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Pronunciation |
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(meth
il DOE
pa) |
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U.S. Brand
Names |
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Aldomet® |
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Generic
Available |
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Yes |
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Canadian Brand
Names |
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Apo®-Methyldopa; Dopamet®;
Medimet®; Novo-Medopa®; Nu-Medopa |
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Synonyms |
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Methyldopate Hydrochloride |
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Pharmacological Index |
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False Neurotransmitter |
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Use |
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Management of moderate to severe hypertension |
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Pregnancy Risk
Factor |
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B |
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Pregnancy/Breast-Feeding
Implications |
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Clinical effects on the fetus: Crosses the placenta. Hypotension reported. A
large amount of clinical experience with the use of these drugs for the
management of hypertension during pregnancy is available. Available evidence
suggests safe use during pregnancy and breast-feeding.
Breast-feeding/lactation: Crosses into breast milk at extremely low levels.
American Academy of Pediatrics considers compatible with breast-feeding.
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Contraindications |
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Hypersensitivity to methyldopa or any component; active hepatic disease;
liver disorders previously associated with use of methyldopa; on monoamine
oxidase inhibitors; bisulfite allergy if using oral suspension or
injectable |
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Warnings/Precautions |
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Monitor for hemolytic anemia, positive Coombs' test, and liver dysfunction. A
diuretic may be needed for weight gain or edema management. Its CNS side effects
prevent it from being used frequently. It is the drug of choice for treatment of
hypertension in pregnancy. Do use oral suspension or injectable if bisulfite
allergy. |
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Adverse
Reactions |
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>10%: Cardiovascular: Peripheral edema
1% to 10%:
Central nervous system: Drug fever, mental depression, anxiety, nightmares,
drowsiness, headache
Gastrointestinal: Dry mouth
<1% (Limited to important or life-threatening symptoms): Orthostatic
hypotension, bradycardia (sinus), sodium retention, sexual dysfunction,
gynecomastia, hyperprolactinemia, thrombocytopenia, hemolytic anemia, positive
Coombs' test, leukopenia, transient leukopenia or granulocytopenia, cholestasis
or hepatitis and heptocellular injury, increased liver enzymes, jaundice,
cirrhosis, dyspnea, SLE-like syndrome |
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Overdosage/Toxicology |
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Symptoms of overdose include hypotension, sedation, bradycardia, dizziness,
constipation or diarrhea, flatus, nausea, vomiting
Hypotension usually responds to I.V. fluids, Trendelenburg positioning, or
vasoconstrictors. Treatment is primarily supportive and symptomatic; can be
removed by hemodialysis. |
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Drug
Interactions |
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Iron supplements can interact and cause a significant increase in
blood pressure.
Barbiturates and TCAs may reduce response to methyldopa.
Beta-blockers, MAO inhibitors, phenothiazines, and sympathomimetics:
Hypertension, sometimes severe, may occur.
Lithium: Methyldopa may increase lithium toxicity; monitor lithium levels.
Tolbutamide, haloperidol, anesthetics, and levodopa effects/toxicity are
increased with methyldopa. |
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Stability |
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Injectable dosage form is most stable at acid to neutral pH; stability of
parenteral admixture at room temperature (25°C): 24 hours;
stability of parenteral admixture at refrigeration temperature
(4°C): 4 days; standard diluent: 250-500 mg/100 mL
D5W |
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Mechanism of
Action |
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Stimulation of central alpha-adrenergic receptors by a false transmitter that
results in a decreased sympathetic outflow to the heart, kidneys, and peripheral
vasculature |
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Pharmacodynamics/Kinetics |
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Peak hypotensive effect: Oral, parenteral: Within 3-6 hours
Duration: 12-24 hours
Distribution: Crosses the placenta; appears in breast milk
Protein binding: <15%
Metabolism: Intestinally and in the liver
Half-life: 75-80 minutes; End-stage renal disease: 6-16 hours
Elimination: Most (85%) metabolites appearing in the urine within 24 hours
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Usual Dosage |
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Children:
Oral: Initial: 10 mg/kg/day in 2-4 divided doses; increase every 2 days as
needed to maximum dose of 65 mg/kg/day; do not exceed 3 g/day.
I.V.: 5-10 mg/kg/dose every 6-8 hours up to a total dose of 65 mg/kg/24 hours
or 3 g/24 hours
Adults:
Oral: Initial: 250 mg 2-3 times/day; increase every 2 days as needed; usual
dose 1-1.5 g/day in 2-4 divided doses; maximum dose: 3 g/day.
I.V.: 250-500 mg every 6-8 hours; maximum dose: 1 g every 6 hours
Dosing interval in renal impairment:
Clcr >50 mL/minute: Administer every 8 hours.
Clcr 10-50 mL/minute: Administer every 8-12 hours.
Clcr <10 mL/minute: Administer every 12-24 hours.
Hemodialysis: Slightly dialyzable (5% to 20%) |
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Dietary
Considerations |
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Avoid natural licorice (causes sodium and water retention and increases
potassium loss); dietary requirements for vitamin B12 and folate may
be increased with high doses of methyldopa |
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Monitoring
Parameters |
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Blood pressure, standing and sitting/lying down, CBC, liver enzymes, Coombs'
test (direct); blood pressure monitor required during I.V.
administration |
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Test
Interactions |
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Methyldopa interferes with the following laboratory tests: urinary uric acid,
serum creatinine (alkaline picrate method), AST (colorimetric method), and
urinary catecholamines (falsely high levels) |
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Cardiovascular
Considerations |
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Methyldopa is not routinely used for the treatment of essential hypertension.
However, it is still used in the management of pregnancy-associated
hypertension. Although the drug crosses the placenta and may cause hypotension,
there is a large body of experience using this drug in the treatment of
pregnancy-associated hypertension. Overall, the medication appears to be safe
during pregnancy and lactation. Important side effects to note are hemolytic
anemia, drowsiness, and depression. |
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Mental Health: Effects
on Mental Status |
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May cause drowsiness, dizziness, anxiety, nightmares, or
depression |
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Mental Health:
Effects on Psychiatric
Treatment |
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Contraindicated with MAOIs; may rarely cause leukopenia; use caution with
clozapine and carbamazepine; associated with lithium toxicity; use alternative
antihypertensive agent; methyldopa may interact with psychotropics; monitor
blood pressure and clinical status |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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Anticholinergic side effects can cause a reduction of saliva production or
secretion. This may result in discomfort and dental disease (ie, caries, oral
candidiasis and periodontal disease) |
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Patient
Information |
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Take as directed. Do not skip dose or discontinue without consulting
prescriber. Follow recommended diet and exercise program. Do not use OTC
medications which may affect blood pressure (eg, cough or cold remedies, diet
pills, stay-awake medications) without consulting prescriber. This medication
may cause altered color of urine (normal); drowsiness, dizziness, or impaired
judgment (use caution when driving or engaging in tasks that require alertness
until response to drug is known); postural hypotension (use caution when rising
from sitting or lying position or when climbing stairs); or dry mouth or nausea
(frequent mouth care or sucking lozenges may help). Report altered CNS status
(eg, nightmares, depression, anxiety, increased nervousness); sudden weight gain
(weigh yourself in the same clothes at the same time of day once a week);
unusual or persistent swelling of ankles, feet, or extremities; palpitations or
rapid heartbeat; persistent weakness, fatigue, or unusual bleeding; or other
persistent side effects. |
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Nursing
Implications |
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Transient sedation or depression may be common for first 72 hours of therapy;
usually disappears over time; infuse over 30 minutes; assist with
ambulation |
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Dosage Forms |
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Injection, as methyldopate hydrochloride: 50 mg/mL (5 mL, 10 mL)
Suspension, oral: 250 mg/5 mL (5 mL, 473 mL)
Tablet: 125 mg, 250 mg, 500 mg |
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References |
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Johnston GD and Smith AM,
"Management of Overdose Due to Antihypertensive Agents," Adverse Drug React
Acute Poisoning Rev, 1990, 9(2):75-89.
Shnaps Y, Almog S. Halkin H, et al, "Methyldopa Poisoning," J Toxicol Clin
Toxicol, 1982, 19(5):501-3. |
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