Dwacand H16/12.5

Dwacand H16/12.5

Dwacand H16/12.5

Anti Hypertensive

- Candesartan cilexetil: is a prodrug, which is rapidly converted to the active drug, candesartan, by
  ester hydrolysis during absorption from the gastrointestinal tract. Candesartan is an angiotensin II
  receptor antagonist, selective for AT1 receptors, with tight binding to and slow dissociation from the
  receptor. It has no agonist activity. Candesartan does not influence ACE or other enzyme systems
  usually associated with the use of ACE inhibitors. Since there is no effect on the degradation of
  kinins, or on the metabolism of other substances, such as substance P, angiotensin II receptor
  antagonists are unlikely to be associated with cough. Candesartan does not bind to or block other
  hormone receptors or ion channels known to be important in cardiovascular regulation.
  The antagonism of the AT1 receptors results in dose related increases in plasma renin levels, 
  angiotensin I and angiotensin II levels, and a decrease in plasma aldosterone concentration.
- Hydrochlorothiazide: inhibits the active reabsorption of sodium, mainly in the distal kidney
  tubules, and promotes the excretion of sodium, chloride and water. The renal excretion of  potassium
  and magnesium increases dose-dependently, while calcium is reabsorbed to a greater extent.
  Hydrochlorothiazide decreases plasma volume and extracellular fluid and reduces cardiac output and
  blood pressure. During long-term therapy, reduced peripheral resistance contributes to the blood
  pressure reduction.
- Candesartan and hydrochlorothiazide: have additive antihypertensive effects. In hypertensive
  patients, Dwacand®-H causes an effective and long-lasting reduction in arterial blood pressure
  without reflex increase in heart rate. 
- Absorption And Distribution: Candesartan cilexetil is rapidly and completely bioactivated by ester
  hydrolysis from the gastrointestinal tract to candesartan. The average absolute bioavailability of
  candesartan is approximately 40%. The mean peak serum concentration (Cmax) is reached in 3 - 4
  hours after oral dministration. Candesartan is highly bound to plasma proteins (more than 99%). 
  The evident volume of distribution of candesartan is 0.1 L/kg. The pharmacokinetics of
  candesartan is not gender related. The area under the serum concentration versus time curve
  (AUC) of candesartan is not significantly affected by food. Hydrochlorothiazide: is rapidly
  absorbed from the gastrointestinal tract with an absolute  bioavailability of approximately 70%.
  Concomitant intake of food increases the absorption by approximately 15%. The bioavailability
  may decrease in patients with cardiac failure and pronounced oedema. The plasma protein binding
  of hydrochlorothiazide is approximately 60%. The apparent volume of distribution is
  approximately 0.8 L/kg.
- Metabolism and Elimination: Candesartan is mainly excreted unchanged in urine and bile.
   It undergoes minor hepatic metabolism to an inactive metabolite.The terminal half-life of
  candesartan is approximately 9 hours.Total plasma clearance of candesartan is about 0.37ml/
  min/kg, with a renal clearance of about 0.19 ml/min/kg. Following an oral dose of 14 C-labelled
  candesartan cilexetil, approximately 26% of the dose is excreted in the urine as candesartan and 
  7% as an inactive metabolite while approximately 56% of the dose is recovered in the faeces as
  candesartan and 10% as the inactive metabolite.
- Hydrochlorothiazide is not metabolized and is excreted almost entirely as unchanged drug by
  glomerular filtration and active tubular secretion.The terminal t1/ 2 of hydrochlorothiazide is
  approximately 8 hours. Approximately 70% of an oral dose is eliminated in the urine within 48
  hours.The half-life of ydrochlorothiazide remains unchanged (approximately 8 h) after
  administration of hydrochlorothiazide in combination with candesartan cilexetil. No additional
  accumulation of hydrochlorothiazide occurs after repeated doses of the combination compared to
  monotherapy. The terminal t1/ 2 of hydrochlorothiazide is prolonged in patients with renal
  impairment.

Indecation

- Dwacand®-H is indicated for essential hypertension, where monotherapy with candesartan cilexetil 
  or hydrochlorothiazide is not sufficient

Dosage & Administration

- The recommended dose of Dwacand®-H is one tablet once daily. 
- Most of the antihypertensive effect is usually attained within 4 weeks of initiation of treatment.
- Dwacand®-H should be taken once daily with or without food.
- Use in the elderly: No initial dosage adjustment is necessary in elderly patients.
- In patients with mild to moderate renal impairment whose creatinine clearance is ≥ 30 ml/min/
  1.73m2  BSA : Dose titration of candesartan cilexetil is recommended before treatment with

- Each tablet of Dwacand®-H 16/ 12.5  contains: 
  Candesartan Cilexetil                      16 mg.
  Hydrochlorothiazide                    12.5 mg. 
- Each tablet of Dwacand®-H 8/ 12.5  contains:  
  Candesartan Cilexetil                       8 mg. 
  Hydrochlorothiazide                   12.5 mg

- Hypersensitivity to Candesartan, Hydrochlorothiazide or to any of the components.
- Severe renal impairment (creatinine clearance <30 ml/min/1.73 m2 BSA).
- Severe hepatic impairment and/or cholestasis.
- Refractory hypokalaemia and hypercalcaemia.
- Gout.

- No drug interactions of clinical significance have been identified for candesartan cilexetil. 
- The antihypertensive effect of Dwacand®-H may be enhanced by other antihypertensives. 
- The potassium depleting effect of hydrochlorothiazide could be expected to be potentiated by other 
  drugs associated with potassium loss and hypokalaemia (e.g. other kaliuretic diuretics, laxatives, 
  amphotericin, carbenoxolone, penicillin G sodium, salicylic acid derivates). 
- Diuretic-induced hypokalaemia and hypomagnesaemia predisposes to the potential cardiotoxic effects 
  of digitalis glycosides and antiarrhythmics. Periodic monitoring of serum potassium is recommended 
  when Dwacand®-H is administered with such drugs.
- Dwacand®-H may increase in serum lithium concentrations and toxicity and careful monitoring of 
  serum lithium concentrations is recommended 
- NSAIDs may decrease  the diuretic, natriuretic and antihypertensive effect of hydrochlorothiazide 
- Colestipol or cholestyramine reduce the absorption of hydrochlorothiazide.
- Nondepolarizing skeletal muscle relaxants effects (e.g. tubocurarine) may be potentiated by 
  hydrochlorothiazide.
- Hydrochlorothiazide may increase serum calcium levels due to decreased excretion. If calcium 
  supplements or Vitamin D must be prescribed, serum calcium levels should be monitored and dosage 
  adjusted accordingly.
- The hyperglycaemic effect of beta-blockers and diazoxide may be enhanced by hydrochlorothiazide. 
- Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of 
  hydrochlorothiazide by decreasing gastrointestinal motility and stomach emptying rate. 
- Hydrochlorothiazide may increase the risk of adverse effects caused by amantadine. 
- hydrochlorothiazide may reduce the renal excretion of cytotoxic drugs (e.g. cyclophosphamide, 
  methotrexate) and potentiate their myelosuppressive effects.
- The risk for hypokalaemia may be increased during concomitant use of steroids or 
  adrenocorticotropic hormone (ACTH). 
- Postural hypotension may become aggravated by simultaneous intake of alcohol, barbiturates or 
  anaesthetics.
- Treatment with a thiazide diuretic may impair glucose tolerance. Dosage adjustment of antidiabetic 
  drugs, including insulin, may be required. 
- Hydrochlorothiazide may cause the arterial response to pressor amines (e.g. adrenaline) to decrease 
  but not enough to exclude a pressor effect. 
- Hydrochlorothiazide may increase the risk of acute renal insufficiency especially with high doses of 
  iodinated contrast media.
- There is no clinically significant interaction between hydrochlorothiazide and food

- Dwacand®-H should not be used in pregnancy. If pregnancy is detected during treatment, 
- Dwacand®-H should be discontinued. 
- Dwacand®-H should not be given during breast-feeding

  Nervous system disorders: Dizziness/vertigo.
Candesartan cilexetil:
- Leukopenia, neutropenia and agranulocytosis, Hyperkalaemia, hyponatraemia, Dizziness, headache,
  Nausea, Increased liver enzymes, abnormal hepatic function or hepatitis, Angioedema, rash, urticaria,
  pruritus, Back pain, arthralgia, myalgia, Renal impairment, including renal failure in susceptible patients.
Hydrochlorothiazide:
Common: Hyperglycaemia, hyperuricaemia, electrolyte imbalance (including hyponatraemia and
  hypokalaemia), Light-headedness, vertigo, Glycosuria, Weakness, Increases in cholesterol and 
  triglycerides.
uncommon: Postural hypotension, Anorexia, loss of appetite, gastric irritation, diarrhoea, constipation, 
  Rash, urticaria, photosensitivity reactions, 
Rare: Leucopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anaemia, bone marrow
  depression, haemolytic anaemia, Anaphylactic reactions, Sleep disturbances, depression, restlessness, 
  Paraesthesia, Transient blurred vision, Cardiac arrhythmias, Necrotising angitis (vasculitis, cutaneous
  vasculitis), Respiratory distress (including pneumonitis and pulmonary oedema), Pancreatitis, Jaundice
  (intrahepatic cholestatic jaundice), Toxic epidermal necrolysis, cutaneous lupus erythematosus-like
  reactions, reactivation of cutaneous lupus erythematosus, Muscle spasm, Renal dysfunction and
  interstitial nephritis, Fever, Increases in BUN and serum creatinine.
  If you get any side effects, talk to your doctor, pharmacist or nurse. 
- This includes any side effects not listed in this leaflet. you can report side effect directly via the: 
  http\\www.modernpharmaye.com\adrs.pdf
  and send to us on: adrs@modernpharmaye.com

Overdose:
- The main Symptoms of an overdose of candesartan cilexetil is likely to be symptomatic hypotension
  and dizziness. 
- The main manifestation of an overdose of hydrochlorothiazide is acute loss of fluid and electrolytes.
  Symptoms such as dizziness, hypotension, thirst, tachycardia, ventricular arrhythmias sedation/ 
  impairment of consciousness and muscle cramps can also be observed.
- Induction of vomiting or gastric lavage should be considered.
 

- When Dwacand®-H is used in patients with impaired renal function, a periodic monitoring of  
  potassium, creatinine and uric acid levels is recommended. There is no experience regarding the
  administration of Dwacand®-H in patients with a recent kidney transplantation. 
- Dwacand®-H should be used with caution in patients with bilateral renal artery stenosis or stenosis of
  the artery to a solitary kidney becuase  candesartan cilexetile  may increase blood urea and serum
  creatinine .

- Dwacand®-H should be used with caution in patients with impaired hepatic function or progressive
  liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. 
- Risk of hypotension in patients with intravascular volume and/or sodium depletion.Therefore, the use of
  Dwacand®-H is not recommended until this condition has been correcte

- Dwacand®-H should be used with particular caution in patients suffering from aortic or mitral stenosis,
  or obstructive hypertrophic cardiomyopathy as with all vasodilators.
- Dwacand®-H is not recommended in  Patients with primary hyperaldosteronism, because patients they
  will not respond to antihypertensive drugs acting through inhibition of the renin-angiotensin-aldosterone
  system.

- Periodic determination of serum electrolytes should be performed at appropriate intervals. Thiazides,
  including hydrochlorothiazide, can cause fluid or electrolyte imbalance (hypercalcaemia, hypokalaemia,
  hyponatraemia, hypomagnesaemia and hypochloraemic alkalosis). 
- Concomitant use of Dwacand®-H with potassium-sparing diuretics, potassium supplements or salt
  substitutes or other drugs that may increase serum potassium levels (e.g. heparin sodium) may lead to
  increases in serum potassium. 
- Treatment with a thiazide diuretic may impair glucose tolerance. Dosage adjustment of antidiabetic  
  drugs, including insulin, may be required. Latent diabetes mellitus may become manifest during thiazide
  therapy

- Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy.  
  However, at the 12.5 mg dose contained in Dwacand®-H minimal or no effects were reported. 
-Thiazide diuretics increase serum uric acid concentration and may precipitate gout in susceptible 
  patients

- As with any antihypertensive agent, excessive blood pressure decrease in patients with ischaemic  


  heart disease or atherosclerotic cerebrovascular disease could result in a myocardial infarction or 
  stroke. Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a 
  history of allergy or bronchial asthma, but are more likely in patients with such a history.
  

- Dwacand®-H 16 / 12.5  : Blister of 10 tablets, pack of 2 blisters. 
- Dwacand®-H  8 / 12.5: Blister of 10 tablets, pack of 2 blisters

Store in a dry place at a temperature not exceeding 30 ºC.