Nebivolol + Valsartan

Nebivolol + Valsartan is used for: Hypertension

Hypertension Indicated for hypertension, to lower blood pressure and reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarction May be used as initial therapy (if not controlled on valsartan 80 mg or <10 mg nebivolol) or be substituted for its components in patients already receiving nebivolol 5 mg and valsartan 80 mg 1 tablet (ie, 5 mg/80 mg) PO once daily

Renal impairment Mild or moderate (CrCl >60 mL/min): No dosage adjustment is required Moderate and severe: Not studied

May taken with or without food

Severe bradycardia Heart block greater than first degree (if no pacemaker) Patients with cardiogenic shock Decompensated cardiac failure Sick sinus syndrome (unless a permanent pacemaker is in place) Patients with severe hepatic impairment (Child-Pugh >B) Patients who are hypersensitive to any component of this product Do not coadminister aliskiren with an angiotensin receptor blocker (ARB) (eg, valsartan) in patients with diabetes; dual blockade of renin-angiotensin system increases risk of hypotension, hyperkalemia, and renal impairment

Discontinue as soon as possible when pregnancy is detected; valsartan affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury or death. Fetal toxicity: ARB (eg, valsartan) use during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Black Box Warnings, Pregnancy) Increased risk of symptomatic hypotension in patients with activated renin-angiotensin-aldosterone system (eg, volume/ and/or salt-depleted) Do not abruptly discontinue nebivolol in patients with coronary artery disease; severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias reported Worsening heart failure or fluid retention may occur during nebivolol therapy because of its beta-blocking effects Generally, patients with bronchospastic diseases should not receive beta-blockers Long-term beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures Beta-blockers may mask manifestations of hypoglycemia, particularly tachycardia Beta-blockers may mask clinical signs of hyperthyroidism (eg, tachycardia) Do not abruptly discontinue beta-blockers While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge; these patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions In patients with known or suspected pheochromocytoma, initiate an alpha-blocker prior to the use of any beta-blocker ARBs associated with increased serum potassium levels; monitor closely Monitoring Parameters Monitor glucose as beta-blockers may mask symptoms of hypoglycemia. Monitor closely serum potassium levels Monitor renal function in susceptible patients.

Pregnancy Nebivolol: Neonates of women with hypertension who are treated with beta-blockers during pregnancy may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression Valsartan Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, and skeletal deformations, including skull hypoplasia, hypotension, and death In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus In patients taking an ARB during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment Fetal testing may be appropriate, based on the week of gestation Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury Lactation Unknown if distributed in human breast milk Because of the potential for beta-blockers to produce serious adverse reactions in nursing infants, especially bradycardia, and the potential for valsartan to affect postnatal renal development in nursing infants, advise females not to breastfeed during treatment

Nebivolol Nebivolol is a CYP2D6 substrate; avoid coadministration with CYP2D6 inhibitors (eg, quinidine, propafenone, fluoxetine, paroxetine) Do not use with other beta-blockers Monitor closely if coadministered with catecholamine-depleting drugs (eg, reserpine, guanethidine); the added beta-blocking action of nebivolol may produce excessive reduction of sympathetic activity If coadministered with clonidine, discontinue nebivolol for several days before the gradual tapering of clonidine Digitalis glycosides: Coadministration increases risk of bradycardia; monitor Nebivolol can exacerbate effects of myocardial depressants or inhibitors of atrioventricular conduction (eg, certain calcium channel blockers, especially the phenylalkylamine class [eg, verapamil] and benzothiazepine class [eg, diltiazem]) Valsartan Concomitant use with other agents that block the renin-angiotensin system, potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium, or other agents that may increase potassium levels (eg, heparin) may result in hyperkalemia Coadministration with NSAIDs or COX-2 inhibitors may result in renal function deterioration, especially in elderly patients, volume-depleted (including diuretics) patients, or those with renal impairment Use of ARBs with ACE inhibitors or with aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function Coadministration with aliskiren in patients with diabetes is contraindicated Coadministration with lithium increase serum lithium levels and toxicity Contraindicated (3) aliskiren mavorixafor sparsentan

Side effects of Nebivolol + Valsartan : 1-10% Increased serum potassium by >20% (4.4%) Frequency Not Defined Symptomatic hypotension

Nebivolol: Competitive and selective beta1-receptor antagonist; has little or no effect on beta2 receptors at doses <10 mg; lacks intrinsic sympathomimetic and membrane stabilizing activity at therapeutically relevant concentrations; reduces systemic vascular resistance Valsartan: Blocks binding of angiotensin II to type 1 angiotensin receptors, causing a lowering in blood pressure; blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II