Co-Diovan Special Precautions

Serum electrolyte changes: Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other drugs that may increase potassium levels (heparin, etc.) should be used with caution.
Thiazide diuretics can precipitate new onset hypokalemia or exacerbate pre-existing hypokalemia. Thiazide diuretics should be administered with caution in patients with conditions involving enhanced potassium loss, for example, salt-losing nephropathies and pre-renal (cardiogenic) impairment of kidney function. If hypokalemia is accompanied by clinical signs (e.g. muscular weakness, paresis, or ECG alterations), Co-Diovan should be discontinued. Correction of hypokalemia and any coexisting hypomagnesemia is recommended prior to the initiation of thiazides. Potassium and magnesium serum concentrations should be checked periodically. All patients receiving thiazide diuretics should be monitored for imbalances in electrolytes, particularly potassium.
Thiazide diuretics can precipitate new onset hyponatremia and hypochloremic alkalosis or exacerbate pre-existing hyponatremia. Hyponatremia, accompanied by neurological symptoms (nausea, progressive disorientation, apathy), has been observed in isolated cases. Regular monitoring of serum sodium concentrations is recommended.
Patients with sodium- and/or volume-depletion: In severely sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with Co-Diovan. Co-Diovan should be used only after correction of any pre-existing sodium and/or volume depletion otherwise the treatment should start under close medical supervision.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an i.v. infusion of normal saline. Treatment can be continued once the blood pressure has stabilized.
Patients with renal artery stenosis: Co-Diovan should be used with caution to treat hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis to a solitary kidney, since blood urea and serum creatinine may increase in such patients.
Patients with renal impairment: Renal function has a marked effect on the kinetics of hydrochlorothiazide (see Pharmacology: Pharmacokinetics: Special Populations: Renal Impairment under Actions). Co-Diovan should be used with caution in patients with moderate renal impairment (creatinine clearance >30 mL/min). Periodic checks of serum potassium, creatinine, and uric acid levels are advisable.
Patients with severe renal impairment (creatinine clearance <30 mL/min) should not take Co-Diovan (see Contraindications).
Patients with hepatic impairment: In patients with mild to moderate hepatic impairment without cholestasis, Co-Diovan should be used with caution (see Pharmacology: Pharmacokinetics: Special Populations: Hepatic Impairment under Actions). Patients with severe hepatic impairment, biliary cirrhosis, or cholestasis should not take Co-Diovan (see Contraindications).
Angioedema: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue, has been reported in patients treated with valsartan; some of these patients previously experienced angioedema with other drugs, including ACE inhibitors. Co-Diovan should be immediately discontinued in patients who develop angioedema, and Co-Diovan should not be re-administered.
Systemic lupus erythematosus: Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate systemic lupus erythematosus.
Other metabolic disturbances: Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.
Like other diuretics, hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.
Thiazides decrease urinary calcium excretion and may cause mild elevation of serum calcium in the absence of known disorders of calcium metabolism. Since hydrochlorothiazide can increase serum calcium concentrations, it should be used with caution in patients with hypercalcemia. Marked hypercalcemia unresponsive to thiazide withdrawal or ≥12 mg/dL may be evidence of an underlying thiazide independent hypercalcemic process.
Pathological changes in the parathyroid gland of patients with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. If hypercalcemia occurs, further diagnostic clarification is necessary.
General: Hypersensitivity reactions to hydrochlorothiazide are more likely in patients with allergy and asthma.
Acute Angle-Closure Glaucoma: Hydrochlorothiazide, a sulfonamide, has been associated with an idiosyncratic reaction resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute-angle closure glaucoma can lead to permanent vision loss.
The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatment may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle closure glaucoma may include a history of sulfonamide or penicillin allergy.
Patients with heart failure/post-myocardial infarction: In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors or angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia, and in rare cases with acute renal failure and/or death. Evaluation of patients with heart failure or post-myocardial infarction should always include assessment of renal function.
Dual Blockade of the Renin-Angiotensin System (RAS): Caution is required while co-administering ARBs, including valsartan, with other agents blocking the RAS, such as ACEIs or aliskiren (see Dual blockade of the Renin-Angiotensin-System (RAS) with ARBs, ACEIs, or aliskiren under Interactions).
Non-melanoma skin cancer: An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based on Danish National Cancer Registry. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.
Patients taking HCTZ should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures, such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined, potentially including histological examination of biopsies. The use of HCTZ may also need to be reconsidered in patients who have experienced previous NMSC (see Adverse Reactions).
Acute Respiratory Toxicity: Very rare severe cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported after taking hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after hydrochlorothiazide intake. At the onset, symptoms include dyspnoea, fever, pulmonary deterioration, and hypotension. If diagnosis of ARDS is suspected, Co-Diovan should be withdrawn and appropriate treatment given. Hydrochlorothiazide should not be administered to patients who previously experienced ARDS following hydrochlorothiazide intake.