Dosing and uses of fosinopril-hydrochlorothiazide
Adult dosage forms and strengths
fosinopril/hydrochlorothiazide
tablet
- 10mg/12.5mg
- 20mg/12.5mg
Hypertension
10 mg/12.5 mg PO qDay initially
Dosage range: 10-80 mg/12.5-50 mg per day PO
Combination therapy indicated for patients whose blood pressure is not adequately controlled with fosinopril or hydrochlorothiazide monotherapy
Renal Impairment
CrCl < 30 mL/min or serum creatinine ≥ 3 mg/dL: Use not recommended
CrCl ≥ 30 mL/min: Dose adjustment not necessary
Hepatic Impairment
Metabolism of active metabolite fosinoprilat will be reduced in progressive liver disease; use caution
Pediatric dosage forms and strengths
Safety and efficacy not established
fosinopril-hydrochlorothiazide adverse (side) effects
Fosinopril
>10%
- Dizziness (1.6-11.9%)
1-10%
- Cough (2.2-9.7%)
- Headache (3.2%)
- Hyperkalemia (2.6%)
- Diarrhea (2.2%)
- Orthostatic hypotension (1.4-1.9%)
- Fatigue (1-2%)
Frequency not defined
- Angioedema
- ARF if renal artery stenosis
- Aplastic anemia
- Neutropenia
- Arthralgia
- Interstitial nephritis
- Vasculitis
- Rash
Hydrochlorothiazide
<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
Frequency not defined
- Anorexia
- Epigastric distress
- Hypotension
- Orthostatic hypotension
- Photosensitivity
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
Hypersensitivity to ACE inhibitors, thiazides or sulfonamides
History of hereditary or angioedema associated with previous ACE inhibitor treatment
Pregnancy (2nd and 3rd trimesters): significant risk of fetal/neonatal morbidity and mortality (due to fosinopril)
Anuria or renal artery stenosis
Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)
Cautions
Begin combination therapy only after failed monotherapy
Severe renal impairment, hepatic impairment
Risk of hypotension, especially with CHF
Coadministration with mTOR inhibitors (eg, temsirolimus) may increased risk for angioedema
Renal impairment may occur
Neutropenia/agranulocytosis reported
Cough may occur within the first few months
Cholestatic jaundice may occur
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
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd & 3rd trimesters)
Lactation: enters breast milk; contraindicated
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 fosinopril-hydrochlorothiazide
Mechanism of action
Competitively inhibits angiotensin-converting enzymes, resulting in decreased plasma angiotensin II concentrations; BP may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion; increases renal blood flow
Absorption
Bioavailability: 36%
Distribution
Protein bound: 99.4%
Vd: SmalL
Metabolism
75% present as active fosinoprilat, 20-30% as a glucuronide conjugate of fosinoprilat, and 1-5% as a p-hydroxy metabolite of fosinoprilat
Elimination
Half-life: 12 hr (fosinoprilat); 14 hr (heart failure)
Total body clearance: 26-39 mL/min
Excretion: 50% urine; 50% feces
Hemodialysis: 2%
Peritoneal dialysis: 7%
