CO-CAPS METHYDOPA

Posology Use in adults:

Initial dosage: Usually 250 mg two or three times a day, for two days. The maximum recommended daily dosage is 3 g. Many patients experience sedation for two or three days when therapy with Methyldopa 250 mg capsules is started or when the dose is increased.

When increasing the dosage , therefore ,it may be desirable to increase the evening dose first. Withdrawal of Methyldopa 250 mg capsules is followed by return of hypertension, usually within 48 hours. This is not complicated generally by an overshoot of blood pressure.

Patients with renal impairment:

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

Other antihypertensives:

Therapy with Methyldopa 250 mg capsules 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,’ Methyldopa 250 mg capsules 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 Methyldopa 250 mg capsules is added to 50 mg of hydrochlorothiazide, the two agents may be given together once daily.

Paediatric Population:

Initial dosage is based on 10 mg/kg of bodyweight daily in 2-4 oral doses. 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.

Method of administration:

Oral

Sedation, usually transient , may occur during the in 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<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.

Pyrexia Investigations Positive Coombs test, positive tests for antinuclear antibody, LE cells, and rheumatoid factor, abnormal liver- function tests, increased blood urea Not known 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. uk/yellowcard.

If anaemia is confirmed, test 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 Coombs test. 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 leukopenia, with primary effect on granulocytes has been reported rarely. The granulocyte count returned to normal on discounting 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. 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, abnormalities in liver function, or jaundice occur, therapy should be withdrawn.

1 • depression • on therapy with monoamine oxidase inhibitors(MAOIs) • with a catecholamine-secreting tumour such as phaeochromocytoma or paraganglioma • with porphyria