Co-Diovan Drug Interactions

valsartan + hydrochlorothiazide




Full Prescribing Info
Drug Interactions
Valsartan-hydrochlorothiazide: The following drug interactions may occur due to both components (valsartan and/or hydrochlorothiazide) of Co-Diovan: Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors, angiotensin II receptor antagonists or thiazides. Since renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity may presumably be increased further with Co-Diovan. Therefore, careful monitoring of serum lithium concentrations is recommended during concomitant use.
Valsartan: The following potential drug interactions may occur due to the valsartan component of Co-Diovan: Dual blockade of the Renin-Angiotensin-System (RAS) with ARBs, ACEIs, or aliskiren: The concomitant use of ARBs, including valsartan, with other agents acting on the RAS is associated with an increased incidence of hypotension, hyperkalemia, and changes in renal function compared to monotherapy. It is recommended to monitor blood pressure, renal function and electrolytes in patients on Co-Diovan and other agents that affect the RAS (see PRECAUTIONS).
The concomitant use of ARBs - including valsartan - or of ACEIs with aliskiren, should be avoided in patients with severe renal impairment (GFR < 30 mL/min) (see PRECAUTIONS).
The concomitant use of ARBs - including valsartan - or of ACEIs with aliskiren is contraindicated in patients with Type 2 diabetes (see CONTRAINDICATIONS).
Potassium: Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may alter potassium levels (heparin, etc.) should be used with caution and with frequent monitoring of potassium.
Non-Steroidal Anti-Inflammatory Agents (NSAIDs) including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): When angiotensin II antagonists are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur. Furthermore, in patients who are elderly, volume-depleted (including those on diuretic therapy), or have compromised renal function, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function. Therefore, monitoring of renal function is recommended when initiating or modifying the treatment in patients on valsartan who are taking NSAIDs concomitantly.
Transporters: The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. Co-administration of inhibitors of the uptake transporter (e.g., rifampin, ciclosporin) or efflux transporter (e.g., ritonavir) may increase the systemic exposure to valsartan.
In monotherapy with valsartan, no drug interactions of clinical significance have been found with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Hydrochlorothiazide: The following potential drug interactions may occur due to the thiazide component of Co-Diovan: Other anti-hypertensive drugs: Thiazides potentiate the antihypertensive action of other antihypertensive drugs (e.g. guanethidine, methyldopa, beta-blockers, vasodilators, calcium channel blockers, ACE inhibitors, Angiotensin Receptor Blockers (ARBs) and Direct Renin Inhibitors (DRIs)).
Skeletal muscle relaxants: Thiazides, including hydrochlorothiazide, potentiate the action of skeletal muscle relaxants such as curare derivatives.
Medicinal products affecting serum potassium levels: The hypokalemic effect of diuretics may be increased by concomitant administration of kaliuretic diuretics, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G, salicylic acid derivatives or antiarrhythmics (see PRECAUTIONS).
Medicinal products affecting serum sodium levels: The hyponatremic effect of diuretics may be intensified by concomitant administration of drugs such as antidepressants, antipsychotics, antiepileptics, etc. Caution is advised in long-term administration of these drugs (see PRECAUTIONS).
Antidiabetic agents: Thiazides may alter glucose tolerance. It may be necessary to adjust the dosage of insulin and of oral antidiabetic agents.
Digitalis glycosides: Thiazide-induced hypokalemia or hypomagnesemia may occur as unwanted effects, favoring the onset of digitalis-induced cardiac arrhythmias (see PRECAUTIONS).
NSAIDs and Cox-2 selective inhibitors: Concomitant administration of NSAIDs (e.g. salicylic acid derivative, indomethacin) may weaken the diuretic and antihypertensive activity of the thiazide component of Co-Diovan. Concurrent hypovolemia may induce acute renal failure.
Allopurinol: Co-administration of thiazide diuretics (including hydrochlorothiazide) may increase the incidence of hypersensitivity reactions to allopurinol.
Amantadine: Co-administration of thiazide diuretics (including hydrochlorothiazide) may increase the risk of adverse effects caused by amantadine.
Antineoplastic agents (e.g. cyclophosphamide, methotrexate): Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
Anticholinergic agents: 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. Conversely prokinetic drugs such as cisapride may decrease the bioavailability of thiazide-type diuretics.
Ion exchange resins: Absorption of thiazide diuretics, including hydrochlorothiazide, is decreased by cholestyramine or colestipol. However, staggering the dosage of hydrochlorothiazide and resin such that hydrochlorothiazide is administered at least 4 h before or 4-6 h after the administration of resins would potentially minimize the interaction.
Vitamin D: Administration of thiazide diuretics, including hydrochlorothiazide, with vitamin D or with calcium salts may potentiate the rise in serum calcium.
Ciclosporin: Concomitant treatment with ciclosporin may increase the risk of hyperuricemia and gout-type complications.
Calcium salts: Concomitant use of thiazide type diuretics may lead to hypercalcemia by increasing tubular calcium reabsorption.
Diazoxide: Thiazide diuretics may enhance the hyperglycaemic effect of diazoxide.
Methyldopa: There have been reports in the literature of hemolytic anemia occurring with concomitant use of hydrochlorothiazide and methyldopa.
Alcohol, barbiturates or narcotics: Concomitant administration of thiazide diuretics with alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension.
Pressor amines: Hydrochlorothiazide may reduce the response to pressor amines such as noradrenaline. The clinical significance of this effect is uncertain and not sufficient to preclude their use.
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