Dwacand 8

Dwacand 8

Dwacand 8

Anti Hypertensive

-Candesartan cilexetil is a prodrug suitable for oral use. It is rapidly converted to the

active drug, Candesartan, by ester hydrolysis during absorption from the

gastrointestinal tract. Candesartan is highly selective, long lasting and no

competitive antagonist specific for AT1 angiotensin II receptor with tight binding to

and slow dissociation from the receptor, consequently it inhibits angiotensin II

induced vasoconstrictor and aldosterone-secreting effects.

-The antagonism of the angiotensin II (AT1) receptors results in dose related

increases in plasma renin levels, angiotensin I and angiotensin II levels, and a

decrease in plasma aldosterone concentration.

-Candesartan does not inhibit ACE, which converts angiotensin I to angiotensin II

and degrades bradykinin. Candesartan does not affect ACE and gives no

potentiation of bradykinin or substance P. In controlled clinical trials comparing

candesartan with ACE inhibitors, the incidence of cough was lower in patients

receiving candesartan cilexetil.

-Candesartan does not bind to or block other hormone receptors or ion channels

known to be important  in cardiovascular regulation.

-Candesartan causes a dose-dependent, long-lasting reduction in blood pressure. The

antihypertensive action is due to reduced peripheral resistance, while heart rate,

stroke volume and cardiac output are not affected. There is no evidence of serious or

exaggerated first dose hypotension or rebound effect after cessation of Candesartan treatment.

-Candesartan is effective in all grades of hypertension. Candesartan provides

effective and smooth blood pressure reduction over 24 hours. 

-Dwacand® is similarly effective in patients regardless of age and gender.

-Dwacand® increases renal blood flow, and does not influence or increase

glomerular filtration rate while the renal vascular resistance and filtration fraction

are reduced.

-Candesartan has no adverse effects on blood glucose or lipid profile.

-The average absolute bioavailability of candesartan is approximately 35 %

following oral administration of Candesartan cilexetil.

-The mean peak serum concentration (Cmax) is reached 3 - 4 hours after the tablet

intake.

-The candesartan serum concentrations increase linearly with increasing doses in the

therapeutic dose range.

-Candesartan is highly bound to plasma protein (more than 99 %).

-The evident volume of distribution of candesartan is 0.13/kg.

-The terminal half-life of candesartan is approximately 9 hours. There is no

accumulation following multiple doses.

-Following an oral dose of radioactively labelled candesartan cilexetil, approximately 26 % of the dose is excreted in the urine as candesartan and 7 % as inactive metabolites while approximately 56 % of the dose is recovered in the faeces as candesartan and 10 % as inactive metabolites

Indecation

-The recommended initial and maintenance dose of Dwacand® is 8 mg or 16 mg

once daily.

-In patients who require further blood pressure reduction, a dose increased to 16 mg

once daily is recommended.

-The maximal antihypertensive effect is attained within 4 weeks of initiation of

treatment.

-No initial dosage adjustment is necessary in elderly patients.

-No initial dosage adjustment is necessary in patients with mild renal impairment

(i.e. creatinine clearance ≥ 30 ml/min/1.73m2 BSA). In patients with severe renal

impairment (i.e. creatinine clearance < 30ml/ min/1.73m2 BSA), the clinical

experience is limited and a lower initial dose of 4 mg should be considered.

-No initial dosage adjustment is necessary in patients with mild to moderate hepatic

function.

-No experience available to date in patients with severe impairment hepatic function

(e.g. cirrhotic patients).

-Dosage in heart failure: The usual recommended initial dose of Dwacand® is 4

mg once daily.

-Up-titration to the target dose of 32 mg once daily or the highest tolerated dose is

done by doubling the dose at intervals of at least 2 weeks.

-In patients with less than optimal blood pressure reduction on Candesartan,

combination with a thiazide diuretic is recommended.

-Children and adolescences 6 to 18 years of age: the recommended starting dose is

4mg once daily. In some patients whose blood pressure is not adequately controlled,

patient weighting < 50kg the dose can be increased to a maximum of 8mg once daily, while for patient weighting ≥ 50kg the dose can be increased to 8mg once

daily and 16mg once daily.

-Dwacand® can be taken alone or in combination with antihypertensive drugs 

such as thiazide diurtics or calcium antagonists.

-Dwacand® should be taken once dialy with or without food.

-Candesartan Cilexetil must not be given to children under 1 year of age due to the

potential risk to the developing kidneys.

Dosage & Administration

-The recommended initial and maintenance dose of Dwacand® is 8 mg or 16 mg

once daily.

-In patients who require further blood pressure reduction, a dose increased to 16 mg

once daily is recommended.

-The maximal antihypertensive effect is attained within 4 weeks of initiation of

treatment.

-No initial dosage adjustment is necessary in elderly patients.

-No initial dosage adjustment is necessary in patients with mild renal impairment

(i.e. creatinine clearance ≥ 30 ml/min/1.73m2 BSA). In patients with severe renal

impairment (i.e. creatinine clearance < 30ml/ min/1.73m2 BSA), the clinical

experience is limited and a lower initial dose of 4 mg should be considered.

-No initial dosage adjustment is necessary in patients with mild to moderate hepatic

function.

-No experience available to date in patients with severe impairment hepatic function

(e.g. cirrhotic patients).

-Dosage in heart failure: The usual recommended initial dose of Dwacand® is 4

mg once daily.

-Up-titration to the target dose of 32 mg once daily or the highest tolerated dose is

done by doubling the dose at intervals of at least 2 weeks.

-In patients with less than optimal blood pressure reduction on Candesartan,

combination with a thiazide diuretic is recommended.

-Children and adolescences 6 to 18 years of age: the recommended starting dose is

4mg once daily. In some patients whose blood pressure is not adequately controlled,

patient weighting < 50kg the dose can be increased to a maximum of 8mg once daily, while for patient weighting ≥ 50kg the dose can be increased to 8mg once

daily and 16mg once daily.

-Dwacand® can be taken alone or in combination with antihypertensive drugs 

such as thiazide diurtics or calcium antagonists.

-Dwacand® should be taken once dialy with or without food.

-Candesartan Cilexetil must not be given to children under 1 year of age due to the

potential risk to the developing kidneys.

 Each tablet of  Dwacand  8 contains:

       Candesartan Cilexetil  8 mg.

  Candesartan Cilexetil  16 mg.

-Dwacand® is contraindicated in patients who are hypersensitive to any of its

components.

-No drug interactions of clinical significance have been found. Compounds which

have been investigated in clinical studies include hydrochlorothiazide, warfarin,

digoxin, oral contraceptives (i.e.ethinylestradiol/levonorgestrel), glibenclamide,

nifedipine and enalapril.

-The antihypertensive effect of Dwacand® may be enhanced by other

antihypertensives.

-Concomitant use of potassium-sparing diuretics, potassium supplements, salt

substitutes containing potassium, or other drugs that may increase potassium levels

(e.g. heparin) may lead to increases in serum potassium. Since lithium toxicity has

been reported, careful monitoring of serum lithium levels is recommended during

concomitant administration of lithium and Dwacand® tablets, since lithium

reabsorption at renal tubule is increased.

-Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen,

diclofenac, celecoxib or etoricoxib, combining these medications may reduce the

effects of candesartan in lowering blood pressure. In addition, these medications

may affect your kidney function, especially when they are used together frequently

or chronically.

-If pregnancy is detected during treatment, Dwacand® should be discontinued

immediately. The use of angiotensin converting enzyme inhibitors (ACEI) during

the second or third trimesters of pregnancy has been associated with foetal and

neonatal injury.

-It is not known whether candesartan is excreted in human milk.

-Breast-feeding should be discontinued if the use of Dwacand® is considered

essential.

-The safety and tolerability of Dwacand® (Candesartan Cilexetil) was shown to be

comparable to that if placebo in double-blinding clinical studies.

-Dwacand® was well tolerated and adverse events were mild and transient and

showed no association with dose or age or gender.

-Withdrawals from treatment due to adverse events were similar with  candesartan

cilexetil and placebo

-The common adverse events reported were: dizziness/Vertigo, headache, back pain and respiratory tract infection.

-A group of very rare side effects were observed like swelling of the face, lips, tongue and/or throat, a reduction in red and white blood cells, skin rash, lumpy rash, itching , back pain , pain in joints and muscles, nausea, cough.

- Sore throat is a very common side effect in childern.

-In general, there were no clinically important influences of Canartan on routine

laboratory variables. In postmarketing surveillance, very rare cases (<1/ 10000),

were reported slightly more often with Candesartan Cilexetil than with placebo

including increase in liver enzymes, hepatitis, leucopenia, neutropenia,

agranulocytosis, rash, urticaria, angioedema and hyponatremia, but no routine

monitoring of laboratory variables is usually necessary for patients receiving

Candesartan Cilexetil.

 

Overdose:

-Based on pharmacological considerations, the main result of an overdose is likely

to be hypotension and dizziness.

-Concomitant use of Dwacand® with potassium-sparing diuretics, may

theoretically result in increased serum potassium levels. If co-administration is

considered necessary, caution is adviced.

-Physician should know if patient is receiving Dwacand® because of possible

hypotension during surgery in patients treated with angiotensin-II antagonists.

-Physician should know if the patient has a disease of the adrenal gland called

 Conn,s syndrome ( also called primary hyperaldosteronism).

Warnings:

-Intravascular volume depletion: In patients with intravascular volume depletion

(such as those receiving high dose diuretics ), Symptomatic hypotension may occur,

hence, this condition should be corrected before administration of Dwacand®.

-Renal artery stenosis: Other drugs that affect the renin-angiotensin- aldosterone

system, i.e. angiotensin converting enzyme (ACE) inhibitors, have been associated

with increased blood urea  and serum creatinine in patients with bilateral renal artery

stenosis or stenosis of the artery to a solitary kidney. Although not proved, probably

this may occur also with angiotensin II receptor antagonists such as Candesartan Cilexetil.

-Dwacand® 16 : Blister of 10 tablets, pack of 2 blisters.

-Dwacand®  8 : Blister of 10 tablets, pack of 2 blisters.

-In dry place store below 25ºC.