ADVANTEC Tablet

For the treatment of hypertension. The fixed dose combination is not indicated for initial therapy.

Dosage and Administration

The usual starting dose is 1 tablet per day with or without food.

To minimize dose dependent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration

A patient whose blood pressure is not controlled on 25mg of hydrochlorothiazide once daily can expect an incremental effect from ADVANTEC. A patient whose blood pressure is controlled on 25mg of hydrochlorothiazide but is experiencing decreases in serum potassium can expect the same or incremental blood pressure effects from ADVANTEC and serum potassium may improve.

See the package insert about the details below.

Renal Impaired Patients

Hepatic Impaired Patients

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

- In patients with anuria or hypersensitivity to other sulfonamide-derived drugs, due to hydrochlorothiazide component in the preparation.

- In concomitant use with other antihypertensive drugs like, dofetilide.

- In patients with more severe renal impairment.

Adverse reactions reported are mild and transient in nature and have only infrequently required discontinuation of therapy.

Common

Back pain, dizziness, flu-like symptoms, headache, upper respiratory infection.

Less common

Abdominal pain, change in amount of urine, increased sweating, unusual thirst, fainting, gastrointestinal disorders, mood swings.

Rare

Persistent sore throat, cough, fever, unusual fatigue, unusual bleeding or bruising, pale skin and eyes, dark urine, chest pain, irregular heartbeats, joint pain.

See the package insert about the details below.

Candesartan Cilexetil

Lithium

Hydrochlorothiazide

When administered concurrently the following drugs may interact with thiazide diuretics

Alcohol, barbiturates or narcotics

Anti-diabetic (Oral agents and insulin)

Cholestyramine and colestipol resins

Corticosteroids, ACTH

Pressor amines (norepinephrine)

Skeletal muscle relaxant (tubocurarine)

Lithium

NSAIDs

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, ADVANTEC should be discontinued as soon as possible.

Nursing Mothers

Hydrochlorothiazide is excreted in breast milk but it is not known whether candesartan is excreted in human milk. Because of the potential for adverse effects 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

Candesartan Cilexetil

Impaired Renal Function

Hydrochlorothiazide

- Impaired hepatic function

- Impaired renal function

- Hypersensitivity reaction

- Cause exacerbation or activation of systemic lupus erythematosus

- Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

- Thiazides may decrease urinary calcium excretion.

Candesartan Cilexetil

Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensinⅡby selectively blocking the binding of angiotensinⅡto the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathways for angiotensinⅡsynthesis.

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 iron channels known to be important in cardiovascular regulation.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensinⅡ, so co-administration of an angiotensinⅡreceptor antagonist tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is unknown.