Methyldopa


Generic Medicine Info
Indications and Dosage
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.
Administration
May be taken with or without food.
Contraindications
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).
Special Precautions
Patients with severe bilateral cerebrovascular disease. Patients undergoing surgery. Renal or history of hepatic impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
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.
PO: B; IV/Parenteral: C
Patient Counseling Information
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.
Overdosage
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.
Drug Interactions
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).
Lab Interference
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.
Action
Description: 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).
Pharmacokinetics:
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.
Chemical Structure

Chemical Structure Image
Methyldopa

Source: National Center for Biotechnology Information. PubChem Database. Methyldopa, CID=38853, https://pubchem.ncbi.nlm.nih.gov/compound/Methyldopa (accessed on Jan. 22, 2020)

Storage
Store between 20-25ºC. Protect from light.
ATC Classification
C02AB - Methyldopa ; Used in the treatment of hypertension.
References
Aldomet 250 mg Tablets (Aspen Pharma Trading Limited). MHRA. https://products.mhra.gov.uk. Accessed 12/05/2021.

Anon. Methyldopa. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 12/05/2021.

Anon. Methyldopa. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 12/05/2021.

Buckingham R (ed). Methyldopa. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/05/2021.

Dopatab M 250 Tablet (Hovid Berhad). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 12/05/2021.

Joint Formulary Committee. Methyldopa. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/05/2021.

Methyldopa 125 mg Tablets (Bristol Laboratories Limited). MHRA. https://products.mhra.gov.uk. Accessed 12/05/2021.

Methyldopa Tablets, USP (Accord Healthcare Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 12/05/2021.

Mylan New Zealand Ltd. Methyldopa Mylan 250 mg Tablet data sheet 16 July 2018. Medsafe. http://www.medsafe.govt.nz. Accessed 12/05/2021.

Disclaimer: This information is independently developed by MIMS based on Methyldopa from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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