Hextan/Hextan Plus Drug Interactions

Hextan: Losartan, administered for 12 days, did not affect the pharmacokinetics of pharmacodynamics of a single dose of warfarin. Losartan did not affect the pharmacokinetics of oral or intravenous digoxin. Coadministration of losartan and cimetidine led to an increase of about 18% in AUC of losartan but did not affect the pharmacokinetics of its active metabolite. Coadministration of losartan and phenobarbital led to a reduction of about 20% in the AUC of losartan and that of its active metabolite. There is no pharmacokinetic interaction between losartan and hydrochlorothiazide.
Hextan Plus: Losartan: Rifampicin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated.
As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium. Co-medication is not advisable.
As with other medicines which affect the excretion of sodium, lithium excretion may be reduced.
Therefore, serum lithium levels should be monitored carefully if lithium salts are to be coadministered with angiotensin II receptor antagonists.
When angiotensin II antagonists are administered simultaneously with NSAIDs (i.e. selective COX-2 inhibitors, acetylsalicylic acid at anti-inflammatory doses) and non-selective NSAIDs, attenuation of the antihypertensive effect may occur.
Concomitant use of angiotensin II antagonists or diuretics and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
In some patients with compromised renal function who are being treated with non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists may result in a further deterioration of renal function. These effects are usually reversible.
Other substances inducing hypotension like tricyclic antidepressants, antipsychotics, baclofene, amifostine: Concomitant use with these drugs that lower blood pressure, as main or side-effect, may increase the risk of hypotension.
Hydrochlorothiazide: When given concurrently, the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, narcotics or antidepressants: Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): The treatment with a thiazide may influence the glucose tolerance.
Dosage adjustment of the antidiabetic drug may be required. Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.
Other antihypertensive drugs: Additive effect.
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 percent, respectively.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., adrenaline): 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 relaxant.
Lithium: Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity; concomitant use is not recommended.
Medicinal products used in the treatment of gout (probenecid, sulfinpyrazone and allopurinol).
Dosage adjustment of uricosuric medicinal products may be necessary since hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary.
Coadministration of a thiazide may increase the incidence of hypersensitivity reactions to allopurinol.
Anticholinergic agents (e.g. atropine, biperiden): Increase of the bioavailability to thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.
Cytotoxic agents (eg cyclophosphamide, methotrexate): Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.
Salicylates: In case of high dosages of salicylates hydrochlorothiazide may enhance the toxic effect of the salicylates on the central nervous system.
Methyldopa: There have been isolated reports of haemolytic anaemia occurring with concomitant use of hydrochlorothiazide and methyldopa.
Cyclosporine: Concomitant treatment with cyclosporine may increase the risk of hyperuricaemia and gout-type complications.
Digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia may favour the onset of digitalis-induced cardiac arrhythmias.
Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum potassium and ECG is recommended when Losartan/ hydrochlorothiazide is administered with medicinal products affected by serum potassium disturbances (e.g. digitalis glycosides and antiarrhythmics) and with the following torsades de pointes (ventricular tachycardia)-inducing medicinal products (including some antiarrhythmics), hypokalaemia being a predisposing factor to torsades de pointes (ventricular tachycardia): Class Ia antiarrythmics (eg quinidine, hydroquinidine, disopyramide).
Class III antiarrythmics (eg amiodarone, sotalol, dofetilide, ibutilide).
Some antipsychotics (eg thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol).
Others (eg bepridil, cisapride, diphemanil, erythromycin IV, halofantrin, mizolastin, pentamidine, terfenadine, vincamine IV).
Calcium salts: Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium supplements must be prescribed, serum calcium levels should be monitored and calcium dosage should be adjusted accordingly.
Laboratory Test Interactions: Because of their effects on calcium metabolism, thiazides may interfere with tests for parathyroid function.
Carbamazepine: Risk of symptomatic hyponatremia.
Clinical and biological monitoring is required.
Iodine Contrast Media: In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially with high doses of the iodine product. Patients should be rehydrated before the administration.
Amphotericin B (parenteral), corticosteroids, ACTH or stimulant laxatives: Hydrochlorothiazide may intensify electrolyte imbalance, particularly hypokalaemia.