e, probably via CYP3A4 (plasma concentration increases by approximately 50% and the effect of amlodipine is increased). The possibility that more potent inhibitors of CYP3A4 (i.e. ketoconazole, itraconazole, ritonavir) may increase the plasma concentration of amlodipine to a greater extent than diltiazem cannot be excluded.
CYP3A4 inducers (anticonvulsant agents [e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone], rifampicin, Hypericum perforatum [St. John's wort])
Co-administration may lead to reduced plasma concentrations of amlodipine. Clinical monitoring is indicated, with possible dosage adjustment of amlodipine during the treatment with the inducer and after its withdrawal.
Valsartan and HCT
Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day), and non-selective NSAIDs
NSAIDS can attenuate the antihypertensive effect of both angiotensin II antagonists and hydrochlorothiazide when administered simultaneously. Furthermore, concomitant use of Exforge HCT and NSAIDs may lead to worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, as well as adequate hydration of the patient.
Medicinal products affected by serum potassium disturbances
Periodic monitoring of serum potassium and ECG is recommended when a hydrochlorothiazide containing product is administered with agents affected by serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics) and the following agents that induce torsades de pointes (which include some antiarrhythmics), hypokalaemia being a predisposing factor for torsades de pointes.
- Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide)
- Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide)
- Some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol, methadone)
- Others (e.g. bepridil, cisapride, diphemanil, erythromycin i.v., halofantrin, ketanserin, mizolastin, pentamidine, moxifloxacine, terfenadine, vincamine i.v.)
HCT
Alcohol, anaesthetics and sedatives
Potentiation of orthostatic hypotension may occur.
Amantadine
Thiazides, including hydrochlorothiazide, may increase the risk of adverse reactions caused by amantadine.
Anticholinergic agents (e.g. atropine, biperiden)
The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents (e.g. atropine, biperiden), apparently due to a decrease in gastrointestinal motility and the stomach emptying rate.
Antidiabetic medicinal products (e.g. insulin and oral antidiabetic agents)
It may prove necessary to readjust the dosage of insulin and of oral antidiabetic agents.
− Metformin
Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.
Beta blockers and diazoxide
Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta blockers may increase the risk of hyperglycaemia. Thiazide diuretics, including hydrochlorothiazide, may enhance the hyperglycaemic effect of diazoxide.
Carbamazepine
Patients receiving hydroc |
