ADVANT Tablet

For the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

DOSAGE AND ADMINISTRATION

ADVANT may be administered with or without food. Dosage must be individualized. Blood pressure response is dose related over the range of 2-32mg. The usual recommended starting dose is 16mg once daily when it is used as monotherapy in patients who are not volume depleted. ADVANT can be administered once or twice daily with total daily doses ranging from 8mg to 32mg. Langer doses do not appear to have a greater effect, and there is relatively little experience with such doses. Most of the antihypertensive effect is present within 2 weeks, and maximal blood pressure reduction is generally obtained within 4-6 weeks of treatment with ADVANT.

If blood pressure is not controlled by ADVANT alone, a diuretic may be added. ADVANT may be administered with other antihypertensive agents.

See the package insert about the details below.

- Hepatic impaired patients

- Volume depleted patients

In patients who are hypersensitive to this drug to any component of this product.

Body as a Whole: asthenia, fever.

Central and Peripheral Nervous System: paresthesia, vertigo.

Gastrointestinal System Disorder: dyspepsia, gastroenteritis.

Heart Rate and Rhythm Disorders: tachycardia, palpitation.

Metabolic and Nutritional Disorders: creatinine phosphokinase increased, hyperglycemia, hypertriglyceridemia, hyperuricemia.

Musculoskeletal System Disorders: myalgia.

Platelet/Bleeding-Clotting Disorders: epistaxis.

Psychiatric Disorders: anxiety, depression, somnolence.

Respiratory System Disorders: dyspnea.

Skin and Appendages Disorders: rash, sweating increased.

Urinary System Disorders: hematuria.

Other reported events seen less frequently included angina pectoris, myocardial infarction, and angioedema. Adverse events occurred at about the same rates in men and women, older and younger patients, and black and non black patients.

Following adverse effects are rarely reported:

Digestive: abnormal hepatic function and hepatitis

Hematologic: neutropenia, leukopenia and agranulocytosis.

Metabolic and Nutritional Disorders: hyperkalemia, hyponatremia.

Renal: renal impairment, renal failure.

Skin and Appendages Disorders: pruritus and urticaria.

- Because candesartan is not significantly metabolized by the CYP450 system and at therapeutic concentrations has no effects on P450 enzymes, interactions with drugs that inhibit or are metabolized by those enzymes would be expected.

- No significant drug interactions have been reported in studies of candesartan cilexetil given with other drugs such as glyburide, nifedipine, digoxin, warfarin, hydrochlorothiazide, and oral contraceptives in healthy volunteers.

- Since both, ACE inhibitors and angiotensin receptor blockers, can increase the concentrations of potassium in the blood, other medications that can increase the concentration of potassium in the blood, such as spironolactone, and potassium supplements, should be used cautiously with candesartan.

- Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors, and with some angiotensinⅡreceptor antagonists. An increase in serum lithium concentration has been reported during concomitant administration of lithium with candesartan cilexetil, so careful monitoring of serum lithium levels is recommended during concomitant dose.

Pregnancy

When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus, When pregnancy is detected, candesartan cilexetil should be discontinued as soon as possible.

Nursing Mothers

It is not known whether candesartan is excreted in human milk but because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

See the package insert about the details below.

- Hypotension in Volume- and Salt-Depleted Patients

- Impaired Renal Function

Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensinⅡby selectively blocking the binding of angiotensinⅡto the AT, receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathways for angiotensinⅡsynthesis.

There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity for the AT1 receptor than for the AT2 receptor. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensinⅡfrom angiotensinⅠ, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kininaseⅡ), it does not affect the response to bradykinin. Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Blockade of the angiotensinⅡon renin secretion, but the resulting increased plasma renin activity and angiotensinⅡcirculating levels do not overcome the effect of candesartan on blood pressure.