INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ABECARD 8TM (tablets)
ABECARD 16TM (tablets)
ABECARD 32TM (tablets)

SCHEDULING STATUS
S3

PROPRIETARY NAMES
(and dosage form)

ABECARD 8TM (tablets)
ABECARD 16
TM (tablets)
ABECARD 32
TM (tablets)

COMPOSITION
ABECARD 8
: Each tablet contains 8 mg
candesartan cilexetil
ABECARD 16: Each tablet contains 16 mg candesartan cilexetil
ABECARD 32: Each tablet contains 32 mg candesartan cilexetil
Contains sugar (lactose monohydrate).
The other ingredients are: croscarmellose sodium, hydroxypropylcellulose, magnesium stearate, maize starch, triethyl citrate.

PHARMACOLOGICAL CLASSIFICATION
A 7.1.3 Other hypotensives

PHARMACOLOGICAL ACTION
Pharmacodynamic properties
Candesartan is a nonpeptide angiotensin II receptor antagonist that selectively blocks the binding of angiotensin II to the AT1 receptors. Angiotensin II stimulates the adrenal cortex to synthesise and secrete aldosterone, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. By blocking the binding of angiotensin II to the AT1 receptors, candesartan causes vasodilation and decreases the effects of aldosterone. The antagonism of the AT1 receptors results in dose-related increases in plasma renin levels, angiotensin I and II levels, and a decrease in plasma aldosterone concentration.
Hypertension
Antihypertensive action is caused by the decreased systemic peripheral resistance. The heart-rate, stroke volume and cardiac output will not be affected by candesartan. Candesartan increases renal blood flow and either has no effect on, or increases glomerular filtration rate while renal vascular resistance and filtration fractions are reduced.
Heart failure
Candesartan decreases pulmonary capillary wedge pressure, systemic vascular resistance and aldosterone levels. Candesartan increases plasma renin activity and angiotensin II concentration.
Pharmacokinetic properties
Absorption and distribution
Candesartan cilexetil is an inactive ester prodrug that is completely hydrolysed to the active form, candesartan, during absorption from the gastrointestinal tract. Peak plasma levels are obtained 3 to 4 hours after oral administration. Candesartan is not affected by food. Candesartan is highly plasma-protein bound (more than 99%). The volume of distribution of candesartan is 0,1 litres/kg. The candesartan serum concentration increases linearly with increasing doses in the therapeutic dose range.
Metabolism and elimination
The terminal elimination half-life is approximately 9 hours.
Elimination after oral administration: Renal –33%; Faecal –67%
Candesartan is not removable by haemodialysis.
Elimination of candesartan is primarily as unchanged substance in the urine and, by the biliary route, in the faeces. Minor hepatic metabolism of candesartan occurs by O-deethylation to form an inactive metabolite.
Plasma clearance is about 0,37 mL/min per kg. Renal clearance is 0,19 mL/min per kg.
Pharmacokinetics in special populations
Elderly patients (65 years and older)
In elderly patients the Cmax and AUC of candesartan are respectively increased by approximately 50% and 80%, compared with young adults.
Renal impairment
In patients with mild (creatinine clearance 60-90 mL/min), moderate (creatinine clearance 30-60 mL/min) and severe (creatinine clearance 15-30 mL/min) renal impairment, the Cmax and AUC of candesartan increased during repeated dosing. In patients with severe renal impairment both the t
1/2 and AUC of candesartan were approximately double those of persons with normal renal function. No information is available on patients with more severe renal failure, i.e. creatinine clearance below 15 mL/min.
Hepatic impairment
A significant increase in the mean AUC of candesartan of respectively 30% and 145% was observed in patients with mild hepatic impairment and patients with moderate to severe hepatic impairment. No data are available on patients with cholestasis or severe hepatic impairment.

INDICATIONS
ABECARD
is indicated for mild to moderate hypertension. It may either be given as monotherapy, or for enhanced efficacy, in combination with other antihypertensive agents such as thiazide diuretics and dihydropyridine calcium antagonists.
Heart failure: Treatment with ABECARD can reduce mortality, reduce hospitalisation due to heart failure and improve symptoms in patients with impaired left ventricular systolic function (LVEF < 40%).

CONTRA-INDICATIONS
Hypersensitivity to any of the components of ABECARD.
A history of angioedema related to previous therapy with ACE-inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines.
Hereditary or idiopathic angioedema.
Hypertrophic obstructive cardiomyopathy (HOCM).
Severe renal function impairment (creatinine clearance less than 30 mL/min).
Bilateral renal artery stenosis.
Renal artery stenosis in patients with a single kidney.
Aortic stenosis.
Concomitant therapy with potassium-sparing diuretics such as spironolactone, triamterene, amiloride (see INTERACTIONS).
Porphyria.
Lithium therapy: Concomitant administration with ABECARD may lead to toxic blood concentrations of lithium.
Pregnancy and lactation (see PREGNANCY AND LACTATION).
Safety and efficacy have not been established in children.

WARNINGS AND SPECIAL PRECAUTIONS
Warnings: Should a woman become pregnant while taking ABECARD, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine(see CONTRA-INDICATIONS and PREGNANCY AND LACTATION).
Special precautions:
General
Treatment with medicines that affect the renin-angiotensin-aldosterone system has been associated with acute hypotension, uraemia, oliguria or acute renal failure in patients whose vascular tone and renal function mainly depend on the activity of this system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis).
Excessive blood pressure decrease in patients with ischaemic heart disease or ischaemic cerebrovascular disease could result in myocardial infarction or stroke.
Hypotension
Hypotension may occur during treatment with ABECARD in heart failure patients and in hypertensive patients with intravascular volume depletion. Caution should be observed when initiating therapy and correction of hypovolaemia should be attempted; a lower dose may also be required (see DOSAGE AND DIRECTIONS FOR USE).
Renal artery stenosis
Increases in serum creatinine or blood urea have occurred in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney (see CONTRA-INDICATIONS).
Renal impairment
Changes in renal function may be anticipated in susceptible patients treated with ABECARD. Periodic monitoring of serum potassium and creatinine levels is recommended in hypertensive patients with renal impairment.
Monitoring of patients with heart failure should include periodic assessments of renal function, especially in elderly patients and patients with impaired renal function. During dose titration of ABECARD, monitoring of serum creatinine and potassium is recommended.
There is no experience regarding the administration of ABECARD in patients with a recent kidney transplant.
Hepatic impairment
For patients with moderate hepatic impairment, consideration should be given to initiation of ABECARD at a lower dose. No initial dosage adjustment is necessary in patients with mild hepatic impairment (see DOSAGE AND DIRECTIONS FOR USE). No information is available on the use of ABECARD in patients with severe hepatic function impairment.
Hyperkalaemia
The concurrent use of ABECARD with potassium-sparing diuretics, salt substitutes, potassium supplements or any medicine that may increase potassium in patients, may lead to increases in serum potassium in hypertensive patients.
Since hyperkalaemia may occur, serum potassium concentrations should be monitored in patients with heart failure.
Concomitant administration with ACE-inhibitors or a potassium-sparing diuretic is not recommended (see CONTRAINDICATIONS and INTERACTIONS).
Heart failure
Caution should be observed when initiating ABECARD in heart failure patients; these patients commonly have some reduction in blood pressure when given ABECARD and may require a temporary reduction in dose and/or diuretic and volume repletion.
Anaesthesia and surgery
Due to blockade of the renin-angiotensin system patients may experience hypotension during anaesthesia and surgery when receiving ABECARD. In case of severe hypotension it may be necessary to administer intravenous fluids and/or vasopressors.
Lactose
ABECARD
contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take ABECARD.
Effects on ability to drive and use machines
The effect of ABECARD on the ability to drive and use machines has not been studied. When driving vehicles or operating machines, it should be taken into account that dizziness or weakness may occur during treatment.

INTERACTIONS
Combinations containing any of the following medications, depending on the amount present, may also interact with ABECARD:
Other antihypertensives. The antihypertensive effect of ABECARD may be enhanced.
Potassium-sparing diuretics such as spironolactone, potassium supplements and salt substitutes containing potassium may increase potassium levels. In heart failure patients treated with ABECARD, hyperkalaemia may occur especially when taken concomitantly with these medicines (see CONTRA-INDICATIONS).
Diuretics. Concurrent use with ABECARD may have additive hypotensive effects.
Lithium. Serum lithium level increases and toxicity have been reported with concomitant use (see CONTRA-INDICATIONS).

PREGNANCY AND LACTATION
Pregnancy
(see CONTRA-INDICATIONS)
Safety in pregnancy and lactation has not been established (see CONTRA-INDICATIONS). When pregnancy is planned or confirmed ABECARD should be discontinued. Medicines affecting the renin-angiotensin system, such as ABECARD, can cause embryonic toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women.
Women of childbearing age should ensure effective contraception.
Lactation
It is not known whether ABECARD is distributed into human breast milk. ABECARD is distributed into the milk of lactating rats.
Because of the potential for adverse effects on the nursing infant, breastfeeding should be discontinued if the use of ABECARD is considered essential.

DOSAGE AND DIRECTIONS FOR USE
Dosage in hypertension
The recommended initial dose of ABECARD is 8 mg once daily.
The usual maintenance dose is 8 to 16 mg once daily.
The maximum antihypertensive effect is attained within 4 weeks.
In some patients whose blood pressure is not adequately controlled, the dose can be increased to a maximum of 32 mg once daily.
Concomitant therapy
ABECARD
may be used as monotherapy or if necessary, concomitantly with other antihypertensive agents, such as thiazide diuretics and dihydropyridine calcium antagonists, e.g. amlodipine.
Special patient populations:
Use in elderly (65 years and older)
No initial dosage adjustment is required for elderly patients with normal renal and hepatic function.
Use in children
The safety and efficacy of ABECARD have not been established in children.
Use in impaired renal function
No initial dose adjustment is necessary for patients with mild to moderate renal impairment (i.e. creatinine clearance >30 mL/min per 1,73 m2 BSA). ABECARD is contra-indicated in patients with severe renal impairment (<15-30 mL/min per 1,73 m2 BSA).
Use in hepatic impairment
No initial dosage adjustment is required in patients with mild to moderate hepatic impairment (see WARNINGS AND SPECIAL PRECAUTIONS).
There is no experience available in patients with severe hepatic impairment and/or cholestasis (see CONTRA-INDICATIONS).
Use in black patients
The antihypertensive effect of ABECARD may be less in black than non-black (Caucasian, Asian and other) patients.
Consequently, up-titration of ABECARD and concomitant therapy (such as thiazide diuretics) may be more frequently needed for blood pressure control in black than non-black patients.
Dosage in heart failure
The usual recommended initial dose of ABECARD is 4 mg once daily with a target dose of 32 mg once daily. This is achieved by doubling the dose at approximately 2 week intervals, as tolerated by the patient (see WARNINGS AND SPECIAL PRECAUTIONS).
Concomitant therapy
ABECARD
may be given concomitantly with other cardiac failure treatment, such as ACE-inhibitors, beta-blockers, diuretics and digitalis or a combination of these medicinal products.
Special patient populations
Elderly (65 years or older)
No initial dose adjustment is necessary for elderly patients with normal renal and hepatic function.
Children
The safety and efficacy of ABECARD have not been established in children.
Directions for use
ABECARD
may be taken with or without food.

SIDE EFFECTS
The following side effects may occur
Infections and infestations
Frequent:Respiratory infections.
Blood and lymphatic system disorders
Less frequent:Leukopenia, neutropenia, agranulocytosis, thrombocytopenia.
Immune system disorders
Less frequent:Angioedema.
Metabolism and nutrition disorders
Frequent:Hyperkalaemia.
Less frequent:Hyponatraemia.
Nervous system disorders
Frequent:Headache, dizziness/vertigo.
Cardiac disorders
Less frequent:Angina pectoris, myocardial infarction.
Vascular disorders
Frequent:Hypotension.
Respiratory, thoracic and mediastinal disorders
Less frequent:Pharyngitis, rhinitis, upper respiratory tract infection, and cough.
Gastrointestinal disorders
Less frequent:Nausea.
Hepato-biliary disorders
Less frequent:Abnormal hepatic function, increased liver enzymes, hepatitis.
Skin and subcutaneous tissue disorders
Less frequent:Urticaria, pruritus, rash.
Musculoskeletal and connective tissue disorders
Less frequent:Hyperuricaemia or gout, back pain, myalgia, arthralgia.
Renal and urinary disorders
Frequent:Impaired renal function.
Less frequent:Renal failure in susceptible patients (see WARNINGS AND SPECIAL PRECAUTIONS).
Investigations
Less frequent:Increases in creatinine, urea and potassium. Decreases in haemoglobin and hematocrit values.
Raised liver enzyme values.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
The symptoms of an overdosage of ABECARD would be dizziness, hypotension and tachycardia. Bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.
ABECARD can NOT be removed by haemodialysis.

IDENTIFICATION
ABECARD 8
: Round, biconvex, approximately 8  mm in diameter, white to off-white tablets with a breaking notch on one side and embossed on the same side with “C8”.
ABECARD 16: Round, biconvex, approximately 8 mm in diameter, white to off-white tablets with a breaking notch on one side and embossed on the same side with “C16”.
ABECARD 32: Round, biconvex, approximately 10,5 mm in diameter, white to off-white tablets with a breaking notch on one side and embossed on the same side with “C32”.

PRESENTATION
Packs of 28 or 30 tablets packed in transparent PVC/PVDC/Aluminium blisters in a cardboard carton.

STORAGE INSTRUCTIONS
Store in the original packaging (blisters in the carton) at or below 25ºC.
KEEP MEDICINE OUT OF THE REACH OF CHILDREN.

REGISTRATION NUMBERS
ABECARD 8
: 46/7.1.3/0231;
ABECARD 16: 46/7.1.3/0232;
ABECARD 32: 46/7.1.3/0233

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATES OF REGISTRATION
Lasara Traders (Pty) Ltd
Suite C, Rubenstein Ridge, 617 Rubenstein Drive, Moreleta Park, 0181

MARKETED BY
Forrester Pharma (Pty) Ltd
13 Pasita Street, Rosen Heights, Rosen Park, Bellville, 7530

DATE OF PUBLICATION OF THIS PACKAGE INSERT
11 June 2015

New addition to this site: November 2016
Source: Pharmaceutical Industry

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