Fortzaar Tablet 100 mg. 25 mg Tablets

FORTZAAR is indicated for the treatment of hypertension in patients established on identical doses of the individual agents.

The maximum dose is one tablet of FORTZAAR (100 mg losartan potassium and 25 mg hydrochlorothiazide) once daily (see section 4.1). The maximum antihypertensive effect is usually attained within three weeks after initiation of therapy. Special populations FORTZAAR should not be initiated in patients who are intravascularly volume-depleted (e.g. those treated with high-dose diuretics). FORTZAAR is not recommended for patients with severe renal impairment or for patients with hepatic impairment (see section 4.3 and section 4.4). FORTZAAR should not be used as initial therapy in elderly patients. Paediatric population: N/A Method of administration FORTZAAR may be administered with other antihypertensive agents, such as calcium channel blockers and beta-blockers. FORTZAAR may be administered with or without food.

• Hypersensitivity to losartan, hydrochlorothiazide or any of the other ingredients of FORTZAAR.
• 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).
• Anuria.
• 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 or amiloride (see section 4.5).
• Porphyria.
• FORTZAAR should not be given to patients with Addison's disease.
• Hypersensitivity to sulphonamides or to other sulphonamide-derived medicines.
• Lithium therapy: Concomitant administration with FORTZAAR may lead to toxic blood concentrations of lithium (see section 4.5).
• Pregnancy and lactation (see section 4.6).
• Hepatic impairment.
• The concomitant use of FORTZAAR with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1,73 m2) (see sections 4.4 and 4.5).
• Concomitant use of fluoroquinolones with ACE inhibitors/Renin-Angiotensin receptor blockers is contraindicated in patients with moderate to severe renal impairment.
• Paediatric Use Safety and efficacy in children have not been established.

Should a woman become pregnant while receiving FORTZAAR, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine (see sections 4.3 and 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 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 ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended. Dual blockade of RAAS through the combined use of FORTZAAR and aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1,73 m2) (see section 4.3). If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

Hypotension and electrolyte/fluid imbalance In patients who are intravascularly volume-depleted (e.g. those treated with high-dose diuretics), symptomatic hypotension may occur. These conditions should be corrected prior to administration of FORTZAAR or a lower starting dose should be used (see section 4.2). Periodic determination of serum electrolytes must be performed at appropriate intervals.

Metabolic and endocrine effects Hydrochlorothiazide, a component of FORTZAAR, therapy may impair glucose tolerance. Dosage adjustment of antidiabetic medicines including insulin, may be required (see section 4.5).

Hydrochlorothiazide, a component of FORTZAAR, may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. FORTZAAR should be discontinued before carrying out tests for parathyroid function.

Increases in cholesterol and triglyceride levels may be associated with hydrochlorothiazide, a component of FORTZAAR, therapy. Hydrochlorothiazide, a component of FORTZAAR, therapy may precipitate hyperuricaemia and/or gout.

Concomitant use with Lithium Concomitant administration of lithium with FORTZAAR may lead to toxic blood concentrations of lithium (see section 4.5).

Hepatic and renal impairment FORTZAAR is not recommended for patients with hepatic impairment or severe renal impairment (see section 4.3 and section 4.2). As a consequence of inhibiting the renin-angiotensin system, changes in renal function including renal failure have been reported.

Concomitant use of fluoroquinolones and ACE inhibitors/Renin-Angiotensin receptor blockers 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 ACE inhibitors/Renin-Angiotensin receptor blockers.

FORTZAAR may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Similar effects have been reported with losartan (see section 4.3).

Increases in serum potassium Concomitant use of other medicines that may increase serum potassium may lead to hyperkalaemia (see section 4.5).

Other In patients receiving hydrochlorothiazide, a component of FORTZAAR, hypersensitivity reactions may occur with or without a history of allergy or bronchial asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of hydrochlorothiazide, as contained in FORTZAAR.

Non-Melanoma Skin Cancer An increased risk of non-melanoma skin cancer (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC] with increasing cumulative dose of hydrochlorothiazide has been observed in epidemiological studies. Photosensitising actions of hydrochlorothiazide could act as a possible mechanism for non-melanoma skin cancer. Patients taking hydrochlorothiazide should be informed of the risk of non-melanoma skin cancer and advised to take preventive measures to reduce sun and artificial UVA exposure. Patients should regularly check their skin for new lesions and promptly report suspicious skin lesions to their physicians for evaluation. The use of hydrochlorothiazide may also need to be reconsidered in patients who have experienced previous non-melanoma skin cancer (see also section 4.8).

Lactose FORTZAAR contains lactose. Patients with rare hereditary problems of galactose intolerance, e.g. galactosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption should not take FORTZAAR.

Losartan potassium In clinical pharmacokinetic trials no interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital (see hydrochlorothiazide, alcohol, barbiturates or narcotics below) ketoconazole and erythromycin. Rifampicin and fluconazole have been reported to reduce levels of the active metabolite of FORTZAAR. The clinical consequences of these interactions have not been evaluated.

Concomitant use of medicines that block angiotensin II or its effects and potassium-sparing diuretics (e.g. spironolactone, triamterene and amiloride), potassium supplements, salt substitutes containing potassium or other medicines that may increase serum potassium (e.g. trimethoprim-containing products) may lead to increases in serum potassium. Lithium excretion may be reduced. Therefore, serum lithium levels should be monitored carefully, if lithium salts are co-administered with FORTZAAR.

Non-steroidal anti-inflammatory medicines (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of FORTZAAR. In patients with compromised renal function (e.g. elderly patients or patients who are volume-depleted including those on diuretic therapy) being treated with non-steroidal anti-inflammatory drugs (NSAIDs), the co-administration of FORTZAAR may result in a further deterioration of renal function, including possible acute renal failure. Therefore, the combination should be administered with caution in patients with compromised renal function.

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 aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see section 4.3 and section 4.4).

Concomitant use of fluoroquinolones and ACE inhibitors/Renin-Angiotensin receptor blockers may precipitate acute kidney injury (see section 4.3).

Hydrochlorothiazide (HCTZ) When administered concurrently, the following medicines may interact with HCTZ diuretics: Alcohol, barbiturates or narcotics: potentiation of orthostatic hypotension may occur. Antidiabetic medication (oral agents and insulin): dosage adjustment of the antidiabetic medicine may be required. Other antihypertensive medication: additive effect or potentiation. Cholestyramine and colestipol resins: absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 %, respectively. FORTZAAR should therefore be administered one hour before the intake of the resin. Corticosteroids, ACTH or glycyrrhizin (found in liquorice): intensified electrolyte depletion, particularly hypokalaemia. Pressor amines (e.g. norepinephrine): possible decreased response to pressor amines but not sufficient to preclude their use. Skeletal muscle relaxants: response to non-depolarising agents may be increased. Lithium: should not be given with FORTZAAR. Diuretic medicines reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with FORTZAAR (see section 4.3). Non-steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 Inhibitors: the administration of these medicines can reduce the diuretic, natriuretic and antihypertensive effects of FORTZAAR.

Women of childbearing potential/Contraception in males and females Women of childbearing age should ensure effective contraception while on FORTZAAR.

Pregnancy FORTZAAR is contraindicated for use during pregnancy (see section 4.3). When pregnancy is planned or confirmed, FORTZAAR should be discontinued. Medicines affecting the renin-angiotensin system, such as FORTZAAR, can cause foetal and neonatal morbidity and mortality when administered to pregnant women.

Breastfeeding Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. Women taking FORTZAAR should not breastfeed their infants (see section 4.3).

Fertility N/A

No studies on the reactions on the ability to drive and use machines have been performed. However, when driving vehicles or operating machinery it must be borne in mind that dizziness or drowsiness may occur when taking antihypertensive therapy, in particular during initiation of treatment or when the dose is increased.

Adverse reactions from clinical trials In controlled clinical trials for essential hypertension, the following adverse experiences were reported in patients treated with FORTZAAR and are shown in decreasing order of frequency within body system: Very common ( u2265 1/10), common ( u2265 1/100, < 1/10), uncommon ( u2265 1/1 000, < 1/100) and rare ( u2265 1/10 000, < 1/1 000) Nervous system disorders Common: dizziness General disorders and administration site conditions Common: asthenia/fatigue.

Losartan In controlled clinical trials for essential hypertension, the following adverse experiences were reported in patients treated with losartan potassium and are shown in decreasing order of frequency within body system: Very common ( u2265 1/10), common ( u2265 1/100, < 1/10), uncommon ( u2265 1/1 000, < 1/100) and rare ( u2265 1/10 000, < 1/1 000) Infections and infestations Common: upper respiratory infection Psychiatric disorders Common: insomnia Nervous system disorders Very common: headache Common: dizziness Cardiac disorders Common: palpitation, tachycardia Vascular disorders Uncommon: orthostatic hypotension Respiratory, thoracic and mediastinal disorders Common: cough, pharyngitis, nasal congestion, sinus disorder Gastrointestinal disorders Common: diarrhoea, nausea, abdominal pain, dyspepsia Skin and subcutaneous tissue disorders Uncommon: rash Musculoskeletal, connective tissue and bone disorders Common: back pain, muscle cramps General disorders and administration site conditions Common: asthenia/fatigue, oedema/swelling, chest pain Investigations Common: hyperkalaemia, elevations of ALT.

Hydrochlorothiazide In controlled clinical trials for essential hypertension, the following adverse experiences were reported in patients treated with hydrochlorothiazide and are shown in decreasing order of frequency within body system: Events are classified within body system categories and enumerated in order of decreasing frequency using the following definitions: Common: ( u2265 1/100, < 1/10), uncommon; ( u2265 1/1 000, < 1/100), rare: ( u2265 1/10 000, 1/10 000, including isolated reports) Blood and the lymphatic system disorders Rare: thrombocytopenia Very rare: leukopenia; agranulocytosis; haemolytic anaemia Metabolic and nutrition disorders Uncommon: anorexia; hyperuricaemia Rare: hyperglycaemia Nervous system disorders Rare: paraesthesia; headache Vascular disorders Uncommon: hypotension, (including orthostatic hypotension) Respiratory, thoracic and mediastinal disorders Very rare: respiratory distress including pneumonitis and pulmonary oedema Gastrointestinal disorders Uncommon: nausea; vomiting Rare: diarrhoea; constipation Very rare: pancreatitis Hepatobiliary disorders Rare: jaundice (intrahepatic cholestatic jaundice) Skin and subcutaneous tissue disorders Uncommon: rash; urticaria Rare: photosensitivity Very rare: necrotising angiitis (vasculitis and cutaneous vasculitis) Renal and urinary disorders Rare: glycosuria. The following clinical trials side effects have been reported with the use of either losartan or hydrochlorothiazide, but the frequencies are unknown: Infections and infestations Sialadenitis Blood and the lymphatic system disorders Aplastic anaemia Metabolic and nutrition disorders Electrolyte imbalance including hyponatraemia and hypokalaemia Psychiatric disorders Restlessness Eye disorders Xanthopsia, transient blurred vision Ear and labyrinth disorders Vertigo Vascular disorders Hypotension and/or postural hypotension Gastrointestinal disorders Gastric irritation Skin and subcutaneous tissue disorders Purpura Musculoskeletal, connective tissue and bone disorders Cramping, muscle spasm Renal and urinary disorders Renal dysfunction, interstitial nephritis, renal failure General disorders and administration site conditions Fever, weakness. Post-marketing experience Adverse reactions from spontaneous reporting The following adverse reactions have been reported in post-marketing experience; they are derived from spontaneous reports for which precise incidences cannot be determined therefore, the frequency is unknown: Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Non-melanoma skin cancer (basal cell carcinoma, squamous cell carcinoma).

Losartan potassium The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor the active metabolite can be removed by haemodialysis.

Hydrochlorothiazide The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis. If digoxin has also been administered, hypokalaemia may accentuate cardiac dysrhythmias. The degree to which hydrochlorothiazide is removed by haemodialysis has not been established.