ALDOMET TABLETS 125MG

Active substance: METHYLDOPA

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
ALDOMET® Tablets 125 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
‘Aldomet’ Tablets 125 mg, contain methyldopa equivalent to 125 mg
anhydrous methyldopa.

3

PHARMACEUTICAL FORM
Yellow, film-coated tablets.
‘Aldomet’ Tablets 125 mg are marked ‘ALDOMET MSD 135’.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
In the treatment of hypertension.

4.2

Posology and method of administration
General considerations: Methyldopa is largely excreted by the kidney, and
patients with impaired renal function may respond to smaller doses.
Withdrawal of ‘Aldomet’ is followed by return of hypertension, usually within
48 hours. This is not complicated generally by an overshoot of blood pressure.
Therapy with ‘Aldomet’ may be initiated in most patients already on treatment
with other antihypertensive agents by terminating these antihypertensive
medications gradually, as required. Following such previous antihypertensive
therapy, ‘Aldomet’ should be limited to an initial dose of not more than 500
mg daily and increased as required at intervals of not less than two days.
When methyldopa is given to patients on other antihypertensives the dose of
these agents may need to be adjusted to effect a smooth transition.
When 500 mg of ‘Aldomet’ is added to 50 mg of hydrochlorothiazide, the two
agents may be given together once daily.

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 3
g.
Oral therapy - Children: initial dosage is based on 10 mg/kg of bodyweight
daily in 2-4 oral doses. The daily dosage is then increased or decreased until
an adequate response is achieved. The maximum dosage is 65 mg/kg or 3.0 g
daily, whichever is less.
Use in the elderly: The initial dose in elderly patients should be kept as low as
possible, not exceeding 250 mg daily; an appropriate starting dose in the
elderly would be 125 mg b.d. increasing slowly as required, but not to exceed
a maximum daily dosage of 2 g. Syncope in older patients may be related to
an increased sensitivity and advanced arteriosclerotic vascular disease. This
may be avoided by lower doses.

4.3

Contraindications
‘Aldomet’ is contra-indicated in patients with:
• active hepatic disease, such as acute hepatitis and active cirrhosis

hypersensitivity (including hepatic disorders associated with previous
methyldopa
therapy) to any component of these products
• depression
• on therapy with monoamine oxidase inhibitors (MAOIs).
‘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
Acquired haemolytic anaemia has occurred rarely; should symptoms suggest
anaemia, haemoglobin and/or haematocrit determinations should be made. If
anaemia is confirmed, tests should be done for haemolysis. If haemolytic
anaemia is present, ‘Aldomet’ should be discontinued. Stopping therapy, with
or without giving a corticosteroid, has usually brought prompt remission.
Rarely, however, deaths have occurred.

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 doserelated, the lowest incidence occurring in patients receiving 1 g or less of
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 crossmatch 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 leucopenia, 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, also may 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 bloodcell count are advisable before therapy and at intervals during the first six
weeks to twelve weeks of therapy, or whenever an unexplained fever occurs.
Should fever, abnormality in liver function, or jaundice occur, therapy should
be withdrawn. If related to methyldopa, the temperature and abnormalities in
liver function will then return to normal. Methyldopa should not be used
again in these patients. Methyldopa should be used with caution in patients
with a history of previous liver disease or dysfunction.
Patients may require reduced doses of anaesthetics when on methyldopa. If
hypotension does occur during anaesthesia, it can usually be controlled by
vasopressors. The adrenergic receptors remain sensitive during treatment with
methyldopa.
Dialysis removes methyldopa; therefore, hypertension may recur after this
procedure.
Rarely, involuntary choreoathetotic movements have been observed during
therapy with methyldopa in patients with severe bilateral cerebrovascular
disease. Should these movements occur, therapy should be discontinued.

‘Aldomet’ should be used with extreme caution in patients, or in near relatives
of patients, with hepatic porphyria.
Interference with laboratory tests:
Methyldopa may interfere with the measurement of urinary uric acid by the
phosphotungstate method, serum creatinine by the alkaline picrate method,
and AST (SGOT) by colorimetric method.
Interference with
spectrophotometric methods for AST (SGOT) analysis has not been reported.
As methyldopa fluoresces at the same wavelengths as catecholamines,
spuriously high amounts of urinary catecholamines may be reported
interfering with a diagnosis of phaeochromocytoma.
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.
Rarely, when urine is exposed to air after voiding, it may darken because of
breakdown of methyldopa or its metabolites.

4.5

Interaction with other medicinal products and other forms of interaction
Lithium:
When methyldopa and lithium are given concomitantly the patient should be
monitored carefully for symptoms of lithium toxicity.
Other antihypertensive drugs:
When methyldopa is used with other antihypertensive drugs, potentiation of
antihypertensive action may occur. The progress of patients should be
carefully followed to detect side reactions or manifestations of drug
idiosyncrasy.
Other classes of drug:
The antihypertensive effect of ‘Aldomet’ may be diminished by
sympathomimetics, phenothiazines, tricyclic antidepressants and MAOIs (see
4.3 ‘Contra-indications’). In addition, phenothiazines may have additive
hypotensive effects.
Iron:
Several studies demonstrate a decrease in the bioavailability of methyldopa
when it is ingested with ferrous sulphate or ferrous gluconate. This may
adversely affect blood pressure control in patients treated with methyldopa.

4.6

Pregnancy and lactation
‘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 and breast
milk.
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 or who are breast-feeding their newborn infant requires
that anticipated benefits be weighed against possible risks.

4.7

Effects on ability to drive and use machines
‘Aldomet’ may cause sedation, usually transient, during the initial period of therapy
or whenever the dose is increased. If affected, patients should not carry out activities
where alertness is necessary, such as driving a car or operating machinery.

4.8

Undesirable effects
The following reactions have been reported:
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:
eruption, toxic epidermal necrolysis.

Rash as in eczema or lichenoid

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.

4.9

Overdose
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).
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
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 of oral methyldopa is variable and incomplete. Bioavailability
after oral administration averages 25%. 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. Renal excretion
accounts for about two thirds of drug clearance from plasma.

5.3

Preclinical safety data
No relevant information.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Tablet-core: cellulose powder, anhydrous citric acid; collodial silicon dioxide;
ethylcellulose; guar gum; magnesium stearate; sodium calcium edetate;
Tablet-coating: propylene glycol; anhydrous citric acid; hypromellose;
quinoline yellow aluminium lake E104; red iron oxide E172; talc; titanium
dioxide, carnauba wax.

6.2

Incompatibilities
None known.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Keep containers well closed and store below 25°C, protected from light.

6.5

Nature and contents of container
White polyethylene bottle of 100 tablets with turquoise polyethylene closure,
or PVC aluminium blister packs of 60 tablets.

6.6

Special precautions for disposal
None.

7.

MARKETING AUTHORISATION HOLDER
Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus
Dublin 24
Ireland

8

MARKETING AUTHORISATION NUMBER(S)
PL 39699/0011

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Licence first granted: 21 February 1974
Licence last renewed: 05 September 2001

10

DATE OF REVISION OF THE TEXT
19/12/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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