Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Intrapharm Laboratories Limited, The Courtyard Barns, Choke Lane, Cookham Dean, Maidenhead, Berkshire, SL6 6PT
Methyldopa tablets are contraindicated in patients with:
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 tablets 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 dose-related, 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 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 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 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.
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.
Methyldopa Tablets should be used with extreme caution in patients, or in near relatives of patients, with hepatic porphyria.
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 or paraganglioma.
It is important to recognise this phenomenon before a patient with a possible phaeochromocytoma or paraganglioma 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.
Rarely, when urine is exposed to air after voiding, it may darken because of breakdown of methyldopa or its metabolites.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
When methyldopa and lithium are given concomitantly the patient should be monitored carefully for symptoms of lithium toxicity.
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. Concurrent use of verapamil and methyldopa can intensify sinus bradycardia.
The antihypertensive effect of methyldopa may be diminished by sympathomimetics, tricyclic antidepressants, phenothiazine derivatives and monoamine oxidase inhibitors (MAOIs), when administered concomitantly with these drugs (see 4.3 ‘Contra-indications’). In addition, phenothiazines may have additive hypotensive effects.
Concomitant administration of methyldopa with thiazide diuretics and other antihypertensive agents, general anaesthetics and levodopa enhances the antihypertensive effect.
The toxicity of haloperidol may be increased by concurrent use. Monoamine oxidase inhibitors should be discontinued before treatment with methyldopa.
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.
Methyldopa has been used under close medical supervision for the treatment of hypertension during pregnancy. There is no clinical evidence of foetal abnormalities or effect on 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 is present in cord blood and appears in 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.
Caution should be observed when driving or operating machinery, as methyldopa therapy may result in drowsiness, dizziness, light headedness, involuntary choreoathetotic movements in patients with severe cerebrovascular disease. The patient should be advised accordingly on initiation of therapy and/or increase in dosage.
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).
Not known: Bradycardia, aggravation of angina pectoris, myocarditis, pericarditis, atrioventricular block
Not known: Haemolytic anaemia, bone-marrow depression, leucopenia, granulocytopenia, thrombocytopenia, eosinophilia
Not known: Sedation (usually transient), headache, paraesthesia, Parkinsonism, VIIth nerve paralysis, choreoathetosis, mental impairment, carotid sinus syndrome, dizziness*, light-headedness*, symptoms of cerebrovascular insufficiency (may be due to lowering of blood pressure)
Not known: Nasal Stuffiness
Not known: Nausea, vomiting, abdominal distension, constipation, flatus, diarrhoea, colitis, mild dryness of mouth, sore or ‘black’ tongue, pancreatitis
Not known: Rash as in eczema or lichenoid eruption, toxic epidermal necrolysis, angioedema, urticaria
Not known: Lupus-like syndrome, mild arthralgia with or without joint swelling, myalgia
Not known: Hyperprolactinaemia
Not known: Sialadentis
Not known: Orthostatic hypotension (decrease daily dosage)
Not known: 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
Not known: Liver disorders including hepatitis, jaundice
Not known: Breast enlargement, gynaecomastia, amenorrhoea, lactation, impotence, failure of ejaculation
Not known: Psychic disturbances including nightmares, reversible mild psychoses or depression, decreased libido
Not known: Positive Coombs test, positive tests for antinuclear antibody, LE cells, and rheumatoid factor, abnormal liver-function tests, rise in blood urea
* 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.
Reporting of 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 website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None known.
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