Methyldopa


Concise Prescribing Info
Indications/Uses
HTN.
Dosage/Direction for Use
Adult : PO Monotherapy: Initial: 250 mg bid-tid for 2 days; adjust at intervals of at least 2 days. Maintenance: 500-2,000 mg/day. Max: 3,000 mg/day. Combination therapy: Initial: Max 500 mg/day in divided doses. IV As methyldopate HCl: 250-500 mg 6 hrly over 30-60 min. Max: 1,000 mg 6 hrly.
Dosage Details
Intravenous
Hypertension
Adult: As methyldopate HCl: 250-500 mg 6 hrly over 30-60 min as required. Max: 1,000 mg 6 hrly.
Child: 20-40 mg/kg or 600-1,200 mg/m2 daily in equally divided doses 6 hrly. Max: 65 mg/kg, 2,000 mg/m2 or 3,000 mg daily, whichever is least.

Oral
Hypertension
Adult: Monotherapy: Initially, 250 mg bid-tid for 2 days; adjust at intervals of at least 2 days according to response. Maintenance: 500-2,000 mg daily. Max: 3,000 mg daily. Combination therapy: Initial dose should not exceed 500 mg daily in divided doses.
Child: <12 yr Initially, 10 mg/kg or 300 mg/m2 daily in 2-4 divided doses; adjust at intervals of at least 2 days according to response. Max: 65 mg/kg, 2,000 mg/m2 or 3,000 mg daily, whichever is least.
Elderly: Initially, 125 mg bid; gradually increase according to response. Max: 2,000 mg daily.
Renal Impairment
May respond to smaller doses.
Administration
May be taken with or without food.
Reconstitution
Add the required dose to 100 mL of dextrose 5% inj. Alternatively, the required dose may be administered in dextrose 5% inj in a concentration of 100 mg/10 mL.
Contraindications
Active liver disease (e.g. acute hepatitis, active cirrhosis) or depression. Concomitant use w/ MAOIs.
Special Precautions
Patient w/ history of haemolytic anaemia, liver disease or depression; parkinsonism, hepatic porphyria. Not intended for the treatment of phaeochromocytoma. Renal or hepatic impairment. Childn, elderly. Pregnancy and lactation.
Adverse Reactions
Drowsiness, orthostatic hypotension, nausea, headache, weakness, fatigue, decreased libido, impotence, impaired concentration and memory, mild psychoses, depression, disturbed sleep, nightmares, paraesthesias, Bell's palsy, parkinsonism, involuntary choreoathetotic movements, oedema, fluid retention, exacerbation of angina pectoris, bradycardia, syncope, prolonged carotid sinus hypersensitivity, paradoxical HTN, GI disturbances (e.g. nausea, vomiting, diarrhoea, constipation), black/sore tongue, inflamed salivary glands, dry mouth, fever, eosinophilia, liver function disturbances, hepatitis, lupus-like syndrome, rashes, lichenoid and granulomatous eruptions, toxic epidermal necrolysis, flu-like syndrome, nocturia, uraemia, nasal congestion, retroperitoneal fibrosis, hyperprolactinaemia, breast enlargement (including gynaecomastia), galactorrhoea, amenorrhoea. Rarely, pancreatitis and colitis, immune thrombocytopenia, reversible leucopenia (primarily granulocytopenia).
Potentially Fatal: Hepatic necrosis, haemolytic anaemia, hypersensitivity myocarditis.
PO: B; IV/Parenteral: C
Patient Counseling Information
May impair ability to drive or operate machinery.
MonitoringParameters
Monitor BP, blood counts, liver enzymes; direct Coombs' test.
Overdosage
Symptoms: Acute hypotension, brain and GI malfunction (e.g. excessive sedation, weakness, bradycardia, dizziness, light-headedness, constipation, distension, flatus, diarrhoea, nausea, vomiting). Management: Symptomatic treatment. Induce emesis or perform gastric lavage if ingestion is recent. Infusions may help promote urinary excretion. May admin sympathomimetic agents.
Drug Interactions
Potentiation of hypotensive effects w/ diuretics and other antihypertensives. Reduced metabolism w/ COMT inhibitors (e.g. entacapone). Sympathomimetics may antagonise the hypotensive effects of methyldopa. Paradoxical antagonism of hypotensive effects w/ TCAs, antipsychotics and β-blockers. May increase lithium toxicity.
Potentially Fatal: Diminished hypotensive effect w/ MAOIs.
Lab Interference
Positive Coombs' test. May interfere w/ 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 w/ the diagnosis of phaeochromocytoma.
Action
Description: Methyldopa stimulates central α-adrenergic receptors by a false neurotransmitter (α-methylnorepinephrine) which results in reduced sympathetic tone and fall in BP.
Onset: 4-6 hr.
Duration: 12-24 hr (single oral dose); 24-48 hr (multiple oral dose); 10-16 hr (IV).
Pharmacokinetics:
Absorption: Variably and incompletely absorbed from the GI tract. Bioavailability: Approx 50%. Time to peak plasma concentration: 2-4 hr (oral).
Distribution: Crosses the blood-brain barrier and placenta; enters breast milk (small amounts). Volume of distribution: 0.23 L/kg. Plasma protein binding: Minimal (10-15%).
Metabolism: Extensively metabolised; converted to active α-methylnorepinephrine via decarboxylation in the CNS.
Excretion: Via urine, mainly as unchanged drug and the O-sulfate conjugate. Biphasic elimination half-life: Approx 1.7 hr (initial phase); more prolonged (2nd phase).
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 20-25°C.
ATC Classification
C02AB - Methyldopa ; Used in the treatment of hypertension.
References
Anon. Methyldopa. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 12/10/2015.

Buckingham R (ed). Methyldopa. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com/. Accessed 09/10/2015.

McEvoy GK, Snow EK, Miller J et al (eds). Methyldopa, Methyldopate Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 09/10/2015.

Methyldopate Hydrochloride Injection, Solution (American Regent, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 12/10/2015.

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