Osarstad 80

Valsartan.

Active ingredient: Valsartan 80 mg.
The tablet can be divided into 2 equal doses.
Excipients/Inactive Ingredients: Lactose monohydrate and cellulose powder, croscarmellose sodium, silica colloidal anhydrous, magnesium stearate, hypromellose, opadry 03F84934 pink (components of opadry 03F84934: Hypromellose, titanium dioxide, talc, polyethylene glycol, iron oxide red).

Hypertension: Treatment of essential hypertension in adults, and hypertension in children and adolescents 6 to 18 years of age.
Recent myocardial infarction: Treatment of clinically stable adult patients with symptomatic heart failure or asymptomatic left ventricular systolic dysfunction after a recent (12 hours-10 days) myocardial infarction.
Heart failure: Treatment of adult patients with symptomatic heart failure when ACE-inhibitors are not tolerated or in beta-blocker intolerant patients as add-on therapy to ACE-inhibitors when mineralocorticoid receptor antagonists cannot be used.

Administration: Osarstad 80 Tablets may be taken independently of a meal and should be administered with water.
Dosage: Hypertension: The recommended starting dose of valsartan is 80 mg once daily. The antihypertensive effect is substantially present within 2 weeks, and maximal effects are attained within 4 weeks. In some patients whose blood pressure is not adequately controlled, the dose can be increased to 160 mg and to a maximum of 320 mg.
Valsartan may also be administered with other antihypertensive agents. The addition of a diuretic such as hydrochlorothiazide will decrease blood pressure even further in these patients.
Recent myocardial infarction: In clinically stable patients, therapy may be initiated as early as 12 hours after a myocardial infarction.
After an initial dose of 20 mg^(*) twice daily, valsartan should be titrated to 40 mg (1/2 of the Osarstad 80 tablet), 80 mg, and 160 mg twice daily over the next few weeks.
The target maximum dose is 160 mg twice daily. In general, it is recommended that patients achieve a dose level of 80 mg twice daily by two weeks after treatment initiation and that the target maximum dose, 160 mg twice daily, be achieved by three months, based on the patient's tolerability. 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, e.g. thrombolytics, acetylsalicylic acid, beta blockers, statins, and diuretics. The combination with ACE inhibitors is not recommended.
Evaluation of post-myocardial infarction patients should always include assessment of renal function.
Heart failure: The recommended starting dose of valsartan is 40 mg (1/2 of Osarstad 80 tablet) twice daily. Up titration to 80 mg and 160 mg twice daily should be done at intervals of at least two weeks 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.
Valsartan may be administered with other heart failure therapies. However, the triple combination of an ACE-inhibitor, valsartan and a beta-blocker or a potassium-sparing diuretic is not recommended.
Evaluation of patients with heart failure should always include assessment of renal function.
Additional information on special populations: Elderly: No dose adjustment is required in elderly patients.
Renal impairment: No dose adjustment is required for adult patients with a creatinine clearance > 10 ml/min. Concomitant use of valsartan with aliskiren is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m²).
Diabetes mellitus: Concomitant use of valsartan with aliskiren is contraindicated in patients with diabetes mellitus.
Hepatic impairment: Valsartan is contraindicated in patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis. In patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg.
Paediatric hypertension: Children and adolescents 6 to 18 years of age: The initial dose is 40 mg (1/2 of Osarstad 80 tablet) once daily for children weighing below 35 kg and 80 mg once daily for those weighing 35 kg or more. The dose should be adjusted based on blood pressure response. For maximum doses studied in clinical trials as follows.
≥ 18 kg to < 35 kg: 80 mg.
≥ 35 kg to < 80 kg: 160 mg.
≥ 80 kg to ≤ 160 kg: 320 mg.
Doses higher than those listed have not been studied and are therefore not recommended.
Children less than 6 years of age: Safety and efficacy of valsartan in children aged 1 to 6 years have not been established.
Use in paediatric patients aged 6 to 18 years with renal impairment: 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.
Use in paediatric patients aged 6 to 18 years with hepatic impairment: As in adults, valsartan is contraindicated in paediatric patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis. There is limited clinical experience with valsartan in paediatric patients with mild to moderate hepatic impairment. The dose of valsartan should not exceed 80 mg in these patients.
Paediatric heart failure and recent myocardial infarction: Valsartan 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.
* Other preparation should be used for dose less than 40 mg.

Symptoms: Overdose with valsartan may result in marked hypotension, which could lead to depressed level of consciousness, circulatory collapse and/or shock.
Management: 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.

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

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.
Renal impairment: 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 a creatinine clearance > 10 ml/min.
The concomitant use of ARBs - including valsartan - or of ACEIs with aliskiren is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m²).
Hepatic impairment: In patients with mild to moderate hepatic impairment without cholestasis, valsartan 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 Valsartan. Sodium and/or volume depletion should be corrected before starting treatment with Valsartan, 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 valsartan has not been established.
Short-term administration of valsartan 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 valsartan in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism: Patients with primary hyperaldosteronism should not be treated with valsartan 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).
Recent myocardial infarction: 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.
Use of valsartan 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: The risk of adverse reactions, especially hypotension, hyperkalaemia and decreased renal function (including acute renal failure), may increase when valsartan is used in combination with an ACE-inhibitor. In patients with heart failure, the triple combination of an ACE inhibitor, a beta-blocker and valsartan 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 valsartan 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 valsartan 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.
Other conditions with stimulation of the renin-angiotensin system: In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme 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 antagonist, it cannot be excluded that the use of Valsartan may be associated with impairment of the renal function.
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.
Valsartan should be immediately discontinued in patients who develop angioedema, and valsartan 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 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.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive have been performed. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur when taking valsartan.
Use in 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 lo 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.
Use in Children: Renal impairment: 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. The concomitant use of ARBs - including valsartan - or of ACEIs with aliskiren is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m²).
Hepatic impairment: As in adults, valsartan is contraindicated in paediatric patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis. There is limited clinical experience with valsartan in paediatric patients with mild to moderate hepatic impairment. The dose of valsartan should not exceed 80 mg in these patients.

Pregnancy: The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first trimester of pregnancy. The use of AIIRAs is contra-indicated during the second and third trimester of pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first 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 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.
AIIRAs therapy exposure during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for hypotension.
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 breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Adverse reactions are ranked by frequency, the most frequent first, using the following convention: Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (frequency cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.
Hypertension: Blood and lymphatic system disorders: Not known: Decrease in haemoglobin, decrease in haematocrit, neutropenia, thrombocytopenia.
Immune system disorders: Not known: Hypersensitivity including serum sickness.
Metabolism and nutrition disorders: Not known: Increase of serum potassium, hyponatraemia.
Ear and labyrinth disorders: Uncommon: Vertigo.
Vascular disorders: Not known: Vasculitis.
Respiratory, thoracic and mediastinal disorders: Uncommon: Cough.
Gastrointestinal disorders: Uncommon: Abdominal pain.
Hepato-biliary disorders: Not known: Elevation of liver function values including increase of serum bilirubin.
Skin and subcutaneous tissue disorders: Not known: Angioedema, dermatitis bullous, rash, pruritus.
Musculoskeletal and connective tissue disorders: Not known: Myalgia.
Renal and urinary disorders: Not known: Renal failure and impairment. Elevation of serum creatinine.
General disorders and administration site conditions: Uncommon: Fatigue.
Paediatric population: With the exception of isolated gastrointestinal disorders (like abdominal pain, nausea, vomiting) and dizziness, no relevant differences in terms of type, frequency and severity of adverse reactions were identified between the safety profile for paediatric patients aged 6 to 18 years and that previously reported for adult patients.
Hyperkalaemia was more frequently observed in children and adolescents aged 6 to 18 years with underlying chronic kidney disease.
Post-myocardial infarction and/or heart failure (studied in adult patients only): Blood and lymphatic system disorders: Not known: Thrombocytopenia.
Immune system disorders: Not known: Hypersensitivity including serum sickness.
Metabolism and nutrition disorders: Uncommon: Hyperkalaemia.
Not known: Increase of serum potassium, hyponatraemia.
Nervous system disorders: Common: Dizziness, postural dizziness.
Uncommon: syncope, headache.
Ear and labyrinth disorders: Uncommon: Vertigo.
Cardiac disorders: Uncommon: Cardiac failure.
Vascular disorders: Common: Hypotension, orthostatic hypotension.
Not known: Vasculitis.
Respiratory, thoracic and mediastinal disorders: Uncommon: Cough.
Gastrointestinal disorders: Uncommon: Nausea, diarrhoea.
Hepato-biliary disorders: Not known: Elevation of liver function values.
Skin and subcutaneous tissue disorders: Uncommon: Angioedema.
Not known: Dermatitis bullous, rash, pruritus.
Musculoskeletal and connective tissue disorders: Not known: Myalgia.
Renal and urinary disorders: Common: Renal failure and impairment.
Uncommon: Acute renal failure, elevation of serum creatinine.
Not known: Increase in blood urea nitrogen.
General disorders and administration site conditions: Uncommon: Asthenia, fatigue.

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.
Dual blockade of the Renin-Angiotensin System (RAS) with ARBs, ACEIs, or aliskiren: Concomitant use of angiotensin receptor antagonists (ARBs) - including valsartan - or of angiotensin-converting-enzyme inhibitors (ACEIs) with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²) is contraindicated.
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 valsartan. If the combination proves necessary, 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 substances 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. rifampicin, 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, indometacin, hydrochlorothiazide, amlodipine, glibenclamide.
Paediatric population: In hypertension in children and adolescents, where underlying renal abnormalities are common, caution is recommended with the concomitant use of valsartan and other substances that inhibit the renin-angiotensin-aldosterone system which may increase serum potassium. Renal function and serum potassium should be closely monitored.

Store in a well-closed container, in a dry place. Do not store above 30°C.

Angiotensin II Antagonists

C09CA03 - valsartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.

P₁S₁S₃