The test becomes negative usually within weeks or months of stopping methyldopa.

Prior knowledge of a positive Coombs reaction will aid in evaluating a cross-match for transfusion. If a patient with a positive Coombs reaction shows an incompatible minor cross-match, an indirect Coombs test should be performed. If this is negative, transfusion with blood compatible in the major cross-match may be carried out. If positive, the advisability of transfusion should be determined by a haematologist.

Reversible leukopenia, with primary effect on granulocytes has been reported rarely. The granulocyte count returned to normal on discontinuing therapy. Reversible thrombocytopenia has occurred rarely.

Occasionally, fever has occurred within the first three weeks of therapy, sometimes associated with eosinophilia or abnormalities in liver-function tests. Jaundice, with or without fever, may also occur. Its onset is usually within the first two or three months of therapy. In some patients the findings are consistent with those of cholestasis. Rare cases of fatal hepatic necrosis have been reported. Liver biopsy, performed in several patients with liver dysfunction, showed a microscopic focal necrosis compatible with drug hypersensitivity. Liver-function tests and a total and differential white blood-cell count are advisable before therapy and at intervals during the first six weeks to twelve weeks of therapy, or whenever an unexplained fever occurs.

 

 

As methyldopa fluoresces at the same wavelengths as catecholamines, spuriously high amounts of urinary catecholamines may be reported interfering with a diagnosis of catecholamine-secreting tumours such as phaeochromocytoma or paraganglioma.

It is important to recognise this phenomenon before a patient with a possible phaeochromocytoma is subjected to surgery. Methyldopa does not interfere with measurements of VMA (vanillylmandelic acid) by those methods which convert VMA to vanillin. Methyldopa is contraindicated for the treatment of patients with a catecholamine-secreting tumour such as phaeochromocytoma or paraganglioma.

 

4.6 Pregnancy and lactation

Pregnancy

‘Aldomet’ has been used under close medical supervision for the treatment of hypertension during pregnancy. There was no clinical evidence that ‘Aldomet’ caused foetal abnormalities or affected the neonate.

Published reports of the use of methyldopa during all trimesters indicate that if this drug is used during pregnancy the possibility of foetal harm appears remote.

Methyldopa crosses the placental barrier and appears in cord blood.

Although no obvious teratogenic effects have been reported, the possibility of foetal injury cannot be excluded and the use of the drug in women who are, or may become pregnant requires that anticipated benefits be weighed against possible risks.

Breast-feeding

Methyldopa appears in breast milk. The use of the drug in breast-feeding mothers requires that anticipated benefits be weighed against possible risks.

4.8 Undesirable effects

Sedation, usually transient, may occur during the initial period of therapy or whenever the dose is increased. If affected, patients should not attempt to drive, or operate machinery. Headache, asthenia or weakness may be noted as early and transient symptoms.

The following convention has been utilised for the classification of frequency: Very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥

1/10,000 and <1/1000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).

System Organ Class

Adverse event term

Frequency

Infections and infestations

Sialoadenitis

Not known

Blood and lymphatic system disorders

Haemolytic anaemia, bone-marrow failure, leukopenia, granulocytopenia, thrombocytopenia, eosinophilia

Not known

Endocrine disorders

Hyperprolactinaemia

Not known

Psychiatric disorders

Psychic disturbances including nightmares, reversible mild psychoses or depression, decreased libido

Not known

Nervous system disorders

Sedation (usually transient), headache, paraesthesia, Parkinsonism, VIIth nerve paralysis, choreoathetosis, mental impairment, carotid sinus syndrome, dizziness, symptoms of cerebrovascular insufficiency (may be due to lowering of blood pressure)

Not known

Cardiac disorders

Bradycardia, angina pectoris, myocarditis, pericarditis, atrioventricular block

Not known

Vascular disorders

Orthostatic hypotension (decrease daily dosage)

Not known

Respiratory, thoracic and mediastinal disorders

Nasal congestion

Not known

Gastrointestinal disorders

Nausea, vomiting, abdominal distension, constipation, flatulence, diarrhoea, colitis, dry mouth, glossodynia, tongue discolouration, pancreatitis

Not known

Hepatobiliary disorders

Liver disorders including hepatitis, jaundice

Not known

Skin and subcutaneous tissue disorders

Rash (eczema, lichenoid eruption), toxic epidermal necrolysis

Not known

Musculoskeletal and connective tissue disorders

Lupus-like syndrome, mild arthralgia with or without joint swelling, myalgia

Not known

Reproductive system and breast disorders

Breast enlargement, gynaecomastia, amenorrhoea, lactation disorder, erectile dysfunction, ejaculation failure

Not known

General disorder and administration site conditions

Asthenia, oedema (and weigh gain) usually relieved by use of a diuretic. (Discontinue methyldopa if oedema progresses or signs of heart failure appear). Pyrexia

Not known

Investigations

Positive Coombs test, positive tests for antinuclear antibody, LE cells, and rheumatoid factor, abnormal liver-function tests, increased blood urea

Not known

Cardiac disorders: Bradycardia, aggravation of angina pectoris, myocarditis, pericarditis.

 

Blood and lymphatic system disorders: Haemolytic anaemia, bone-marrow depression, leucopenia, granulocytopenia, thrombocytopenia, eosinophilia.

 

Nervous system disorders: Sedation (usually transient), headache, paraesthesia, Parkinsonism, Bell’s palsy, involuntary choreoathetotic movements. Impaired mental acuity, prolonged carotid sinus hypersensitivity. Dizziness, light-headedness, and symptoms of cerebrovascular insufficiency (may be due to lowering of blood pressure).

 

Respiratory, thoracic and mediastinal disorders: Nasal stuffiness.

 

Gastrointestinal disorders: Nausea, vomiting, distension, constipation, flatus, diarrhoea, colitis, mild dryness of mouth, sore or ‘black’ tongue, pancreatitis.

 

Skin and subcutaneous tissue disorders: Rash as in eczema or lichenoid eruption, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: Lupus-like syndrome, mild arthralgia with or without joint swelling, myalgia.

 

Endocrine disorders: Hyperprolactinaemia.

 

Infections and infestations: Sialadenitis.

 

Vascular disorders: Orthostatic hypotension (decrease daily dosage).

 

General disorders and administrative site conditions: Asthenia or weakness, oedema (and weight gain) usually relieved by use of a diuretic. (Discontinue methyldopa if oedema progresses or signs of heart failure appear.), drug-related fever.

 

Hepatobiliary disorders: Liver disorders including hepatitis, jaundice.

 

Reproductive system and breast disorders: Breast enlargement, gynaecomastia, amenorrhoea, lactation, impotence, failure of ejaculation.

 

Psychiatric disorders: Psychic disturbances including nightmares, reversible mild psychoses or depression, decreased libido.

 

Investigations: Positive Coombs test, positive tests for antinuclear antibody, LE cells, and rheumatoid factor, abnormal liver-function tests, rise in blood urea

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; the Yellow Card Scheme at www.mhra.gov.uk/yellowcard

4.9 Overdose

 

Symptoms

Acute overdosage may produce acute hypotension with other responses attributable to brain and gastro-intestinal malfunction (excessive sedation, weakness, bradycardia, dizziness, light-headedness, constipation, distension, flatus, diarrhoea, nausea, and vomiting).

 

Management

If ingestion is recent, emesis may be induced or gastric lavage performed. There is no specific antidote. Methyldopa is dialysable. Treatment is symptomatic. Infusions may be helpful to promote urinary excretion. Special attention should be directed towards cardiac rate and output, blood volume, electrolyte balance, paralytic ileus, urinary function and cerebral activity.

 

Administration of sympathomimetic agents may be indicated. When chronic

overdosage is suspected, ‘Aldomet’ should be discontinued.

 

5. PHARMACOLOGICAL PROPERTIES

 

5.1 Pharmacodynamic properties

 

Pharmacotherapeutic group: antiadrenergic agents; ATC code C02AB

Mechanism of action

It appears that several mechanisms of action account for the clinically useful effects of methyldopa and the current generally accepted view is that its principal action is on the central nervous system. The antihypertensive effect of methyldopa is probably due to its metabolism to alpha-methylnoradrenaline, which lowers arterial pressure by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline).

 

5.2 Pharmacokinetic properties

 

Absorption

Absorption of oral methyldopa is variable and incomplete.

 

Distribution

Bioavailability after oral administration averages 25%.

 

Biotransformation

Peak concentrations in plasma occur at two to three hours, and elimination of the drug is biphasic regardless of the route of administration. Plasma half-life is 1.8 ± 0.2 hours.

 

Elimination

Renal excretion accounts for about two thirds of drug clearance from plasma.

 

 

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

 

Licence first granted: 21st  February 1974/ Unlimited Validity

Licence last renewed: 05 September 2001

 

10 DATE OF REVISION OF THE TEXT

 

06th November 2015   29 November 2013

 

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:01-01-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



In Section 7 (Marketing Authorisation Holder), address has been updated

Newly added text
3016 Lake Drive,

Citywest Business Campus,

Dublin 24,

Deleted text
12/13 Exchange Place,
Custom House Docks,
I.F.S.C.,
Dublin 1

In Section 10 (Date of Revision of the Text), date has been updated

Newly added text
January 2015

Deleted text
29 Novenber 2013

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:29-11-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Text in red = new
Text strikethrough = deleted

7 MARKETING AUTHORISATION HOLDER


Aspen Europe Gmbh
Industriestrasse 32 36
D 23843 Bad Oldesloe
Germany

Aspen Pharma Trading Limited

12/13 Exchange Place,

Custom House Docks,

I.F.S.C.,

Dublin 1,

Ireland

 

8 MARKETING AUTHORISATION NUMBER(S)

PL 35468/0012 39699/0053


 

10 DATE OF REVISION OF THE TEXT

 

26/10/2010 29 November 2013

 

 

 

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): NO