Atenolol + Nifedipine

Oral
Hypertension

Oral
Stable angina

CrCl (mL/min)	Dosage
<15	Contraindicated.

Mild to moderate: Dose reduction may be needed. Severe: Contraindicated. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).

Aortic stenosis, bradycardia, cardiogenic shock or decompensated heart failure, recent MI (during or within 1 month) or acute coronary syndrome (within 1 month), hypotension, metabolic acidosis, 2nd- or 3rd-degree heart block, severe peripheral vascular disease, sick sinus syndrome, untreated phaeochromocytoma. Severe renal (CrCl <15 mL/min) and hepatic impairment. Women of childbearing potential and pregnant women; lactation.

Patient with poor cardiac reserve or conduction defects, Prinzmetal's angina, peripheral vascular disease, bronchospastic disease, diabetes mellitus, myasthenia gravis, psoriasis, thyroid disease, history of severe anaphylactic reaction to allergens, repeatedly unsuccessful in vitro fertilisation (in men). Patients undergoing major surgery; shifting from clonidine. Avoid abrupt withdrawal in patients with known ischaemic heart disease; chronic therapy must not be routinely withdrawn before major surgery. May mask the signs and symptoms of hypoglycaemia and hyperthyroidism (e.g. tachycardia). Mild to moderate renal and hepatic impairment. Elderly.

Significant: Anaphylactic reactions; bradycardia, disturbance of AV-conduction (may be exacerbated and result to AV block), precipitation or aggravation of arterial insufficiency (in patients with peripheral vascular disease), induction or exacerbation of psoriasis, exacerbation of hyperthyroidism symptoms or precipitation of thyroid storm (abrupt withdrawal), sperm function impairment.
Ear and labyrinth disorders: Vertigo.
Gastrointestinal disorders: Diarrhea, upset stomach, stomach pain, heartburn.
General disorders and administration site conditions: Fatigue, oedema.
Musculoskeletal and connective tissue disorders: Lupus-like syndrome.
Nervous system disorders: Headache, dizziness.
Psychiatric disorders: Mood changes.
Reproductive system and breast disorders: Gynaecomastia, impotence.
Respiratory, thoracic and mediastinal disorders: Asthma exacerbation.
Skin and subcutaneous tissue disorders: Skin rash.
Vascular disorders: Flushing.

Monitor blood pressure, heart rate, kidney function, serum glucose (in patients with diabetes); signs and symptoms of heart failure, peripheral oedema, and bronchospasm (in patients with existing bronchospastic disease).

Symptoms: Atenolol: Bradycardia, bronchospasm, hypotension, hypoglycaemia, heart block, and acute cardiac failure. Nifedipine: Nausea, vomiting, hypotension, hyperglycaemia, bradycardia, metabolic acidosis, and loss of consciousness. Management: Symptomatic and supportive treatment. Perform gastric lavage to empty the stomach. In cases of bradycardia, administer IV atropine (for 2nd- or 3rd-degree AV block), IV isoproterenol hydrochloride, or use a transvenous cardiac pacemaker. May give vasopressor (e.g. dobutamine, dopamine, epinephrine, norepinephrine) for severe hypotension or IV glucagon if hypotension is refractory to vasopressors. Administration of cardiac glycoside, diuretic, and use of oxygen may be used for heart failure. Hypoglycaemia may be treated with the use of IV dextrose. May consider haemodialysis to increase elimination of atenolol in severe cases.

Nifedipine: May increase the serum concentration of digoxin. May decrease the serum concentration of quinidine. Increased serum concentration with cimetidine.
Atenolol: Concomitant use with NSAIDs (e.g. indometacin) may decrease the hypotensive effect of atenolol. Enhanced hypotensive effect with reserpine.
Potentially Fatal: May cause excessive bradycardia, fatigue, and AV block with Ca-channel blockers with negative inotropic effects (e.g. diltiazem, verapamil).
Nifedipine: Decreased serum concentration with rifampicin.

Nifedipine: Increased absorption and decreased metabolism or clearance with grapefruit or grapefruit juice. Food may decrease the rate but not the extent of absorption.

May falsely increase the spectrophotometric values of urinary vanillylmandelic acid. May cause false-negative aldosterone/renin ratio (ARR).

Description:
Mechanism of Action: When used concomitantly, atenolol inhibits reflex tachycardia caused by nifedipine and nifedipine balances the increase in peripheral resistance caused by atenolol. This results in a synergistic effect on blood pressure reduction and anginal symptoms.
Atenolol is a cardioselective β-blocker that competitively and selectively blocks β1-adrenergic receptors but has little or no effect on β2-receptors except at high doses. The precise mechanism of action of its hypotensive effect is unclear but may be associated with peripheral (especially cardiac) adrenergic receptor inhibition, CNS sympathetic outflow reduction, and/or renal renin release suppression. Additionally, atenolol also produces negative chronotropic and inotropic effects through myocardial β1-adrenergic receptor inhibition.
Nifedipine, a coronary and peripheral vasodilator, is a dihydropyridine Ca-channel blocker. It prevents the influx of extracellular Ca ions to the slow channels or select voltage-sensitive areas of the vascular smooth muscle and myocardium during depolarisation, leading to coronary vascular smooth muscle relaxation and coronary vasodilation. It also decreases peripheral vascular resistance resulting in the reduction of arterial blood pressure.

Onset: Atenolol: β-blocking effect: ≤1 hour (oral).
Nifedipine: Approx 20 minutes (conventional).

Duration: Atenolol: β-blocking effect: 12-24 hours. Antihypertensive: 24 hours (oral).
Pharmacokinetics:
Absorption: Atenolol: Rapidly and incompletely absorbed from the gastrointestinal tract (approx 50%). Time to peak plasma concentration: 2-4 hours (oral).
Nifedipine: Rapidly and almost completely absorbed from the gastrointestinal tract. Food may decrease the rate but not the extent of absorption. Bioavailability: 40-77% (immediate-release); 65-89% (extended-release). Time to peak plasma concentration: 30-60 minutes (immediate-release).
Distribution: Crosses the placenta and enters breast milk.
Atenolol: Well distributed into most tissues and fluids except the brain and CSF. Plasma protein binding: Approx 6-16%.
Nifedipine: Plasma protein binding: Approx 92-98%.
Metabolism: Atenolol: Undergoes little or no metabolism in the liver.
Nifedipine: Extensively oxidised in the liver by CYP3A4 isoenzyme to highly water-soluble, inactive metabolites. Undergoes extensive hepatic first-pass metabolism.
Excretion: Atenolol: Via faeces (50%); urine (40% as unchanged drug). Elimination half-life: Approx 6-7 hours.
Nifedipine: Via urine (60-80% as inactive metabolites); faeces. Elimination half-life: Approx 2-5 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2249, Atenolol. https://pubchem.ncbi.nlm.nih.gov/compound/Atenolol. Accessed Mar. 22, 2024.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4485, Nifedipine. https://pubchem.ncbi.nlm.nih.gov/compound/Nifedipine. Accessed Mar. 22, 2024.

Store below 30°C. Protect from light.

Thuốc chẹn thụ thể bêta / Thuốc đối kháng calci

C07FB03 - atenolol and nifedipine ; Belongs to the class of selective beta-blocking agents in combination with other antihypertensives. Used in the treatment of cardiovascular diseases.

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Joint Formulary Committee. Atenolol. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/02/2024.

Joint Formulary Committee. Nifedipine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/02/2024.