Tareg 40. 80. 160 Tablets 40mg. 80mg. 160 mg FC tablets

Hypertension: Treatment of mild to moderate essential hypertension in adult patients 18 years and older.

Post-myocardial infarction: To improve survival following a recent (12 hours u2013 10 days) myocardial infarction in clinically stable patients with signs, symptoms, or radiological evidence of left ventricular failure and/or with left ventricular systolic dysfunction.

Heart Failure: TAREG is indicated for the treatment of heart failure (NYHA class II u2013 IV).

Posology: Hypertension: The recommended dose of TAREG is 80 mg or 160 mg once daily. The antihypertensive effect is substantially present within 2 weeks and maximal effects are seen after 4 weeks. In patients whose blood pressure is not adequately controlled, the daily dose may be increased to 320 mg, or a diuretic may be added. TAREG may also be administered with other antihypertensive medicines.

Post-myocardial infarction: 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. Achievement of the target dose of 160 mg twice daily should be based on the patientu2019s tolerability to valsartan during titration. If symptomatic hypotension or renal dysfunction occurs, consideration should be given to a dosage reduction. TAREG may be used in patients treated with other post-myocardial infarction therapies, e.g. thrombolytics, acetylsalicylic acid, beta blockers, or statins.

Heart failure: The recommended starting dose of valsartan is 40 mg twice daily. Up-titration to 80 mg and 160 mg twice daily should be done to the highest dose, 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. Evaluation of patients with heart failure should always include assessment of renal function.

NOTE for all indications: No dosage adjustment is required for patients with mild renal impairment (where the creatinine clearance is above 70 mL/min) or for patients with hepatic insufficiency of non-biliary origin and without cholestasis.

Special population Renal impairment NOTE: No dosage adjustment is required for patients with mild and moderate renal impairment (where the creatinine clearance is above 30 to less than 90 mL/min) (see section 4.4). A lower dose should be considered for patients with a history of hepatic impairment (see section 4.4). Paediatric population The safety and efficacy of TAREG have not been established in children. Currently available data are described in section 5.1 and 5.2 but no recommendation on a posology can be made.

Method of administration: TAREG may be taken independently of a meal and should be administered with water.

• Hypersensitivity to valsartan or any of the excipients of TAREG
• A history of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines
• Hereditary or idiopathic angioedema
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Pregnancy and lactation (see section 4.6)
• Severe renal function impairment (CrCl < 30 mL/min/1.73m2)
• Aortic valve stenosis
• Mitral valve stenosis
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride (see section 4.5)
• Porphyria
• Lithium therapy: Concomitant administration with TAREG may lead to toxic serum concentrations of lithium (see section 4.5)
• Concomitant use of TAREG or of angiotensin-converting-enzyme inhibitors (ACEIs) with aliskiren in patients with Type 2 diabetes mellitus (see section 4.5, subsection dual blockade of the RAAS).
• Concomitant use of TAREG with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73m2) (see section 4.5 and 5.1)
• Concomitant use of fluoroquinolones with ACE inhibitors/Angiotensin receptor blockers is contraindicated in patients with moderate to severe renal impairment (Creatinine Clearance u2264 30 mL/min) and in elderly patients.

Sodium- and/or volume-depleted patients: In sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, and/or patients with moderate to severe renal impairment, symptomatic hypotension may occur after initiation of therapy with TAREG. Sodium- and/or volume- depletion should be corrected before starting treatment with TAREG for example, by reducing the diuretic dose. If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once blood pressure has stabilised.

Renal artery stenosis: Since other medicines that affect the renin-angiotensin-aldosterone system (RAAS) may increase blood serum urea and serum creatinine in patients with bilateral or unilateral renal artery stenosis, TAREG should not be used in patients with bilateral renal artery stenosis or unilateral renal artery stenosis. Monitoring of both parameters is recommended as a safety measure. TAREG should not be used in patients with bilateral renal artery stenosis or unilateral renal artery stenosis of an artery to a single kidney, aortic valve stenosis, mitral valve stenosis or hypertrophic obstructive cardiomyopathy (see section 4.3).

Impaired renal function: Should a woman become pregnant while treated with TAREG, the treatment should be stopped promptly and switched to a different class of antihypertensive medicines (see section 4.6). No dosage adjustment is required for patients with mild to moderate renal impairment (where the creatinine clearance is above 30 to u2264 90 mL/min). TAREG is contraindicated in patients with severe renal function impairment (CrCl < 30mL/min). The use of TAREG with aliskiren is contraindicated in patients with severe renal impairment (GFR < 60 mL/min) (see section 4.5, subsection dual blockade of the RAAS).

Concomitant use with fluoroquinolones: The concomitant use of fluoroquinolones with ACE inhibitors/Angiotensin receptor blockers is contraindicated in patients with moderate to severe renal impairment (Creatinine Clearance < 30 mL/min) and in elderly patients. Renal function should be assessed before initiating treatment and monitored during treatment with fluoroquinolones or ACE inhibitors/Angiotensin receptor blockers whether used separately and/or concomitantly. Patients currently treated with concomitant use of ACE inhibitors/Angiotensin receptor blockers and fluoroquinolones should contact their doctor to re-evaluate their treatment.

Hepatic impairment: TAREG is mostly eliminated unchanged in the bile, and patients with biliary obstructive disorders showed lower TAREG clearance (see section 5.2). Particular caution should be exercised when administering valsartan to patients with biliary obstructive disorders. In patients with hepatic impairment without cholestasis, the maximum recommended dose is 80 mg valsartan.

Post-myocardial infarction/Heart failure: Use of TAREG in patients with post-myocardial infarction or heart failure, commonly results in some reduction in blood pressure, but discontinuation of TAREG therapy because of continuing symptomatic hypotension is not usually necessary provided dosing instructions are followed. Caution should be observed when initiating therapy in patients with heart failure or post myocardial infarction (see section 4.2). As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the RAAS, treatment with ACE inhibitors or angiotensin receptor antagonists has been associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or death. Evaluation of patients with heart failure or post-myocardial infarction should always include assessment of renal function. Patients with heart failure given TAREG commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. Caution should be observed when initiating therapy in patients with heart failure (see section 4.2). In patients with heart failure, caution should be observed with concurrent administration of ACE inhibitors, beta-blockers and TAREG as an increase in mortality has been reported on this triple therapy.

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. TAREG should be immediately discontinued in patients who develop angioedema, and TAREG should not be re-administered.

Dual Blockade of the Renin-Angiotensin-Aldosterone System (RAAS): Caution is required while co-administering TAREG, with other medicines blocking the RAAS such as ACEIs or aliskiren (see section 4.3 and 4.5, subsection dual blockade of the RAAS).

Dual blockade of the Renin-Angiotensin-System-Aldosterone System (RAAS) with ARBs, ACEIs, or aliskiren: The concomitant use of TAREG, with other medicines acting on the RAAS is associated with an increased incidence of hypotension, hyperkalaemia, and changes in renal function compared to monotherapy. It is recommended to monitor blood pressure, renal function, and electrolytes in patients on TAREG and other medicines that affect the RAAS (see section 4.4). The concomitant use TAREG with aliskiren, should be avoided in patients with renal impairment (GFR < 60 mL/min) (see section 4.4). The concomitant use of TAREG with aliskiren is contraindicated in patients with Type 2 diabetes mellitus or renal impairment (GFR <60 mL/min/1.73m2) (see section 4.3).

Potassium: Concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium that may lead to increases in serum potassium, and in patients with heart failure, to increase in serum creatinine, are contraindicated. If needed, serum potassium to be monitored.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): When angiotensin II antagonists are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur. Furthermore, in elderly patients, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function. Therefore, monitoring of renal function is recommended when initiating or modifying the treatment in patients on valsartan who are taking NSAIDs concomitantly.

Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported. Concurrent use of lithium and valsartan as contained in TAREG, is contraindicated. Therefore, monitoring of serum lithium levels is recommended, if needed (see section 4.3).

Transporters: The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. 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.

No drug interactions of clinical significance have been found with the following compounds: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide. As TAREG is not metabolised to a significant extent, clinically relevant drug-drug interactions in the form of metabolic induction or inhibition of the cytochrome P450 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, such as diclofenac, furosemide, and warfarin.

Women of childbearing potential/Contraception in males and females: TAREG acts directly on the RAAS and therefore should not be used in women planning to become pregnant. Healthcare professionals prescribing TAREG should counsel women of childbearing potential about the potential risk during pregnancy.

Pregnancy: When pregnancy is detected, TAREG should be discontinued as soon as possible. Not to be used in pregnancy as teratogenicity has been shown in experimental animals. Safety in pregnancy and lactation has not been established (see section 4.3). In case of accidental exposure to TAREG, appropriate foetal monitoring should be considered. Infants whose mothers have taken TAREG should be closely observed for hypotension. There have been reports of spontaneous abortion, oligohydramnios, and newborn renal dysfunction when pregnant women have inadvertently taken valsartan.

Breastfeeding: It is not known whether valsartan is excreted in human milk. Since valsartan was excreted in the milk of lactating rats, mothers taking TAREG should not breastfeed their infants.

Fertility: There is no information on the effects of TAREG on human fertility. Studies in rats did not show any effects of valsartan on fertility.

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 dizziness or weariness may occur. It is advisable to exercise caution when driving or operating machinery.

Frequencies are defined as: very common (u2265 1/10); Common (u2265 1/100, <1/10); uncommon (u2265 1/100, < 1/1 000); rare (u2265 1/10 000, < 1/1 000); very rare ( < 1/10 000)

Table 1: Adverse drug reactions in Hypertension from clinical trials

• Ear and labyrinth system disorders: Uncommon Vertigo
• Respiratory, thoracic, and mediastinal disorders: Uncommon Cough
• Gastrointestinal disorders: Uncommon Abdominal pain
• General disorders and administration site conditions: Uncommon Fatigue

The following events have also been observed during clinical trials in hypertensive patients irrespective of their causal association with the study drug: Arthralgia, asthenia, back pain, diarrhoea, dizziness, headache, insomnia, libido decrease, nausea, oedema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral infections.

Heart failure and/or post-myocardial infarction: The safety profile seen in controlled-clinical studies in patients with heart failure and/or post-myocardial infarction varies from the overall safety profile seen in hypertensive patients. This may relate to the patientu2019s underlying disease.

ADRs that occurred in heart failure and/or post-myocardial infarction patients are listed below.

Table 2: Adverse drug reactions in heart failure and/or post-myocardial infarction from clinical trials

• Nervous system disorders: Common Dizziness, postural dizziness
• Uncommon Syncope, headache
• Ear and labyrinth system disorders: Uncommon Vertigo
• Cardiac disorders: Uncommon Cardiac failure
• Vascular disorders: Common Hypotension, orthostatic hypotension
• Respiratory, thoracic, and mediastinal disorders: Uncommon Cough
• Gastrointestinal disorders: Uncommon Nausea, diarrhoea
• Skin and subcutaneous tissue disorders: Uncommon Angioedema
• Renal and urinary disorders: Common Renal failure and impairment
• Uncommon Acute renal failure, blood creatinine increased
• General disorders and administration site conditions: Uncommon Asthenia, fatigue

The following events have also been observed during clinical trials in patients with heart failure and/or post-myocardial infarction irrespective of their causal association with the study drug: Arthralgia, abdominal pain, back pain, insomnia, libido decrease, neutropenia, oedema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral infections.

Post-marketing adverse drug reactions

Table 1: Adverse drug reactions in Hypertension from post-marketing experience

• Blood and lymphatic system disorders: Not known Haemoglobin decreased, haematocrit decreased, neutropenia, thrombocytopenia
• Immune system disorders: Not known Hypersensitivity including serum sickness
• Metabolism and nutrition disorders: Not known Serum potassium increased
• Vascular disorders: Not known Vasculitis
• Hepato-biliary disorders: Not known Liver function test abnormal including blood bilirubin increase
• 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, serum creatinine increased

Table 2: Adverse drug reactions in heart failure and/or post-myocardial infarction from post-marketing experience

• Blood and lymphatic system disorders: Not known Thrombocytopenia
• Immune system disorders: Not known Hypersensitivity including serum sickness
• Metabolism and nutrition disorders: Uncommon Hyperkalaemia
• Vascular disorder: Not known Vasculitis
• Hepato-biliary disorders: Not known Liver function test abnormal
• Skin and subcutaneous tissue disorders: Not known Dermatitis bullous, rash, pruritus
• Musculoskeletal and connective tissue disorders: Not known Myalgia
• Renal and urinary disorders: Not known Serum urea increased

Overdose with TAREG may result in marked hypotension, which could lead to depressed level of consciousness, circulatory collapse and/or shock. If the ingestion is recent, vomiting should be induced if the patient is conscious. Otherwise, the usual treatment would be intravenous infusion of normal saline solution. TAREG is unlikely to be removed by haemodialysis.