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Medication Safety Issues
Sound-alike/look-alike issues:
Methyldopa may be confused with L-dopa, levodopa
Pronunciation
(meth il DOE pa)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of moderate to severe hypertension
Pregnancy Risk Factor
B
Pregnancy Considerations
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.
Lactation
Enters breast milk/compatible
Breast-Feeding Considerations
Crosses into breast milk at extremely low levels. AAP considers compatible with breast-feeding.
Contraindications
Hypersensitivity to methyldopa or any component of the formulation; active hepatic disease; liver disorders previously associated with use of methyldopa; on MAO inhibitors; bisulfite allergy if using oral suspension or injectable
Warnings/Precautions
Concerns related to adverse effects:
• Hemolytic anemia: May rarely produce hemolytic anemia; positive Coombs' test occurs in 10% to 20% of patients (perform periodic CBCs).
• Hepatic effects: May rarely produce liver disorders; use with caution in patients with previous liver disease or dysfunction.
• Sedation: Usually transient, sedation may occur during initial therapy or whenever the dose is increased.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; may respond to smaller doses. The active metabolites of methyldopa accumulate in uremia.
Special populations:
• Elderly: Use with caution in the elderly; may experience syncope (avoid by giving smaller doses). Not considered a drug of choice.
• Pregnancy: Often considered the drug of choice for treatment of hypertension in pregnancy.
Dosage form specific issues:
• Injection: Do not use injectable if bisulfite allergy.
Other warnings/precautions:
• Tolerance: May occur usually between the second and third month of therapy; adding a diuretic or increasing the dosage of methyldopa frequently restores blood pressure control.
Adverse Reactions
>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): 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
Drug Interactions
COMT Inhibitors: May decrease the metabolism of COMT Substrates. Risk C: Monitor therapy
Iron Salts: May decrease the absorption of Methyldopa. Only oral iron salts are of concern. Exceptions: Ferric Gluconate; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification
Lithium: Methyldopa may enhance the adverse/toxic effect of Lithium. This may occur without notable changes in serum lithium concentrations. Risk C: Monitor therapy
MAO Inhibitors: May enhance the adverse/toxic effect of Methyldopa. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression). Avoid natural licorice (causes sodium and water retention and increases potassium loss). Avoid garlic (may have increased antihypertensive effect).
Storage
Injectable dosage form is most stable at acid to neutral pH. Stability of parenteral admixture at room temperature (25°C) is 24 hours. Stability of parenteral admixture at refrigeration temperature (4°C) is 4 days.
Reconstitution
Standard diluent: 250-500 mg/100 mL D5W
Compatibility
Stable in dextran 6% in NS, D5NS, D5W, sodium bicarbonate 5%, NS.
Y-site administration: Compatible: Esmolol, heparin, meperidine, morphine, theophylline. Variable (consult detailed reference): TPN.
Compatibility when admixed: Compatible: Aminophylline, ascorbic acid injection, chloramphenicol, diphenhydramine, heparin, magnesium sulfate, multivitamins, potassium chloride, promazine, sodium bicarbonate, succinylcholine, verapamil, vitamin B complex with C. Incompatible: Amphotericin B, methohexital.
Mechanism of Action
Stimulation of central alpha-adrenergic receptors by a false transmitter that results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature
Pharmacodynamics/Kinetics
Onset of action: Peak effect: Hypotensive: Oral/parenteral: 3-6 hours
Duration: 12-24 hours
Distribution: Crosses placenta; enters breast milk
Protein binding: <15%
Metabolism: Intestinal and hepatic
Half-life elimination: 75-80 minutes; End-stage renal disease: 6-16 hours
Excretion: Urine (85% as metabolites) within 24 hours
Dosage
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 (maximum dose: 3 g/day): usual dose range (JNC 7): 250-1000 mg/day in 2 divided doses
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%)
Administration: I.V.
Infuse over 30 minutes.
Monitoring Parameters
Blood pressure, standing and sitting/lying down, CBC, liver enzymes, Coombs' test (direct); blood pressure monitor required during I.V. administration
Test Interactions
Methyldopa interferes with the following laboratory tests: urinary uric acid, serum creatinine (alkaline picrate method), AST (colorimetric method), and urinary catecholamines (falsely high levels)
Dietary Considerations
Dietary requirements for vitamin B12 and folate may be increased with high doses of methyldopa.
Patient Education
Do not take any new medication during therapy unless approved by prescriber (especially any cough or cold remedies, diet pills, stay-awake medications). Oral: Take as directed. Do not skip dose or discontinue without consulting prescriber. Follow recommended diet and exercise program. Periodic laboratory tests may be required. 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.
Geriatric Considerations
Because of its CNS effects, methyldopa is not considered a drug of first choice in the elderly. Adjust dose for renal function.
Anesthesia and Critical Care Concerns/Other Considerations
Most effective if used with diuretic. Titrate dose to optimal blood pressure control with minimal side effects. Patients on methyldopa may need less anesthetic agents. Hypotension readily responds to vasopressors because the adrenergic receptors remain sensitive.
It is 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.
Cardiovascular Considerations
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.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Anticholinergic side effects can cause a reduction of saliva production or secretion, contributing to discomfort and dental disease (ie, caries, oral candidiasis, and periodontal disease).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness, dizziness, anxiety, nightmares, or depression
Mental Health: Effects on Psychiatric Treatment
Contraindicated with MAO inhibitors; 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
Nursing: Physical Assessment/Monitoring
Evaluate hepatic and renal status prior to beginning therapy. Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (eg, anything that affects blood pressure). See Administration for infusion specifics (eg, do not use injectable in presence of bisulfite allergy). Assess results of laboratory tests at baseline and regularly during therapy. Monitor therapeutic effectiveness (normotensive) and adverse reactions (eg, hypotension, bradycardia, CNS changes) on a regular basis. Teach patient use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as methyldopate hydrochloride: 50 mg/mL (5 mL) [contains sodium bisulfite]
Tablet: 250 mg, 500 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Methyldopa)
250 mg (120): $25.98
500 mg (60): $25.99
References
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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