Methyldopa

Updated 2013 Jan 18 12:26:53 PM: Methyldopa brands data updatedShow more
updates
Warnings

Warnings:
Methyldopa in Fixed Combination with Hydrochlorothiazide

Should not use initially for the treatment of hypertension. b d

Adjust dosage initially by administering each drug separately. d

Fixed combination may be used if it is determined that the optimum maintenance

dosage corresponds to the ratio in a commercial combination preparation. d

Reevaluate dosage as conditions in the patient warrant. d

Potentially Inappropriate Medication Use in Older Adults:

American Geriatrics Society (AGS) Beers Criteria recommends avoiding centrally

acting alpha agonists in older adults due to high risk of adverse central nervous system
effects (AGS Strong recommendation, Low quality evidence) (2012 AGS Beers Criteria
for potentially inappropriate medication use in older adults [J Am Geriatr Soc 2012
Apr;60(4):616 full-text])

General Information

Description:
Hypotensive agent; centrally acting 2-adrenergic agonist.

b c d e f h

Class:
Class: Central alpha-Agonists

Brands:

United States Brands:

generic methyldopa available

see also methyldopa in DailyMed

Discontinued Brands (US):

Aldomet

Canadian Brands:

generic methyldopa available

see also Health Canada Drug Product Database (DPD)

Combination Products Containing This Drug (Canada):

methyldopa/hydrochlorothiazide (generic)

United Kingdom Brands:

generic methyldopa available

Aldomet
see also methyldopa in British National Formulary (BNF) or electronic Medicines
Compendium (eMC)

Australian Brands:

Aldomet Tablets (see MIMS Online)

Hydopa Tablets (see MIMS Online)

Uses and Efficacy

Uses:

Hypertension:
Used alone or in combination with other classes of antihypertensive agents in the
management of hypertension. c d e f
Thiazide diuretics are considered the preferred initial monotherapy for uncomplicated
hypertension by JNC 7. 144
May be more effective when used with a diuretic.

122 126 127

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

methyldopa dosage. 122 126 127
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.
Initial hypotensive agent of choice for management of hypertension in pregnant
women. 109 110 111 115 118 126 129 130
Preferred oral antihypertensive for women with preeclampsia when delivery likely will be
delayed for more than 48 hours. 148

Hypertensive Crises:
Used IV for the management of hypertensive crises. f Because of the slow onset of action,
other agents (e.g., sodium nitroprusside) are preferred. 126
Avoid excessive falls in BP since they may precipitate renal, cerebral, or coronary
ischemia. 118 126
Dosage and Administration

Administration:
Administer methyldopa orally and methyldopate hydrochloride by IV infusion.

c d e f

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. e

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

c f

Dilution:
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. f Alternatively, dilute the required dose in 5% dextrose in water injection to
provide a solution containing 100 mg/10 mL. f

Rate of Administration:
Administer slowly by IV infusion over 3060 minutes.

Dosage:
Available as methyldopa or methyldopate hydrochloride; dosage expressed in terms of
methyldopa or methyldopate hydrochloride, respectively. c d e f

Pediatric Patients:
Hypertension:
Monotherapy:

Oral:
Initially, 10 mg/kg daily given in 24 divided doses.

c e

Adjust dosage until an adequate response is achieved.

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

b c

Maximum dosage is 65

IV:
Usual dosage: 2040 mg/kg per 24 hours administered in equally divided doses at
6-hour intervals. f
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.

b f

Adults:
Hypertension:
Monotherapy:

Oral:
Initially, 250 mg 2 or 3 times daily for 2 days. b Increase or decrease dosage
every 2 days until an adequate response is achieved. b c c
For maintenance, manufacturers recommend 5002000 mg daily given in 24
divided doses. c

JNC 7 recommends a lower usual dosage range of 125500 mg twice daily;

needed, add another antihypertensive agent to the regimen rather than
increasing maximum dosage >1 g daily because of poor patient tolerance.

144

if

149

IV:
Usual dosage: 250500 mg every 6 hours as required. f Maximum dosage is 1 g
every 6 hours. f
Combination Therapy:

Oral:
Methyldopa in fixed combination with hydrochlorothiazide: Initially, 250 mg of
methyldopa and 15 mg of hydrochlorothiazide given 23 times daily, or 250 mg
of methyldopa and 25 mg of hydrochlorothiazide given twice
daily. b d Alternatively, 500 mg of methyldopa and either 30 or 50 mg of
hydrochlorothiazide once daily. 138 d
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. d
Combination with hypotensive drugs other than thiazide diuretics: Initially,
maximum recommended dosage is 500 mg daily in divided doses. d Adjust
dosage of other hypotensive drugs if necessary. c d

Hypertensive Crises:
IV:

Usual dosage: 250500 mg every 6 hours as required.

Initial goal is to reduce mean arterial BP by no more than 25% (within minutes to 1
hour), then if stable, to 160/100 to 110 mm Hg within the next 26 hours. 126 Avoid
excessive declines in pressure. 126
If this BP is well tolerated and the patient is clinically stable, implement further
gradual reductions toward normal in the next 2448 hours. 148 In patients with aortic
dissection, reduce SBP to <100 mm Hg if tolerated. 148

General:

Hypertension:

Adjust dosage according to the patients BP response and tolerance. b c

Monitor BP during initial titration or subsequent upward dosage adjustment; large or
abrupt reductions in BP generally should be avoided. 126 144
Fixed combination with a thiazide diuretic is not recommended for initial combination
therapy; adjust initial and subsequent dosages by administering each drug separately. b d
Consider fixed combination if the optimum maintenance dosage corresponds to the
ratio in a commercial combination preparation. d
Tolerance to antihypertensive effect may develop; 122 126 127 may be necessary to
increase dosage or use a diuretic concomitantly. 122 126 127 Manufacturers recommend

addition of a thiazide diuretic at any time during methyldopa therapy or if effective BP

control cannot be maintained on 2 g of oral methyldopa daily. c e

Special Populations:

Renal Impairment:
Consider dosage reduction.

b c d f

Geriatric Patients:
Consider dosage reduction to avoid syncope.

e f

(See Geriatric Use under Cautions.)

Prescribing Limits:

Pediatric Patients:
Hypertension:
Oral:

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

IV:

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

Adults:
Hypertension:
Oral:

Maximum 3 g daily as maintenance therapy recommended by manufacturers.

7 recommends maximum 1 g daily because of poor patient tolerance. 149

c e

JNC

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

Maximum 1 g every 6 hours.

Hypertensive Crises:
IV:

Maximum 1 g every 6 hours.

Cautions and Adverse Effects

Contraindications:

Active hepatic disease (e.g., acute hepatitis, active cirrhosis).

under Cautions.)
Liver disorders with previous methyldopa therapy. b c d e f

b f

(See Hepatic Effects

Direct Coombs positive hemolytic anemia with previous methyldopa therapy. b

Concomitant therapy with MAO inhibitors or ferrous sulfate or
gluconate. 123 124 125 c d e c f (See Specific Drugs and Laboratory Tests under Interactions.)
Pheochromocytoma. b e
Known hypersensitivity to methyldopa or any ingredient in formulations, including
sulfites (with IV injection). b f

Warnings/Precautions:

Warnings:
Hematologic Effects:
Positive direct antiglobulin (Coombs) test results reported, usually after 612 months
of therapy; rarely associated with potentially fatal hemolytic anemia. b e n After
discontinuance of the drug, positive Coombs test reverses within weeks to months. b e
At treatment initiation, perform a hemoglobin, hematocrit, or a red blood cell
count. b e Periodic blood counts recommended during therapy to detect hemolytic
anemia. b e
May be useful to obtain a direct Coombs test before treatment initiation and after 6
and 12 months of therapy. b e If a positive Coombs test occurs, perform appropriate
laboratory studies to determine if hemolytic anemia is present. e If there is evidence of
hemolytic anemia, discontinue the drug; do not reinstitute therapy if anemia is related
to methyldopa. b e
Hemolytic anemia usually resolves promptly; if not, corticosteroids may be given and
other causes of anemia should be considered and investigated. b f
If a blood transfusion is required, perform a direct and indirect Coombs test prior to
transfusion. b A positive direct Coombs test alone will not interfere with typing or
crossmatching.c 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. c
Reversible leukopenia (primarily granulocytopenia) and immune thrombocytopenia
reported rarely. b c

Hepatic Effects:
Possible abnormal liver function test results (e.g., increased serum concentrations of
alkaline phosphatase, aminotransferases, and bilirubin and abnormal PT). c e f
Rarely, reversible jaundice, with or without fever, reported, usually within the first 23
months of therapy. c f These effects may be associated with cholestasis, hepatitis,
hepatocellular injury, or cirrhosis. b c Potentially fatal hepatic necrosis reported
rarely. b c
Hepatic dysfunction may represent hypersensitivity reactions.
Reactions under Cautions.)

e n

(See Sensitivity

Assess hepatic function periodically, especially during the first 612 weeks of therapy
or whenever unexplained fever occurs. c f If unexplained fever, abnormal liver function
test results, or jaundice occurs, discontinue methyldopa. b c If methyldopa is the
causative agent, temperature and liver function generally return to normal within a
few months after methyldopa is discontinued; b c f do not reinstitute therapy in such
patients. b c
Use with caution in patients with a history of previous liver disease or
dysfunction. f Use contraindicated in patients with active hepatic disease.
Contraindications under Cautions.)

c f

(See

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

c f

Fever may be associated with eosinophilia or hepatic dysfunction and may represent
hypersensitivity reactions. e n (See Hepatic Effects under Cautions.)
Positive Coombs test and hemolytic anemia may represent hypersensitivity
reactions. n (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. b f Such sensitivity
appears to occur more frequently in asthmatic than in nonasthmatic individuals. b f

General Precautions:
Nervous System Effects:
Involuntary choreoathetotic movements reported rarely in patients with severe
bilateral cerebrovascular disease. c If such symptoms occur, discontinue therapy.

Cardiovascular Effects:
Sodium retention resulting in edema and weight gain reported; b f usually controlled by
concomitant administration of a thiazide diuretic. b f Discontinue therapy if edema
progresses or leads to CHF. b f
Possible paradoxical pressor response following IV administration.

f n

Rebound hypertension has occurred rarely following abrupt withdrawal of oral

methyldopa or following dialysis. b f n

Neonatal Morbidity:
In neonates born to women treated with methyldopa, SBP may be decreased during
the first 23 days after delivery; 112 tremors also have been reported. 113

Specific Populations:
Pregnancy:
Category C (IV injection); f Category B (tablets).

Lactation:
Distributed into milk. b Caution if used in nursing women; b monitor nursing infant
(particularly if preterm) for potential systemic effects of the drug (e.g., decreased
respiration, BP, or alertness). 103

Pediatric Use:
No well-controlled studies in pediatric patients; dosage recommendations based on
published literature. 123 124
Safety and efficacy of preparations containing methyldopa in fixed combination with
hydrochlorothiazide not established. 125

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

126

Possible syncope; may be related to an increased sensitivity to the drug and advanced
arteriosclerotic vascular disease. e f (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. b c d e f

Common Adverse Effects:

Drowsiness or sedation.

Interactions

Specific Drugs and Laboratory Tests:

Drug or Test
Anesthetics

Interaction
Potential for hypotension

b c

Comments
Reduced doses of general
anesthetics may be
required e Hypotension usually
controlled by vasopressor

agents
Antidepressant
s, tricyclic

Possible decreased hypotensive effect

c e

BP monitoring recommended

Additive/potentiated hypotensive
effect b c

Usually used to therapeutic

advantage in antihypertensive
therapy; however, carefully
adjust dosage b and monitor for
adverse effects c

Diuretics

Additive/potentiated hypotensive
effect b c

Usually used to therapeutic

advantage in antihypertensive
therapy; however, carefully
adjust dosage b and monitor for
adverse effects c

Haloperidol

Possible psychomotor retardation,

memory impairment, and inability to
concentrate in nonschizophrenic
patients b

Symptoms resolved upon

discontinuance of haloperidol

Iron
preparations,
oral

Concomitant administration may

decrease oral absorption and alter the
metabolism of methyldopa 116 Possible
increased BP 116

Concomitant administration with

ferrous sulfate or ferrous
gluconate
isnot recommended 138 c

Levodopa

Possible additive hypotensive effect

and toxic CNS effects (e.g., psychosis) b

Use with caution

Lithium

Possible increased risk of lithium

toxicity b

Monitor for lithium toxicity and

adjust therapy accordingly b c

MAO inhibitors

Possible marked hypotensive effect

Phenothiazines

Possible decreased hypotensive effect

Test for AST

May interfere with measurement of

AST by colorimetric methods b c

Test for serum

creatinine

May interfere with measurement of

creatinine by the alkaline picrate
method b c

Test for urinary

catecholamine
s

May cause a false report of elevated

urinary catecholamines c e 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

Antihypertensi
ve agents

Concomitant use
contraindicated 123

124 125

BP monitoring recommended

method at concentrations of the drug

that are several times higher than
therapeutic concentrations b f
Mechanism of Action/Pharmacokinetics

Actions:

Central effects: Appears to stimulate 2-adrenergic receptors in the CNS (mainly in

the medulla oblongata), causing inhibition of sympathetic vasomotor
centers. h Contributes predominantly to hypotensive effects. b h k
Central effects result in reduced peripheral sympathetic nervous system activity,
total peripheral resistance, and BP. b h i
Reduces BP in both supine and standing patients. c
Produces little change in cardiac output and heart rate. b c
Stimulates peripheral 2-adrenergic receptors leading to a decrease in the release of
norepinephrine and a reduction in sympathetic tone. g
Inhibits the decarboxylation of dihydroxyphenylalanine (dopa)the precursor of
norepinephrineand of 5-hydroxytryptophan (5-HTP)the precursor of serotoninin the
CNS and in most peripheral tissues. b c f Not a major mechanism of action. b n
Renal and metabolic effects: Usually does not reduce renal blood flow or GFR. c
Causes sodium and water retention and increased plasma volume. b n
Reduces plasma renin activity (PRA). f
Increases serum prolactin concentrations. b m

Pharmacokinetics:

Absorption:
Bioavailability:
Generally about 50% of an oral dose is absorbed with peak plasma concentrations
usually attained in approximately 36 hours. b

Onset:
Following oral administration, maximum decrease in BP occurs in 46 hours.
Following IV administration, BP begins to decrease in 46 hours.

b c

b f

Duration:
Following discontinuance of oral therapy, BP returns to pretreatment levels within 24
48 hours. c
Following IV administration, hypotensive effect lasts for 1016 hours and hypertension
recurs within 48 hours. b f

Distribution:
Extent:
Crosses the blood-brain barrier.

h j

Methyldopa crosses the placenta in humans

101 102

and is distributed into milk.

101 103

Plasma Protein Binding:

Weakly bound to plasma proteins.

Elimination:
Metabolism:
Metabolized in the brain to -methylnorepinephrine, the pharmacologically active
metabolite. j n Other active metabolites include -methylepinephrine and methyldopamine. k n
Extensively metabolized, probably in the GI tract and the liver, to sulfate
conjugates. b c f

Elimination Route:
49% of an IV dose is excreted in the urine (via glomerular filtration) as the parent drug
and the sulfate conjugate. b f
70% of an oral dose is excreted in the urine as parent drug and metabolites.
Unabsorbed methyldopa is excreted in the feces unchanged.

Half-life:
Plasma half-life is 105 or 90127 minutes for methyldopa or methyldopate,
respectively. d e f

Special Populations:
In patients with renal impairment, renal clearance is decreased.
Removed by hemodialysis and peritoneal dialysis.

b e

b c

Stability and Compatibility

Storage:

Oral:
Tablets:
Tight, light-resistant containers at 1530C. d e Protect methyldopa in fixed combination
with hydrochlorothiazide from moisture and freezing. d

Parenteral:
Solution for Injection:
1530C.

Compatibility:

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral:
Solution Compatibility

HID

Compatible

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
Ringers injection
Sodium bicarbonate 5%
Sodium chloride 0.9%

Drug Compatibility:
Compatible
Aminophylline
Ascorbic acid injection
Chloramphenicol sodium succinate
Diphenhydramine HCl
Heparin sodium
Magnesium sulfate
Multivitamins
Potassium chloride
Sodium bicarbonate
Succinylcholine chloride
Verapamil HCl

Vitamin B complex with C

Incompatible
Amphotericin B
Methohexital sodium
Admixture Compatibility

HID

Compatible
Esmolol HCl
Heparin sodium
Meperidine HCl
Morphine sulfate
Theophylline
Y-Site Compatibility:
Preparations

Tables of Preparations:
Dosage
Forms

Routes

Tablets, filmcoated

Oral

Strengt
hs

Brand
Names

Manufact
urer

Methyldopa
250 mg* Tablets

Mylan,
Teva, UDL

Methyldopa
500 mg* Tablets

Mylan,
Teva, UDL

* available from one or more

manufacturer, distributor, and/or
repackager by generic
(nonproprietary) name
Methyldopa:

Routes

Oral

Dosag
e
Forms

Strengths

Brand Names

Tablets,
filmcoated

250 mg with
Hydrochlorothiazid
e 15 mg*

Methyldopa and
Hydrochlorothiazid
e Tablets

250 mg with
Hydrochlorothiazid

Aldoril ()

Manufact
urer

Merck

e 25 mg*
Methyldopa and
Hydrochlorothiazid
e Tablets
* available from one or
more manufacturer,
distributor, and/or
repackager by generic
(nonproprietary) name
Methyldopa and Hydrochlorothiazide:
Routes
Parente
ral

Dosage
Forms

Injection

Streng
ths
50
mg/mL

Brand Names
Methyldopate Hydrochloride Injection (with
parabens and sulfites)

Manufactur
er
American
Regent

Methyldopate Hydrochloride:

Comparative Pricing:
This pricing information is subject to change at the sole discretion of DS Pharmacy. This
pricing information was updated 02/2014. For the most current and up-to-date pricing
information, please visit www.drugstore.com. Actual costs to patients will vary depending on
the use of specific retail or mail-order locations and health insurance copays.
Methyldopa 250MG Tablets (TEVA PHARMACEUTICALS USA): 120/$25.98 or 180/$28.96
Methyldopa-Hydrochlorothiazide 250-25MG Tablets (MYLAN): 60/$22.99 or 180/$46.97

Medication Cost Assistance Programs:

medication cost assistance programs for Methyldopa from NeedyMeds

Patient Information

Advice to Patients:

Importance of informing clinicians of existing or contemplated concomitant therapy,

including prescription and OTC drugs as well as any concomitant illnesses. e

Importance of women informing clinicians if they are or plan to become pregnant or

plan to breast-feed. e

Importance of informing patients of other important precautionary information. e (See

Cautions.)
Guidelines and Resources

Guidelines:

American Geriatrics Society (AGS) Beers Criteria 2012 recommendation on

potentially inappropriate medication use in older adults can be found in J Am Geriatr Soc
2012 Apr;60(4):616 PDF or at National Guideline Clearinghouse 2012 Nov 5:37706

MEDLINE Search:

to search MEDLINE for (Methyldopa) with targeted search (Clinical Queries for therapy
articles), click here
References

General References Used:

Unless otherwise stated, source material derived from AHFS Drug Information
Essentials. The AHFS Drug Information Essentials database is copyrighted by the
American Society of Health-System Pharmacists, Inc. 2010 ASHP, Bethesda, Maryland
20814. All Rights Reserved. Duplication must be expressly authorized by ASHP, unless
such duplication consists of printing or downloading portions of the data inherent in the
program for non-commercial use. Used with permission.
The American Society of Health-System Pharmacists, Inc. represents that the
database provided hereunder was formulated with a reasonable standard of care, and in
conformity with professional standards in the field. The American Society of HealthSystem Pharmacists, Inc. makes no representations or warranties, express or implied,
including, but not limited to, any implied warranty of merchantability and/or fitness for a
particular purpose, with respect to such database and specifically disclaims all such
warranties and representations. Users are advised that decisions regarding drug therapy
are complex medical decisions requiring the independent, informed decision of an
appropriate health care professional, and the database is provided for informational
purposes only. The entire monograph for a drug should be reviewed for a thorough
understanding of the drugs actions, uses and side effects. The American Society of
Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug in
the database. The information contained in the database is not a substitute for medical
care.

Recommendation Grading Systems Used:

American Geriatrics Society (AGS) Beers Criteria grading system for

recommendations
o
strength of recommendation

Strong - benefits clearly outweigh risks and burden, or risks and

burden clearly outweigh benefits

Weak - benefits finely balanced with risks and burden

Insufficient - insufficient evidence to determine net benefits or risks

o
quality of evidence

High - evidence includes consistent results from well-designed, wellconducted studies in representative populations that directly assess effects on
health outcomes, based on either

2 consistent, higher quality randomized controlled trials

multiple, consistent observational studies with no significant

methodological flaws showing large effects

Moderate - evidence sufficient to determine effects on health

outcomes, but strength of evidence limited by any of

number, quality, size, or consistency of included studies

generalizability to routine practice

indirect nature of evidence on health outcomes

Low - evidence insufficient to assess effects on health outcomes due

to any of

limited number or power of studies

large and unexplained inconsistency between higher quality

studies

important flaws in study design or conduct

gaps in chain of evidence

lack of information on important health outcomes

o
Reference - AGS 2012 Beers Criteria for potentially inappropriate medication
use in older adults (J Am Geriatr Soc 2012 Apr;60(4):616 full-text)

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The participating members of the DynaMed Editorial Team have declared that they
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McMaster University is a partner that provides support in identifying PracticeChanging DynaMed Updates. Over 1,000 practicing physicians from 61 disciplines in 77
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How to Cite:

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References for AHFS DI Essentials:

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