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Fosinopril Sodium / Hydrochlorothiazide

Pronunciation: fos-IN-oh-pril SOE-dee-um HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Fosinopril sodium/Hydrochlorothiazide
- Tablets, oral fosinopril 10 mg/hydrochlorothiazide 12.25 mg
- Tablets, oral fosinopril 20 mg/hydrochlorothiazide 12.5 mg

Pharmacology

Fosinopril

Competitively inhibits angiotensin I–converting enzyme, resulting in the prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor that stimulates aldosterone secretion. This action results in a decrease in sodium and fluid retention, increase in diuresis, and decrease in BP.

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Hydrochlorothiazide

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

For the treatment of hypertension. This fixed combination drug is not intended for the initial therapy of hypertension.

Contraindications

Anuric patients; patients hypersensitive to fosinopril or any other ACE inhibitor, or hydrochlorothiazide or other sulfonamide derivatives.

Dosage and Administration

Adults

PO Combination therapy with once-daily doses of 10 to 20 mg of fosinopril and 12.5 mg of hydrochlorothiazide in the morning. Titrate dose based on clinical effect.

General Advice

  • May be taken with or without food.

Storage/Stability

Store between 59° and 86°F. Protect from moisture.

Drug Interactions

No drug interaction studies have been conducted between fosinopril/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the fosinopril/hydrochlorothiazide combination.

Fosinopril Aldosterone blockers (eg, eplerenone)

May cause serious hyperkalemia, possibly with cardiac arrhythmias. Monitor potassium level periodically and reduce dose of aldosterone blocker if needed.

Aliskiren

May decrease renal excretion of potassium. Closely monitor serum potassium.

Angiotensin II receptor antagonists (eg, valsartan)

Increased risk of renal dysfunction and hyperkalemia. Closely monitor renal function and serum potassium.

Antacids (eg, aluminum, magnesium, simethicone)

May decrease effects of fosinopril. Separate dosing by 2 h.

Antihypertensive agents (eg, propranolol)

Additive or potentiation of hypotensive effects. Closely monitor BP.

Clozapine

May cause excessive decreases in blood pressure and syncope. Consider lower starting dosage of clozapine.

Cyclosporine

Acute renal failure has been reported with coadministration. If renal dysfunction occurs, it may be necessary to stop 1 or both agents.

Gold

Nitroid reactions may occur in patients using injectable gold (sodium aurothiomalate).

Ketorolac (nasal)

May cause decreased antihypertensive effects and the risk of nephrotoxicity may be increased. Monitor BP closely. Periodic measurement of renal function may be necessary.

Lithium

Increased lithium levels may occur. Coadminister with caution.

Mammalian target of rapamycin (mTOR) inhibitors (eg, everolimus, sirolimus)

Increased risk of angioedema, ranging from minor facial edema to life-threatening mouth and throat swelling, may occur.

NSAIDs (eg, naproxen)

The antihypertensive effects may be decreased; risk of NSAID-related nephrotoxicity, including hyperkalemia, may be increased.

Pergolide

May cause profound hypotension. Start with lower doses of pergolide and monitor blood pressure closely. If BP falls, dosage reduction may be needed.

Phenothiazines (eg, chlorpromazine)

May produce a synergistic hypotensive effect with postural syncope. Monitor BP (supine and standing) and adjust dosage of antihypertensive as needed.

Potassium preparations, potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene)

May increase serum potassium levels. Use with caution and monitor serum potassium frequently.

Salicylates (eg, aspirin, bismuth salicylate)

Hypotensive effects may be decreased. Adjust dosage of antihypertensive as needed. May need to stop salicylates if BP control or renal function deteriorates.

Sulfonylureas (eg, glyburide)

Hypoglycemia may occur with coadministration.

Tizanidine

May cause severe hypotension. Monitor BP and coadminister with caution.

Trimethoprim

May cause hyperkalemia and possibly cardiac arrhythmias or cardiac arrest. Closely monitor serum potassium.

Hydrochlorothiazide ACE inhibitors (eg, captopril)

The risk of acute renal dysfunction may be increased. Monitor renal function.

Antihypertensive agents

Additive or potentiation of hypotension effects. Closely monitor BP.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide, reducing GI absorption up to 85% and 43%, respectively. Separate the administration times by as much as possible.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid. If coadministration cannot be avoided, a decreased dosage of 1 or both agents may be required.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Measure plasma concentrations of potassium and magnesium with coadministration.

Dofetilide

Coadministration is contraindicated. Dofetilide plasma concentrations may be increased. Prolongation of the QT interval may occur, increasing the risk of torsades de pointes.

Insulin, sulfonylureas (eg, glyburide)

Hydrochlorothiazide may increase fasting blood glucose and decrease insulin secretion. The effect of oral hypoglycemic agents and insulin may be decreased. Monitor blood glucose and adjust the hypoglycemic dose as needed.

Lithium

Lithium Cl may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Lithium generally should not be given with hydrochlorothiazide.

Loop diuretics (eg, furosemide)

May cause profound diuresis and serious electrolyte abnormalities. Monitor for dehydration and electrolyte abnormalities during combined therapy.

Methenamine

By alkalinizing the urine, hydrochlorothiazide may decrease the effectiveness of methenamine.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Possible increase responsiveness to the muscle relaxant caused by diuretic-induced hypokalemia. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

NSAIDs (eg, ibuprofen, indomethacin)

The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide may be reduced. Monitor BP and the diuretic response.

Potassium preparations, potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene)

May increase serum potassium levels. Use with caution and monitor serum potassium frequently.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.

Tretinoin

The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.

Laboratory Test Interactions

Measurement of serum digoxin with Digi-Tab radioimmunoassay kit may be falsely low.

Adverse Reactions

Cardiovascular

Orthostatic hypotension (2%); flushing, rhythm disturbance, syncope (less than 2%).

CNS

Headache (7%); fatigue (4%); dizziness (3%); depression, numbness/paresthesia, somnolence (less than 2%).

Dermatologic

Pruritus, rash (less than 2%).

EENT

Rhinitis, sinus congestion, tinnitus (less than 2%).

GI

Abdominal pain, diarrhea, dyspepsia/heartburn, gastritis/esophagitis, nausea/vomiting (less than 2%).

Genitourinary

Breast mass, change in libido, dysuria, sexual dysfunction, urinary frequency, UTI (less than 2%).

Lab Tests

Elevated cholesterol/triglycerides/uric acid, hyper- and hypokalemia, hypercalcemia, hypomagnesemia, hypophosphatemia, neutropenia (less than 2%).

Musculoskeletal

Musculoskeletal pain (2%); myalgia/muscle cramps (less than 2%).

Respiratory

Cough (6%); upper respiratory tract infection (2%); pharyngitis (less than 2%).

Miscellaneous

Angioedema, chest pain, edema, fever, viral infection, weakness (less than 2%).

Precautions

Warnings

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.


Monitor

Ensure that volume and/or salt depletion have been corrected before initiating therapy. Monitor and record BP and pulse. Monitor blood sugar in diabetic patient when drug is started or dose is changed. Monitor renal function periodically. Initially and periodically monitor serum electrolytes.


Pregnancy

Category D (second and third trimester); Category C (first trimester). ACE inhibitors (eg, fosinopril) can cause injury or death to fetus if used during second or third trimester. When pregnancy is detected, discontinue as soon as possible.

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hypersensitivity

Serious and/or life-threatening anaphylactoid reactions may occur. Hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma.

Renal Function

Not recommended in patients with severe renal disease. Use with caution; thiazides may precipitate azotemia in such patients.

Hepatic Function

Use with caution.

Angioedema

Angioedema of the face, extremities, lips, tongue, glottis, larynx, and/or intestines may occur. Angioedema associated with laryngeal edema may be fatal.

Electrolyte imbalance

Hyperkalemia, hypokalemia, hypercalcemia, hypophosphatemia, hypomagnesemia, hyponatremia, and/or hypochloremic alkalosis may occur.

Hematologic effects

Agranulocytosis and bone marrow depression have occurred with other ACE inhibitors; neutropenia/agranulocytosis has been associated with thiazide diuretics.

Hepatic effects

ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death.

Hypotension

Decreases in BP may occur, especially in salt- or volume-depleted patients as a result of dialysis, prolonged diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Volume and salt depletion should be corrected before initiating therapy.

Metabolic effects

Thiazides tend to reduce glucose tolerance and raise serum levels of cholesterol, triglycerides, and uric acid.

Systemic lupus erythematosus

May exacerbate or activate SLE.

Overdosage

Symptoms

Dehydration, electrolyte disturbances, hypotension.

Patient Information

  • Advise patient to take prescribed dose once daily without regard to meals.
  • Advise patient to try to take each dose at about the same time each day.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patient to lie or sit down if experiencing dizziness or light-headedness when standing.
  • Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP resulting in light-headedness or fainting.
  • Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
  • Caution patient to avoid unnecessary exposure to UV light (eg, sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid a photosensitivity reaction.
  • Instruct patient to stop taking fosinopril sodium/hydrochlorothiazide and immediately report any of the following symptoms to health care provider: fainting; swelling of the face, lips, eyelids, or tongue; or difficulty breathing.
  • Instruct patient to inform health care provider if a persistent cough develops while taking this medication.
  • Inform women of childbearing age about the consequences of second and third trimester exposure to ACE inhibitors. Advise patients to report pregnancies to their health care providers as soon as possible.
  • Advise patients not to use potassium supplements or salt substitutes containing potassium without consulting their health care provider.
  • Advise patients to promptly report any indication of infection (eg, sore throat, fever), which could be a sign of neutropenia.

Copyright © 2009 Wolters Kluwer Health.

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