Dosing and uses of Uniretic (moexipril/hydrochlorothiazide)
Adult dosage forms and strengths
moexipril/hydrochlorothiazide
tablet
- 7.5mg/12.5mg
- 15mg/12.5mg
- 15mg/25mg
Hypertension
Not for initial therapy
If blood pressure not controlled with moexipril or hydrochlorothiazide monotherapy: 7.5 mg/12.5 mg, 15 mg/12.5 mg OR 15 mg/ 25 mg PO qDay
Increase either or both components based on clinical response
Do not increase hydrochlorothiazide component more often than q2-3Weeks
Doses above moexipril 30 mg/hydrochlorothiazide 50 mg qDay have not been studied
Administration
Dosage adjustment may be required in geriatrics
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
Minimize hydrochlorothiazide dose to minimize electrolyte disturbances
Less effective in African-Americans
Food decreases absorption; manufacturer recommends administration 1 hour before meaL
Pediatric dosage forms and strengths
<18 years: Safety & efficacy not established
Uniretic (moexipril/hydrochlorothiazide) adverse (side) effects
Moexipril
1-10%
- Dizziness
- Hypotension
- Peripheral edema
- Cough
- Headache
- Myalgia
- Hyponatremia
- Pharyngitis
- Sinusitis
- Rash
- Nausea/vomiting
- Hyperkalemia
- Hyponatremia
- Polyuria
Frequency not defined
- Angioedema
- Arrhythmia
- Chest pain
- Pneumonitis
- Syncope
- Proteinuria
- Agranulocytosis (especially if patient has CVD with or without renal impairment)
- Hepatic failure (rare)
- Renal failure
Hydrochlorothiazide
Frequency not defined
- Anorexia
- Epigastric distress
- Hypotension
- Orthostatic hypotension
- Photosensitivity
<1%
- 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
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Anuria
Hypersensitivity to either component or sulfonamides
History of angioedema
Hereditary or idiopathic angioedema
Bilateral renal artery stenosis
Pregnancy (2nd and 3rd trimesters): significant risk of fetal and neonatal morbidity and mortality
Cautions
Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia
Risk of hyperkalemia, especially in patients with renal impairment, DM or those taking concomitant K+-elevating drugs
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
DM, fluid or electrolyte imbalance, hyperuricemia or gout, SLE, liver disease, renal disease
May aggravate digitalis toxicity
Sensitivity reactions may occur with or without history of allergy or asthma
Biliary cirrhosis or biliary obstruction
Apheresis (LDL) with dextran sulfate, hypertrophic cardiomyopathy, collagen vascular disease, hemodialysis with high flux membrane, aortic stenosis
Myelosuppression
Renal impairment may occur
Neutropenia/agranulocytosis reported
Cough may occur within the first few months
Cholestatic jaundice may occur
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)
Avoid concomitant use with lithium
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd & 3rd trimester)
Lactation: inconclusive evidence exists, 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 Uniretic (moexipril/hydrochlorothiazide)
Mechanism of action
Moexipril/hydrochlorothiazide is a fixed-combination tablet that combines an angiotensin-converting enzyme (ACE) inhibitor, moexipril, and a thiazide diuretic, hydrochlorothiazide
Moexipril prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through inhibition of ACE by competing with physiologic substrate (angiotensin I) for active site of ACE; inhibition of ACE initially results in decreased plasma angiotensin II concentrations & consequently, blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion
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
MoexipriL
- Half-life: 1 hr (moexepril); 2-9 hr (moexiprilat)
- Duration: 24 hr
- Onset: 1-2 hr (peak effect)
- Total body clearance: 441 mL/min (Moexipril); 223 mL/min (moexiprilat)
- Excretion: Feces (50%); urine (13%)
- Peak plasma time: 1.5 hr
- Bioavailability: 13-22%
- Protein bound: 90% (moexepril); 50-70% (moexeprilat)
- Vd: 180 L
- Metabolism: extensively metabolized in liver, minimally metabolized at intestinal wall
- Metabolites: Moexiprilat (active)
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
