Valsaram Special Precautions

Volume and/or salts depleted patients: In placebo-controlled clinical trials, excessive hypotension was seen in 0.4% of patients with uncomplicated hypertension treated with this medicine. Symptomatic hypotension may occur in patients with activated renin-angiotensin system receiving angiotensin receptor blocker (ARB antagonist) (i.e. volume and/or salts depleted patients taking high doses of diuretics). It is recommended to correct such conditions prior to administration or to closely supervise on initiating treatment with this drug. If hypotension occurs upon drug administration, lay patients down and if necessary, instillate with saline solution. Treatment can be continued after blood pressure is stabilized.
Hyperkalemia: On concomitant therapy with potassium adjuvant, potassium sparing diuretics, salt substitute containing potassium or other drugs (i.e. heparin) which may increase potassium level, attention should be paid and potassium level should be periodically monitored.
Renal artery stenosis: As this drug can increase blood urea and serum creatinine in patients with bilateral or unilateral renal artery stenosis, or patients with single kidney syndrome who stenosis occurred, it is recommended to monitor in safety aspect.
Kidney transplantation: There is no information which can prove its safety in kidney transplantation patients.
Angioedema: Angioedema (including larynx and glottis swelling) which causes respiratory obstruction and/or swelling of face, mouth and tongue in patients receiving valsartan was reported, some of these patients have experienced angioedema caused by other drugs as same as ACE inhibitors. If angioedema is caused due to this drug, administration should be discontinued immediately and should not be resumed.
Heart failure or myocardial infarction: In general, care should be taken when using calcium channel blockers such as amlodipine to patients with congestive heart failure (NYHA class III or IV stage).
In placebo-control studies (PRAISE-2) with patients with non-ischemic heart failure of NYHA class III or IV, it was reported that amlodipine is associated with increase of pulmonary edema in spite that it remarkably reduces worsening of heart failure. Administration of angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin receptor blocker to patients whose renal function is dependent to activation of renin-angiotensin-aldosterone system is associated with hypouresis and/or progressive azotemia and (rarely) acute renal impairment and/or death. Evaluation on patients after heart failure or myocardial infarction should include renal function evaluation always.
Acute myocardial infarction: Increase of incidence, prevalence period or severity of angina or acute myocardial infarction have been rarely reported in patients (especially, coronary artery disease patients) who start receiving calcium channel blockers (i.e. amlodipine) or increase doses.
Aortic stenosis and mitral stenosis, obstructive cardiomyopathy: As same as any other vasodilators, special care should be taken when treating with amlodipine in patients with aortic or mitral stenosis, or obstructive cardiomyopathy.
Dual renin-angiotensin-aldosterone system (RAAS) blockade: Concomitant therapy with other drugs affecting renin-angiotensin-aldosterone system (RAAS) such as angiotensin receptor blocker (ARB) including Valsartan, ACE inhibitors or Aliskiren is not recommended.
Patients with mild-moderate hepatic impairment (It is adequate not to exceed 80 mg of Valsartan daily dose of this drug components in patients with mild-moderate hepatic impairment).
Valsartan: Since an initial drug administration may cause temporary sudden drop in blood pressure (involved with syncope and decreased consciousness), discontinue drug administration and take an adequate measure in this case. Also, initiate treatment with low dose for the following patients and in case of increasing dose, keep full observation on the patients and slowly increase it: Patients undergoing dialysis; Patients taking diuretics (Especially, as symptomatic hypotension may rarely occur in severe salt- or volume-depleted patients, attention should be paid); Patients under strict salt restriction.
In case of severe salt- or volume-depleted patients due to high doses of diuretics, symptomatic hypotension may rarely arise at the start of treatment. Correction of this condition prior to administration of the combination of amlodipine and valsartan by decreasing diuretic dose. In case of hypotension occurrence, lay patients down and if necessary, instillate with saline solution. Treatment can be continued after blood pressure is stabilized.
Patients with renal artery stenosis: On short term administration to 12 patients with renovascular hypertension involved with second unilateral renal artery stenosis, significant change was not derived in hemodynamics of kidney, serum creatinine and BUN. However, as this drug can increase blood urea and serum creatinine in patients with bilateral or unilateral renal artery stenosis, it is recommended to monitor in safety aspect. Since this drug may rapidly worsen renal function due to reduction of renal blood flow and decline of glomerular filtration rate in patients with bilateral or unilateral renal artery stenosis, administration should be avoided except for a case that this treatment is unavoidable.
A daily dose of this drug should not exceed 80 mg for patients with mild and moderate hepatic impairment. Since this drug is mostly excreted to bile as an unchanged form and exhibits low clearance in biliary obstructive patients, do not use this drug in such patients. It has been reported that plasma concentration is elevated about 2 times comparing with healthy adults when patients with mild to moderate hepatic impairment administer this drug.
Although this drug decreases blood pressure in most cases of patients after heart failure of myocardial infarction occurrence, it is not necessary to discontinue treatment due to continuous hypotension symptom. When initiating treatment for patients with heart failure or patients after myocardial infarction occurrence, care should be taken.
As a result of renin-angiotensin-aldosterone system inhibition, renal function change is expected in sensitive patients.
Treating with angiotensin-converting enzyme inhibitor (ACE inhibitors) or angiotensin receptor blocker to patients whose renal function is dependent to activation of renin-angiotensin-aldosterone system is associated with hypouresis and/or progressive azotemia and (rarely) acute renal impairment and/or death.
Similar results have been reported in this drug too. Evaluation on patients after heart failure or myocardial infarction should include renal function evaluation always.
Triple therapy of ACE inhibitors, beta blocker and Valsartan are not recommended in patient with heart failure. It is because if beta blocker and ACE inhibitor are concomitantly administered, morbidity and death rates are increased due to heart failure.
In a few patients with heart failure, elevation of BUN, creatinine and potassium level was observed. Such phenomenon is very slight and temporary and may occur mostly in patients with renal injury. Dose decrease of this drug and/or diuretics, and discontinuation should be considered.
As there is a concern that hyperkalemia may be worsened in hyperkalemia patient, administration should be avoided with an exception of inevitability of treatment. Also, serum potassium level should be observed since it may induce hyperkalemia in patients whose serum potassium level easily increases due to renal function disorder and diabetes, etc.
There is no experience in patients receiving kidney transplantation.
Amlodipine: Patients with heart failure: In long term, placebo-control studies (PRAISE-2) with patients with non-ischemic heart failure of NYHA class III or IV, in spite that Amlodipine did not show significant difference in worsening rate of heart failure when compared with placebo, it was associated with increase of pulmonaryedema report.
Patients with hepatic function impairment: As same as all the other calcium antagonists, half-life of Amlodipine was prolonged in patients with hepatic function impairment, and recommendable dose was not established for these patients.
Since gradual hypotensive action is shown even after discontinuation as plasma concentration half-life is long. In case of administering another hypotensive drug after discontinuation, dose and administration interval should be carefully set and administered with care under close medical supervision.
As effect is expressed slowly, effect may not be expected for unstable angina which requires emergency medical treatment.
General Cautions: Caution on driving and operating a machine: A clinical test of influence on driving and operating a machine has not been conducted. It should be considered that dizziness and fatigue may intermittently occur when driving and operating a machine. As same as the other antihypertensive drugs, special care should be taken when driving or operating a machine.
Influence on Clinical Findings: There were only a few patients whose examination value has remarkable changed from basal level among patients with hypertension receiving Valsartan/Amlodipine. Amlodipine/Valsartan concomitant group (5.5%) and Valsartan single group (5.5%) showed higher blood urea nitrogen (BUN) than placebo group (4.5%).
Elevation of hepatic function examination value was occasionally reported upon valsartan administration, it is not high enough to specially monitor clinical findings on patients with essential hypertension taking this drug.
Use in Children: It is not recommended as safety and effectiveness of this drug have not been established in pediatric patients under 18 years old.
Use in the Elderly: When using similar doses both in adults and elderly, excellent tolerability on both components were resulted and therefore, normal dose is recommended.