Dizant

Dizant

valsartan

Manufacturer:

Korea United Pharma

Distributor:

Pharma 3
Full Prescribing Info
Contents
Valsartan.
Description
Each tablet of Dizant contains valsartan 80 mg.
Action
Pharmacology: Toxicology: Hypertrophy of the renal juxtaglomerular cells was also seen in both species. All changes were considered to be caused by the pharmacological action of valsartan and valsartan:hydrochlorothiazide which is synergistic (potentiation is about 10-fold compared to valsartan alone) rather than additive, producing prolonged hypotension, particularly in marmosets. For therapeutic doses of valsartan and valsartan:hydrochlorothiazide in humans, the hypertrophy of the renal juxtaglomerular cells does not seem to have any relevance.
In rats, maternally toxic doses (600 mg/kg/day) during the last days of gestation and lactation led to lower survival, lower weight gain and delayed development (pinna detachment and ear-canal opening) in the offspring. These doses in rats (600 mg/kg/day) are approximately 18 times the maximum recommended human dose on an mg/m2 basis (calculations assume an oral dose of 320 mg/day and a 60-kg patient).
In nonclinical safety studies, high doses of valsartan (200-600 mg/kg body weight) caused in rats a reduction of red blood cell parameters (erythrocytes, hemoglobin, hematocrit) and evidence of changes in renal hemodynamics (slightly raised plasma urea and renal tubular hyperplasia, and basophilia in males). These doses in rats (200 mg/kg/day and 600 mg/kg/day) are approximately 6 and 18 times the maximum recommended human dose on a mg/m2 basis (calculations assume an oral dose of 320 mg/day and a 60-kg patient).
In marmosets at similar doses, the changes were similar though more severe, particularly in the kidney where the changes developed to a nephropathy which included raised urea and creatinine.
Indications/Uses
Essential hypertension.
Heart Failure: Treatment of heart failure [New York Heart Association (NYHA) class II-IV] in patients who are intolerant of angiotensin-converting enzyme (ACE) inhibitors.
Post-Myocardial Infarction: Reduces cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction.
Dosage/Direction for Use
Essential Hypertension: Recommended Starting Dose: 80 mg once daily when used as monotherapy in patients who are not volume-depleted. Valsartan may be used over a dose range of 80-320 mg daily, administered once-daily. Valsartan may be taken independently of a meal and should be administered with water.
Valsartan may also be given with other tablets at the same time.
The antihypertensive effect is substantially present within 2 weeks and maximal reduction is generally attained after 4 weeks.
If additional antihypertensive effect is required over the starting dose range, the dose may be increased to a maximum of 320 mg or a diuretic may be added. Addition of a diuretic has a greater effect than dose increases beyond 80 mg.
Children and Adolescents: The safety and efficacy of valsartan have not been established in children and adolescents (<18 years).
Elderly >75 years: Recommended Dose: A lower starting dose of 40 mg once daily.
Renal Impairment: Mild Renal Impairment [creatinine clearance (CrCl) 20-50 mL/min]: No specific dosage adjustment is recommended. Moderate Renal Impairment (CrCl 10-20 mL/min): Starting Dose: A lower dose of 40 mg once daily.
Severe Renal Impairment or Undergoing Dialysis (CrCl <10 mL/min): These patients have never received valsartan.
Intravascular Volume Depletion: For those patients who have intravascular volume depletion (eg, those treated with high dose diuretics who are unable to have their dose of diuretic reduced), a starting dose of 40 mg is recommended.
Hepatic Impairment: Mild to Moderate: Treatment should commence at a dose of 40 mg once daily. A daily dose of 80 mg should not be exceeded. Severe: Patients with severe hepatic impairment, cirrhosis or biliary obstruction should not use valsartan.
Heart Failure: Recommended Starting Dose: 40 mg twice daily. Up titration to 80 mg and 160 mg twice daily should be done to the highest dose, as tolerated by the patient. Consideration should be given to reducing the dose of concomitant diuretics. The maximum daily dose administered in clinical trials is 320 mg in divided doses. The triple combination of an ACE inhibitor, a β-blocker and valsartan is not recommended.
Post-Myocardial Infarction: Therapy may be initiated as early as 12 hrs after a myocardial infarction. After an initial dose of 20 mg twice daily, valsartan therapy should be titrated to 40 mg, 80 mg and 160 mg twice daily over the next few weeks. The starting dose is provided by the 40-mg divisible tablet. Achievement of the target dose of 160 mg twice daily should be based on the patient's tolerability to valsartan during titration. If symptomatic hypotension or renal dysfunction occurs, consideration should be given to a dosage reduction. Valsartan may be used in patients treated with other post-myocardial infarction therapies eg, thrombolytics, acetylsalicylic acid, β-blockers and statins.
Renal Impairment: In the indication of post-myocardial infarction no dosage adjustment is required for patients with mild to moderate renal impairment (CrCl >10 mL/min). There are currently no data available in post-myocardial patients with severe renal impairment (CrCl <10 mL/min) or undergoing dialysis. Valsartan should therefore be used with caution in such patients, with appropriate assessment of renal function.
Hepatic Impairment: Mild to Moderate: Doses >80 mg twice daily should only be considered if the clinical benefit is likely to outweigh the possible risk associated with increased exposure of valsartan. Patients with severe hepatic impairment, cirrhosis or biliary obstruction should not use valsartan.
Administration: Dizant can be taken with or without food and should be administered with water.
Overdosage
Symptoms: Overdose with valsartan may result in marked hypotension, which could lead to depressed levels of consciousness, circulatory collapse and/or shock.
Valsartan is unlikely to be removed by hemodialysis.
Treatment: The therapeutic measures depend on the time of ingestion and the type and severity of the symptoms; stabilization of the circulatory condition is of prime importance. If hypotension occurs, the patient should be placed in a supine position and blood volume correction should be undertaken.
Contraindications
Hypersensitivity to valsartan, hydrochlorothiazide, other sulfonamide-derived medicinal products or to any of the excipients of Dizant.
Severe renal impairment (CrCl <10 mL/min) and hepatic impairment.
Anuria, cirrhosis, biliary obstruction, biliary cirrhosis and cholestasis.
Use in pregnancy: The use of angiotensin II receptor antagonists (AIIRAs) is not recommended during the 1st trimester of pregnancy. The use of AIIRAs is contraindicated during the 2nd and 3rd trimester of pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the 1st trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with AIIRAs, similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative anti­hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately and if appropriate, alternative therapy should be started.
Angiotensin II receptor antagonist therapy exposure during the 2nd and 3rd trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Should exposure to AIIRAs have occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for hypotension.
Special Precautions
Sodium- and/or Volume-Depleted Patients: In severely sodium- and/or volume­-depleted patients eg, those receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with valsartan or valsartan/hydrochlorothiazide.
For Dizant, those patients whose diuretic dose cannot be reduced in order to correct their sodium and/or volume depletion a starting dose of 40 mg is recommended.
Valsartan/hydrochlorothiazide should be used only after correction of any preexisting 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 IV infusion of normal saline. Treatment can be continued once the blood pressure has stabilized.
Post-Myocardial Infarction: Use of valsartan in patients with post-myocardial infarction commonly results in some reduction in blood pressure, but discontinuation of valsartan therapy because of continuing symptomatic hypotension is not usually necessary if the dosing instructions are followed.
Caution should be observed when initiating therapy in patients with post-myocardial infarction.
As a consequence of inhibiting the RAAS, changes in renal function may be anticipated in susceptible individuals. Evaluation of patients with post­-myocardial infarction should always include assessment of renal function.
Renal Artery Stenosis: Short-term administration of valsartan to 12 patients with renovascular hypertension secondary to unilateral renal artery stenosis did not induce any significant changes in renal hemodynamics, serum creatinine or blood urea nitrogen (BUN). However, since other drugs that affect the RAAS may increase blood urea and serum creatinine in patients with bilateral or unilateral renal artery stenosis, monitoring is recommended as a safety measure. In patients with unilateral or bilateral renal artery stenosis or stenosis to a solitary kidney, the safe use of valsartan/hydrochlorothiazide has not been established.
Hepatic Impairment: Based on pharmacokinetic data which demonstrate significantly increased (approximately 2-fold increase) plasma concentrations of valsartan in mild to moderately hepatically-impaired patients, a lower dose is recommended in patients with hypertension. In these patients, the dose of 80 mg should not be exceeded but doses >80 mg twice daily should only be considered if the clinical benefit is likely to outweigh the possible risk associated with increased exposure of valsartan. Patients with severe hepatic impairment, cirrhosis, biliary obstruction are contraindicated from using valsartan (see Contraindications).
In patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg. Valsartan/hydrochlorothiazide should be used with particular caution in patients with biliary obstructive disorders and in pa­tients with severe hepatic impairment. Hepatic disease does not significantly affect the pharmacokinetics of hydrochlorothiazide.
Renal Impairment: As a consequence of inhibiting the RAAS, increases of blood urea and serum creatinine, and changes in renal function including renal failure (very rarely) have been reported particularly in patients with preexisting renal dysfunction or those with severe cardiac insufficiency.
Serum potassium should be monitored in renally-impaired or elderly patients if they are also taking potassium supplement.
No dosage adjustment is required for patients with renal impairment with a CrCl ≥30 mL/min.
Effects on the Ability to Drive or Operate Machinery: When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or weariness may occur.
As with other antihypertensive agents, it is advisable to exercise caution when driving or operating machinery.
Use in Lactation: Because no information is available regarding the use of valsartan during breastfeeding, valsartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.
It is not known whether valsartan is excreted in human milk. Valsartan was excreted in the milk of lactating rats. Hydrochlorothiazide crosses the placenta and is excreted in human milk. Thus, it is not advisable to use valsartan/hydrochlorothiazide in lactating mothers.
Use in Children: Valsartan and valsartan/hydrochlorothiazide is not recommended for use in children and adolescents <18 years due to a lack of data on safety and efficacy.
Use in Elderly: A somewhat higher systemic exposure to valsartan was observed in some elderly subjects than in young subjects; however, this has not been shown to have any clinical significance. No dose adjustment is required in the elderly.
Use In Pregnancy & Lactation
Use in Pregnancy: The use of angiotensin II receptor antagonists (AIIRAs) is not recommended during the 1st trimester of pregnancy. The use of AIIRAs is contraindicated during the 2nd and 3rd trimester of pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the 1st trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with AIIRAs, similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative anti­hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately and if appropriate, alternative therapy should be started.
Angiotensin II receptor antagonist therapy exposure during the 2nd and 3rd trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Should exposure to AIIRAs have occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for hypotension.
Use in Lactation: Because no information is available regarding the use of valsartan during breastfeeding, valsartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.
It is not known whether valsartan is excreted in human milk. Valsartan was excreted in the milk of lactating rats. Hydrochlorothiazide crosses the placenta and is excreted in human milk. Thus, it is not advisable to use valsartan/hydrochlorothiazide in lactating mothers.
Adverse Reactions
Medicines and their possible adverse effects can affect individual people in different ways. The following are some of the adverse effects that are known to be associated with Dizant. Because an adverse effects is stated as follows, it does not mean that all people using Dizant will experience that or any adverse effect.
Dizziness, fatigue, increased level of potassium in the blood, decrease in the number of a type of white blood cell (neutrophil) in the blood (neutropenia), decrease in the number of platelets in the blood (thrombocytopenia), decreased kidney function, fainting (syncope), diarrhea, pain in the muscles and joints, headache, temporary taste disturbance, disturbances of liver function, cough, nosebleeds (epistaxis).
Drug Interactions
Compounds which have been studied in clinical trials include cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. Used together with cimetidine, the systemic exposure of valsartan may be marginally increased. A combination with glibenclamide may cause a decrease in the systemic exposure to valsartan.
As valsartan is not metabolized to a significant extent, clinically relevant drug-drug interactions in the form of metabolic induction or inhibition of the cytochrome P450 (CYP450) system are not expected with valsartan. Although valsartan is highly bound to plasma proteins, in vitro studies have not shown any interaction at this level with a range of molecules which are also highly protein bound eg, diclofenac, furosemide and warfarin.
Concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium. Co-medication is not advisable.
Combination with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): When angiotensin II antagonists are administered simultaneously with NSAIDs [ie, selective cyclooxygenase (COX)-2 inhibitors, acetylsalicylic acid (>3 g/day) and nonselective NSAIDs], attenuation of the antihypertensive effect may occur.
As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function including possible acute renal failure and an increase in serum potassium, especially in patients with poor preexisting renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically thereafter.
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Very rare cases have also been reported with AIIRAs.
Co-administration of lithium and valsartan should be undertaken with caution. If this combination proves essential, serum lithium level monitoring is recommended during concomitant use.
Caution For Usage
Instructions for Use and Handling: Do not preserve in other containers in order to maintain quality of the drug and avoid misuse.
Storage
Store at temperatures not exceeding 30°C.
Presentation/Packing
FC tab 80 mg (light peach, round, engraved with "UT" on one side and "V" and "V" on the scored side) x 98's.
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