Dosing and uses of Hydra-Zide (hydralazine/hydrochlorothiazide)
Adult dosage forms and strengths
hydralazine/hydrochlorothiazide
capsule
- 25mg/25mg
- 50mg/50mg
Hypertension
Not for initial therapy
Usual dose: 25 mg/25 mg PO BId
Maximum: 50 mg/50 mg PO BId
Dosage strength determined by individual titration
Renal Impairment
Cumulative effects of thiazides may develop with impaired renal function
Use caution in dosing/titrating patients with renal dysfunction
Other Information
Dosage adjustment may be required in geriatrics
To minimize dose-independent side effects, begin combination therapy only after patient fails to achieve desired effect with monotherapy
Pediatric dosage forms and strengths
<18 years: Safety/efficacy not established
Hydra-Zide (hydralazine/hydrochlorothiazide) adverse (side) effects
Frequency not defined
Hydralazine (Common)
- Chest pain, hypotension, palpitations, tachycardia
- Headache, peripheral neuropathy
- Anorexia, diarrhea, nausea, vomiting
- Dyspnea, nasal congestion
Hydrochlorothiazide (Common)
- Hypotension
- Phototoxicity
- Anorexia
- Epigastric distress
- Hypokalemia
Hydralazine (Less Common)
- Agranulocytosis
- Hepatotoxicity
- Leukopenia
- SLE syndrome
Hydrochlorothiazide (Less Common)
- Confusion, dizziness, fatigue, headache, vertigo
- Erythema multiforme skin reactions including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, purpura, rash
- Nausea, vomiting
- Anaphylaxis
- Anemia
- Hypomagnesemia, hyponatremia, hypochloremia, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypercholesterolemia,
- Muscle weakness or cramps
Warnings
Black box warnings
Do not use fixed dose combination for intial treatment of hypertension
Hypertension requires gradual titration according to individual patient requirements
Contraindications
Anuria
Hypersensitivity to either component or sulfonamides
Dissecting aortic aneurysm
Mitral valve rheumatic heart disease
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
May induce SLE-type syndrome (usually at doses >200 mg/d); instruct patients to report joint/chest pain or fever; consider discontinuation if occurs
DM, fluid or electrolyte imbalance, hyperuricemia or gout, liver disease, renal disease
May aggravate digitalis toxicity
Sensitivity reactions may occur with or without history of allergy or asthma
CVA, severe renal impairment, volume depletion, preexisting hypotension, concurrency with other hypotensive agents
CAD (potential contraindication)
Discontinue slowly to avoid rapid rise in Bp
Risk of male sexual dysfunction
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Pregnancy and lactation
Pregnancy category: C
Lactation: enters breast milk; compatible
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 Hydra-Zide (hydralazine/hydrochlorothiazide)
Half-Life
hydralazine: 3-5 hr
hydrochlorothiazide: 6-15 hr
Absorption
Rate and extent of absorption of hydralazine and hydrochlorothiazide from fixed-dose combination data not available; values are for agents given singly
hydralazine bioavailability: 38-50% slow acetylator; 22-30% rapid acetylator
hydrochlorothiazide: 70% bioavailability
Onset
hydralazine: 1 hr
hydrochlorothiazide: initial diuresis 2 hr; HTN 3-4 d
Duration
hydralazine: 3-8 hr
hydrochlorothiazide: diuresis 6-12 hr; HTN up to 1 wk
Vd
hydralazine: 0.3-8.2 L/kg
hydrochlorothiazide: 3-4 L/kg
Peak Plasma Time
hydrochlorothiazide: 1.5-2.5 hr
Protein Bound
hydralazine: 88-98%
hydrochlorothiazide: 40%
Metabolism
hydralazine: significantly metabolized in liver by acetylation; slow and rapid acetylator
hydrochlorothiazide: minimally metabolized
Metabolites: phthalazine and pyruvic acid hydrazone metabolites (inactive)
Clearance
hydrochlorothiazide 335 mL/min
Excretion
hydralazine: feces 3-12%, urine 3-14%
hydrochlorothiazide: urine 50-70%
Dialyzable
hydrochlorothiazide: no
Mechanism of action
Hydralazine/hydrochlorothiazide is a fixed-combination tablet that combines a vasodilator, hydralazine and a thiazide diuretic, hydrochlorothiazide
Hydralazine, a direct vasodilator, dilates arterioles with little effect on veins; decreases systemic resistance
Hydrochlorothiazide, a thiazide diuretic, inhibits Na reabsorption in distal renal tubules resulting in increased excretion of Na+ and water, also K+ and H+ ions
