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CO-CAPS METHYDOPA 250MG

Active substance(s): METHYLDOPA

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Co-Caps Methyldopa 250 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Methyldopa (equivalent to Anhydrous Methyldopa) BP 250 mg

For excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Capsule

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Anti-hypertensive

4.2

Posology and method of administration
Adults:

250-500 mg six hourly. In severe cases, up to 1 g six-hourly.

Elderly:

The initial dose in elderly patients should be kept as low as possible, not
exceeding 250 mg daily. Maximum daily dosage of 2 g.

Children:

Initial dosage is based on 10 mg/kg of bodyweight daily in 2-4 oral doses.
The daily dosage then is increased or decreased until an adequate response
is achieved, the maximum dosage is 65 mg/kg or 3.0 g daily, whichever is
less

Method of administration: Oral

4.3

Contraindications

Active liver disease, such as acute hepatitis and active cirrhosis. Hypersensitivity to
the drug or to any component of Methyldopa 250mg. Depression.
Phaeochromocytoma. Porphyria.
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, Methyldopa 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 direct
Coombs test. Which may affect blood cross-matching. From the reports of
different investigators, the incidence averages up to 20% of patients. A positive
Coombs test rarely develops in the first six months of therapy.

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.
Caution is required in patients with renal impairment (start with small dose as there may
be increased sensitivity to hypotensive and sedative effect).
Methyldopa should be given with caution in patients with history of depression.
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 blood count are advisable 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, hypotension may recur after this procedure.
Rarely, involuntary choreo-athetotic movements have been observed during therapy with
Methyldopa in patients with severe bilateral cerebrovascular disease.
Should these movements occur, therapy should be discontinued.
Methyldopa 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 calorimetric 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. Methydopa 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 the
breakdown of methyldopa or its metabolites.

4.5

Interaction with other medicinal products and other forms of interaction
Interaction with lithium may cause neurotoxicity without increased plasma
concentrations.
Potentiaton of the antihypertensive action of methyldopa may occur when this
drug is used with other hypertensive agents, alcohol, alprostadil, anaesthetics,
antidepressants (concomitant use with MAOIs should be avoided),
antipsychotics, anxiolytics and hypnotics, beta-blockers, calcium-channel
blockers, diuretics, moxisylyte, the muscle relaxants baclofen and tizanidine,
nitrates, ACE inhibitors, adrenergic neurone blockers, alpha-blockers,
angiotensin-II receptor antagonists, aldesleukin, levodopa and possibly
entacapone. Acute hypotension has been reported with salbutamol infusion.
The hypotensive effect of methyldopa is antagonised by NSAIDs,
corticosteroids, iron, oestrogens and combined oral contraceptives.
Methyldopa antagonises the antiparkinsonian effect of dopaminergics. There is
an increased risk of extrapyramidal side effects when methyldopa is
given with amantadine.

4.6

Pregnancy and lactation
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 nursing their newborn infant requires that
anticipated benefits be weighed against possible risks.

4.7

Effects on ability to drive and use machines
None stated.

4.8

Undesirable effects
Sedation usually transient may occur during the initial period of therapy or
whenever the dose is increased. Headache, asthenia or weakness may be noted as
early and transient symptoms.
The following reactions have been reported:
Central Nervous System: Sedation (usually transient), headache, asthenia or
weakness, paraesthesiae, parkinsonism, Bell’s palsy, involuntary choreoathetotic
movements. Psychic disturbances including nightmares, impaired mental acuity and
reversible mild psychoses or depression. Dizziness, light-headedness, and symptoms
of cerebrovascular insufficiency (may be due to lowering of blood pressure).
Cardiovascular: Bradycardia, prolonged caroteid sinus hypersensitivity, aggravation
of angina pectoris. Orthostatic hypotension (decrease daily dosage). Oedema (and
weight gain) usually relieved by use of a diuretic. (Discontinue methyldopa if
oedema progresses or signs of heart failure appear).
Gastro-intestinal: Nausea, vomiting, distension, constipation, flatus, diarrhoea,
colitis, mild dryness of mouth, sore or ‘black’ tongue, stomatitis, pancreatitis,
sialadenitis.
Hepatic: Liver disorders including hepatitis, jaundice, abnormal liver function tests.
Haematological: Positive Coombs test, haemolytic anaemia, bone marrow
depression, leucopenia, granulocytopenia, thrombocytopenia and eosinophilia..
Positive tests for anti-nuclear antibody. LE cells, and rheumatoid factor.
Allergic: Drug-related fever and abnormal liver function tests with jaundice and
hepatocellular damage, lupus erythematous-like syndrome, myocarditis and
pericarditis.

Dermatological: Rash as in eczema or lichenoid eruption, toxic epidermal
necrolysis.
Other: Nasal stuffiness, rise in blood urea, breast enlargement, gynaecomastia,
hyperprolactinaemia, amenorrhoea, lactation, failure of ejaculation, impotence,
decreased libido, mild arthralgia with or without joint swelling, myalgia.

4.9

Overdose
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.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Methyldopa acts centrally by stimulating alpha-adrenergic receptors. It inhibits
the decarboxylation of dopa to dopamine but this action does not appear to be
responsible for its hypotensive effect. It is suggested that a metabolite, alphamethylnoradrenaline, may act as a false transmitter in the central nervous system.
Methyldopa reduces the tissue concentrations of dopamine, noradrenaline,
adrenaline, and serotonin.
When administered by mouth its effects may appear after about two hours and
reach a maximum in 6 to 8 hours, although the maximum hypotensive effect may
not occur until the second day of treatment; some effect is still usually apparent
until 48 hours after a dose.

5.2

Pharmacokinetic particulars
Methyldopa is completely absorbed from the gastro-intestinal tract. It is partly
conjugated, mainly to the O-sulphate, and is excreted by the kidneys. Elimination
follows a biphasic pattern. Plasma protein binding is reported to be minimal. It
crosses the placenta and small amounts appear in breast milk.

5.3

Preclinical safety data
Not applicable

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Starch 1500
Sodium Starch Glycollate
Magnesium Stearate
Gelatin
Titanium Dioxide (E171)
Tartrazine (E102)

6.2

Incompatibilities
None stated

6.3

Shelf life
36 months

6.4

Special precautions for storage
Store below 25°C in a dry place. Protect from light. Keep container well
closed.

6.5

Nature and contents of container
High density polystyrene with polythene lids and/or polypropylene containers
with polypropylene or polythene lids and polythene or polyurethane inserts
Pack sizes: 100 and 500

6.6

Special precautions for disposal
No special instructions

7

MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
Boumpoulinas 11, 3rd Floor
NICOSIA
CYPRUS
P.C. 1060
CYPRUS

8

MARKETING AUTHORISATION NUMBER(S)
PL 33414/0062

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
26/11/1987

10

09/02/1998

DATE OF REVISION OF THE TEXT
26/08/1997

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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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