INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
ZARTAN 50 mg film coated tablets
ZARTAN 100 mg film coated tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

ZARTAN 50 mg film coated tablets
ZARTAN 100 mg film coated tablets

COMPOSITION:
Each ZARTAN 50 mg film coatedtabletcontains 50 mg losartan potassium
Each ZARTAN 100 mg film coated tablet contains 100 mg losartan potassium

PHARMACOLOGICAL CLASSIFICATION:
A7.1.3 Other hypotensives

PHARMACOLOGICAL ACTION:
Losartan is a nonpeptide angiotensin II receptor antagonist with high affinity and selectivity for the AT1 receptor, without binding to or blocking other hormone receptors or ion channels important in cardiovascular regulation. Angiotensin II is a potent vasoconstrictor, a primary active hormone of the renin-angiotensin system and a major determinant of the pathophysiology of hypertension. Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by inhibiting the binding of angiotensin II to the AT1 receptor.
Pharmacokinetics:
Following oral administration, bioavailability is approximately 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite (which has greater pharmacological activity than losartan) and some inactive metabolites. About 14% of intravenously or orally administered dose is converted to its active metabolite. The mean peak concentrations of losartan and its active metabolite are reached in 1 hour and 3 - 4 hours respectively.
Both losartan and carboxylic acid metabolite are greater than, or equal to 99% bound to plasma proteins. The distribution volume of losartan is 34 litres.
The terminal half-life of losartan is 2 hours and its active metabolite is 6-9 hours.
Losartan is excreted in the urine, and in the faeces, as unchanged drug and metabolites. Following oral dosing, about 35% of the dose is excreted in the urine and about 60% in the faeces. Neither losartan nor the active metabolite can be removed by haemodialysis.
Plasma concentrations of losartan are not altered in patients with impaired renal function and a creatinine clearance above 10 mL/min. Compared to patients with normal renal function, the AUC for losartan is approximately 2-fold greater in patients on haemodialysis.
Pharmacodynamics:
Losartan is a specific antagonist of the angiotensin II receptor type AT1; it does not inhibit ACE (kininase II), the enzyme that degrades bradykinin. Removal of angiotensin II negative feed back on renin secretion leads to increased plasma renin activity, during losartan administration. A 2 to 3-fold increase in angiotensin II in plasma comes as a result of increases in plasma renin activity. However, antihypertensive activity and suppression of plasma aldosterone concentration are apparent, indicating effective angiotensin II receptor blockade. After discontinuation of losartan, plasma renin activity and angiotensin levels declined.

INDICATIONS:
ZARTAN is indicated for the treatment of hypertension.

CONTRA-INDICATIONS:
Patients who are hypersensitive to any component of this product.
The use of ZARTAN during pregnancy and lactation is contra-indicated (see “PREGNANCY AND LACTATION”). ZARTAN should be discontinued as soon as possible, when pregnancy is suspected.
Safety and efficacy has not been established in children.

WARNINGS:
Women of childbearing age should ensure adequate contraception.
ZARTAN is contra-indicated in pregnancy and should be used with care, if at all, during breast-feeding.
ZARTAN should be used with caution in patients with bilateral renal artery stenosis or stenosis of an artery to a single kidney, aortic valve stenosis, and hypertrophic obstructive cardiomyopathy.
Symptomatic hypotension may occur after initiation of ZARTAN.
Reduced doses must be considered in patients with hepatic impairment.

INTERACTIONS:
Combinations containing any of the following medications, depending on the amount present, may also interact with ZARTAN:

•	Non-steroidal anti-inflammatory drugs (NSAIDs) may antagonise the antihypertensive effect of ZARTAN.
•	Concurrent use with sympathomimetics may reduce the antihypertensive effects of ZARTAN.
•	Potassium-sparing diuretics, potassium containing medication or potassium supplements used concurrently with ZARTAN may result in hyperkalemia since reduction of aldosterone production induced by ZARTAN may lead to elevation of serum potassium.

PREGNANCY AND LACTATION:
Pregnancy: (see “CONTRA-INDICATIONS”)

•	ZARTAN should be discontinued as soon as possible, when pregnancy is suspected.
•	ZARTAN should not to be used in pregnancy as teratogenicity has been shown in experimental animals.

Lactation:

•	Safety has not been established.

DOSAGE AND DIRECTIONS FOR USE:
The usual starting and maintenance dose is 50 mg once daily for most patients. The maximum antihypertensive effect is achieved 3 - 6 weeks after initiation of therapy. The dose may be increase to 100 mg once daily.
For patients with intravascular volume-depletion (e.g. those treated with high-dose diuretics), a starting dose of 25 mg once daily should be considered (see “SPECIAL PRECAUTIONS”).
No initial dosage adjustment is necessary for the elderly patients or for patients with renal impairment, including patients on dialysis. A lower dose should be considered for patients with a history of hepatic impairment (see “SPECIAL PRECAUTIONS”).
ZARTAN may be administered with other antihypertensive agents of a different class.
ZARTAN may be administered with or without food.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-Effects:
The following side-effects may occur:
Hypersensitivity:
The following side effects have been reported and frequencies are unknown: Angioedema (involving swelling of the face, lips, and/or tongue) has been reported in patients treated with ZARTAN.
Gastrointestinal:
Less Frequent: Diarrhoea, dyspepsia, nausea
Buccal:
Less Frequent: Taste disturbances, complete taste loss
Skin:
Less Frequent: Urticaria, rash, atypical cutaneous lymphoid infiltrates
Cardiovascular:
Less Frequent: Palpitation, tachycardia
The following side effects have been reported and frequencies are unknown: Hypotension
Musculoskeletal:
Less Frequent: Back pain, muscle cramps, leg pain
The following side effects have been reported and frequencies are unknown: Myalgia
Nervous/Psychiatric:
Frequent: Headache
Less Frequent: Dizziness, insomnia, migraine
Respiratory:
Less Frequent: Cough, nasal congestion, pharyngitis, sinus disorder, upper respiratory infection
Hepatic:
Less Frequent: Raised liver enzymes values, severe acute hepatotoxicity,
The following side effects have been reported and frequencies are unknown: Cholestasis
Haematological:
Less Frequent: Symptomatic anaemia, decreased haemoglobin concentrations
The following side effects have been reported and frequencies are unknown: Neutropenia
Pancreatic:
Less Frequent:        Acute pancreatitis
Body as a Whole:
Less Frequent: Abdominal pain, asthenia/fatigue, chest pain, fatigue and oedema/swelling
Renal:
The following side effects have been reported and frequencies are unknown: Impaired renal function

Special Precautions:
Patients with volume-depletion (e.g. those treated with high-dose diuretics) may experience hypotension, which may be minimised by initiating treatment with a low dose of ZARTAN. Halving of the dose should be considered for patients with a history of hepatic impairment (see “DOSAGE AND DIRECTIONS FOR USE”).
Since hyperkalemia may occur, serum-potassium concentrations should be monitored, especially in the elderly and patients with renal impairment and the concomitant use of potassium-sparing diuretics should generally be avoided (see “INTERACTIONS”).
When impaired renal function is present, changes in renal function as a consequence of inhibiting the renin-angiotensin system including renal failure have been reported in susceptible individuals. These changes in renal function may be reversible upon discontinuation of ZARTAN therapy, in some patients.
In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and (less frequently) with acute renal failure and/or death. Similar outcomes are likely with ZARTAN therapy.
Agents affecting the renin-angiotensin system may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. These changes in renal function may be reversible upon discontinuation of ZARTAN therapy.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
The symptoms of an overdosage of ZARTAN would be hypotension and tachycardia. Bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither ZARTAN nor the active metabolite can be removed by haemodialysis.

IDENTIFICATION:
ZARTAN 50 mg is a white, coated, round biconvex, scored tablet embossed “3L”10 mm tablet.
ZARTAN 100 mg is a white, coated, oval biconvex tablet embossed “4L”9,2 x 18,3 mm tablet.

PRESENTATION:
ZARTAN 50 and100 mg tablets are packed in PVC/PVDC/
Aluminium blister strips of 10 tablets. Three strips will be packed in an outer carton.

STORAGE INSTRUCTIONS:
Store in a dry place below 25ºC.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS:
ZARTAN 50 mg: 41/7.1.3/0287
ZARTAN 100 mg: 41/7.1.3/0289

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE:
Pharma Dynamics (Pty) Ltd.
F02 Grapevine House
Steenberg Office Park
Westlake
7945

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
10 August 2007

New addition to this site: March 2008
Source: Pharmaceutical Industry
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