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Quinaretic (Quinapril Hydrochloride / Hydrochlorothiazide) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

Potassium Supplements and Potassium-Sparing Diuretics: As noted above ("Derangements of Serum Electrolytes"), the net effect of QUINARETIC 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 QUINARETIC, a thiazide diuretic is coadministered with the ACE inhibitor. QUINARETIC and lithium should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

Tetracycline and Other Drugs That Interact with Magnesium: Simultaneous administration of tetracycline with quinapril reduced the absorption of tetracycline by approximately 28% to 37%, possibly due to the high magnesium content in quinapril tablets. This interaction should be considered if coprescribing quinapril and tetracycline or other drugs that interact with magnesium.

Other Agents:

Drug interaction studies of quinapril and other agents showed:

  • Multiple dose therapy with propranolol or cimetidine has no effect on the pharmacokinetics of single doses of quinapril.

  • The anticoagulant effect of a single dose of warfarin (measured by prothrombin time) was not significantly changed by quinapril coadministration twice daily.

  • Quinapril treatment did not affect the pharmacokinetics of digoxin.

  • No pharmacokinetic interaction was observed when single doses of quinapril and hydrochlorothiazide were administered concomitantly.

When administered concurrently, the following drugs may interact with thiazide diuretics:

  • Alcohol, Barbiturates, or Narcotics-potentiation of orthostatic hypotension may occur.

  • Antidiabetic Drugs (oral hypoglycemic agents and insulin)-dosage adjustments of the antidiabetic drug may be required.

  • Cholestyramine and Colestipol Resin-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.

  • Corticosteroids, ACTH-intensified electrolyte depletion, particularly hypokalemia.

  • Pressor Amines (eg, norepinephrine)-possible decreased response to pressor amines, but not sufficient to preclude their therapeutic use.

  • Skeletal Muscle Relaxants, Nondepolarizing (eg, tubocurarine)-possible increased responsiveness to the muscle relaxant.

  • Nonsteroidal Antiinflammatory Drugs-the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be reduced by concurrent administration of nonsteroidal antiinflammatory agents.

OVERDOSAGE

No specific information is available on the treatment of overdosage with QUINARETIC or quinapril monotherapy; treatment should be symptomatic and supportive. Therapy with QUINARETIC should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures.

The oral median lethal dose of quinapril/hydrochlorothiazide in combination ranges from 1063/664 to 4640/2896 mg/kg in mice and rats. Doses of 1440 to 4280 mg/kg of quinapril cause significant lethality in mice and rats. In single-dose studies of hydrochlorothiazide, most rats survived doses up to 2.75 g/kg.

Data from human overdoses of ACE inhibitors are scanty; the most likely manifestation of human quinapril overdosage is 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 quinapril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of quinapril overdose.

No data are available to suggest physiological maneuvers (eg, maneuvers to change the pH of the urine) that might accelerate elimination of quinapril and its metabolites. Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat.

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

CONTRAINDICATIONS

QUINARETIC is contraindicated in patients who are hypersensitive to quinapril or hydrochlorothiazide and in patients with a history of angioedema related to previous treatment with an ACE inhibitor.

Because of the hydrochlorothiazide components, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

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