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  • Diovan
    / Novartis


    Active Ingredient
    Valsartan 40, 80 ,160 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    28 X 40 mg

    partial basket chart 86388 4476

    Film Coated Tablets

    28 X 80 mg

    partial basket chart 58661 4456

    Film Coated Tablets

    28 X 160 mg

    partial basket chart 58662 4457

    Dosage

    Hypertension (only 80mg and 160 mg): The recommended dose of Diovan is 80 mg once daily for most patients. The antihypertensive effect is substantially present within 2 weeks and maximal effects are seen after 4 weeks. In some patients whose blood pressure is not adequately controlled, the dose may be increased to 160 mg, or a greater decrease in BP may be achieved by adding in a thiazide diuretic.
    Diovan may also be administered with other antihypertensive agents.
    Heart failure (40 mg, 80 mg and 160 mg): The recommended starting dose of Diovan is 40 mg twice daily. Uptitration 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.
    Post-myocardial infarction (40 mg, 80 mg and 160 mg): Therapy may be initiated as early as 12 hours 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 dose reduction.
    Valsartan may be used in patients treated with other post-myocardial infarction therapies, e.g. thrombolytics, acetylsalicylic acid, beta blockers, statins.
    Use in patients over 75 years: A lower starting dose of 40 mg once daily is recommended.
    Use in patients with renal impairment: 
    Hypertension:
     No initial dose adjustment is required in patients with mild renal impairment (i.e.creatinine clearance 20-50 ml/min). For patients with moderate to severe renal impairment or patients on dialysis, a lower starting dose of 40 mg once daily is recommended.
    Heart Failure: Evaluation of patients with heart failure should always include assessment of renal function.
    Post myocardial infarction: In the indication of current myocardial infarction no dosage adjustment is required for patients with mild renal impairment. There are currently no data available in post myocardial patients with severe renal impairment (serum creatinine ≥ 221 μmol/l). Diovan should therefore be used with caution in such patients, with appropriate assessment of renal function
    Concomitant use of Diovan with Aliskiren is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m²).
    Patients with Hepatic impairment:
    Hypertension: Use in patients with mild to moderate hepatic impairment:
    Treatment should commence at dose of 40 mg once daily. A daily dose of 80mg valsartan should not be exceed. Patients with severe hepatic impairment, cirrhosis or biliary obstruction should not use Diovan.
    Post-myocardial infarction: Use in patients with mild to moderate hepatic impairment:Doses higher than 80mg 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 Diovan.
    Use in patients with intravascular volume depletion: For those patients who have intravascular volume depletion (e.g. those treated with high dose diuretics who are unable to have their dose of diuretic reduced) a starting dose of 40 mg is recommended.
    Paediatric population: Diovan is not recommended for the treatment of heart failure or recent myocardial infarction in children and adolescents below the age of 18 years due to the lack of data on safety and efficacy.
    Diovan must not be used in combination with Aliskiren in patients with diabetes mellitus.
    Method of administration: Diovan may be taken independently of a meal and should be administered with water.


    Indications

    Hypertension (Diovan 80 mg & 160 mg): Treatment of hypertension.
    Heart failure (Diovan 40 mg, 80 mg & 160 mg): Diovan is indicated for the treatment of heart failure (NYHA class II-IV) in patients who are intolerant of angiotensin converting enzyme inhibitors. In a controlled clinical trial, Diovan significantly reduced hospitalizations for heart failure. There is no evidence that Diovan provides added benefits when it is used with an adequate dose of an ACE inhibitor.
    Myocardial infarction (Diovan 40 mg, 80 mg &  160 mg): Diovan is indicated to improve survival following myocardial infarction in clinically stable patients with signs, symptoms or radiological evidence of left ventricular failure and/or with left ventricular systolic dysfunction.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.
    Severe hepatic impairment, biliary cirrhosis, and cholestasis.
    Second and third trimester of pregnancy.
    Concomitant use of Diovan with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²)


    Special Precautions

    Hyperkalaemia: Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other agents that may increase potassium levels (heparin, etc.) is not recommended. Monitoring of potassium should be undertaken as appropriate.
    Impaired renal function: There is currently no experience on the safe use in patients with a creatinine clearance <10 ml/min and patients undergoing dialysis, therefore valsartan should be used with caution in these patients. No dose adjustment is required for adult patients with creatinine clearance >10 ml/min.
    Hepatic impairment: In patients with mild to moderate hepatic impairment without cholestasis, Diovan should be used with caution.
    Sodium- and/or volume-depleted patients: 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 Diovan. Sodium and/or volume depletion should be corrected before starting treatment with Diovan, for example by reducing the diuretic dose.
    Renal artery stenosis: In patients with bilateral renal artery stenosis or stenosis to a solitary kidney, the safe use of Diovan has not been established.
    Short-term administration of Diovan to twelve patients with renovascular hypertension secondary to unilateral renal artery stenosis did not induce any significant changes in renal haemodynamics, serum creatinine, or blood urea nitrogen (BUN). However, other agents that affect the renin-angiotensin system may increase blood urea and serum creatinine in patients with unilateral renal artery stenosis, therefore monitoring of renal function is recommended when patients are treated with valsartan.
    Kidney transplantation: There is currently no experience on the safe use of Diovan in patients who have recently undergone kidney transplantation.
    Primary hyperaldosteronism: Patients with primary hyperaldosteronism should not be treated with Diovan as their renin-angiotensin system is not activated.
    Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
    As with all other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).
    Pregnancy: Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive 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.
    Recent-myocardial infarction (40 mg, 80 mg and 160 mg): The combination of captopril and valsartan has shown no additional clinical benefit, instead the risk for adverse events increased compared to treatment with the respective therapies. Therefore, the combination of valsartan with an ACE inhibitor is not recommended.
    Caution should be observed when initiating therapy in post-myocardial infarction patients. Evaluation of post-myocardial infarction patients should always include assessment of renal function (see section 4.2).
    Use of Diovan in post-myocardial infarction patients commonly results in some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension is not usually necessary provided dosing instructions are followed.
    Heart Failure (40 mg, 80 mg and 160 mg): The risk of adverse reactions, especially hypotension, hyperkalaemia and decreased renal function (including acute renal failure), may increase when Diovan is used in combination with an ACE inhibitor. In patients with heart failure, the triple combination of an ACE inhibitor, a beta blocker and Diovan has not shown any clinical benefit. This combination apparently increases the risk for adverse events and is therefore not recommended. Triple combination of an ACE inhibitor, a mineralocorticoid receptor antagonist and valsartan is also not recommended. Use of these combinations should be under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
    Caution should be observed when initiating therapy in patients with heart failure. Evaluation of patients with heart failure should always include assessment of renal function.
    Use of Diovan in patients with heart failure commonly results in some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension is not usually necessary provided dosing instructions are followed.
    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 ACE inhibitors has been associated with oliguria and/or progressive azotaemia and in rare cases with acute renal failure and/or death. As valsartan is an angiotensin II receptor blocker, it cannot be excluded that the use of Diovan may be associated with impairment of the renal function.
    ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
    History of 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. Diovan should be immediately discontinued in patients who develop angioedema, and Diovan should not be re-administered.
    Dual Blockade of the Renin-Angiotensin-Aldosterone System (RAAS): There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia, and decreased renal function (including acute renal failure). Dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or Aliskiren is therefore not recommended.
    If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
    Paediatric population
    Impaired renal function: Use in paediatric patients with a creatinine clearance <30 ml/min and paediatric patients undergoing dialysis has not been studied, therefore valsartan is not recommended in these patients. No dose adjustment is required for paediatric patients with a creatinine clearance >30 ml/min. Renal function and serum potassium should be closely monitored during treatment with valsartan. This applies particularly when valsartan is given in the presence of other conditions (fever, dehydration) likely to impair renal function.
    Impaired hepatic function: As in adults, Diovan is contraindicated in paediatric patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis. There is limited clinical experience with Diovan in paediatric patients with mild to moderate hepatic impairment. The dose of valsartan should not exceed 80 mg in these patients.


    Side Effects

    Post-myocardial infarction and/or heart failure: Common: Dizziness, Postural dizziness, Hypotension, Orthostatic hypotension, Renal failure and impairment.
    See prescribing information for full details.


    Drug interactions

    Dual blockade of the Renin-Angiotensin-Aldosterone System (RAAS) with ARBs, ACEIs, or aliskiren: Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.
    Concomitant use not recommended
    Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists including with Diovan. If the combination proves necessary, a careful monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may presumably be increased further.
    Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substance that may increase potassium levels: If a medicinal product that affects potassium levels is considered necessary in combination with valsartan, monitoring of potassium plasma levels is advised.
    Caution required with concomitant use
    Non-steroidal anti-Inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid( >3 g/day), and non-selective NSAIDs: 
    When Angiotensin II antagonists are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, as well as adequate hydration of the patient.
    Transporters: In vitro data indicates that valsartan is a substrate of the hepatic uptake transporter OATP1B1/OATP1B3 and the hepatic efflux transporter MRP2. The clinical relevance of this finding is unknown. Co-administration of inhibitors of the uptake transporter (e.g. rifampin, ciclosporin) or efflux transporter (e.g. ritonavir) may increase the systemic exposure to valsartan. Exercise appropriate care when initiating or ending concomitant treatment with such drugs.
    Others: In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan or any of the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.


    Pregnancy and Lactation

    Pregnancy:T he use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contrindicated during the second and third trimester of pregnancy.
    Lactation: Because no information is available regarding the use of valsartan during breastfeeding, Diovan is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
    See prescribing information for full details.


    Overdose

    Symptoms: Over dosage with Diovan may result in marked hypotension, which could lead to depressed level of consciousness, circulatory collapse and/or shock.
    Treatment: The therapeutic measures depend on the time of ingestion and the type and severity of the symptoms; stabilisation 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.
    Valsartan is unlikely to be removed by haemodialysis.


    Manufacturer
    Novartis Farmaceutica S.A., Spain
    Licence holder
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