Hydrochlorothiazide Valsartan

A 43-year-old woman reported depression and attempted suicide after taking valsartan in combination with hydrochlorothiazide for hypertension (670). The patient was also taking atenolol, but the time course and complete resolution after withdrawal of valsartan/hydrochlorothiazide suggested that this was a drug-induced episode of depression. 

VALSARTAN/HYDROCHLOROTHIAZIDE (Diovan HCT tablets 12.5 mg hydrochlorothiazide and 80 mg valsartan, tablets 12.5 mg hydrochlorothiazide and 160 mg valsartan, tablets 25 mg hydrochlorothiazide and 160 mg valsartan) Valsartan is an antihypertensive combination. Valsartan antagonizes the effect of angiotensin II (vasoconstriction and aldosterone secretion) by blocking the angiotensin-II receptor (AT, receptor) in vascular smooth muscle and the adrenal gland, producing decreased BP. Hydrochlorothiazide (HCTZ) increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium. They are used in hypertension. 

A 71-year-old man with type 2 diabetes taking amlodipine, warfarin, valsartan, hydrochlorothiazide, atenolol, and rosiglitazone was given fenofibrate. The HDL cholesterol fell from 0.96 to 0.60 mmol/1 but rose to 0.80 mmol/1 on changing the rosiglitazone to pioglitazone. 

Valsartan (22) is an orally active, angiotensin II antagonist that is marketed under the name Diovan by Novartis for hypertension. Novartis has also developed a combination therapy, valsartan plus hydrochlorothiazide, for the second-line therapy of hypertension. The synthesis is straightforward from a stereochemical viewpoint because a chiral pool synthesis is used. The stereogenic center is derived from L-valine (Scheme 31.17).220 223... 

The efficacy of aliskiren monotherapy and aliskiren in combination with the diuretic hydrochlorothiazide (HCT), aliskiren in combination with the angiotensin receptor blocker (ARB) valsartan, and aliskiren in combination with the ACE inhibitor ramipril in reducing mean sitting diastolic blood pressure (msDBP) have been reported (Table 3). From a pooled analysis of several placebo-controlled clinical trials, the approved doses of 150 and 300 mg aliskiren provide a placebo-subtracted reduction in msDBP of 3.2 and... 

Losartan was proved to be more effective for stroke prevention in patients with hypertension and LVH than the beta adrenoceptor blocker atenolol in the LIFE Study [8]. Furthermore, losartan in a comparative trial with hydrochlorothiazide/ atenolol [38], valsartan [39] were shown to inhibit the cognitive decline associated with hypertension in the elderly patients. 

Ullrich H, Passenberg P, Agelink MW. Episodes of depression with attempted suicide after taking valsartan with hydrochlorothiazide. Dtsch Med Wochenschr 2003 128(48) 2534-6. 

Scholze J, Probst G, Bertsch K. Valsartan alone and in combination with hydrochlorothiazide in general practice. Clin Drug Invest 2000 20 1-7. 

Transporter absorptive effects predominant Examples. Acyclovir, Amiloride -, Amoxicillin Atenolol Atropine, Bidisomide Bisphosphonates Captoprit, Cefazolin Cetirizine Cimetidine Ciprofloxacin, Cloxacillin Dicloxacillin Erythromycin - -, Famotidine Fexofenadine Folinic acid Furosemide, Ganciclovir Hydrochlorothiazide, Lisinopril Metformin Methotrexate, Nadolol Penicillins Pravastatin Ranitidine Tetracycline Trimethoprim Valsartan Zalcitabine... 

Angiotensin-II-receptor antagonists (ARBs) are approved for the treatment of hypertension. In addition, irbesartan and losartan are approved for diabetic nephropathy, losar-tan is approved for stroke prophylaxis, and valsartan is approved for heart failure patients who are intolerant of angiotensin-converting enzyme (ACE) inhibitors. The efficacy of ARBs in lowering blood pressure (BP) is comparable with that of other established antihypertensive drugs, with an adverse-effect profile similar to that of placebo. ARBs also are available as fixed-dose combinations with hydrochlorothiazide. 

Symptomatic hypotension may occur when an angiotensin II receptor antagonist is started in patients taking high-dose diuretics. Potassium levels may be either increased, decreased or not affected. No clinically relevant pharmacokinetic interactions appear to occur between candesartan, eprosartan, irbesartan, losartan, telmisartan or valsartan and hydrochlorothiazide, although the bioavailability of hydrochlorothiazide may be modestly reduced. Similarly, there is no clinically significant pharmacokinetic interaction between valsartan and furosemide. 

Class 3 (Low Permeability, High Solrrbility) Atropine, Aciclovir, Valsartan, Gan-cyclovir, Didanosine, Dicloxacillin, Zaldtabine, Lomefloxacin, Methyldopa, Meth-otrexatum. Nadolol, Pravastatin, Ranitidine, TetracycUne, Famotidine, Cefazolin, Ciprofloxacin, Erythromycin, Atenolol, Hydrochlorothiazide, Metformin. ... 

Satana, E. Altinay, S. Goger, N.G. Ozkan, S.A. Senttlrk, Z. Simultaneous determination of valsartan and hydrochlorothiazide in tablets by first-derivative ultraviolet spectrophotometry and LC, J.Pharm.Biorned.Anal., 2001, 26, 1009-1013. 

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