CODIVAN 80mg/12.5mg Novartis treatment for hypertension (2 blisters x 14 tablets)

Valsartan is an Angiotensin II receptor antagonist with a strong and specific activity, oral. Valsartan selectively acts on the AT1 receptor sub -receptor that this receptor controls the activity of angiotensin II. Angiotensin II concentration increases in plasma after using AT1 receptor blockers with valsartan that can irritate AT2 receptors that are not blocked and this makes counterweight with the efficiency of the AT1 receptor. Valsartan does not have any co -operating activity for AT1 receptors and has a lot of affinity with AT1 receptors many times stronger (20,000 times) compared to the AT1 receptor.

Valsartan does not inhibit the enzyme transferring angiotensin (ACE), named Kininase II, capital transferred angiotensin I into angiotensin II and bradykinin divestment. The side effects related to Bradykinin does not occur. In clinical trials that compare Valsartan treatment groups with Angiotensin (ACE) medications inhibitors (ACE), the rate of dry cough is significantly lower (P

The action position of thiazide diuretics mainly occurs on the distance of the kidney. On the kidney shell, it is associated with a highly affinity receptor with the main cohesion position to promote diuretic effects and it inhibits Naci transport in the distance. The effect of the thiazide is that through inhibition of Na+Ci- transportation, perhaps thanks to the position of Ci-location dispute, therefore affecting the mechanism of reabsorption of electrolytes: directly increasing the excretion of Na and CL with equivalent volume, indirectly diuretic leading to decreased plasma volume, resulting in enhancing the activity of renin in plasma, enhancing Aldosterone excretion, increasing the amount of urinary secretion and decreasing the level of urination, reducing the amount of urination and reducing the level of urination and decreasing the concentration of the concentration, reducing the amount of urination in the urine. The relationship between Renin-Losterone is intermediate by Angiotensin II, so the use in combination with antagonistic drugs with Angiotensin II recovery recovery is lost due to diuretics of this group.

pharmacokinetics

valsartan

Absorption: After drinking Valsartan alone, the peak concentration of the plasma of Valsartan is achieved in 2-4 hours. Valsartan's absolute biology is 23%. When Valsartan taken with food, the area under the plasma concentration curve of Valsartan decreased 48%, although the plasma concentration at 8 hours after taking the drug in the hunger and full group was the same.

Distribution: The distribution volume in the stable state of Valsartan after intravenous injection is about 17 liters, indicating that Valsartan is not distributed into wide tissues. Valsartan is strongly connected to serum protein (94 - 97%), mainly serum albumin.

Metabolic: Valsartan is not highly metabolized, only about 20% of the dose is found in the form of metabolites. A hydroxy metabolite has been determined in low plasma (less than 10% of AUC valsartan). This metabolic substance is an inactive pharmaceutical.

Elimination: Valsartan is mainly eliminated by feces (about 83% of the dose) and urine (about 13% of the dose), mainly in a constant form. After intravenous injection, the clearance of Valsartan in plasma is about 2 l/h and the renal clearance is 0.62 l/h (about 30% of the total amount of liberation). Valsartan's half -life is 6 hours.

hydrochlorothiazide

Absorption: Absorb hydrochlorothiazide very quickly after oral (Tmax is about 2 hours). The area below the average curve increases linearly and ratio according to the dose within the treatment dose range. The absolute bioavailability of hydrochlorothiazide is 70% after drinking.

Distribution: Expression distribution volume is 4 - 8 l/kg. Hydrochlorothiazide in the circulation associated with serum protein (40-70%), mainly serum albumin. Hydrochlorothiazide also accumulates in erythrocytes approximately 3 times higher in plasma.

Metabolism: Hydrochlorothiazide is excreted mainly in constant form.

Elimination: Hydrochlorothiazide plasma is sold from 6 to 15 hours in the end. More than 95% of the absorption dose is excreted in urine in the form of no no.

valsartan/hydrochlorothiazide

The system of systemicity of hydrochlorothiazide is reduced to 30% when used in combination with Valsartan. Valsartan's pharmacological pharmacology is not significantly affected when used in combination with hydrochlorothiazide. This interaction does not affect the combination of drugs between Vallsartan and Hydrochlorothiazide, because in clinical control studies shows that when used in combination, the anti -hypertension effect is much stronger than the single use of each drug or placebo.

When experiencing side effects of the drug, it is necessary to stop using and notify the doctor or go to the nearest medical facility for timely treatment.

Concomitance Angiotensin ARBS receptor antagonists - including Valsartan - or ACEIS and Aliskiren inhibitors for patients with diabetes Type II.

Be cautious when using

Changes in serum electrolytes

Be careful when using potassium supplements, potassium diuretic, salt -containing potassium replacement, or drugs that increase the concentration of potassium in serum (heparin, ...). Thiazide diuretics can promote the onset of hypokalemia or worsen existing potassium potassium. Thiazide diuretics should be used cautiously in patients with significant potassium -related conditions, such as renal impairment (the cause of the heart) and kidney disease. If hypotension is accompanied by clinical signs (such as weakness, muscle paralysis, or transforming on ECG), CO-icovan should be stopped. Should adjust the condition of hypokalemia and hypoglycemia available before starting the use of thiazide. The concentration of potassium and serum magnesium should be checked periodically. All patients using thiazide diuretics should be monitored with an insomnia, especially potassium.

Thiazide diuretics can promote the onset of hypoglycemia and alkaline infection due to hypoglycemia or exacerbate the existing sodium hypoglycemia. Hypoglycemia, neurological symptoms (nausea, loss of progression, dazzling state) have been observed in particular cases. Regular monitoring of sodium levels in serum is also recommended.

Cases of salt loss and/or severe loss of severe circulatory volume such as high doses of diuretics, hypotension with rare symptoms that may occur after the start of co-set treatment. Co-iavan should only be used after adjusting any circulating and/or sodium losses, if not treated, it should start under strict medical supervision.

Should be cautious when using co-sets to treat hypertension. In patients with one or both sides of the kidney artery or narrowing on the patient, there is only one kidney because of the blood urea and serum creatinine can increase in these patients.

Evala, including larynx swelling and bars, causes obstruction of the airway and/or swelling of the face, lips, throat, and/or tongue that have been reported in patients treated with Valsartan, some of these patients who have previously been angry with other drugs including angiotensin transferring enamel inhibitors. Co-icovan should be stopped immediately in angioed development patients, and should not be reused by co-sets.

There have been reports on thiazide diuretics, including hydrochlorothiazide that worsen or activate systemic lupus erythematosus.

Thiazide diuretics, including hydrochlorothiazide, can change the ability to tolerate glucose and increase the concentration of cholesterol and triglyceride.

Like other diuretics, hydrochlorothiazide can increase the concentration of uric acid in the serum due to reduction in the clearance of uric acid and can cause or worsen blood uric acid hyperkemis and promote gout in sensitive patients.

Thiazide reduces calcium secretion in urine and may cause slight increase in serum in the absence of calcium metabolic disorders.

Common hypersensitivity reactions to hydrochlorothiazide in patients with allergies and asthma.

Hydrochlorothiazide, which is a sulfonamide, has been associated with a special reaction that leads to an acute transient myopia and acute angle glaucoma. Symptoms include an acute onset of vision loss or eyeballs and typically occurring within hours to a few weeks after starting the medication. Excavation angle increased angle untreated can lead to permanent vision loss. The prerequisite is to stop hydrochlorothiazide as quickly as possible. The risk factor for increasing glaucoma of acute angle may include a history of allergy sulfonamide or penicillin.

Patients with heart failure/myocardial infarction in patients with renal function depending on the activity of the renin-angiotensin-aldosterone system (such as patients with severe congestive heart failure), treatment with transferring medication or Angiotensin receptor-related drug-related antagonistic drugs related to progressive urinary discharge and/or hyperconemosis, and in a rare case associated with acute renal failure and/or death. Evaluation of patients with heart failure or after myocardial infarction should always come with kidney function assessment.

Be cautious when treating the Renin - Angiotensin Arbs receptor, including Valsartan, with other Renin - Angiotensin blockade drugs such as enamel inhibitors or Aliskiren.

The ability to drive and operate machinery

Be careful when driving and operating machinery.

Pregnancy

Due to the mechanism of operation of Angiotensin II antagonists, the risk of fetal impact cannot be excluded. Using Angiotensin (ACE) (ACE) (a group of enzymes that act on the renin-angiotensin-aldosterone-RAAS system) for pregnant women in the middle and the last 3 months is reported to cause damage or death for the fetus growing in the uterus. In addition, in rescue data, the use of angiotensin transferring enamel inhibitors in the first 3 months is related to the potential risk of birth defects. There has been a report on spontaneous miscarriage, amniotic fluid and kidney dysfunction in newborns when pregnant women accidentally drink Valsartan.

Thiazide diuretics, including hydrochlorothiazide related to jaundice or platelets in the fetus in the uterus and babies, and may also be related to other side effects that have occurred on adults.

contraindicated use of co-sets during pregnancy.

The period of breastfeeding

It is unclear whether Valsartan is excreted through breast milk or not. Valsartan is excreted in breast milk. Hydrochlorothiazide passes the placenta and is excreted through breast milk. Therefore, do not use co-set for breastfeeding women.

Drug interaction

lithium: Increasing the level of lithium in the blood can be reversed and toxic has been reported when used simultaneously lithium with ACE inhibitors, Angiotensin II anti -receptor or thiazide. Because lithium's renal clearance decreases due to thiazide, the risk of toxicity of lithium can be increased with Co-icovan. Therefore, careful monitoring of blood lithium concentration during the recommended coordination treatment process.

Double blockade drugs Renin - Angiotensin (RAS) include Angiotensin receptor antagonistic drugs, Yeast inhibitors or Aliskiren:

Concomitance the Angiotensin receptor antagonist (ARBS), including Valsartan, with other drugs that work on the Renin - Angiotensin system that is associated with an increase in the rate of hypotension, hyperkalemia, and changes in renal function compared to single therapy. It is necessary to recommend monitoring blood pressure, kidney and electrolyte function in patients using co -sets and other drugs on the Renin - Angiotensin Ras system.

It is necessary to avoid simultaneous use of Angiotensin receptor antagonists including valsartan or ACEI enzyme inhibitors with Aliskiren in patients with severe renal impairment (GFR glomerular filtration speed

Simultaneous use of ARBS - including Valsartan - or ACEI transfer inhibitors with Aliskiren is contraindicated for patients with diabetes Type 2.

Valsartan Unit does not have a significant drug interaction with the following drugs: Cimetidine, Warfarin, Furosemide, Digoxin, Atenolol, Indomethacin, Hydrochlorothiazide, Amlodipine, Glibenclamide.

Potassium: Be careful when using potassium supplements, potassium diuretics, salt -containing salt, or drugs that change the concentration of potassium in serum (heparin, ...) and must regularly check the potassium concentration in serum patient serum.

Non-steroid anti-inflammatory (NSAIDs) including selective inhibitors Cycloxygenase-2 (COX-2 inhibitors): When angiotensin II drugs are used simultaneously with NSAIDs, the effect of lowering blood pressure may be impaired. Moreover, in older patients, impaired volume (including those who treat diuretics), or suffer from kidney function, and use Angiotensin II and NSAIDs can lead to an increased risk of worsening kidney function. Therefore, monitoring kidney function is recommended when starting or changing treatment at patients using Valsartan with simultaneous use of NSAID drugs.

Transport: The result from a test in a human tube on a human liver shows that Valsartan is a substrate of the transportation that absorbs drugs into the liver 0ATP1B1 and the drug transportation out of MRP2 liver. Simultaneous treatment of absorbent transportation inhibitors (rifampin, ciclosporin) or transportation (ritonavir) may increase the contacts of valsartan in the body.

Other anti -hypertension drugs: Thiazide increases the effectiveness of hypotension of other hypertension drugs (such as guanethidine, methyldopa, beta blockers, vasodilators, calcium channel blockers, angiotensin (ACE) enzymes inhibitors, angiotensin receptor blockers (ARB) and direct inhibitors of threadin inhibitors (Dris)).

Musculoskeletal pills: Thiazide including hydrochlorothiazide increases musculoskeletal activity as a derivative of Curare.

Medications affect the concentration of potassium in serum: The effect of reducing potassium potassium of diuretics may increase due to simultaneous use with diuretics to excrete potassium, corticosteroids, actheric, amphoticin, carbenoxolone, penicillin g and derivatives of salicylic acid or anti -arrhythmia.

The drug affects the amount of sodium in serum: The effect of reducing sodium of diuretics can be enhanced by simultaneous use of drugs such as antidepressants, anti -psychotic drugs, anti -epileptic drugs, etc.

Anti -diabetic drugs: Thiazide can change glucose tolerance. The dose of insulin may be needed and oral diabetes.

Digitalis glycosides: Thiazide side effects can be lower potassium or blood magnesium, making it possible to arise the arrhythmia caused by digitalis.

Non-steroid anti-inflammatory drugs (NSAIDs) and selective inhibition of COX-2: Use in combination with nonsteroidal anti-inflammatory drugs (such as the derivative of Salicylic Acid, Indomethacin) can reduce the diuretics and anti-hypertension effect of the thiazide ingredient in Co-govan. Reducing blood volume at the same time can lead to acute renal failure.

Allopurinol: Using a combination of thiazide diuretics (including hydrochlorothiazide) may increase the rate of hypersensitivity reactions to allopurinol.

Amantadine: Using a combination of thiazide diuretics (including hydrochlorothiazide) may increase the risk of adultery due to Amantadine.

Anti -cancer drugs (such as cyclophosphamide, methotrexate): Used in combination with thiazide diuretics can reduce the excretion through the kidneys for cytotoxic drugs and increase the bone marrow inhibition effect of these drugs.

anti -cholinergic drugs: Biological use of thiazide diuretics may increase due to anti -cholinenergic drugs (such as atropine, biperiden), obviously due to reducing stomach - intestinal motility and gastric empty speed. On the contrary, peristalsis such as Cisaprid can reduce the bioavailability of thiazide diuretics.

Ion exchange resin: The absorption of thiazide diuretics, including hydrochlorothiazide, will be reduced by cholestyramin or colestipol. However, alternating alternating hydrochlorothiazide and resin as when hydrochlorothiazide is used at least 4 hours before or 4-6 hours after use. Resin is likely to minimize interaction.

Vitamin D: When using thiazide diuretics, including hydrochlorothiazide, with vitamin D or calcium salts, there is a risk of increasing calcium concentration in serum.

ciclosporin: When combined with cyclosporine can cause an increased risk of hyperuricemia and complications of gout.

Calcium salt: When used with thiazide diuretics, it can lead to increased blood calcium due to increased calcium reabsorption in the renal tubules.

diazoxide: Thiazide diuretics can cause hyperglycemia of diazoxide.

methyldopa: There have been reports in hemolytic anemia occurring when using simultaneously hydrochlorothiazide and methyldopa.

Alcohol, barbiturat or narcotic groups: simultaneous use of thiazide diuretics with alcohol, barbiturates, narcotic substances can increase the ability to lower posture blood pressure.

Pressor amines: Hydrochlorothiazide can reduce response to pressors amines like Noradrenaline. The clinical significance of this effect is uncertain and not enough to prevent the use of these drugs.