Dosing and uses of methyldopa/hydrochlorothiazide
Adult dosage forms and strengths
methyldopa/hydrochlorothiazide
tablet
- 250mg/15mg
- 250mg/25mg
Hypertension
Not for initial therapy
Usual starting dose: 250 mg methyldopa/15-25 mg hydrochlorothiazide PO q12hr; alternatively 500 mgmethyldopa/30-50 mg hydrochlorothiazide PO qDay
Avoid hydrochlorothiazide doses >50 mg qDay
Dosage strength determined by individual titration
Renal Impairment
Use caution in dosing/titrating patients with renal dysfunction
Cumulative effects of thiazides may develop with impaired renal function; dose adjustment may be necessary; if CrCl < 30 mL/min avoid use; azotemia may be precipitated
Administration
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy
Since both components have a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours, not complicated by overshoot of blood pressure
Pediatric dosage forms and strengths
<18 years: Safety/efficacy not established
Geriatric dosage forms and strengths
Dose reduction may be necessary depending on patient's renal function
methyldopa/hydrochlorothiazide adverse (side) effects
Frequency not defined
Methyldopa
- Angina
- Arthralgia
- Bradycardia
- Orthostatic hypotension
- Depression
- Dizziness
- Lethargy
- Sedation
- Rash, liver toxicity
- Gynecomastia
- Impotence
- Dry mouth
- Nausea/vomiting
- Hemolytic anemia
- Thrombocytopenia, lupus-like syndrome
Hydrochlorothiazide
- Anorexia
- Epigastric distress
- Hypotension
- Orthostatic hypotension
- Photosensitivity
- Anaphylaxis
- Anemia
- Confusion
- Erythema multiforme
- Stevens-Johnson syndrome
- Exfoliative dermatitis including toxic epidermal necrolysis
- Hypomagnesemia
- Dizziness
- Headache
- Hyperuricemia
Warnings
Black Box Warning
Not indicated for initial therapy of hypertension; before initiating therapy requires therapy titrated to the individual patient; if fixed combination represents determined dosage for each individual agent; use may be more convenient in patient management; treatment of hypertension must be reevaluated as conditions in each patient warrant
Contraindications
Anuria
Renal decompensation
Hypersensitivity to either component or sulfonamides
Mitral valve rheumatic heart disease
Active liver disease, such as acute hepatitis and active cirrhosis
Liver disorders previously associated with methyldopa therapy
Concomitant therapy with monoamine oxidase (MAO) inhibitors
Cautions
This fixed-combination drug is not indicated for initial therapy of hypertension; requires therapy titrated to the individual patient before fixed-combination drug therapy initiated
DM, fluid or electrolyte imbalance, hyperuricemia or gout, liver disease, renal disease, SLE, hypotension
May aggravate digitalis toxicity
Sensitivity reactions may occur with or w/o history of allergy or asthma
Risk of male sexual dysfunction
CHF, dialysis pts (increased risk of hypertension following procedure), edema, hemolytic anemia, severe bilateral CVd
Avoid abrupt withdrawaL
Risk of decreased libido and impotence in men
May impair ability to perform hazardous tasks
Tolerance develops on prolonged therapy, especially if no concurrent diuretic (methyldopa causes Na and water retention)
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Interferes with some lab tests
Pregnancy and lactation
Pregnancy category: C
Lactation: both components appear in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of methyldopa/hydrochlorothiazide
Mechanism of action
Hydrochlorothiazide; methyldopa combines 2 antihypertensive agents with different mechanisms to lower blood pressure; effects of hydrochlorothiazide and methyldopa on blood pressure are additive
Thiazide diuretics lower blood pressure by increasing the excretion of sodium, whereas methyldopa may lower blood pressure by stimulating central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity.
Pharmacokinetics
Methyldopa
- Onset: 4-6 hr (PO, IV) hypotensive effect
- Vd: 0.23 L/kg
- Protein binding: 10-15%
- Bioavailability: 42%
- Half-life: 1.5-2 hr; prolonged in end stage renal disease
- Peak plasma time: 2-4 hr
- Excretion: Urine (70%)
- Metabolism: Intestinal and hepatic
- Duration: 12-24 hr (single dose); 24-48 hr (multiple dose)
Hydrochlorothiazide
- Half-Life: 6-15 hr
- Bioavailability: 70%
- Onset: 2 hr (diuresis); 4-6 hr (peak effect)
- Duration: 6-12 hr (diuresis); 1 wk (HTN)
- Vd: 3.6-7.8 L/kg
- Peak Plasma:1.5-2.5 hr
- Protein Bound: 68%
- Metabolism: Minimally metabolized
- Clearance: 335 mL/min
- Excretion: Urine 50-70%
- Dialyzable: No
