NEBIVOLOL

Indications & Dose:

Essential hypertension

• BY MOUTH

Adult: 5 mg daily

Elderly: Initially 2.5 mg daily, then increased if necessary to 5 mg daily

Hypertension in patient with renal impairment l

• BY MOUTH

Adult: Initially 2.5 mg once daily, then increased if necessary to 5 mg once daily

Adjunct in stable mild to moderate heart failure l

• BY MOUTH

Adult 70 years and over: Initially 1.25 mg once daily for 1–2 weeks, then increased if tolerated to 2.5 mg once daily for 1–2 weeks, then increased if tolerated to 5 mg once daily for 1–2 weeks, then increased if tolerated to 10 mg once daily 

Contraindications:

Severe bradycardia, Heart block greater than first degree, 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

Side Effects:

Depression . oedema

BREAST FEEDING Manufacturers advise avoidance.

HEPATIC IMPAIRMENT No information available—manufacturer advises avoid.

RENAL IMPAIRMENT Manufacturer advises avoid in heart failure if serum creatinine greater than 250 micromol/litre.

Cautions:

Precautions:

Interaction:

Drug-Drug

Digoxin: Concomitant administration of NEBIVOLOL (10 mg once daily) and digoxin (0.25 mg once daily) for 10 days in 14 healthy adult individuals resulted in no significant changes in the pharmacokinetics of digoxin or nebivolol

Warfarin: Administration of NEBIVOLOL (10 mg once daily for 10 days) led to no significant changes in the pharmacokinetics of nebivolol or R- or S-warfarin following a single 10 mg dose of warfarin. Similarly, nebivolol has no significant effects on the anticoagulant activity of warfarin, as assessed by Prothrombin time and INR profiles from 0 to 144 hours after a single 10 mg warfarin dose in 12 healthy adult volunteers.

Diuretics: No pharmacokinetic interactions were observed in healthy adults between nebivolol (10 mg daily for 10 days) and furosemide (40 mg single dose), hydrochlorothiazide (25 mg once daily for 10 days), or spironolactone (25 mg once daily for 10 days).

Ramipril: Concomitant administration of NEBIVOLOL (10 mg once daily) and ramipril (5 mg once daily) for 10 days in 15 healthy adult volunteers produced no pharmacokinetic interactions.

Losartan: Concomitant administration of NEBIVOLOL (10 mg single dose) and losartan (50 mg single dose) in 20 healthy adult volunteers did not result in pharmacokinetic interactions.

Fluoxetine: Fluoxetine, a CYP2D6 inhibitor, administered at 20 mg per day for 21 days prior to a single 10 mg dose of nebivolol to 10 healthy adults, led to an 8-fold increase in the AUC and 3-fold increase in Cmax for dnebivolol

Histamine-2 Receptor Antagonists: The pharmacokinetics of nebivolol (5 mg single dose) were not affected by the co-administration of ranitidine (150 mg twice daily). Cimetidine (400 mg twice daily) causes a 23% increase in the plasma levels of d-nebivolol.

Charcoal: The pharmacokinetics of nebivolol (10 mg single dose) were not affected by repeated coadministration (4, 8, 12, 16, 22, 28, 36, and 48 hours after nebivolol administration) of activated charcoal

Sildenafil: The co-administration of nebivolol and sildenafil decreased AUC and Cmax of sildenafil by 21 and 23% respectively. The effect on the Cmax and AUC for d-nebivolol was also small ( < 20%). The effect on vital signs (e.g., pulse and blood pressure) was approximately the sum of the effects of sildenafil and nebivolol.

Other Concomitant Medications: Utilizing population pharmacokinetic analyses, derived from hypertensive patients, the following drugs were observed not to have an effect on the pharmacokinetics of nebivolol: acetaminophen, acetylsalicylic acid, atorvastatin, esomeprazole, ibuprofen, levothyroxine sodium, metformin, sildenafil, simvastatin, or tocopherol.

Protein Binding: No meaningful changes in the extent of in vitro binding of nebivolol to human plasma proteins were noted in the presence of high concentrations of diazepam, digoxin, diphenylhydantoin, enalapril, hydrochlorothiazide, imipramine, indomethacin, propranolol, sulfamethazine, tolbutamide, or warfarin. Additionally, nebivolol did not significantly alter the protein binding of the following drugs: diazepam, digoxin, diphenylhydantoin, hydrochlorothiazide, imipramine, or warfarin at their therapeutic concentrations.

Warnings:

Adverse Effects:

Lactations:

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

Patient And Carer Advice: