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Pronunciation
(meth il DOE pa)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of moderate-to-severe hypertension
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies. Methyldopa crosses the placenta and appears in cord blood. Methyldopa is considered an appropriate agent for the treatment of hypertension in pregnancy.
Lactation
Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
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: May be inappropriate in this age group due to a risk of bradycardia and depression (Beers Criteria). 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
Metabolism/Transport Effects
Substrate of COMT
Drug Interactions
COMT Inhibitors: May decrease the metabolism of COMT Substrates. Risk C: Monitor therapy
Iobenguane I 123: Methyldopa may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Iron Salts: May decrease the serum concentration of Methyldopa. Exceptions: Ferric Gluconate; Ferumoxytol; 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
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
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.
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
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
Elderly: Initiate at the lower end of the dosage range.
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
Oral: Follow recommended diet and exercise program. Periodic laboratory tests may be required. This medication may cause altered color of urine (normal), drowsiness, dizziness, impaired judgment, postural hypotension, dry mouth, or nausea. Report altered CNS status (eg, nightmares, depression, anxiety, increased nervousness); sudden weight gain; unusual or persistent swelling of ankles, feet, or extremities; palpitations or rapid heartbeat; persistent weakness or fatigue; or unusual bleeding.
Geriatric Considerations
Because of its CNS effects, methyldopa is not considered a drug of first choice in the elderly. Adjust dose for renal function.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria severity: High).
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.
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 treatment. Monitor for hypotension, bradycardia, or CNS changes on a regular basis.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 50 mg/mL (5 mL)
Tablet, oral: 250 mg, 500 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Methyldopa)
250 mg (120): $25.98
Extemporaneously Prepared
A 50 mg/mL oral suspension may be made with tablets and either unpreserved Simple Syrup, N.F. or a 1:1 mixture of simple syrup (containing 0.5% citric acid) and hydrochloric acid 0.2 N. Crush ten 250 mg tablets in a glass mortar and reduce to a fine powder. To make formulation with unpreserved simple syrup, add small portions of vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 50 mL; transfer to a calibrated bottle; rinse the mortar and pestle several times with vehicle, and add quantity of vehicle sufficient to make 50 mL. To make formulation with the second vehicle, mix powdered tablets with 25 mL of hydrochloric acid 0.2 N (0.73% w/v); dilute this mixture to 50 mL with simple syrup containing 0.5% citric acid by the method described above. Label "shake well" and "protect from light." Stable for 14 days when stored in glass prescription bottles in the dark at room temperature or refrigerated.
Newton DW, Rogers AG, Becker CH, et al, "Extemporaneous Preparation of Methyldopa in Two Syrup Vehicles," Am J Hosp Pharm, 1975, 32(8):817-21.
References
ACOG Committee on Practice Bulletins, "ACOG Practice Bulletin. Chronic Hypertension in Pregnancy. ACOG Committee on Practice Bulletins," Obstet Gynecol, 2001, 98(1):suppl 177-85.
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
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 January 2012
Content last modified January 2012
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