Azisan Plus 40/12.5 Tablet

Azisan Plus 40/12.5 Tablet is used for: Hypertension, Treatment of hypertension in patients not adequately controlled with monotherapy or as initial therapy in patients likely to need multiple drugs to help achieve blood pressure goals

Adult Oral Hypertension 1 tab (40 mg/12.5 mg) once daily. May increase to 40 mg/25 mg after 2-4 weeks as needed to achieve blood pressure goals; not to exceed 40 mg/25 mg daily Switching from ARB or diuretic monotherapy: Initiate with 40 mg/12.5 mg PO qDay

Safety and efficacy not established

Renal impairment Mild-to-moderate (eGFR 30 mL/min/1.73 sq.meter or greater): No dose adjustment required Severe (eGFR <30 mL/min/1.73 sq.meter): Safety and effectiveness not established Chlorthalidone may precipitate azotemia

May be taken with or without food.

Hypersensitivity. Patient w/ anuria. Concomitant use w/ aliskiren in patients w/ diabetes. Pregnancy.

Hyperuricemia Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone or other thiazide diuretics Fetal toxicity When pregnancy is detected, discontinue as soon as possible; drugs affecting renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death Thiazides cross the placental barrier and appear in cord blood; adverse reactions include fetal or neonatal jaundice and thrombocytopenia Hypotension in volume or salt depleted patients In patients with an activated renin-angiotensin system, symptomatic hypotension may occur after initiation of treatment; such patients are probably not good candidates to start therapy with more than one drug Electrolytes Hypokalemia is a dose-dependent adverse reaction that may develop with chlorthalidone; Edarbyclor attenuates chlorthalidone-associated hypokalemia Coadministration of digitalis may exacerbate adverse effects of hypokalemia Thiazide diuretics can cause hyponatremia and hypokalemia; drugs that inhibit the renin angiotensin system can cause hyperkalemia; monitor serum electrolytes periodically Monitoring Parameters Monitor renal function in patients with renal impairment. Consider discontinuing Edarbyclor with progressive renal impairment Monitor serum electrolytes periodically

Pregnancy Drug can cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death; most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in first trimester have not distinguished drugs affecting renin-angiotensin system from other antihypertensive agents; when pregnancy is detected, discontinue drug as soon as possible Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean section and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly Oligohydramnios in pregnant women who use drugs affecting renin-angiotensin system in the second and third trimesters can result in reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death Perform serial ultrasound examinations to assess the intra-amniotic environment; closely observe infants with histories of in utero exposure to drug for hypotension, oliguria, and hyperkalemia; in neonates with a history of in utero exposure to drug, if oliguria or hypotension occurs, support blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function Thiazides cross the placenta; use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults Lactation There is limited information regarding presence of azilsartan in human milk, effects on breastfed infant, or on milk production; azilsartan is present in rat milk; thiazide-like diuretics like chlorthalidone are excreted in human milk; because of potential for adverse effects on nursing infant, advise a nursing woman that breastfeeding is not recommended during therapy

Elderly, vol-depleted patients or w/ compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, w/ angiotensin II receptor antagonists (including azilsartan) may result in deterioration of renal function, including possible acute renal failure. NSAIDS increase risk of renal dysfunction and interfere with antihypertensive effect. Dual blockade of the renin angiotensin system w/ angiotensin receptor blockers, ACE inhibitors or aliskiren is associated w/ increased risks of hypotension, hyperkalemia & changes in renal function (including acute renal failure). Concomitant use w/ aliskiren. Renal clearance of lithium is reduced by diuretics, such as chlorthalidone increasing the risk of lithium toxicity. Contraindicated (2) aliskiren sparsentan Serious - Use Alternative (20) aliskiren aminolevulinic acid oral aminolevulinic acid topical benazepril captopril enalapril fosinopril isocarboxazid lisinopril lithium lofexidine methyl aminolevulinate moexipril perindopril potassium phosphates, IV quinapril ramipril squill trandolapril tretinoin

Side effects of Azilsartan + Chlorthalidone : 1-10% Dizziness (8.9%) Fatigue (2%) Hypotension (1.7%) <1% Syncope (0.3%)

Angiotensin II blocker; displaces angiotensin II from AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water absorption, and hypertrophic responses Chlorthalidone produces diuresis with increased excretion of sodium and chloride at the cortical diluting segment of the ascending limb of Henle’s loop of the nephron

Azisan Plus 40/12.5 40mg + 12.5mg Tablet manufactured by Renata PLC.. Its generic name is Azilsartan + Chlorthalidone. Azisan Plus 40/12.5 is availble in Bangladesh. Farmaco BD drug index information on Azisan Plus 40/12.5 Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.