Methyldopa Methyldopa Description

Dosage Form: tablets
250 mg and 500 mg
Rx only
Methyldopa Description
Methyldopa is an antihypertensive and is the L-isomer of alpha-Methyldopa. It is levo-3(3,4-dihydroxyphenyl)-2-methylalanine sesquihydrate. Methyldopa is supplied as tablets
for oral administration, containing 250 mg and 500 mg of Methyldopa. The amount of
Methyldopa is calculated on the anhydrous basis. Its molecular formula is C10H13NO4•1
1/2 H2O, with a molecular weight of 238.24, and its structural formula is:
Methyldopa is a white to yellowish white, odorless fine powder and is sparingly soluble
in water.
The tablets contain the following inactive ingredients: colloidal silicon dioxide,
croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose,
polydextrose, polyethylene glycol, sodium lauryl sulfate, titanium dioxide, triacetin,
FD&C yellow #6 aluminum lake and FD&C blue #2 aluminum lake.
Methyldopa - Clinical Pharmacology
Methyldopa is an aromatic-aminoacid decarboxylase inhibitor in animals and in man.
Although the mechanism of action has yet to be conclusively demonstrated, the
antihypertensive effect of Methyldopa probably is due to its metabolism to alphamethylnorepinephrine, which then lowers arterial pressure by stimulation of central
inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of
plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue
concentration of serotonin, dopamine, norepinephrine, and epinephrine.
Only Methyldopa, the L-isomer of alpha-Methyldopa, has the ability to inhibit dopa
decarboxylase and to deplete animal tissues of norepinephrine. In man, the
antihypertensive activity appears to be due solely to the L-isomer. About twice the dose
of the racemate (DL-alpha-Methyldopa) is required for equal antihypertensive effect.
Methyldopa has no direct effect on cardiac function and usually does not reduce
glomerular filtration rate, renal blood flow, or filtration fraction. Cardiac output usually is
maintained without cardiac acceleration. In some patients the heart rate is slowed.
Normal or elevated plasma renin activity may decrease in the course of Methyldopa
Methyldopa reduces both supine and standing blood pressure. It usually produces highly
effective lowering of the supine pressure with infrequent symptomatic postural
hypotension. Exercise hypotension and diurnal blood pressure variations rarely occur.
Pharmacokinetics and Metabolism
The maximum decrease in blood pressure occurs four to six hours after oral dosage. Once
an effective dosage level is attained, a smooth blood pressure response occurs in most
patients in 12 to 24 hours. After withdrawal, blood pressure usually returns to
pretreatment levels within 24–48 hours.
Methyldopa is extensively metabolized. The known urinary metabolites are: αMethyldopa mono-O-sulfate; 3-0-methyl-α-Methyldopa; 3,4-dihydroxyphenylacetone; αMethyldopamine; 3-0-methyl-α-Methyldopamine and their conjugates.
Approximately 70 percent of the drug which is absorbed is excreted in the urine as
Methyldopa and its mono-O-sulfate conjugate. The renal clearance is about 130 mL/min
in normal subjects and is diminished in renal insufficiency. The plasma half-life of
Methyldopa is 105 minutes. After oral doses, excretion is essentially complete in 36
Methyldopa crosses the placental barrier, appears in cord blood, and appears in breast
Indications and Usage for Methyldopa
Read more:
methyldopa (Oral route, Intravenous
Commonly used brand name(s):
In the U.S.
Available Dosage Forms:
Therapeutic Class: Antihypertensive
Pharmacologic Class: Alpha-Adrenergic Agonist
Uses For methyldopa
Methyldopa belongs to the general class of medicines called antihypertensives. It is used
to treat high blood pressure (hypertension).
High blood pressure adds to the work load of the heart and arteries. If it continues for a
long time, the heart and arteries may not function properly. This can damage the blood
vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney
failure. High blood pressure may also increase the risk of heart attacks. These problems
may be less likely to occur if blood pressure is controlled.
Methyldopa works by controlling impulses along certain nerve pathways. As a result, it
relaxes blood vessels so that blood passes through them more easily. This helps to lower
blood pressure.
Methyldopa is available only with your doctor's prescription.
Before Using methyldopa
In deciding to use a medicine, the risks of taking the medicine must be weighed against
the good it will do. This is a decision you and your doctor will make. For methyldopa, the
following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to methyldopa or
any other medicines. Also tell your health care professional if you have any other types of
allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products,
read the label or package ingredients carefully.
Although there is no specific information comparing use of methyldopa in children with
use in other age groups, methyldopa is not expected to cause different side effects or
problems in children than it does in adults.
Dizziness or lightheadedness and drowsiness may be more likely to occur in the elderly,
who are more sensitive to the effects of methyldopa.
Animal studies have revealed no evidence of harm to the fetus,
however, there are no adequate studies in pregnant women OR
animal studies have shown an adverse effect, but adequate
studies in pregnant women have failed to demonstrate a risk to
the fetus.
Breast Feeding
Studies in women suggest that this medication poses minimal risk to the infant when used
during breastfeeding.
Interactions with Medicines
Using methyldopa with any of the following medicines is not recommended. Your doctor
may decide not to treat you with this medication or change some of the other medicines
you take.
Using methyldopa with any of the following medicines is usually not recommended, but
may be required in some cases. If both medicines are prescribed together, your doctor
may change the dose or how often you use one or both of the medicines.
Using methyldopa with any of the following medicines may cause an increased risk of
certain side effects, but using both drugs may be the best treatment for you. If both
medicines are prescribed together, your doctor may change the dose or how often you use
one or both of the medicines.
Ferric Ammonium Citrate
Interactions with Food/Tobacco/Alcohol
Certain medicines should not be used at or around the time of eating food or eating
certain types of food since interactions may occur. Using alcohol or tobacco with certain
medicines may also cause interactions to occur. Discuss with your healthcare professional
the use of your medicine with food, alcohol, or tobacco.
Other Medical Problems
The presence of other medical problems may affect the use of methyldopa. Make sure
you tell your doctor if you have any other medical problems, especially:
Angina (chest pain) or
Parkinson's disease—Methyldopa may make these conditions worse
Kidney disease or
Liver disease—Effects of methyldopa may be increased because of slower
removal from the body
Mental depression (history of)—Methyldopa can cause mental depression
Pheochromocytoma—Methyldopa may interfere with tests for the condition; in
addition, there have been reports of increased blood pressure
If you have taken methyldopa in the past and developed liver problems
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Proper Use of methyldopa
In addition to the use of the medicine your doctor has prescribed, treatment for your high
blood pressure may include weight control and care in the types of foods you eat,
especially foods high in sodium. Your doctor will tell you which of these are most
important for you. You should check with your doctor before changing your diet.
Many patients who have high blood pressure will not notice any signs of the problem. In
fact, many may feel normal. It is very important that you take your medicine exactly as
directed and that you keep your appointments with your doctor even if you feel well.
Remember that methyldopa will not cure your high blood pressure but it does help
control it. Therefore, you must continue to take it as directed if you expect to lower your
blood pressure and keep it down. You may have to take high blood pressure medicine for
the rest of your life . If high blood pressure is not treated, it can cause serious problems
such as heart failure, blood vessel disease, stroke, or kidney disease.
To help you remember to take your medicine, try to get into the habit of taking it at the
same time each day.
The dose of methyldopa will be different for different patients. Follow your doctor's
orders or the directions on the label. The following information includes only the average
doses of methyldopa. If your dose is different, do not change it unless your doctor tells
you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the
number of doses you take each day, the time allowed between doses, and the length of
time you take the medicine depend on the medical problem for which you are using the
For oral dosage form (suspension or tablets):
o For high blood pressure:
ƒ Adults—250 milligrams (mg) to 2 grams a day. This is divided
into two to four doses.
ƒ Children—Dose is based on body weight or size and must be
determined by your doctor. The usual dose is 10 mg per kilogram
(kg) (4.5 mg per pound) of body weight a day. This is divided into
two to four doses. Your doctor may increase the dose as needed.
For injection dosage form:
o For high blood pressure:
ƒ Adults—250 to 500 mg mixed in 100 milliliters (mL) of solution
(5% dextrose) and slowly injected into a vein every six hours as
ƒ Children—Dose is based on body weight and must be determined
by your doctor. The usual dose is 20 to 40 mg per kg (9.1 to 18.2
mg per pound) of body weight. This is mixed in a solution (5%
dextrose) and slowly injected into a vein every six hours as needed.
Missed Dose
If you miss a dose of methyldopa, take it as soon as possible. However, if it is almost
time for your next dose, skip the missed dose and go back to your regular dosing
schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture,
and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Precautions While Using methyldopa
It is important that your doctor check your progress at regular visits to make sure that
methyldopa is working properly.
Do not take other medicines unless they have been discussed with your doctor. This
especially includes over-the-counter (nonprescription) medicines for appetite control,
asthma, colds, cough, hay fever, or sinus problems, since they may tend to increase your
blood pressure.
If you have a fever and there seems to be no reason for it, check with your doctor. This is
especially important during the first few weeks you take methyldopa, since fever may be
a sign of a serious reaction to methyldopa.
Before having any kind of surgery (including dental surgery) or emergency treatment,
make sure the medical doctor or dentist in charge knows that you are taking methyldopa.
Methyldopa may cause some people to become drowsy or less alert than they are
normally. This is more likely to happen when you begin to take it or when you increase
the amount of medicine you are taking. Make sure you know how you react to
methyldopa before you drive, use machines, or do anything else that could be dangerous
if you are not alert.
Dizziness, lightheadedness, or fainting may occur, especially when you get up from a
lying or sitting position. Getting up slowly may help, but if the problem continues or gets
worse, check with your doctor.
Methyldopa may cause dryness of the mouth. For temporary relief, use sugarless candy
or gum, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth
continues to feel dry for more than 2 weeks, check with your medical doctor or dentist.
Continuing dryness of the mouth may increase the chance of dental disease, including
tooth decay, gum disease, and fungus infections.
Tell the doctor in charge that you are taking methyldopa before you have any medical
tests. The results of some tests may be affected by methyldopa.
Read more:
Turk J Pediatr. 2008 Nov-Dec;50(6):592-4.
A newborn with positive antiglobulin test
whose mother took methyldopa in
Ozdemir OM, Ergin H, Ince T.
Department of Pediatrics, Pamukkale University Faculty of Medicine, Denizli, Turkey.
Methyldopa is known to cause the production of autoantibodies against red blood cells
(RBCs), leading to a positive direct antiglobulin test (DAT) and hemolytic anemia. In
about 20% of patients taking methyldopa, IgG autoantibodies develop against RBCs.
However, most of the patients do not have hemolysis. A small percentage of such DATpositive patients, about 2% of those taking methyldopa, develop an autoimmune
hemolytic anemia (AIHA). The fact that the DAT is positive in the newborn with
unconjugated hyperbilirubinemia is considered as an isoimmune hemolytic disease
caused by blood group incompatibility. In this article, a newborn with jaundice and
positive DAT without hemolysis is reported. Her mother had the history of taking
methyldopa in her pregnancy. Thus, when newborns are detected with positive DAT and
jaundice, without blood group incompatibility, mothers should be questioned regarding
drugs used in their pregnancy.
Treating Hypertension in Pregnancy:
Oral Drugs for Mild/Moderate
Oral Drugs for Mild/Moderate Hypertension
There is no clear consensus on the management of mild to moderate hypertension in
pregnancy to optimise pregnancy outcomes.[4] Nevertheless, national hypertension
societies of the US, Canada and Australasia all list methyldopa, labetalol and long-acting
nifedipine as acceptable oral antihypertensive agents if drug therapy is required in
pregnant women with mild to moderate hypertension.[4-6] Some of the most commonly
used antihypertensive medications in pregnancy and suggested dosage regimens are
provided in table 2 .
Methyldopa - A Drug of First Choice
Methyldopa is a drug of first choice for control of mild to moderate hypertension in
pregnancy and is the most widely prescribed antihypertensive for this indication in
several countries, including the US and the UK.[1,2] The wide use of this drug in
pregnancy reflects the fact that it has the best documented maternal and fetal safety
record, including favourable long term (4.5 to 7.5 year) paediatric follow-up data.[1]
During long term use in pregnancy, methyldopa does not alter maternal cardiac output or
blood flow to the uterus or kidneys,[1,2] and for all these reasons is generally considered
the agent of choice for chronic blood pressure control in pregnancy.[1]
Labetalol -- A Reasonable Alternative
The combined
and ß-adrenoceptor blocker labetalol is a peripheral vasodilator which
has been shown to be effective in pre-eclamptic and non-proteinuric hypertension in
pregnancy.[1] Available data suggest that the antihypertensive effect is not associated with
compromised renal or uterine blood flow.[1] In a randomised comparative trial of 263
pregnant women with mild to moderate hypertension, treatment with either labetalol or
methyldopa achieved significantly lower maternal blood pressures throughout gestation
compared with no medication, and there were no differences among the 3 groups with
respect to various clinical outcomes (e.g. gestational age at delivery, birthweight, fetal
growth retardation).[7] However, because the safety record of labetalol in pregnancy is not
as well established as that of methyldopa, labetalol should probably be considered a
second-line agent for pregnant women with chronic hypertension requiring long term
drug therapy.[1]
ß-Blockers Useful in Late Pregnancy...
While earlier studies suggested that administration of ß-blockers (particularly those
without intrinsic sympathomimetic activity[8]) during pregnancy might increase the
chance of intrauterine growth retardation, recent studies have been more reassuring on
this point.[1] Nevertheless, the available data are insufficient to rule out unrecognised
adverse effects of early and prolonged use of ß-blockers in pregnancy. When used for
short periods (<6 weeks) during the third trimester, ß-blockers are effective and well
tolerated provided there are no signs of intrauterine growth impairment.[1]
...But Avoid Atenolol
Use of the cardioselective ß-blocker atenolol early in pregnancy in women with chronic
hypertension has been shown to result in significantly lower birthweights compared with
placebo and other antihypertensive agents.[9,10] The results of these and other studies
indicate that treatment with atenolol is associated with fetal growth impairment and that
this effect is related to duration of therapy.[9-11] Thus, atenolol should be avoided in early
pregnancy and used only with caution in later pregnancy;[1] some advise avoidance of
atenolol altogether in pregnancy.[2]
Calcium Antagonists for Late Pregnancy
When administered in late pregnancy, oral calcium antagonists have been shown to
reduce maternal blood pressure in pregnant women with mild to moderate hypertension,
including those with pre-eclampsia, without apparent adverse fetal or perinatal effects.[1,2]
However, little is known about the effects of long term administration of these drugs in
pregnant women, particularly in the first trimester.[1] Among the calcium antagonists,
nifedipine has been the best studied in pregnancy and the drug has been used extensively
in later pregnancy.[1,2]
Hydralazine a Possibility
Oral hydralazine, a direct vasodilator, is effective as monotherapy or as add-on therapy to
methyldopa in the long term management of chronic hypertension in pregnancy.[1]
Hydralazine appears to be reasonably safe for the fetus although a few cases of fetal
thrombocytopenia have been reported.[1] In general, effective long term antihypertensive
therapy with hydralazine (e.g. for chronic hypertension in pregnancy) often requires
combination therapy (typically with a sympatholytic agent such as methyldopa or a ßblocker) and such combinations also help attenuate reflex sympathetic activation
associated with hydralazine.[2]
Avoid ACE Inhibitors...
Administration of ACE inhibitors during the second and third trimesters can result in a
number of fetal adverse effects, including growth retardation, renal failure, persistent
patent ductus arteriosus, respiratory distress syndrome, fetal hypotensive syndrome, and
prepartum death.[12] Although the magnitude of the risk is unknown, these agents are
contraindicated in at least the second and third trimesters.[1,2] Furthermore, while ACE
inhibitors may be safe in early pregnancy, women taking these agents should be warned
about the possible risks of this class of drugs in pregnancy and advised to discontinue
ACE inhibitor therapy before or when they become pregnant.[1] Since the teratogenic risk
of ACE inhibitors is thought to be related to a direct pharmacological effect of the drugs
on fetal physiology, angiotensin II receptor antagonists are also not recommended in
...And Diuretics
While diuretics have been reported to prevent pre-eclampsia by reducing blood pressure,
they are rarely prescribed as antihypertensive agents during pregnancy because they
reduce maternal plasma volume and can cause electrolyte disturbances.[1]
Methyldopa a Safe Antihypertensive
During Pregnancy
OB/GYN News, June 1, 2001 by Bruce Jancin
Methyldopa is an old and frequently overlooked agent that, in the setting of hypertension
in pregnancy, is suddenly transformed into first-line therapy, Dr. Jill Davies said at a
conference on obstetrics and gynecology sponsored by the University of Colorado.
"Aldomet [methyldopa] is a category B medication. It has the longest safety record for
treatment of hypertension in pregnancy. So even though outside of pregnancy it's not
even close to being considered a first-line agent, we still consider it first-line therapy in
pregnancy because of its safety record," said Dr. Davies of the university.
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The most problematic class of antihypertensive agents in pregnancy are the angiotensinconverting enzyme inhibitors. They are particularly teratogenic and have been linked to
congenital skull defects, oligohydramnios, nephrotoxicity, intrauterine growth retardation,
hypoplastic lungs, and increased perinatal mortality.
[beta]-blockers, while not teratogenic, have been associated with ill effects on the fetus,
most commonly intrauterine growth retardation. Of course, hypertensive patients are
already predisposed to fetal growth restriction due to their underlying blood pressure
disorder. However, [beta]-blockers have also been linked to growth retardation when
prescribed as antiarrhythmic agents in normotensive pregnant women.
"This makes sense because [beta]-blockers lower the blood pressure systemically, which
lowers uterine perfusion pressure, Dr. Davies noted.
[Methyldopa-induced acute reactive
hepatitis in pregnancy, drug-metabolizing
capacity of the liver]
[Article in Hungarian]
Ozsvár Z, Solymossi Z, Monostory K.
Fejér Megyei Szent György Kórház Infektológiai Osztály Székesfehérvár Seregélyesi út
3. 8000. [email protected]
Alpha-methyldopa is a regularly used antihypertensive drug during pregnancy.
Methyldopa, which decreases the sympathoadrenal system, is the first drug of choice
since decades. The reactive hepatitis is not frequent, but known serious side effect of
alpha-methyldopa. In non-pregnant women the estimated rate of manifest hepatotoxicity
is 2.5-10%. In our case, gestation hypertension developed at the 21st gestation week of a
35 year-old pregnant woman. Oral methyldopa, a central alpha adrenergic blocker
therapy was introduced. On the 23rd gestation week acute hepatitis developed. During
differential diagnosis of hepatitis, the etiology of methyldopa was taken into account.
Viral and autoimmune origin was rolled out. No fetal aberration was found during
ultrasound examination. The function of drug metabolizing function from blood was
measured by CYP phenotyping (CYP gene expression analysis). CYP3A4 enzyme plays
a primary role in the metabolism of nifedipine. Antihypertensive therapy was changed
from methyldopa to nifedipine. Nifedipine dosage was based on the value of CYP3A4
gene expression. With the reduced nifedipine therapy (30 mg daily), blood pressure was
successfully under control. The diagnosis of alpha-methyldopa induced hepatitis was
based on anamnesis, clinical picture and the results of chemical and radiological
examination and confirmed by the level of drug-metabolizing capacity. The gestation
hepatotoxicity of alpha-methyldopa was reported first in 1969 by Elkington Smith, who
suggested the monitoring of serum aminotransferase during alpha-methyldopa therapy in
pregnancy in their case report. Our case report confirms that monitoring of serum
aminotransferase level is still valuable when treating a pregnant woman with alphamethyldopa.
N Z Med J. 2009 Aug 21;122(1301):53-6.
Methyldopa-induced autoimmune
haemolytic anaemia revisited.
Thomas A, James BR, Graziano SL.
Department of Medicine, SUNY Upstate Medical University, Syracuse, NY-13202, USA.
[email protected]
Drug-induced haemolytic anaemia is a commonly encountered clinical situation.
Methyldopa-induced haemolytic anaemia, once the most common cause of drug induced
haemolysis, is now rarely seen due to decline in its use. We report a case of methyldopa
induced immune haemolytic anaemia in a young woman where the diagnosis was initially
missed. The major mechanisms of drug induced immune haemolysis and unique
characteristics of methyldopa induced haemolysis are also outlined.