Nebivolol and valsartan in combination are available as Byvalsan and Nebicard-V. Nebivolol is a selective beta-1 blocker while valsartan is an angiotensin receptor blocker.
Nebivolol and valsartan (Byvalsan) Uses:
-
Hypertension:
- Hypertension Management.
Nebivolol and valsartan (Byvalsan) Dose in Adults
Nebivolol and valsartan Dose in the treatment of Hypertension:
-
P/O:
- Initial therapy and patients not controlled on valsartan 80 milligram or nebivolol ≤10 milligram: Nebivolol 5 milligram/valsartan 80 milligram once everyday.
Note:
- May be replaced for individual components in patients so far receiving nebivolol 5 milligrams and valsartan 80 milligrams.
Nebivolol and valsartan (Byvalsan) Dose in Children
Not indicated for use in children.
Pregnancy Risk Category: D
- [US Boxed Warning]
- Drugs that interfere with the renin-angiotensin system can damage or even kill a developing foetus.
- Refer to the individual monographs. Once you are aware that you are pregnant, discontinue use as soon as possible.
Use of valsartan and nebivolol during lactation:
- It is unknown if nebivolol and valsartan are breastmilk components.
- Due to the possibility of major adverse effects in breastfed infants, manufacturers do not advise breastfeeding.
Byvalsan Dose in Kidney Disease:
-
CrCl 30 to 80 millilitre per minute:
- Consult the unique monographs.
-
CrCl <30 millilitre per minute:
- Not recommended as initial treatment.
Byvalsan Dose in Liver disease:
-
Mild impairment (Child-Pugh class A):
- No dosage change is required.
-
Moderate impairment (Child-Pugh class B):
- No initial dosage modification is necessary
-
Severe impairment (Child-Pugh class C):
- Use is contraindicated.
Nebivolol and valsartan (Byvalsan) Side effects
See individual agents for reactions (Nebivolol and Valsartan).
Contraindications to Nebivolol and valsartan (Byvalsan):
- Hypersensitivity to valsartan, nebivolol or any other component of the formulation
- Bradycardia severe
- Heart block is more severe than the first-degree.
- Cardiogenic shock
- Heart failure that has been decompensated
- Sinusitis (unless a permanent pacemaker has been installed)
- Severe hepatic impairment (Child Puugh class C).
- Patients with diabetes mellitus should use aliskiren concurrently
Warnings and precautions
-
Anaphylactic reactions
- Use nebivolol with caution if you have a history of severe allergic responses to a variety of allergens.
- Beta-blockers can make patients more sensitive to repeated challenges.
- Patients taking beta-blockers may have anaphylaxis (e.g., epinephrine), which can lead to ineffective treatment or undesirable side effects.
-
Angioedema
- Some angiotensin II receptor inhibitors can cause the rare adverse effect of angioedema (ARBs). Anytime during therapy, but especially after the first dose, it can happen.
- It might affect the head and neck (perhaps harming the airway), or it might even affect the bowel (presenting as abdominal pain).
- Patients who have angioedema resulting from ACE-inhibitor therapy or idiopathic angioedema may be at greater risk.
- Frequent monitoring over a long period may be necessary, particularly if the tongue, glottis or larynx is involved. This is because they can cause obstruction to the airways.
- Patients who have had previous airway surgery may be at greater risk for airway obstruction.
- Stop all therapy immediately if angioedema develops
- It is crucial to be aggressive in early management.
- IM administration of epinephrine might be required.
- Patients who have angioedema caused by ARBs should not be readministered.
-
Hyperkalemia:
- This may happen when you take valsartan.
- Renal insufficiency, potassium supplements, diabetes mellitus, concurrent use of potassium-sparing diuretics, and potassium-containing salts are all risk factors.
- These agents should be used with caution.
- Pay attention to potassium.
-
Hypotension
- Patients who have been treated with high-dose diuretics or salt-depleted may experience symptoms of hypotension.
- .Pre-administration accurate volume depletion.
- The brief hypotensive response does not warrant depriving you of future medical care.
-
Renal function deterioration:
- In patients whose GFR depends on efferent arterial vasoconstriction and have limited renal bloodflow (such as kidney artery stenosis or heart failure), valsartan may result in a loss in renal function and an increase in serum creatinine (angiotensin II).
- Oliguria, acute renal failure, or progressive azotemia can result from deterioration.
- Small increases in serum creatinine may happen after starting.
- Patients with significant and progressive impairment of renal function should be considered for discontinuation.
-
Mitral and aortic stenosis:
- Patients with severe aortic/mitral stenosis should not use valsartan.
-
Bronchospastic Disease:
- Patients suffering from bronchospastic diseases should not be given beta-blockers.
-
Diabetes:
- Patients with diabetes mellitus should be cautious.
- Nebivolol can mask hypoglycemia symptoms and may even cause it.
-
Heart failure:
- Patients with heart failure should be treated cautiously and monitored for signs of deterioration.
- Patients should be stabilized on the heart-feilling regimen before initiating beta-blockers.
-
Hepatic impairment
- Patients with moderate hepatic impairment should not be treated as an initial treatment. The recommended starting dose for these patients is not to use the combination product.
- Patients with severe hepatic impairment are advised to avoid this medication.
-
Myasthenia gravis:
- Patients with myasthenia gravis should be cautious when using nebivolol.
-
Raynaud and peripheral vascular disease (PVD).
- Nebivolol may cause arterial insufficiency symptoms, which can be exacerbated in patients with Raynaud and PVD.
- Be careful and check for arterial obstruction.
-
Untreated Pheochromocytoma
- A good alpha-blockade must be in place before any beta-blocker can be used.
-
Psoriasis:
- Beta-blocker may be associated with psoriasis exacerbation or induction, but cause and effect are not well established.
-
Renal artery stenosis
- Patients with unstented unilateral/bilateral kidney artery stenosis should not be given valsartan.
- If unstented bilateral renal arterial stenosis exists, it is best to avoid using this device.
-
Renal impairment
- Patients with severe impairment are not advised to use this combination product.
-
Thyroid disease:
- Nebivolol, such as tachycardia, may conceal hyperthyroidism symptoms.
- Monitor and treat thyrotoxicosis if it has been suspected, of course.
- Sudden withdrawal can exacerbate symptoms of hyperthyroidism and precipitate thyroid storm.
Nebivolol and valsartan: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Acetylcholinesterase Inhibitors |
May enhance the bradycardic effect of Beta-Blockers. |
|
Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Alpha1-Blockers |
Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1Blockers. The risk associated with ophthalmic products is probably less than systemic products. |
|
Aminoquinolines (Antimalarial) |
May decrease the metabolism of Beta-Blockers. |
|
Amiodarone |
May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. |
|
Amphetamines |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Angiotensin II |
Receptor Blockers may diminish the therapeutic effect of Angiotensin II. |
|
Antipsychotic Agents (Phenothiazines) |
May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]). |
|
Barbiturates |
May lower the level of beta-blockers in the serum. |
|
Barbiturates |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Benperidol |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Beta2-Agonists |
The bronchodilatory impact of beta2-agonists may be lessened by beta-blockers (beta1 selective). Particular attention should be paid to nonselective beta-blockers or beta1 selective beta-blockers at larger doses. |
|
Bradycardia-Causing Agents |
May intensify other bradycardia-causing agents' bradycardic effects. |
|
Bretylium |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. In patients taking AV blocking medications, bretylium may also strengthen atrioventricular (AV) blockade. |
|
Brigatinib |
May lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by brutinib. |
|
Brimonidine (Topical) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Bupivacaine |
Beta-Blockers may increase the serum concentration of Bupivacaine. |
|
Calcium Channel Blockers (Nondihydropyridine) |
May enhance the hypotensive effect of BetaBlockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. |
|
Cardiac Glycosides |
Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. |
|
Cholinergic Agonists |
Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. |
|
CycloSPORINE (Systemic) |
CycloSPORINE's hyperkalemic impact may be enhanced by angiotensin II receptor blockers (Systemic). |
|
CYP2D6 Inhibitors (Moderate) |
Nebivolol serum concentration can rise. |
|
CYP2D6 Inhibitors (Strong) |
Nebivolol serum concentration can rise. |
|
Dapoxetine |
Angiotensin II Receptor Blockers' orthostatic hypotensive action might be improved. |
|
Dexmethylphenidate |
May diminish the therapeutic effect of Antihypertensive Agents. |
|
Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Dipyridamole |
May enhance the bradycardic effect of Beta-Blockers. |
|
Disopyramide |
May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. |
|
Drospirenone |
Drospirenone's hyperkalemic impact may be enhanced by angiotensin II receptor blockers. |
|
DULoxetine |
The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications. |
|
Eltrombopag |
May raise the level of OATP1B1/1B3 (SLCO1B1/1B3) Substrates in the serum. |
|
EPINEPHrine (Nasal) |
The therapeutic effects of epinephrine may be diminished by beta-blockers (Beta1 Selective) (Nasal). |
|
EPINEPHrine (Oral Inhalation) |
The therapeutic effects of epinephrine may be diminished by beta-blockers (Beta1 Selective) (Oral Inhalation). |
|
Epinephrine (Racemic) |
Epinephrine's therapeutic impact may be diminished by beta-blockers (Beta1 Selective) (Racemic). |
|
EPINEPHrine (Systemic) |
The therapeutic effects of epinephrine may be diminished by beta-blockers (Beta1 Selective) (Systemic). |
|
Eplerenone |
Angiotensin II Receptor Blockers' hyperkalemic impact might be strengthened. |
|
Gemfibrozil |
May raise the level of OATP1B1/1B3 (SLCO1B1/1B3) Substrates in the serum. |
|
Heparin |
Agents indicated as exceptions should be examined in separate drug interaction monographs. |
|
Heparins (Low Molecular Weight) |
Angiotensin II Receptor Blockers' hyperkalemic impact might be strengthened. |
|
Herbs (Hypertensive Properties) |
Angiotensin II Receptor Blockers' hyperkalemic impact might be strengthened. |
|
Herbs (Hypotensive Properties |
May lessen the effectiveness of antihypertensive agents. |
|
HydroCHLOROthiazide |
May intensify Valsartan's hypotensive effects. The serum concentration of HydroCHLOROthiazide may rise in response to Valsartan. |
|
Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
|
Insulins |
Beta-Blockers may enhance the hypoglycemic effect of Insulins. |
|
Ivabradine |
Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. |
|
Lacosamide |
Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. |
|
Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
|
Lidocaine (Systemic) |
Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). |
|
Lidocaine (Topical) |
Beta-Blockers may increase the serum concentration of Lidocaine (Topical). |
|
Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Mepivacaine |
Beta-Blockers may increase the serum concentration of Mepivacaine. |
|
Methoxyflurane |
May enhance the hypotensive effect of Beta-Blockers. |
|
Methylphenidate |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Midodrine |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicorandil |
May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. |
|
Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
NIFEdipine |
May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. |
|
Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
|
Nonsteroidal Anti-Inflammatory Agents |
May diminish the antihypertensive effect of BetaBlockers. |
|
Nonsteroidal Anti-Inflammatory Agents |
Nonsteroidal Anti-Inflammatory Agents' negative/toxic effects may be amplified by angiotensin II receptor blockers. In particular, the combination may cause a marked decline in renal function. Angiotensin II Receptor Blockers' therapeutic impact may be lessened by non-steroidal anti-inflammatory drugs. Both glomerular filtration rate and renal function may be considerably reduced by the combination of these two drugs. |
|
Opioids (Anilidopiperidine) |
May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. |
|
Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
|
Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Potassium Salts |
May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. |
|
Potassium-Sparing Diuretics |
Potassium-Sparing Diuretics may have a stronger hyperkalemic impact when used with Angiotensin II Receptor Blockers. |
|
Propafenone |
May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. |
|
Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Ranolazine |
May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. |
|
Regorafenib |
May enhance the bradycardic effect of Beta-Blockers. |
|
Reserpine |
May enhance the hypotensive effect of Beta-Blockers. |
|
Rifamycin Derivatives |
May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. |
|
Ruxolitinib |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. Management: The Canadian product labelling for roxolitinib advises against using it in conjunction with medications that can cause bradycardia whenever feasible. |
|
Selective Serotonin Reuptake Inhibitors |
May raise the level of beta-blockers in the serum. Citalopram, Escitalopram, and FluvoxaMINE are exceptions. |
|
Sulfonylureas |
Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. |
|
Tacrolimus (Systemic) |
Tacrolimus's hyperkalemic impact may be enhanced by angiotensin II receptor blockers (Systemic). |
|
Teriflunomide |
May raise the level of OATP1B1/1B3 (SLCO1B1/1B3) Substrates in the serum. |
|
Terlipressin |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. |
|
Theophylline Derivatives |
Theophylline derivatives may not have the same bronchodilatory action when used with beta-blockers (Beta1 Selective). Management: Keep an eye out for decreased theophylline effectiveness when using any beta-blocker at the same time. |
|
Tofacitinib |
Compared to nonselective medicines, beta-1 selective drugs are less likely to antagonise theophylline, but selectivity may be lost at larger dosages. |
|
Trimethoprim |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. |
|
Yohimbine |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Aliskiren |
The hypotensive effects of angiotensin II receptor blockers may be strengthened by aliskiren. Angiotensin II Receptor Blockers' nephrotoxic effects may be made worse by aliskiren. Treatment: It is not advised for diabetic patients to take aliskiren along with ACEIs or ARBs. Combination therapy should be avoided in other patients, especially when CrCl is less than 60 mL/min. If combined, keep a close eye on your blood pressure, potassium, and creatinine levels. |
|
Alpha2-Agonists |
May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine. |
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Angiotensin-Converting Enzyme Inhibitors |
Angiotensin II Receptor Blockers may make angiotensin-converting enzyme inhibitors more harmful or toxic. Angiotensin-Converting Enzyme Inhibitors' serum levels may rise in response to angiotensin II receptor blockers. Management: According to US labelling, it is not advisable to take telmisartan and ramipril. It is unclear whether another ACE inhibitor and ARB combo would be any safer. When possible, take into account alternatives to the mix. |
|
Antihepaciviral Combination Products |
Could raise the serum level of valsartan. Management: If these drugs are used in combination, take into account lowering the valsartan dose and monitoring for signs of hypotension and deteriorating renal function, according to the US prescribing instructions for antihepaciviral combination products. |
|
Ceritinib |
Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. |
|
Dronedarone |
May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in betablocker dose. |
|
Ergot Derivatives |
Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. |
|
Fingolimod |
Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. |
|
Grass Pollen Allergen Extract (5 Grass Extract) |
Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. |
|
Lithium |
It's possible that angiotensin II receptor blockers will raise the level of lithium in the blood. Management: After adding an angiotensin II receptor antagonist, it will probably be necessary to lower the dosage of lithium. |
|
Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
|
Siponimod |
Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. |
|
Sodium Phosphates |
Angiotensin II Receptor Blockers may make sodium phosphates more nephrotoxic. In particular, there may be an increased risk of acute phosphate nephropathy. Treatment: You might want to temporarily stop taking ARBs or look into alternatives to the oral sodium phosphate bowel preparation in order to prevent this combo. Maintaining appropriate hydration and properly monitoring renal function should be done if the combination cannot be avoided. |
|
Tolvaptan |
May raise the level of OATP1B1/1B3 (SLCO1B1/1B3) Substrates in the serum. |
|
Risk Factor X (Avoid combination) |
|
|
Bromperidol |
The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications. Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol. |
|
Floctafenine |
May intensify the hazardous or harmful effects of beta-blockers. |
|
Methacholine |
Beta-Blockers might make methacholine's harmful or toxic effects worse. |
|
Rivastigmine |
May enhance the bradycardic effect of Beta-Blockers. |
Monitoring parameters:
- Blood pressure.
- Renal function.
- Baseline and periodic electrolyte panels.
- Serum glucose (in diabetic patients).
How to administer Nebivolol and valsartan (Byvalsan)?
P/O:
- Administer with or without food.
Mechanism of action of Nebivolol and valsartan (Byvalsan):
Nebivolol:
- Highly-selective inhibition of beta-adrenergic nerve receptors
- Doses of =10 mg nebivolol block beta-1 receptors preferentially.
- Nebivolol also causes an endothelium-derived, nitric oxide dependent vasodilation which, unlike other beta-blockers reduces systemic vascular resistance.
Valsartan:
- Direct antagonism of angiotensin II receptors (AT2) is possible, but not with ACE inhibitors.
- Angiotensin II is removed from the AT1 receptor. It is then produced. This lowers AT1-induced vasoconstriction and aldosterone, catecholamine, and arginine vasopressin releases, as well as water intake and hypertrophic reactions. This results in a more effective blockade of cardiovascular effects of angiotensin II and lower side effects that the ACE inhibitors.
See individual agents (Nebivolol and Valsartan)
International Brands of Nebivolol and valsartan:
- Byvalson
- Nebicard-V
Nebivolol and valsartan Brand Names in Pakistan:
No Brands Available in Pakistan.
