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Fosinopril and Hydrochlorothiazide (Fosinopril Sodium / Hydrochlorothiazide) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

Dual Blockade of the Renin-Angiotensin System (RAS)

Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on fosinopril and hydrochlorothiazide and other agents that affect the RAS.

Do not co-administer aliskiren with fosinopril and hydrochlorothiazide in patients with diabetes. Avoid use of aliskiren with fosinopril and hydrochlorothiazide in patients with renal impairment (GFR <60 ml/min).

Potassium supplements and potassium-sparing diuretics: As noted above (“Derangements of Serum Electrolytes”), the net effect of fosinopril sodium and hydrochlorothiazide may be to elevate a patient’s serum potassium, to reduce it, or to leave it unchanged. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia. If concomitant use of such agents is indicated, they should be given with caution, and the patient’s serum potassium should be monitored frequently.

Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. Because renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity is presumably raised further when, as in therapy with fosinopril sodium and hydrochlorothiazide tablets, a thiazide diuretic is coadministered with the ACE inhibitor. Fosinopril sodium and hydrochlorothiazide and lithium should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

Antacids: In a clinical pharmacology study, serum levels and urinary excretion of fosinoprilat were reduced when fosinopril was coadministered with an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) suggesting that antacids may impair absorption of fosinopril. If concomitant administration of these agents is indicated, dosing should be separated by 2 hours.

Gold: Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including fosinopril sodium and hydrochlorothiazide.

Other: The bioavailability of unbound fosinoprilat is not altered by coadministration of fosinopril with aspirin, chlorthalidone , cimetidine, digoxin, metoclopramide, nifedipine, propranolol, propantheline, or warfarin. Other ACE inhibitors have had less than additive effects with beta-adrenergic blockers, presumably because drugs of both classes lower blood pressure by inhibiting parts of the renin-angiotensin system.

Interaction studies with warfarin have failed to identify any clinically important effects of fosinopril on the serum concentration or clinical effects of the anticoagulant.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged.

Thiazides may decrease arterial responsiveness to norepinephrine, but not enough to preclude effectiveness of the pressor agent for therapeutic use.

Thiazides may increase the responsiveness to tubocurarine.

The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be reduced by concurrent administration of nonsteroidal anti-inflammatory agents; the effects (if any) of these agents on the antihypertensive effect of fosinopril sodium and hydrochlorothiazide have not been studied.

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

Cholestyramine and Colestipol Resins:Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

OVERDOSAGE

To obtain up-to-date information about the treatment of overdose, a good resource is a certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient.

No specific information is available on the treatment of overdosage with fosinopril sodium and hydrochlorothiazide tablets; treatment should be symptomatic and supportive. Therapy with fosinopril sodium and hydrochlorothiazide should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures.

In rats, single oral doses of 2600 mg/kg of fosinopril were associated with significant lethality. In single-dose studies of hydrochlorothiazide, most rats survived doses of up to 2750 mg/kg. Both doses are more than 6000 times (on a mg/kg basis) the maximum recommended daily dose of either fosinopril or hydrochlorothiazide in fosinopril sodium and hydrochlorothiazide.

Data from human overdoses of fosinopril are scanty, but the most common manifestation of human fosinopril overdosage is likely to be hypotension. In human hydrochlorothiazide overdose, the most common signs and symptoms observed have been those of dehydration and electrolyte depletion (hypokalemia, hypochloremia, hyponatremia). If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

Laboratory determinations of serum levels of fosinopril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of fosinopril overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of fosinopril and its metabolites. Fosinoprilat is poorly removed from the body by hemodialysis or peritoneal dialysis.

Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of fosinopril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of fosinopril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat fosinopril overdose by infusion of normal saline solution.

CONTRAINDICATIONS

Fosinopril sodium and hydrochlorothiazide is contraindicated in patients who are anuric. Fosinopril sodium and hydrochlorothiazide is also contraindicated in patients who are hypersensitive to fosinopril, to any other ACE inhibitor, to hydrochlorothiazide, or other sulfonamide-derived drugs, or any other ingredient or component in the formulation. Hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma.

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