Valtensi

Valtensi 80 mg: Each film-coated tablet contains Valsartan 80 mg.
Valtensi 160 mg: Each film-coated tablet contains Valsartan 160 mg.
Valsartan is (S)N-{[2'-(1H-tetrazol-5-yl) biphenyl-4-yl] methyl} - valine.

Mechanism of Action: The active hormone in the renin-angiotensin aldosterone system (RAAS) is angiotensin II, which is formed from angiotensin I through angiotensin-converting enzyme (ACE). Angiotensin II binds to receptors that is located in cell membranes of various tissues. It has various physiological effects, including direct and indirect involvement in regulating blood pressure. As a powerful vasoconstrictor, angiotensin II increases sodium retention and stimulates aldosterone secretion. Valsartan in oral active form, strong and specific to angiotensin II (Ang II) antagonist receptors. It acts selectively on the AT1 receptor subtype which is responsible for all the effects of angiotensin II. Increased plasma levels of Ang II accompanied by AT1 blockade by valsartan can stimulate unblocked AT2 receptors, which appear to offset the effects of AT1 receptors. Valsartan does not exhibit any partial agonist activity at the AT1 receptor and has much (about 20,000 fold) greater affinity for the AT1 receptor than for the AT2 receptor. Valsartan does not inhibit ACE, also known as kinase II, which converts Ang I to Ang II and decreases bradykinin. Because there is no effect on ACE and no potentiation of bradykinin and P substance, coughing is not caused by angiotensin II antagonists. Valsartan is not bound or block other hormone receptors or Ion channels which play an important role in cardiovascular regulation.

Hypertension: Valsartan is used to treat hypertension. Valsartan can be used alone or in combination with other antihypertensive agents.
Heart failure: Valsartan is used to treat heart failure (NYHA class II-IV) in non-tolerant patients on ACE inhibitors. Valsartan significantly reduces the risk of hospitalization in patients with heart failure. There is no evidence that valsartan provides additional benefits when consumed with ACE inhibitors.
Post myocardial infarction: Improved survival in patients with myocardial infarction is clinically stable with some signs, symptoms or radiological evidence of left ventricular failure and/or with left ventricular systolic dysfunction.

Hypertension: The recommended dose is 80 mg once a day, regardless of race, age, or gender. Antihypertensive effects appear substantially after 2 weeks and maximum effects are seen after 4 weeks. Patients with blood pressure are not well controlled, the daily dose can be increased to 160 mg, or can be added a diuretic. Valsartan can be combined with other antihypertensive drugs.
Heart failure: The recommended starting dose is 40 mg twice daily. Titration of doses to 80 mg and 160 mg twice daily should be carried out until the highest dose is reached, which can be tolerated by the patient. Considerations for reducing diuretics given together should be done. The maximum daily dose given in clinical trials is 320 mg in divided doses. Concomitant use with ACE inhibitors and beta blockers is not recommended. Evaluation in patients with heart failure must always be accompanied by an examination of the assessment of kidney function.
Post myocardial infarction: Therapy can be started as early as possible 12 hours after myocardial infarction. After an initial dose of 20 mg twice daily, valsartan must be titrated to 40 mg, 80 mg, 160 mg twice daily for the next few weeks. The initial dose is 40 mg which can be divided.
The achievement of a target dose of 160 mg twice daily must be based on the tolerability of the patient during dose titration. If symptomatic hypotension or renal dysfunction occurs, dose reduction must be considered. Valsartan can be used in post-myocardial infarction patients treated with other therapies, such as thrombolytic, acetylsalicylic acid, beta blockers and statins. Evaluation in patients after myocardial infarction must always be accompanied by an examination of kidney function.
Note for all indications: No dose adjustment is needed for patients with renal impairment or for patients with nonbiliary liver insufficiency and without cholestasis.
Use in children and adolescents: The efficacy and safety of Valsartan has not been established in children and adolescents at under the age of 18.

Valsartan overdose can cause severe hypotension which can reduce the level of awareness, circulatory collapse and/or shock. If a new patient swallows this drug, an attempt can be made so that the patient vomits. If not, the treatment that can be given is a normal infusion of intravenous saline. Valsartan cannot be removed by hemodialysis.

Hypersensitivity to valsartan or one component of this drug. Pregnancy (see Use in Pregnancy & Lactation); Severe liver disorders, Cirrhosis, Biliary obstruction.

Patients who lack sodium and/or body fluids: In patients with severe sodium and/or body fluid deficiency such as those who receive high doses of diuretics, symptomatic hypotension can rarely occur after starting with Valsartan. Conditions for sodium deficiency and/or body fluids must be treated before starting treatment, for example by reducing the dose of diuretic. If hypotension occurs, the patient must be placed in the supine position and if necessary, given a normal IV saline infusion. Treatment can be continued after the blood pressure has stabilized.
Renal artery stenosis: Short-term administration for 12 patients with secondary renovascular hypertension unilateral renal artery stenosis did not cause significant changes in renal hemodynamics, serum creatinine or BUN. However, because other drugs that affect RAAS can increase blood urea and serum creatinine in patients with bilateral or unilateral renal artery stenosis, safety monitoring is recommended.
Impaired kidney function: Dose adjustment is not required for patients with impaired kidney function. However, in severe cases (creatinine clearance <10 ml/min) data are not available, and therefore care must be taken. Liver disorders. Based on pharmacokinetic data, which shows an increase of about 2-fold plasma concentrations of valsartan in patients with mild to moderate hepatic impairment, doses >80 mg daily should be considered if clinical benefits tend to outweigh the risks that might be associated with increased exposure to valsartan.
Heart failure/post myocardial infarction: Use of Valsartan in patients with heart failure or post myocardial infarction usually causes a decrease in blood pressure, but discontinuation of Valsartan therapy due to symptoms of ongoing hypotension is usually not necessary during administration initial dose followed. Caution must be observed when starting therapy in patients with heart failure or post myocardial infarction (see Dosage & Administration). As an RAAS inhibitor, it can anticipate changes in kidney function in susceptible individuals. In patients with severe heart failure whose renal function depends on RAAS activity, treatment with ACE inhibitors and angiotensin receptor antagonists is associated with oliguria and/or progressive azotemia and (rarely) with acute kidney failure and/or death. Evaluation of patients with heart failure or post myocardial infarction should always include examination of kidney function. In patients with heart failure, attention must be observed with three combinations of ACE inhibitors, beta blockers and (angiotensin II ARBs) receptor blockers).
Effects on the ability to drive or operate machinery: As with other antihypertensives, it is recommended to be careful when driving or operating machinery.
Renal impairment: As predicted for substances whose clearance is only 30% of the total plasma clearance, there is no correlation between kidney function and valsartan exposure in the systemic circulation. Therefore, dosage adjustments are not necessary for patients with impaired kidney function. There was no study in patients undergoing dialysis. However, valsartan is very strongly bound to plasma proteins and cannot be removed during dialysis.
Liver impairment: About 70% of the absorbed dose is secreted in the bile in an unchanging form. Valsartan does not go through an extensive biotransformation process and as suspected valsartan exposure to the systemic canal does not correlate with liver dysfunction. No dose adjustment is needed in patients with insufficiency that are not derived from the bile duct and without cholestasis. The AUC of valsartan has doubled in patients with cirrhosis or bile duct obstruction.
Use in the Elderly: In elderly patients, a higher valsartan systemic exposure was observed compared with younger patients. However, this has not yet shown clinical significance and a lower initial dose is recommended for elderly patients.

Pregnancy: Due to the mechanism of action of angiotensin II antagonists, the risks that occur in the fetus cannot be avoided. Utero exposed to ACE inhibitors during the second and third trimesters of pregnancy has been reported to cause injury and death in developing fetuses. Besides, in retrospective data, the use of ACE inhibitors in the first trimester carries a risk of birth defects. Some reports cause the use of valsartan during pregnancy can cause spontaneous abortion, oligohydramnios and kidney disorders at birth. As a drug that works directly on RAAS, Valsartan is not recommended to be given during pregnancy (see Contraindications) or women planning for pregnancy. Professional health professionals who prescribe the RAAS group should provide counseling to pregnant women regarding the possible risks when taking this drug during pregnancy. When signs of pregnancy appear during the use of therapy, the use of valsartan is stopped immediately.
Breastfeeding: It is not known whether valsartan will be excreted in breast milk. Valsartan is excreted in breast milk in nursing mice. Thus the use of valsartan is not recommended for nursing mothers.

Hypertension: Vascular and lymphatic system disorders: Decrease in the amount of hemoglobin and hematocrit, neutropenia, and thrombocytopenia.
Immune system disorders: Hypersensitivity and serum disorders.
Metabolic and nutritional disorders: Increase in serum potassium levels.
Hearing and labyrinth disorders: Vertigo.
Vascular disorders: Vasculitis.
Respiratory, thoracic and mediastinal disorders: Cough.
Indigestion: Abdominal pain.
Hepato-biliary disorders: Increase in liver action including increase in serum bilirubin.
Skin and subcutaneous tissue disorders: Angioedema, dermatitis bollus, rash and pruritus.
Musculoskeletal and connective tissue disorders: Myalgia.
Kidney and urinary disorders: Kidney disorders, increase in serum creatinine levels, increase in BUN level.
General disorders at the site of administration: Fatigue.
Other events have also been observed in patients with irrespective hypertension who have an association with valsartan: Arthralgia, asthenia, back pain, dizziness, headache, insomnia, decreased libido, nausea, edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections, viral infections.
Post myocardial infarction and/or heart failure: Side effects that may occur in patients after myocardial infarction and/or heart failure are:
Vascular and lymphatic system disorders: Thrombocytopenia.
Immune system disorders: Hypersensitivity and serum disorders.
Metabolic and nutritional disorders: Hypercalcemia; unknown: increased serum potassium levels.
Hearing and labyrinth disorders: Vertigo.
Heart disorders: Heart failure.
Vascular disorders: Hypotension, orthostatic hypotension; unknown: vasculitis.
Respiratory, thoracic and mediastinal disorders: Cough.
Indigestion: Nausea, diarrhea.
Hepato-biliary disorders: Increased liver action.
Skin and subcutaneous tissue disorders: Angioedema; unknown: rash and pruritus.
Musculoskeletal and connective tissue disorders: Myalgia.
Kidney and urinary disorders: Renal failure; acute renal impairment, elevated creatinine levels; increased levels of BUN.
General disorders at the site of administration: Asthenia and fatigue.
Other disorders observed in patients with post-myocardial infarction and/or heart failure are not related to drug studies: Arthralgia, abdominal pain, back pain, insomnia, decreased libido, neutropenia, edema, pharyngitis, rhinitis, sinusitis, upper respiratory infections and viruses.

No clinically significant drug interactions found. Compounds that have been studied in clinical trials include Cimetidine, Warfarin, Furosemide, Digoxin, Atenolol, Indomethacin, Hydrochlorothiazide, Amlodipine and Glibenclamide.
Valsartan is not metabolized to significant, clinically relevant interactions between drugs in the cytochrome P450 system with valsartan are not expected. Although valsartan is strongly bound to plasma proteins, at the in vitro test level it does not show interactions with various molecules that are also strongly bound to plasma proteins such as Diclofenac, Furosemide and warfarin.
Potassium: Concurrent use of potassium-sparing diuretics (for example: Spironolactone, triamterene, amloride), potassium supplements or a potassium salt substitute can cause an increase in serum potassium. If a combination of drugs is considered necessary, caution is recommended.
NSAIDs include selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors): When the angiotensin II antagonist drug is given continuously with NSAIDs, attenuation from hypertension can occur. Also to elderly patients, volume-deplete (including administration of diuretic therapy), or patients who have abnormalities in kidney function, concomitant use with angiotensin II antagonists and NSAIDs can increase the risk of kidney damage. Therefore, monitoring of renal function is recommended when starting or modifying treatment in patients taking Valsartan and NSAIDs simultaneously.

Store under 30°C, protected from light.

Angiotensin II Antagonists

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

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