Methyldopa

Oral
Hypertension
Adult: Monotherapy: Initially, 250 mg bid or tid for 2 days. May increase or decrease at intervals of at least 2 days according to response. Maintenance: 500-2,000 mg daily in 2-4 divided doses. Max: 3,000 mg daily. Combination therapy with other antihypertensive agents: Initially, 500 mg daily in divided doses; increased as necessary at intervals of at least 2 days. Administer new dosage increases in the evening to minimise sedation.
Child: Initially, 10 mg/kg daily in 2-4 divided doses. May increase or decrease according to response. Max: 65 mg/kg or 3,000 mg daily, whichever is less.
Elderly: Initially, 125 mg bid. Gradually increase according to response. Max: 2,000 mg daily.
Renal impairment: Lower doses may be sufficient.

May be taken with or without food.

Active liver disease (e.g. acute hepatitis, active cirrhosis), liver disorders associated with previous use of methyldopa, catecholamine-secreting tumour (e.g. phaeochromocytoma, paraganglioma), porphyria, depression. Concurrent administration of MAOIs (e.g. phenelzine).

Patients with severe bilateral cerebrovascular disease. Patients undergoing surgery. Renal or history of hepatic impairment. Children and elderly. Pregnancy and lactation. Patient Counselling This drug may cause drowsiness, if affected, do not drive or operate machinery. Monitoring Parameters Monitor blood pressure (standing and sitting/lying down), CBC, liver enzymes (periodically during the 1st 6-12 weeks or when unexplained fever occurs). Direct Coombs test before initiation of therapy and at 6 and 12 months is recommended.

Significant: Oedema, weight gain, reversible granulocytopenia and thrombocytopenia, sedation, fever, jaundice, depression. Blood and lymphatic system disorders: Bone marrow depression, leucopenia, eosinophilia. Cardiac disorders: Bradycardia, angina pectoris, myocarditis, pericarditis, atrioventricular block. Endocrine disorders: Hyperprolactinaemia. Gastrointestinal disorders: Nausea, vomiting, abdominal distension, constipation, flatulence, diarrhoea, colitis, xerostomia, glossodynia, melanoglossia, sialoadenitis, pancreatitis. General disorders and administration site conditions: Asthenia. Hepatobiliary disorders: Hepatitis. Immune system disorders: Lupus-like syndrome. Investigations: Positive Coombs test, positive tests for antinuclear antibody, LE cells, and rheumatoid factor, abnormal LFT, increased BUN. Musculoskeletal and connective tissue disorders: Mild arthralgia, myalgia. Nervous system disorders: Bell's palsy, headache, paraesthesia, parkinsonism, choreoathetosis, carotid sinus syndrome, dizziness, symptoms of cerebrovascular insufficiency. Psychiatric disorders: Nightmares, impaired mental acuity, reversible mild psychosis. Reproductive system and breast disorders: Breast hypertrophy, gynaecomastia, amenorrhoea, lactation, decreased libido, erectile dysfunction, ejaculation failure. Respiratory, thoracic and mediastinal disorders: Nasal congestion. Skin and subcutaneous tissue disorders: Rash (i.e. eczema, lichenoid eruption), urticaria, toxic epidermal necrolysis. Vascular disorders: Orthostatic hypotension.
Potentially Fatal: Hepatic necrosis, haemolytic anaemia.

Symptoms: Acute hypotension, excessive sedation, weakness, bradycardia, dizziness, lightheadedness, constipation, abdominal distention, flatus, diarrhoea, nausea, vomiting. Management: Symptomatic and supportive treatment. If ingestion is recent, may perform gastric lavage or induce emesis. Administration of sympathomimetic agents may be considered.

May increase lithium toxicity. May potentiate the effect of other antihypertensive drugs (e.g. atenolol). Sympathomimetics (e.g. phenylephrine), phenothiazines (e.g. chlorpromazine), and TCAs (e.g. amitriptyline) may diminish the antihypertensive effect of methyldopa. Iron preparations (e.g. ferrous sulfate) may decrease the serum concentration of methyldopa.
Potentially Fatal: Enhanced adverse or toxic effect with MAOIs (e.g. phenelzine).

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. May interfere with the diagnosis of catecholamine-secreting tumours (e.g. phaeochromocytoma, paraganglioma). May cause false-positive aldosterone/renin ratio.

Methyldopa is metabolised into α-methylnorepinephrine, a false neurotransmitter that stimulates the central inhibitory α-adrenergic receptors resulting in a decreased arterial pressure.
Onset: 3-6 hours (single dose); 48-72 hours (multiple doses).
Duration: 12-24 hours (single dose); 24-48 hours (multiple doses).
Absorption: Variably and partially absorbed from the gastrointestinal tract. Bioavailability: Approx 42%. Time to peak plasma concentration: 2-4 hours.
Distribution: Crosses the blood-brain barrier and placenta; enters breast milk (approx 20-35%). Volume of distribution: 0.23 L/kg. Plasma protein binding: 10-15%.
Metabolism: Extensively metabolised in the liver and gastrointestinal tract. Converted to active α-methylnorepinephrine via decarboxylation in the CNS.
Excretion: Via urine (approx 70%, as unchanged drug and mono-O-sulfate conjugate). Elimination half-life: 1.5-2 hours.

Oral: Store between 20-25°C. Protect from light.

Other Antihypertensives

C02AB - Methyldopa ; Used in the treatment of hypertension.