Dosing and uses of Lopressor HCT, Dutoprol (metoprolol/hydrochlorothiazide)
Adult dosage forms and strengths
metoprolol/hydrochlorothiazide
tablet (Lopressor HCT)
- 50mg/25mg
- 100mg/25mg
- 100mg/50mg
tablet (Dutoprol)
- 25mg/12.5mg
- 50mg/12.5mg
- 100mg/12.5mg
Hypertension
Not indicated for initial therapy; if fixed combination represents dose titrated to patient’s needs, therapy with combination may be more convenient than with separate components
Lopressor HCT: metoprolol tartrate 50-100 mg and hydrochlorothiazide 25-50 mg PO daily in single or divided doses
Dutoprol: metoprolol succinate 25-100mg and hydrochlorothiazide 12.5 mg PO qDay as a single dose
When necessary, another antihypertensive agent may be added, beginning with 50% of usual recommended starting dose to avoid excessive fall in blood pressure
To minimize dose-independent side effects, begin combination therapy only after patient fails to achieve desired effect with monotherapy
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 titrated individual components
Withdraw gradually over a period of about 2 weeks
Geriatric: Start at low end of dosing range and titrate slowly
Pediatric dosage forms and strengths
<18 years: Safety/efficacy not established
Geriatric dosage forms and strengths
Hypertension
Not indicated for initial therapy; if fixed combination represents dose titrated to patient’s needs, therapy with combination may be more convenient than with separate components
Lopressor HCT: metoprolol tartrate 50-100 mg and hydrochlorothiazide 25-50 mg PO daily in single or divided doses
Dutoprol: metoprolol succinate 25-100mg amd hydrochlorothiazide 12.5 mg PO qDay as a single dose
When necessary, another antihypertensive agent may be added, beginning with 50% of usual recommended starting dose to avoid excessive fall in blood pressure
To minimize dose-independent side effects, begin combination therapy only after patient fails to achieve desired effect with monotherapy
Lopressor HCT, Dutoprol (metoprolol/hydrochlorothiazide) adverse (side) effects
No adverse effects specific to combination have been observed; adverse effects limited to those previously reported with metoprolol tartrate and hydrochlorothiazide
1-10%
Metoprolol tartrate
- Bradycardia (3%), cold extremities(1%), constipation (1%), depression (5%), diarrhea (5%), dizziness (10%), dyspepsia (1%), dyspnea (3%), fatigue (10%), headache (10%), heart failure (1%), hypokalemiahypotension (1%), influenza-like symptomsnausea (1%), pruritus (5%), wheezing (1%)
Hydrochlorothiazide
- Anorexia, epigastric distress, hypokalemia, hypotension, phototoxicity
Frequency not defined
Metoprolol tartrate
- Bronchospasm, 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
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
Cardiogenic shock
CHF
Heart block 2°/3°
Hypersensitivity to either component or sulfonamides
Overt cardiac failure
Sick sinus syndrome (unless permanent pacemaker in place)
Severe peripheral vascular disease
Sinus bradycardia
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
Avoid abrupt withdrawaL
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Bronchospastic disease
Cerebrovascular insufficiency
Cardiomegaly
DM, fluid or electrolyte imbalance, hyperuricemia or gout, SLe
Hyperthyroidism or thyrotoxicosis, liver disease
May aggravate digitalis toxicity
Peripheral vascular disease
Pheochromocytoma
Renal impairment
Risk of male sexual dysfunction
Sensitivity reactions may occur with or without 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 Lopressor HCT, Dutoprol (metoprolol/hydrochlorothiazide)
Mechanism of action
Metoprolol/hydrochlorothiazide is a fixed-combination tablet that combines a beta adrenergic receptor blocker, metoprolol tartrate (Lopressor HCT) or metoprolol succinate (Dutoprol) and a thiazide diuretic, hydrochlorothiazide
Metoprolol is a beta-1-selective (cardioselective) adrenergic blocking agent at low doses; at higher doses, it also inhibits beta-2 adrenoreceptors in the bronchial and vascular smooth muscles
While the mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated, it may involve competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; a central effect leading to reduced sympathetic outflow to the periphery; and suppression of renin activity
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
Pharmacokinetics
In comparison to immediate-release metoprolol (tartrate), the plasma metoprolol levels following administration of metoprolol succinate (long-acting) are characterized by lower peaks, longer time to peak and significantly lower peak to trough variation
Bioavailability: 50% (metoprolol); (70%) hydrochlorothiazide
Peak plasma concentration: 10-12 hr (metoprolol succinate); 2 hr (hydrochlorothiazide)
Peak plasma time: 1.5-2 hr (metoprolol tartrate); 1.5-2.5 hr (hydrochlorothiazide)
Onset: Initial diuresis from hydrochlorothiaizde (2 hr); antihypertensive effect: 3-4 days
Duration: 3-6 hr (metoprolol tartrate); 6-12 hr (hydrochlorothiazide)
Half-Life: 9-12 hr (metoprolol); 6-15 hr (hydrochlorothiazide)
Clearance: hydrochlorothiazide 335 mL/min (hydrochlorothiazide)
Excretion: Urine 95% (metoprolol) and 50-70% (hydrochlorothiazide)
Dialyzable: No (hydrochlorothiazide)
Distribution
- Protein Bound: 12% (metoprolol); 40% (hydrochlorothiazide)
- Vd: 5.6 L/kg (metoprolol); 3-4 L/kg (hydrochlorothiazide)
Metabolism
- Metoprolol: hepatic CYP2D6
- Hydrochlorothiazide minimally metabolized