Losartan Co 50 mg/100 mg/12.5 mg/25 mg Tablets

LOSARTAN CO AUSTELL is indicated for the treatment of hypertension in patients established on identical doses of the individual medicines.

Posology
Adults: The usual starting dose of LOSARTAN CO AUSTELL 50/12,5 is one tablet daily. The maximum dose is one tablet of LOSARTAN CO AUSTELL 100/25 (100 mg losartan potassium and 25 mg hydrochlorothiazide) once daily. For patients who do not respond adequately to LOSARTAN CO AUSTELL 50/12,5 the dosage may be increased to one LOSARTAN CO AUSTELL 100/25 tablet once daily. LOSARTAN CO AUSTELL 100/12,5 is available for those patients titrated to 100 mg of LOSARTAN who require additional blood pressure control. No initial dosage adjustment is required in elderly patients. The maximum antihypertensive effect is attained within three weeks after initiation of therapy.
Method of administration
For oral use. LOSARTAN CO AUSTELL may be administered with or without food.

• Hypersensitivity to the losartan potassium, hydrochlorothiazide or to any of the excipients listed in section 6.1
• 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
• Porphyria
• Thiazide diuretics in (fixed dose) combination as with LOSARTAN CO AUSTELL, should not be given to patients with Addison's disease. This therapy is also contraindicated in patients with severe renal impairment or anuria, and in patients who show hypersensitivity to other sulphonamide-derived medicine
• Lithium therapy: Concomitant administration with LOSARTAN CO AUSTELL may lead to toxic blood concentrations of lithium
• Pregnancy and lactation (see section 4.6)
• Hepatic impairment
• Therapy resistant hypokalaemia or hypercalcaemia
• Severe hepatic impairment; cholestasis and biliary obstructive disorders
• Refractory hyponatraemia
• Symptomatic hyperuricaemia/gout
• The concomitant use of LOSARTAN CO AUSTELL with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1,73 m2) (see sections 4.5 and 5.1)

Should a woman become pregnant while receiving LOSARTAN CO AUSTELL, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine (see below and sections 4.3 and 4.6).
Losartan
Angioedema: Patients with a history of angioedema (swelling of the face, lips, throat, and/or tongue) should be closely monitored (see section 4.8).
Hypotension and Intravascular volume depletion
Symptomatic hypotension, especially after the first dose, may occur in patients who are volume- and/or sodium-depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of LOSARTAN CO AUSTELL tablets (see sections 4.2 and 4.3).
Electrolyte imbalances
Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed. Therefore, the plasma concentrations of potassium and creatinine clearance values should be closely monitored; especially patients with heart failure and a creatinine clearance between 30 - 50 mL/min should be closely monitored.
The concomitant use of potassium-sparing diuretics, potassium supplements, potassium containing salt substitutes, or other medicines that may increase serum potassium (e.g., trimethoprim- containing products) with losartan/hydrochlorothiazide is not recommended (see section 4.5).

Losartan potassium
Rifampicin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated. Concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, 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. Concomitant use is not advisable. Lithium excretion may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be co-administered with angiotensin II receptor antagonists. When angiotensin II antagonists are administered simultaneously with NSAIDs (i.e. selective COX-2 inhibitors, acetylsalicylic acid at anti-inflammatory doses and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. Concomitant use of angiotensin II antagonists or diuretics and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. The 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. In some patients with compromised renal function who are being treated with non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists may result in a further deterioration of renal function. These effects are usually reversible.
Clinical trial data have 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 sections 4.3, 4.4, and 5.1).

Women of childbearing potential / contraception in males and females
Women of childbearing age should ensure adequate barrier contraception.
Pregnancy
LOSARTAN CO AUSTELL is contraindicated for use during pregnancy (see section 4.3). When pregnancy is planned or confirmed, LOSARTAN CO AUSTELL should be discontinued. Medicines affecting the renin-angiotensin system, such as LOSARTAN CO AUSTELL, 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 LOSARTAN CO AUSTELL should not breastfeed their infants (see section 4.3).
Fertility
No data on effects of LOSARTAN CO AUSTELL on fertility has been established.

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 occasionally occur when taking antihypertensive therapy, in particular during initiation of treatment or when the dose is increased.

b) Tabulated list of adverse reactions
The tables below show all adverse drug reactions (ADRs) observed during clinical trials and post-market spontaneous reports.
Frequency estimate: Frequent, Less frequent, Not known (cannot be estimated from the available data).

No specific information is available on the treatment of overdose with LOSARTAN CO AUSTELL. Treatment is symptomatic and supportive. Therapy with LOSARTAN CO AUSTELL should be discontinued and the patient observed closely. Suggested measures include induction of emesis if ingestion is recent, and correction of dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. Losartan potassium
Limited data are available in regard to overdose in humans. The most likely manifestation of overdose 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, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalaemia may accentuate cardiac dysrhythmias. The degree to which hydrochlorothiazide is removed by haemodialysis has not been established.