Source: Υπουργείο Υγείας (CY) Revision Year: 2015 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Not recommended for the treatment of phaeochromocytoma (see section 4.4).
Acquired haemolytic anaemia has occurred rarely. Haemoglobin and/or haematocrit determinations should be made if symptoms suggest anaemia. If anaemia is confirmed, haemolysis tests should be done. Dopamet should be discontinued if haemolytic anaemia is present. Stopping therapy, with or without giving a corticosteroid, has usually brought prompt remission. Rarely, however, deaths have occurred.
On continued therapy with methyldopa some patients 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 1g 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.
Rarely reversible leucopenia, with primary effect on granulocytes has been reported. 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.
Therapy should be withdrawn if fever, abnormality in liver function, or jaundice occur. 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. In patients with a history of previous liver disease or dysfunction should be used with caution.
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.
Dopamet 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.
It is important to recognize 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.
Patients should be monitored carefully for symptoms of lithium toxicity when methyldopa and lithium are given concomitantly.
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.
The antihypertensive effect of mehyldopa may be diminished by sympathomimetics, phenothiazines, tricyclic antidepressants and MAOIs. In addition, phenothiazines may have additive hypotensive effects. Interaction with haloperidol has been reported.
According to several studies the bioavailability of methyldopa is decreased 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 was no clinical evidence that methyldopa caused fetal 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 breastfeeding require that anticipated benefits be weighed against possible risks.
Dopamet may cause sedations, 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.
The following reactions have been reported; frequency not known (cannot be estimated from the available data):
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 suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.
No known incompatibilities.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
