Higher frequency of adverse events w/ combined use of ACE inhibitors, ARBs or aliskiren. Amlodipine: Increased bioavailability w/ grapefruit or grapefruit juice. Significant increase in exposure w/ strong or moderate CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin, clarithromycin, verapamil, diltiazem). Varied plasma conc w/ CYP3A4 inducers (eg, carbamazepine, phenobarb, phenytoin, fosphenytoin, primidone, rifampicin, St. John's wort). Increase in exposure of simvastatin. Risk of hyperkalaemia w/ dantrolene infusion. Valsartan: Increased K levels w/ K-sparing diuretics, K supplements, K-containing salt substitutes. Increased systemic exposure w/ inhibitors of the uptake transporter (eg, rifampicin, ciclosporin) or efflux transporter (eg, ritonavir). Hydrochlorothiazide: Potentiated orthostatic hypotension w/ alcohol, barbiturates or narcotics. Increased risk of adverse reactions of amantadine. Increased bioavailability w/ anticholinergic agents (eg, atropine, biperiden) & other medicinal products affecting gastric motility. Decreased bioavailability w/ prokinetic substances (eg, cisapride). Thiazides may alter glucose tolerance. Risk of lactic acidosis w/ metformin. Increased risk of hyperglycaemia w/ β-blockers. Enhanced hyperglycaemic effect of diazoxide. Increased risk of hyperuricaemia & gout-type complications w/ ciclosporin. Reduced renal excretion & potentiated myelosuppressive effects of cytotoxic agents (eg, cyclophosphamide, methotrexate). Thiazide-induced hypokalaemia or hypomagnesaemia may occur, favouring the onset of digitalis-induced cardiac arrhythmias. Increased risk of acute renal failure w/ iodine contrasting agents. Decreased absorption w/ cholestyramine or colestipol. Increased hypokalaemic effect w/ medicinal products affecting serum K level (eg, kaliuretic diuretics, corticosteroids, laxatives, ACTH, amphotericin, carbenoxolone, penicillin G, salicylic acid derivatives, antiarrhythmics). Intensified hyponatraemic effect w/ medicinal products affecting serum Na level (eg, antidepressants, antipsychotics, antiepileptics). Risk of hypokalaemia w/ medicinal products that could induce torsades de pointes eg, class Ia & III antiarrhythmics & some antipsychotics. Dose adjustment of uricosuric medicinal products may be necessary as hydrochlorothiazide may increase uric acid serum level. Increased incidence of hypersensitivity reactions to allopurinol. Risk of haemolytic anaemia w/ methyldopa. Potentiated action of curare derivatives eg, tubocurarine. Potentiated antihypertensive action of other antihypertensive medicinal products (eg, guanethidine, methyldopa, β-blockers, vasodilators, Ca channel blockers, ACE inhibitors, ARBs, direct renin inhibitors). Reduced response to pressor amines (eg, noradrenaline, adrenaline). Potentiated rise in serum Ca w/ vit D or Ca salts. Valsartan & hydrochlorothiazide: Reversible increase in serum conc & toxicity of lithium. Attenuated antihypertensive effect w/ NSAIDs including selective COX-2 inhibitors, ASA (>3 g/day), & non-selective NSAIDs.
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