moexipril/hydrochlorothiazide (Uniretic): Dosing and Uses

Dosing and uses of Uniretic (moexipril/hydrochlorothiazide)

• Adult
• Pediatric

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