The elimination half-life of candesartan is approximately 9 hours. After single and repeated administration, the pharmacokinetics of candesartan are linear for oral doses up to 32 mg of candesartan cilexetil. Candesartan and its inactive metabolite do not accumulate in serum upon repeated once-daily dosing.
After tablet ingestion, the peak serum concentration Cmax is reached after 3 to 4 hours. Food with a high fat content does not affect the bioavailability of candesartan after candesartan cilexetil administration. Hydrochlorothiazide When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5. Metabolism and Excretion Candesartan Cilexetil Total plasma clearance of candesartan is 0.
Biliary excretion contributes to the elimination of candesartan. Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. Distribution Candesartan Cilexetil The volume of distribution of candesartan is 0.
The protein binding is constant at candesartan plasma concentrations well above the range achieved with recommended doses. In rats, it has been demonstrated that candesartan crosses the blood-brain barrier poorly, if at all. It has also been demonstrated in rats that candesartan passes across the placental barrier and is distributed in the fetus.
Hydrochlorothiazide Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. The pharmacokinetics of candesartan were linear in the elderly, and candesartan and its inactive metabolite did not accumulate in the serum of these subjects upon repeated, once-daily administration. Ask your doctor or health care professional how much fluid you need to drink a day. Check with him or her if you get an attack of severe diarrhea, nausea and vomiting, or if you sweat a lot.
The loss of too much body fluid can make it dangerous for you to take this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child, particularly in the second or third trimester. Moderate Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents.
Dosages should be adjusted carefully, according to blood pressure. Among NSAIDs, indomethacin, naproxen, and piroxicam may have the greatest pressor effect, while the effects of sulindac and nabumetone may be significantly less. In patients who are elderly, volume-depleted including those on diuretic therapy , or with compromised renal function who are being treated with NSAIDs, coadministration of angiotensin II receptor antagonists may result in further deterioration of renal function, including acute renal failure.
These effects are usually reversible. Moderate Thiazide diuretics can cause decreased arterial responsiveness to norepinephrine, but the effect is not sufficient to preclude their coadministration. Moderate Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects. Moderate The coadministration of ondansetron with diuretics associated with hypokalemia could increase the risk of QT prolongation.
Potassium levels should be within the normal range prior to and during therapy with ondansetron. Major Patients receiving thiazide diuretics during oprelvekin, rh-IL therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
Coadministration may result in elevated candesartan plasma concentrations. If these drugs are administered concurrently, blood pressure should be monitored closely. Major The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists.
If these drugs are used together, closely monitor for changes in blood pressure. Major The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by diuretics. Moderate Paliperidone may cause orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses of paliperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Moderate Patients receiving a diuretic during treatment with paroxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion SIADH. Discontinuation of paroxetine should be considered in patients who develop symptomatic hyponatremia. Major Cautious use of pasireotide and medicines that can affect potassium or magnesium concentrations such as diuretics is advised. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt.
Correct hypokalemia and hypomagnesemia before pasireotide receipt. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss.
Closely monitor serum electrolytes during pentamidine therapy. Moderate Pentoxifylline has been used concurrently with antihypertensive drugs beta blockers, diuretics without observed problems.
Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced. Moderate Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists.
Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
Moderate Electrolyte disturbances e. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints.
Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics. Major Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics e. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. The clinical significance of this change is unknown.
The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. Moderate Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy.
Prevention of photosensitivity includes adequate protection from sources of UV radiation e. Major Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes TdP. Use of pimozide and medications known to cause electrolyte imbalance may increase the risk of QT prolongation.
Therefore, caution is advisable during concurrent use of pimozide and thiazide diuretics. According to the manufacturer, potassium deficiencies should be correctly prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Moderate Coadministration may lead to hypercalcemia because thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption.
Each mg of calcium polycarbophil contains a substantial amount of calcium approximately mg. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium polycarbophil is used concomitantly, monitoring of serum calcium may be prudent.
Major Potassium salts should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Also, use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists.
Moderate Angiotensin II receptor antagonists ARBs may enhance the hypoglycemic effects of pramlintide by improving insulin sensitivity. Patients receiving an ARB in combination with pramlintide should be monitored for changes in glycemic control.
Moderate Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response acute postural hypotension of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents.
Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however.
This can be therapeutically advantageous, but lower dosages of each agent should be used. Moderate razosin is well-known to produce a 'first-dose' phenomenon. Moderate Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Moderate Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects. Moderate Additive hypotensive effects may be seen when rasagiline is combined with angiotensin II receptor antagonists.
Careful monitoring of blood pressure is suggested during coadministration. Moderate Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of angiotensin II receptor antagonists. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving angiotensin II receptor antagonists concomitantly.
Moderate Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. Moderate Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance.
Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. Moderate Additive hypotensive effects may be seen when selegiline is combined with angiotensin II receptor antagonists. Serotonin norepinephrine reuptake inhibitors: Moderate Patients receiving a diuretic during treatment with sertraline may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion SIADH.
Discontinuation of sertraline should be considered in patients who develop symptomatic hyponatremia. Moderate During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment.
Thus, caution is advisable when silodosin is administered with antihypertensive agents. Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: Moderate Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk.
Moderate Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as diuretics. Minor Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin. Minor Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents e.
Moderate Sulfonamides may cause photosensitization and may increase the photosensitizing effects of thiazide diuretics.
Major Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. Moderate Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia e.
Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors. Moderate Sulfinpyrazone facilitates urinary excretion of uric acid and thereby decreases plasma urate concentrations.
Thiazide diuretics can cause hyperuricemia. Dosage adjustments of sulfinpyrazone may be necessary if thiazides are administered concurrently.
Moderate The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity.
Minor Coadminisitration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic. Moderate Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Moderate Concurrent use of thiopental and alpha-blockers or antihypertensive agents increases the risk of developing hypotension.
Moderate Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. Moderate Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy. Moderate Monitor serum sodium closely if these drugs are used together. Coadministration of tolvaptan and thiazide diuretics increases the risk of too rapid correction of serum sodium.
Moderate Tolvaptan therapy results in an acute reduction in extracellular fluid volume which may result in increased serum potassium. In clinical studies, tolvaptan was administered concomitantly with angiotensin II receptor antagonists.
Serum potassium concentrations should be monitored closely after initiation of tolvaptan therapy in patients receiving angiotensin II receptor antagonists. Moderate Thiazide diuretics and other drugs that decrease renal calcium excretion may increase the risk of hypercalcemia in patients receiving toremifene.
Severe The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
Minor Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone. Moderate Thiazide diuretics can enhance the hypotensive effects of antihypertensive agents or diuretics if given concomitantly.
Moderate Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors SSRIs , serotonin norepinephrine reuptake inhibitors SNRIs , and mirtazapine. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions.
Major Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics.
Moderate Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat.
Frequently monitor serum electrolytes if concomitant use of these drugs is necessary. Moderate Patients receiving a diuretic during treatment with vortioxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion SIADH. Clinically significant hyponatremia has been reported during therapy with vortioxetine.
Discontinuation of vortioxetine should be considered in patients who develop symptomatic hyponatremia. Patients should be monitored for changes in the INR when either of these drugs is initiated or discontinued, or if the dosage is changed. Pregnancy and breast-feeding You must tell your doctor if you think you are or might become pregnant. Breast-feeding Tell your doctor if you are breast-feeding or about to start breast-feeding.
If this happens to you, do not drive or use any tools or machines. If you have been told by your doctor that you have an intolerance to some sugars, such as lactose, contact your doctor before taking this medicine. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. Your resistance to infection may be decreased and you may notice tiredness, an infection or a fever. Exacerbation or activation of systemic lupus erythaematosus has been reported with the use of thiazide diuretics.
This medicinal product contains lactose, as an excipient, and patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Diuretic-induced hypokalaemia and hypomagnesaemia predisposes to the potential cardiotoxic effects of digitalis glycosides and antiarrhythmics.
The absorption of hydrochlorothiazide is reduced by colestipol or cholestyramine. The effect of nondepolarising skeletal muscle relaxants e. Thiazide diuretics may increase serum calcium levels due to decreased excretion.
The hyperglycaemic effect of beta-blockers and diazoxide may be enhanced by thiazides. Thiazide may increase the risk of adverse effects caused by amantadine. Thiazides may reduce the renal excretion of cytotoxic medicinal products e.
Blackwell Scientific 12.5mg, Google Scholar Hypersensitivity Reaction Hypersensitivity reactions to hydrochlorothiazide may occur in candesartan with or without a history of allergy or bronchial asthmacandesartan cilexetil 16mg hydrochlorothiazide 12.5mg, but are more likely in patients with such a history. Renal artery stenosis Medicinal products that affect the renin-angiotensin-aldosterone system, including angiotensin II receptor antagonists AIIRAsmay increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery cilexetil a solitary kidney. Efficacy and tolerability of a combination tablet of candesartan cilexetil and hydrochlorothiazide in insufficiently controlled primary hypertension: Women 12.5mg inform their doctor if they wish to become pregnant or think they might be pregnant. Hydrochlorothiazide dose-dependently increases urinary potassium excretion which may result in hypokalaemia. Diuretic-induced hypokalaemia and hypomagnesaemia predisposes to the potential cardiotoxic effects of digitalis glycosides and antiarrhythmics. Tell your doctor if 16mg notice any of the following: Hemodynamic and hypotensive effects of amlodipine 200mg therapy with chlorothiazide. In the unusual case that there is no appropriate cilexetil to therapy with drugs hydrochlorothiazide the candesartan system for 16mg particular patient, candesartan cilexetil 16mg hydrochlorothiazide 12.5mg, apprise the mother of the potential risk to the fetus. Hydrochlorothiazide data support the use of this combination as an alternative when monotherapy with either agent is not effective, and there are no compelling or specific indications for other drugs.
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