Dosing and uses of Inderide (propranolol/hydrochlorothiazide)
Adult dosage forms and strengths
propranolol/hydrochlorothiazide
tablet
- 40mg/25mg
- 80mg/25mg
Hypertension
Not indicated for initial therapy
Dosage must be determined by individual titration
Usual: propranolol 40 mg/hydrochlorothiazide 25 mg PO BId
For total daily propranolol doses >160 mg, combination is not appropriate; use would lead to excessive thiazide dose
Renal Impairment
Use caution in dosing/titrating patients with renal dysfunction
Cumulative effects of thiazides may develop with impaired renal function
Other Information
Combination may be substituted for the titrated individual components
Withdraw gradually over a period of about 2 weeks
Geriatric: begin at low end of the dosing range; use caution
When necessary, another antihypertensive agent may be added gradually beginning with 50 percent of the usual recommended starting dose to avoid an excessive fall in blood pressure
Pediatric dosage forms and strengths
<18 years: Safety/efficacy not established
Inderide (propranolol/hydrochlorothiazide) adverse (side) effects
No adverse effects specific to the combination have been observed; adverse effects limited to those previously reported with propranolol and hydrochlorothiazide
1-10%
propranoloL
- Bradyarrhythmia, dyspnea, fatigue, hypotension, insomnia, nausea, paresthesia, pruritis, psychotic disorder, vomiting
hydrochlorothiazide
- Anorexia, epigastric distress, hypokalemia, hypotension, phototoxicity
Frequency not defined
propranoloL
- Aggravate CHF, decrease HDL, depression, dermatitis, headache, Erythema multiforme, increase bronchospasm, hypertriglyceridemia, myocardial infarction, Stevens-Johnson syndrome, toxic epidermal necrosis, mask symptoms of hypoglycemia
hydrochlorothiazide
- Anaphylaxis, anemia, confusion, erythema multiforme skin reactions including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, hypomagnesemia, hyponatremia, hypochloremia, dizziness, fatigue, headache, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypercholesterolemia, muscle weakness or cramps, nausea, purpura, rash, vertigo, vomiting
Warnings
Black box warnings
Beta-blockers may exacerbate ischemic heart disease following abrupt withdrawaL
Hypersensitivity to catecholamines has been observed during withdrawaL
Exacerbation of angina and, in some cases, myocardial infarction occurrence after abrupt discontinuation
When discontinuing chronically administered beta-blockers (particularly with ischemic heart disease) gradually reduce dose over 1-2 weeks and carefully monitor; If angina markedly worsens or acute coronary insufficiency develops, reinstate beta-blocker administration promptly, at least temporarily (in addition to other measures appropriate for unstable angina)
Warn patients against interruption or discontinuation of beta-blocker without physician advice
Because coronary artery disease is common and may be unrecognized, slowly discontinue beta-blocker therapy, even in patients treated only for hypertension
Contraindications
Anuria
Bronchial asthma
Cardiogenic shock
CHF, unless secondary to tachyarrhythmia treatable with propranoloL
Heart block 2°/3°
Hypersensitivity to either component or sulfonamides
Overt cardiac failure
Sinus bradycardia, sick sinus syndrome (unless permanent pacemaker in place)
Cautions
Anesthesia/surgery (myocardial depression); chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, however the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Avoid abrupt withdrawaL
bronchospastic disease
cerebrovascular insufficiency
CHF, cardiomegaly
DM, fluid or electrolyte imbalance, hyperuricemia or gout, SLe
Hyperthyroidism or thyrotoxicosis, liver disease
May aggravate digitalis toxicity
Myasthenic conditions
Peripheral vascular disease
Renal impairment
Risk of male sexual dysfunction
Sensitivity reactions may occur with or w/o history of allergy or asthma
Pregnancy and lactation
Pregnancy category: C
Lactation: excreted 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 Inderide (propranolol/hydrochlorothiazide)
Half-Life
propranolol: 1.1-9.9 hr
hydrochlorothiazide: 6-15 hr
Absorption
propranolol: 30-70% bioavailability
hydrochlorothiazide: 70% bioavailability
Onset
propranolol: Beta blockade 1-2 hr; HTN 2-3 wk
hydrochlorothiazide: initial diuresis 2 hr; HTN 3-4 d
Duration
propranolol: 6 hr
hydrochlorothiazide: diuresis 6-12 hr; HTN up to 1 wk
Vd
propranolol: 6 L/kg
hydrochlorothiazide: 3-4 L/kg
Peak Plasma Time
propranolol: 2 hr
hydrochlorothiazide: 1.5-2.5 hr
Protein Bound
propranolol: 93%
hydrochlorothiazide: 40%
Metabolism
propranolol : hepatic, P450 enzyme CYP2D6, first-pass metabolism
hydrochlorothiazide: minimally metabolized
metabolites: 4-hydroxypropranolol (active)
Clearance
hydrochlorothiazide 335 mL/min
Excretion
propranolol: urine 40%, feces 55-60%
hydrochlorothiazide: urine 50-70%
Dialyzable
propranolol: no
hydrochlorothiazide: no
Mechanism of action
Propranolol hydrochloride/hydrochlorothiazide is a fixed-combination tablet that combines a Beta adrenergic receptor blocker, propranolol hydrochloride, and a thiazide diuretic, hydrochlorothiazide
Propranolol hydrochloride is a nonselective beta-blocker that reduces chronotropic, inotropic and vasodilator responses to beta-adrenergic stimulation by competing for available binding sites that stimulate the beta-adrenergic receptors. The drug controls hypertension through incompletely understood mechanisms
Hydrochlorothiazide is a thiazide diuretic that inhibits Na reabsorption in distal renal tubules resulting in increased excretion of Na+ and water, also K+ and H+ ions
