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Tekturna HCT (Aliskiren / Hydrochlorothiazide) - Drug Interactions, Contraindications, Overdosage, etc

 
 



      DRUG INTERACTIONS

No drug interaction studies have been conducted with Tekturna HCT and other drugs, although studies with the individual aliskiren and hydrochlorothiazide components are described below.

Aliskiren

Effects of Other Drugs on Aliskiren

Based on in vitro studies, aliskiren is metabolized by CYP 3A4.

Irbesartan:  Coadministration of irbesartan reduced aliskiren Cmax up to 50% after multiple dosing.

P-glycoprotein Effects: Pgp (MDR1/Mdr1a/1b) was found to be the major efflux system involved in absorption and disposition of aliskiren in preclinical studies. The potential for drug interactions at the Pgp site will likely depend on the degree of inhibition of this transporter. Coadministration of aliskiren with Pgp substrates or weak to moderate inhibitors such as atenolol, digoxin, and amlodipine did not result in clinically relevant interactions.

Atorvastatin:  Coadministration of atorvastatin resulted in about a 50% increase in aliskiren Cmax and AUC after multiple dosing.

Ketoconazole: Coadministration of 200 mg twice-daily ketoconazole, a potent Pgp inhibitor, with aliskiren resulted in an approximate 80% increase in plasma levels of aliskiren. A 400-mg once-daily dose was not studied but would be expected to increase aliskiren blood levels further.

Cyclosporine: Coadministration of 200 mg and 600 mg cyclosporine, a highly potent Pgp inhibitor, with 75 mg aliskiren resulted in an approximately 2.5-fold increase in Cmax and 5-fold increase in AUC of aliskiren. Concomitant use of aliskiren with cyclosporine is not recommended.

Drugs with no clinically significant effects: Coadministration of lovastatin, atenolol, warfarin, furosemide, digoxin, celecoxib, hydrochlorothiazide, ramipril, valsartan, metformin and amlodipine did not result in clinically significant increases in aliskiren exposure.

Effects of Aliskiren on Other Drugs

Aliskiren does not inhibit the CYP450 isoenzymes (CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1, and CYP 3A) or induce CYP 3A4.

Furosemide: When aliskiren was coadministered with furosemide, the AUC and Cmax of furosemide were reduced by about 30% and 50%, respectively. Patients receiving furosemide could find its effect diminished after starting aliskiren.

Drugs with no clinically significant effects:  Coadministration of aliskiren did not significantly affect the pharmacokinetics of lovastatin, digoxin, valsartan, amlodipine, metformin, celecoxib, atenolol, atorvastatin, ramipril or hydrochlorothiazide.

Warfarin :  The effects of aliskiren on warfarin pharmacokinetics have not been evaluated.

Hydrochlorothiazide

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

Alcohol, barbiturates, or narcotics :  Potentiation of orthostatic hypotension may occur.

Antidiabetic drugs (oral agents and insulin ) :  Dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs :  Additive effect or potentiation.

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.

Corticosteroids, ACTH :  Intensified electrolyte depletion, particularly hypokalemia.

Pressor amines   (e.g., norepinephrine ) :  Possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine ) :  Possible increased responsiveness to the muscle relaxants.

Lithium :  Should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and increase the risk of lithium toxicity. Refer to the package insert for lithium before use of such preparation with Tekturna HCT.

Nonsteroidal anti-inflammatory d rugs :  In some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Tekturna HCT and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

      OVERDOSAGE

Aliskiren

Limited data are available related to overdosage in humans. The most likely manifestation of overdosage would be hypotension. If symptomatic hypotension should occur, supportive treatment should be initiated.

H ydrochlorothiazide

The most common signs and symptoms of overdose observed in humans are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

      CONTRAINDICATIONS

Because of the hydrochlorothiazide component, Tekturna HCT is contraindicated in patients with anuria or hypersensitivity to sulfonamide-derived drugs [ s ee Warnings and Precautions (5.6) and Adverse Reactions (6.1) ]. Hypersensitivity reactions may range from urticaria to anaphylaxis [ s ee Adverse Reactions (6.1) ].

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