Zartan FC tablets

ZARTAN is indicated for

• the treatment of hypertension
• renal protection in type 2 diabetic patients with hypertension and proteinuria.

Hypertension

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 increased to 100 mg once daily.

Renal protection in type 2 diabetic patients with hypertension and proteinuria

The usual starting dose is 50 mg once daily. The dose may be increased to 100 mg once daily based on blood pressure response. ZARTAN may be administered with other antihypertensive agents (e.g. diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting agents) as well as with insulin and other commonly used hypoglycaemic agents (e.g. sulfonylureas, glitazones and glucosidase inhibitors).

Special populations

Patients with intravascular volume-depletion

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 section 4.4).

Renal impairment

No initial dosage adjustment is necessary for the elderly patients or for patients with renal impairment, including patients on dialysis.

Hepatic impairment

A lower dose should be considered for patients with a history of hepatic impairment (see section 4.4).

Elderly

No dose adjustment is necessary in elderly patients.

Paediatric population

Safety and efficacy in children has not been established.

Method of administration

For oral use. ZARTAN may be administered with other antihypertensive medicines of a different class. ZARTAN may be administered with or without food.

Missed dose

Doctors should advise patients who forget to take ZARTAN to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

• Hypersensitivity to losartan potassium or to any of the ingredients of ZARTAN (see section 6.1).
• Concomitant use of fluoroquinolones with Angiotensin receptor blockers, such as ZARTAN, is contraindicated in patients with moderate to severe renal impairment (Creatinine Clearance u2264 30 mL/min) and in elderly patients.
• 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) or for patients with hepatic impairment.
• Bilateral renal artery stenosis.
• Renal artery stenosis in patients with a single kidney.
• Aortic stenosis, left ventricular outflow track obstruction.
• Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride (see section 4.5).
• Porphyria.
• Lithium therapy: Concomitant administration with ZARTAN may lead to toxic blood concentrations of lithium (see section 4.5).
• Pregnancy and lactation (see section 4.6).
• The concomitant use of ZARTAN with renin inhibitors, such as aliskiren-containing products, is contraindicated (see section 4.4).
• Paediatric use: The safety and efficacy in children has not been established.

Should a woman become pregnant while receiving ZARTAN, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine (see section 4.6).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers (ARBs) or renin inhibitors, such as aliskiren, may increase the risk of hypotension, hyperkalaemia and decreases renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ZARTAN and renin inhibitors such as aliskiren, is therefore contraindicated (see section 4.3). ZARTAN should not be used concomitantly with renin inhibitors such as aliskiren (see section 4.3).

Fluoroquinolones

Concomitant use of fluoroquinolones and ARBs, such as ZARTAN, may precipitate acute kidney injury in patients, especially those with moderate to severe renal impairment and elderly patients (see section 4.3). Renal function should be assessed before initiating treatment and monitored during treatment, with fluoroquinolones or ARBs, such as ZARTAN, whether used separately and/or concomitantly.

Volume depletion

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 section 4.2).

Electrolyte imbalance

Since hyperkalaemia 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 section 4.5).

Renal impairment

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.

Medicines 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.

Liver function impairment

Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, a dose of 25 mg should be considered for patients with a history of hepatic impairment (see section 4.2).

Porphyria

Limited information is available regarding the effect of antihypertensive medicines in patients with porphyria. Safety of losartan in patients with porphyria has not been fully established and is therefore contraindicated (see section 4.3).

Information on excipients of ZARTAN

ZARTAN contains mannitol and may have a laxative effect.

Dual blockade of the RAAS with ARBs, ACE inhibitors, or aliskiren

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or renin inhibitors such as aliskiren, is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (see sections 4.3 and 4.4).

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

Fluoroquinolones

Concomitant use of fluoroquinolones and ARBs, such as ZARTAN may precipitate acute kidney injury. The mechanism of the possible interaction between the different classes of medicines, over and above different mechanisms of kidney damage, is unknown (see section 4.3).

Non-steroidal anti-inflammatory drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs (NSAIDs) (selective COX-2 inhibitors, acetylsalicylic acid and at anti-inflammatory doses and non-selective NSAIDs) may antagonise the antihypertensive effect of ZARTAN. Concomitant use may lead to an increased risk of worsening renal function, including possible acute renal failure and an increase in serum potassium, especially in patients with poor pre-existing renal function. Combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically thereafter.

Sympathomimetics

Concurrent use with sympathomimetics may reduce the antihypertensive effects of ZARTAN.

Potassium

Potassium-sparing diuretics, potassium containing medicine or potassium supplements used concurrently with ZARTAN may result in hyperkalaemia since reduction of aldosterone production induced by ZARTAN may lead to elevation of serum potassium. Concomitant use with medicines which retain potassium (e.g. amiloride, triamterene, spironolactone) or increase potassium levels (e.g. heparin), and/or potassium salt substitutes containing potassium may lead to increases in serum potassium and co-medication is not advised.

Lithium

Concomitant administration of lithium with ZARTAN may increase serum lithium concentrations and toxicity. Co-administration should be with caution and serum lithium levels should be monitored.

In clinical pharmacokinetic trials, no interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Rifampin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated.

Women of childbearing potential / Contraception in males and females

Women of childbearing age should ensure effective contraception.

Pregnancy

Safety in pregnancy and lactation has not been established (see section 4.3). When pregnancy is planned or confirmed, ZARTAN should be discontinued. Medicines affecting the renin-angiotensin system, such as ZARTAN, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women.

Breastfeeding

It is not known whether losartan is excreted in human milk. Safety of breast feeding in mothers taking ZARTAN has not been established. However, significant levels of losartan and the active metabolite were shown to be present in rat milk (see section 4.3.).

Dizziness or drowsiness may occasionally occur when taking antihypertensive therapy, in particular during initiation of treatment or when the dose is increased. Patients should be advised to be cautious when driving vehicles or operating machinery or performing potentially hazardous tasks until they are reasonably certain that their performance is not affected by ZARTAN.

Summary of the safety profile

Tabulated summary of adverse reactions

System Organ Class

Frequency

Side effects

Infections and Infestations

Frequent

Upper respiratory tract infections

Blood and lymphatic system disorders

Less frequent

Frequency unknown

Symptomatic anaemia, decreased haemoglobin concentrations

Neutropenia, thrombocytopenia

Immune system disorders

Less frequent

Angioedema (involving swelling of the face, lips, and / or tongue), anaphylaxis, vasculitis

Endocrine disorders

Less frequent

Acute pancreatitis

Psychiatric disorders

Frequent

Insomnia

Nervous system disorders

Frequent

Less frequent

Headache, vertigo

Dizziness, migraine, dysgeusia

Cardiac disorders

Less frequent

Palpitations, tachycardia

Vascular disorders

Less frequent

Frequency unknown

Hypotension

Oedema /swelling, vasculitis, including Henoch-Schu00f6nlein purpura

Respiratory, thoracic and mediastinal disorders

Frequent

Cough, nasal congestion, pharyngitis, sinus disorder

Gastrointestinal disorders

Less frequent

Frequency unknown

Diarrhoea, dyspepsia, nausea, abdominal pain

Taste disturbances, complete taste loss, vomiting

Hepatobiliary disorders

Frequency unknown

Raised liver enzymes values, severe acute hepatotoxicity, cholestasis, hepatitis

Skin and subcutaneous tissue disorders

Less frequent

Frequency unknown

Urticaria, rash

Pruritus, erythroderma, photosensitivity, atypical cutaneous lymphoid infiltrates

Musculoskeletal, connective tissue and bone disorders

Less frequent

Frequency unknown

Back pain, muscle cramps, leg pain

Myalgia, arthralgia

Renal and urinary disorders

Frequency unknown

Impaired renal function

Reproductive system and breast disorders

Frequency unknown

Erectile dysfunction, impotence

General disorders and administrative site conditions

Frequent

Frequency unknown

Asthenia/fatigue, chest pain, oedema/swelling

Malaise*

Investigations

Frequent

Frequency unknown

Hyperkalaemia, elevations of alanine amino transferase (ALT), hyponatraemia

Liver function abnormalities

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the online service for adverse drug reaction reporting by following the link: https://www.sahpra.org.za/Publications/Index/8 .

An email can be sent directly to the company, [email protected], to ensure safety of the product.

Signs and symptoms:

The symptoms of an overdosage of ZARTAN would be hypotension and tachycardia. Bradycardia could occur from parasympathetic (vagal) stimulation.

Management of overdose:

If symptomatic hypotension should occur, supportive treatment should be instituted.