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Methyldopa (Monograph)

Drug class: beta-Adrenergic Blocking Agents

Methyldopa (Systemic) is also contained as an ingredient in the following combinations:
Methyldopa and Hydrochlorothiazide

Medically reviewed by on Apr 10, 2024. Written by ASHP.


    Methyldopa in Fixed Combination with Hydrochlorothiazide
  • Should not use initially for the treatment of hypertension.

  • Adjust dosage initially by administering each drug separately.

  • Fixed combination may be used if it is determined that the optimum maintenance dosage corresponds to the ratio in a commercial combination preparation.

  • Reevaluate dosage as conditions in the patient warrant.


Hypotensive agent; centrally acting α2-adrenergic agonist.

Uses for Methyldopa


Used alone or in combination with other classes of antihypertensive agents in the management of hypertension.

Not considered a preferred agent for initial management of hypertension according to current guidelines for the management of hypertension in adults, but may be used as add-on therapy if BP not adequately controlled with the recommended antihypertensive drug classes (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics).

Generally reserved as a last-line treatment option because of the drug's ability to cause substantial adverse CNS effects, especially in geriatric patients.

May be more effective when used with a diuretic.

Use of a diuretic may prevent tolerance to methyldopa and permit reduction of methyldopa dosage.

Also has been used with other hypotensive agents, permitting a reduction in the dosage of each drug and, in some patients, minimizing adverse effects while maintaining BP control.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200


SBP (mm Hg)

DBP (mm Hg)









Hypertension, Stage 1




Hypertension, Stage 2




The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Consider initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes in patients with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Recommended by ACOG and other experts as an appropriate drug of choice in pregnant women who require antihypertensive therapy.

Hypertensive Crises

Has been used IV for the management of hypertensive crises. Because of the slow onset of action, other agents (e.g., labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside) are preferred.

Methyldopa Dosage and Administration


BP Monitoring and Treatment Goals


Administer methyldopa orally and methyldopate hydrochloride by IV infusion.

Usually administer orally; may be administered IV if parenteral administration is required.

IM or sub-Q administration not recommended because of unpredictable absorption.

Oral Administration

Minimize adverse effects (e.g., drowsiness) by initiating dosage increases in the evening.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.


Dilute methyldopate hydrochloride injection in 5% dextrose in water injection.

Add the required dose of the drug to 100 mL of 5% dextrose in water injection. Alternatively, dilute the required dose in 5% dextrose in water injection to provide a solution containing 100 mg/10 mL.

Rate of Administration

Administer slowly by IV infusion over 30–60 minutes.


Available as methyldopa or methyldopate hydrochloride; dosage expressed in terms of methyldopa or methyldopate hydrochloride, respectively.

Pediatric Patients


Initially, 10 mg/kg daily given in 2–4 divided doses.

Adjust dosage until an adequate response is achieved. Maximum dosage is 65 mg/kg daily, or 3 g daily, whichever is less.


Usual dosage: 20–40 mg/kg per 24 hours administered in equally divided doses at 6-hour intervals.

Maximum dosage is 65 mg/kg daily, or 3 g daily, whichever is less.

When BP is controlled, should substitute oral therapy at the same dosage.



Initially, 250 mg 2 or 3 times daily for 2 days. Increase or decrease dosage every 2 days until an adequate response is achieved.

For maintenance therapy, manufacturers recommend 0.5–2 g daily given in 2–4 divided doses.

Some experts state usual dosage range of 0.25–1 g daily in 2 divided doses; if needed, add another antihypertensive agent to the regimen rather than increasing maximum dosage to >1 g daily (poor patient tolerance).


Usual dosage: 250–500 mg every 6 hours as required. Maximum dosage is 1 g every 6 hours.

Combination Therapy

Fixed combination with a thiazide diuretic is not recommended for initial combination therapy; adjust initial and subsequent dosages by administering each drug separately. Consider fixed combination if the optimum maintenance dosage corresponds to the ratio in a commercial combination preparation.

Methyldopa in fixed combination with hydrochlorothiazide: Initially, 250 mg of methyldopa and 15 mg of hydrochlorothiazide given 2–3 times daily, or 250 mg of methyldopa and 25 mg of hydrochlorothiazide given twice daily. Alternatively, 500 mg of methyldopa and either 30 or 50 mg of hydrochlorothiazide once daily.

If tolerance occurs, add separate dosages of methyldopa or replace the fixed combination with each drug separately until the new effective dosage is reestablished by titration.

Combination with hypotensive drugs other than thiazide diuretics: Initially, maximum recommended dosage is 500 mg daily in divided doses. Adjust dosage of other hypotensive drugs if necessary.

Prescribing Limits

Pediatric Patients


Maximum 65 mg/kg daily, or 3 g daily, whichever is less.


Maximum 65 mg/kg daily, or 3 g daily, whichever is less.



Maximum 3 g daily as maintenance therapy recommended by manufacturers. Some experts recommend maximum 1 g daily because of poor patient tolerance.

Combination therapy with hypotensive drugs other than thiazide diuretics: Initially, maximum 500 mg daily in divided doses.


Maximum 1 g every 6 hours.

Special Populations

Renal Impairment

Consider dosage reduction.

Geriatric Patients

Consider dosage reduction to avoid syncope. (See Geriatric Use under Cautions.)

Cautions for Methyldopa




Hematologic Effects

Positive direct antiglobulin (Coombs’) test results reported, usually after 6–12 months of therapy; rarely associated with potentially fatal hemolytic anemia. After discontinuance of the drug, positive Coombs’ test reverses within weeks to months.

At treatment initiation, perform a hemoglobin, hematocrit, or a red blood cell count. Periodic blood counts recommended during therapy to detect hemolytic anemia.

May be useful to obtain a direct Coombs’ test before treatment initiation and after 6 and 12 months of therapy. If a positive Coombs’ test occurs, perform appropriate laboratory studies to determine if hemolytic anemia is present. If there is evidence of hemolytic anemia, discontinue the drug; do not reinstitute therapy if anemia is related to methyldopa.

Hemolytic anemia usually resolves promptly; if not, corticosteroids may be given and other causes of anemia should be considered and investigated.

If a blood transfusion is required, perform a direct and indirect Coombs’ test prior to transfusion. A positive direct Coombs’ test alone will not interfere with typing or crossmatching. If both the indirect and direct Coombs’ tests are positive, problems with major crossmatching may occur, and the assistance of an expert may be required.

Reversible leukopenia (primarily granulocytopenia) and immune thrombocytopenia reported rarely.

Hepatic Effects

Possible abnormal liver function test results (e.g., increased serum concentrations of alkaline phosphatase, aminotransferases, and bilirubin and abnormal PT).

Rarely, reversible jaundice, with or without fever, reported, usually within the first 2–3 months of therapy. These effects may be associated with cholestasis, hepatitis, hepatocellular injury, or cirrhosis. Potentially fatal hepatic necrosis reported rarely.

Hepatic dysfunction may represent hypersensitivity reactions. (See Sensitivity Reactions under Cautions.)

Assess hepatic function periodically, especially during the first 6–12 weeks of therapy or whenever unexplained fever occurs. If unexplained fever, abnormal liver function test results, or jaundice occurs, discontinue methyldopa. If methyldopa is the causative agent, temperature and liver function generally return to normal within a few months after methyldopa is discontinued; do not reinstitute therapy in such patients.

Use with caution in patients with a history of previous liver disease or dysfunction. Use contraindicated in patients with active hepatic disease. (See Contraindications under Cautions.)

Sensitivity Reactions

Eosinophilia, myocarditis, pericarditis, vasculitis, and lupus-like syndrome reported.

Fever may be associated with eosinophilia or hepatic dysfunction and may represent hypersensitivity reactions. (See Hepatic Effects under Cautions.)

Positive Coombs’ test and hemolytic anemia may represent hypersensitivity reactions. (See Hematologic Effects under Cautions.)

IV formulation contain sulfites, which can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes. Such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

General Precautions

Nervous System Effects

Involuntary choreoathetotic movements reported rarely in patients with severe bilateral cerebrovascular disease. If such symptoms occur, discontinue therapy.

Cardiovascular Effects

Sodium retention resulting in edema and weight gain reported; usually controlled by concomitant administration of a thiazide diuretic. Discontinue therapy if edema progresses or leads to CHF.

Possible paradoxical pressor response following IV administration.

Rebound hypertension has occurred rarely following abrupt withdrawal of oral methyldopa or following dialysis.

Neonatal Morbidity

In neonates born to women treated with methyldopa, SBP may be decreased during the first 2–3 days after delivery; tremors also have been reported.

Specific Populations


Category C (IV injection); Category B (tablets).


Distributed into milk. Caution if used in nursing women; monitor nursing infant (particularly if preterm) for potential systemic effects of the drug (e.g., decreased respiration, BP, or alertness).

Pediatric Use

No well-controlled studies in pediatric patients; dosage recommendations based on published literature.

Safety and efficacy of preparations containing methyldopa in fixed combination with hydrochlorothiazide not established.

Geriatric Use

Possibility exists of greater sensitivity to the drug in some geriatric individuals.

Possible syncope; may be related to an increased sensitivity to the drug and advanced arteriosclerotic vascular disease. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution in patients with a history of previous liver disease or dysfunction.

Renal Impairment

Generally considered to be safe for use; however, reduced dosage may be required.

Common Adverse Effects

Drowsiness or sedation.

Drug Interactions

Specific Drugs and Laboratory Tests

Drug or Test




Potential for hypotension

Reduced doses of general anesthetics may be required

Hypotension usually controlled by vasopressor agents

Antidepressants, tricyclic

Possible decreased hypotensive effect

BP monitoring recommended

Antihypertensive agents

Additive/potentiated hypotensive effect

Usually used to therapeutic advantage in antihypertensive therapy; however, carefully adjust dosage and monitor for adverse effects


Additive/potentiated hypotensive effect

Usually used to therapeutic advantage in antihypertensive therapy; however, carefully adjust dosage and monitor for adverse effects


Possible psychomotor retardation, memory impairment, and inability to concentrate in nonschizophrenic patients

Symptoms resolved upon discontinuance of haloperidol

Iron preparations, oral

Concomitant administration may decrease oral absorption and alter the metabolism of methyldopa

Possible increased BP

Concomitant administration with ferrous sulfate or ferrous gluconate is not recommended


Possible additive hypotensive effect and toxic CNS effects (e.g., psychosis)

Use with caution


Possible increased risk of lithium toxicity

Monitor for lithium toxicity and adjust therapy accordingly

MAO inhibitors

Possible marked hypotensive effect

Concomitant use contraindicated


Possible decreased hypotensive effect

BP monitoring recommended

Test for AST

May interfere with measurement of AST by colorimetric methods

Test for serum creatinine

May interfere with measurement of creatinine by the alkaline picrate method

Test for urinary catecholamines

May cause a false report of elevated urinary catecholamines

Causes fluorescence in urine samples at the same wavelengths as catecholamines

Test for urinary uric acid

May interfere with measurement of uric acid by the phosphotungstate method at concentrations of the drug that are several times higher than therapeutic concentrations

Methyldopa Pharmacokinetics



Generally about 50% of an oral dose is absorbed with peak plasma concentrations usually attained in approximately 3–6 hours.


Following oral administration, maximum decrease in BP occurs in 4–6 hours.

Following IV administration, BP begins to decrease in 4–6 hours.


Following discontinuance of oral therapy, BP returns to pretreatment levels within 24–48 hours.

Following IV administration, hypotensive effect lasts for 10–16 hours and hypertension recurs within 48 hours.



Crosses the blood-brain barrier.

Methyldopa crosses the placenta in humans and is distributed into milk.

Plasma Protein Binding

Weakly bound to plasma proteins.



Metabolized in the brain to α-methylnorepinephrine, the pharmacologically active metabolite. Other active metabolites include α-methylepinephrine and α-methyldopamine.

Extensively metabolized, probably in the GI tract and the liver, to sulfate conjugates.

Elimination Route

49% of an IV dose is excreted in the urine (via glomerular filtration) as the parent drug and the sulfate conjugate.

70% of an oral dose is excreted in the urine as parent drug and metabolites.

Unabsorbed methyldopa is excreted in the feces unchanged.


Plasma half-life is 105 or 90–127 minutes for methyldopa or methyldopate, respectively.

Special Populations

In patients with renal impairment, renal clearance is decreased.

Removed by hemodialysis and peritoneal dialysis.





Tight, light-resistant containers at 15–30°C. Protect methyldopa in fixed combination with hydrochlorothiazide from moisture and freezing.


Solution for Injection




Solution CompatibilityHID


Amino acids 4.25%, dextrose 25%

Dextran 6% in sodium chloride 0.9%

Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Normosol M in dextrose 5% in water

Normosol R

Ringer’s injection

Sodium bicarbonate 5%

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID



Ascorbic acid injection

Chloramphenicol sodium succinate

Diphenhydramine HCl

Heparin sodium

Magnesium sulfate


Potassium chloride

Sodium bicarbonate

Succinylcholine chloride

Verapamil HCl

Vitamin B complex with C


Amphotericin B

Methohexital sodium

Y-Site Compatibility


Esmolol HCl

Heparin sodium

Meperidine HCl

Morphine sulfate



Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name



Dosage Forms


Brand Names



Tablets, film-coated

250 mg*

Methyldopa Tablets

500 mg*

Methyldopa Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Methyldopa and Hydrochlorothiazide


Dosage Forms


Brand Names



Tablets, film-coated

250 mg with Hydrochlorothiazide 15 mg*

Methyldopa and Hydrochlorothiazide Tablets

250 mg with Hydrochlorothiazide 25 mg*

Methyldopa and Hydrochlorothiazide Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Methyldopate Hydrochloride


Dosage Forms


Brand Names




50 mg/mL*

Methyldopate Hydrochloride Injection

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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