DOSAGE AND ADMINISTRATION
DOSAGE MUST BE INDIVIDUALIZED, AS DETERMINED BY TITRATION OF THE INDIVIDUAL COMPONENTS (see boxed WARNING). Once the patient has been successfully titrated, methyldopa and hydrochlorothiazide tablets may be substituted if the previously determined titrated doses are the same as in the combination. The usual starting dosage is one 250 mg/15 mg tablet of methyldopa and hydrochlorothiazide two or three times a day or one 250 mg/25 mg tablet of methyldopa and hydrochlorothiazide two times a day. Alternatively, one 500 mg/30 mg tablet of methyldopa and hydrochlorothiazide or a 500 mg/50 mg tablet of methyldopa and hydrochlorothiazide once daily may be used. Hydrochlorothiazide doses greater than 50 mg daily should be avoided.
Hydrochlorothiazide can be given at doses of 12.5 mg to 50 mg per day when used alone. The usual daily dosage of methyldopa is 500 mg to 2 g. To minimize the sedation associated with methyldopa, start dosage increases in the evening. The maximum recommended daily dose of methyldopa is 3 g.
Occasionally tolerance to methyldopa may occur, usually between the second and third month of therapy. Additional separate doses of methyldopa or replacement of methyldopa and hydrochlorothiazide tablets with single entity agents is necessary until the new effective dose ratio is reestablished by titration.
If methyldopa and hydrochlorothiazide does not adequately control blood pressure, additional doses of other agents may be given. When methyldopa and hydrochlorothiazide is given with antihypertensives other than thiazides, the initial dosage of methyldopa should be limited to 500 mg daily in divided doses and the dose of these other agents may need to be adjusted to effect a smooth transition.
Since both components, methyldopa and hydrochlorothiazide, have a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours. This is not complicated by an overshoot of blood pressure.
Since methyldopa is largely excreted by the kidney, patients with impaired renal function may respond to smaller doses. Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses.
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