propranolol

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications: Genetic Implications

Pronunciation:
proe-pran-oh-lole


Trade Name(s)

  • Hemangeol
  • Inderal
  • Inderal LA
  • InnoPran XL

Ther. Class.
antianginals
antiarrhythmics (Class II)
antihypertensives
vascular headache suppressants

Pharm. Class.
beta blockers

Indications

  • Management of hypertension, angina, arrhythmias, hypertrophic cardiomyopathy, thyrotoxicosis, essential tremors, pheochromocytoma (all but Hemangeol).
  • Also used in the prevention and management of MI, and the prevention of vascular headaches (all but Hemangeol).
  • Proliferating infantile hemangioma requiring systemic therapy (Hemangeol only)

Unlabeled Use(s):

  • Also used to manage alcohol withdrawal, aggressive behavior, antipsychotic-associated akathisia, situational anxiety, and esophageal varices.
  • Post-traumatic stress disorder (PTSD) (ongoing clinical trials at National Institute for Mental Health [NIMH]).

Action

Blocks stimulation of beta1 (myocardial) and beta2  (pulmonary, vascular, and uterine)-adrenergic receptor sites; its mechanism for the treatment of infantile hemangiomas is unknown.

Therapeutic Effect(s):

  • Decreased heart rate and BP.
  • Suppression of arrhythmias.
  • Prevention of MI.
  • Hemangioma resolution

Pharmacokinetics

Absorption: Well absorbed but undergoes extensive first-pass hepatic metabolism.

Distribution: Moderate CNS penetration. Crosses the placenta; enters breast milk.

Protein Binding: 93%.

Metabolism and Excretion: Almost completely metabolized by the liver (primarily for CYP2D6 isoenzyme) Genetic implication (the CYP2D6 enzyme system exhibits genetic polymorphism; ~7% of population may be poor metabolizers and may have significantly ↑ propranolol concentrations and an ↑ risk of adverse effects).

Half-life: 3.4–6 hr.

TIME/ACTION PROFILE (cardiovascular effects)

ROUTEONSETPEAKDURATION
PO30 min60–90 min†6–12 hr
PO–ERunknown6 hr24 hr
IVimmediate1 min4–6 hr
†Following single dose, full effect not seen until several wk of therapy.

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity
  • Uncompensated HF;
  • Pulmonary edema;
  • Cardiogenic shock;
  • Bradycardia, sick sinus syndrome, or heart block (unless pacemaker present);
  • Premature infants with corrected age <5 wk (Hemangeol only)
  • Infants <2 kg (Hemangeol only)
  • Asthma or history of bronchospasm (Hemangeol only)
  • BP <50/30 mmHg (Hemageol only)
  • Pheochromocytoma (Hemangeol only)

Use Cautiously in:

  • Renal or hepatic impairment;
  • Pulmonary disease (including asthma);
  • Diabetes mellitus (may mask signs of hypoglycemia);
  • Thyrotoxicosis (may mask symptoms);
  • History of severe allergic reactions (may ↑ intensity of response);
  • Skeletal muscle disease (may exacerbate myopathy);
  • OB:  Crosses the placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression. May also ↓ blood supply to the placenta, ↑ the risk for premature birth or fetal death, and cause intrauterine growth retardation. May ↑ risk of cardiac and pulmonary complications in the infant during the neonatal time frame. Lactation: Appears in breast milk; use formula if propranolol must be taken;
  • Pedi:  ↑ risk of hypoglycemia, especially during periods of fasting such as before surgery, during prolonged exertion, or with coexisting renal insufficiency;
  • Geri:  ↑ sensitivity to all beta blockers; initial dose reduction and careful titration recommended.

Adverse Reactions/Side Effects

CNS: fatigue, weakness, anxiety, dizziness, drowsiness, insomnia, memory loss, mental depression, mental status changes, nervousness, nightmares

EENT: blurred vision, dry eyes, nasal stuffiness

Resp: bronchospasm, wheezing

CV: ARRHYTHMIAS, BRADYCARDIA, HF, PULMONARY EDEMA, orthostatic hypotension, peripheral vasoconstriction

GI: constipation, diarrhea, nausea

GU: erectile dysfunction, ↓ libido

Derm: ERYTHEMA MULTIFORME, EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, itching, rash

Endo: hyperglycemia, hypoglycemia (↑ in children)

MS: arthralgia, back pain, muscle cramps, myopathy

Neuro: paresthesia

Misc: ANAPHYLAXIS, drug-induced lupus syndrome

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  General anesthesia,  IV phenytoin, and  verapamil  may cause additive myocardial depression.
  • Additive bradycardia may occur with  digoxin.
  • Additive hypotension may occur with other  antihypertensives, acute ingestion of  alcohol, or  nitrates.
  • Levels may be ↓ with chronic  alcohol  use.
  • Concurrent use with  amphetamines,  cocaine,  ephedrine,  epinephrine,  norepinephrine,  phenylephrine, or  pseudoephedrine  may result in unopposed alpha-adrenergic stimulation (excessive hypertension, bradycardia).
  • Concurrent  thyroid  administration may ↓ effectiveness.
  • May alter the effectiveness of  insulin  or  oral hypoglycemics  (dose adjustments may be necessary).
  • May ↓ effectiveness of  beta-adrenergic bronchodilators  and  theophylline.
  • May ↓ beneficial beta cardiovascular effects of  dopamine  or  dobutamine.
  • Use cautiously within 14 days of  MAO inhibitor  therapy (may result in hypertension).
  •  Cimetidine  may ↑ blood levels and toxicity.
  • Concurrent  NSAIDs  may ↓ antihypertensive action.
  •  Smoking  ↑ metabolism and ↓ effects; smoking cessation may ↑ effects.
  • May ↑ levels of  lidocaine  and  bupivacaine.

Route/Dosage

PO (Adults): Antianginal– 80–320 mg/day in 2–4 divided doses or once daily as extended/sustained-release capsules.  Antihypertensive– 40 mg twice daily initially; may be ↑ as needed (usual range 120–240 mg/day; doses up to 1 g/day have been used);  or  80 mg once daily as extended/sustained-release capsules, ↑ as needed up to 120 mg.  InnoPran XL  dosing form is designed to be given once daily at bedtime.  Antiarrhythmic– 10–30 mg 3–4 times daily.  Prevention of MI– 180–240 mg/day in divided doses.  Hypertrophic cardiomyopathy– 20–40 mg 3–4 times daily.  Adjunct therapy of pheochromocytoma– 20 mg 3 times daily to 40 mg 3–4 times daily concurrently with alpha-blocking therapy, started 3 days before surgery is planned.  Vascular headache prevention– 20 mg 4 times daily  or  80 mg/day as extended/sustained-release capsules; may be ↑ as needed up to 240 mg/day.  Management of tremor– 40 mg twice daily; may be ↑ up to 120 mg/day (up to 320 mg have been used).

PO Children: Antihypertensive/antiarrhythmic– 0.5–1 mg/kg/day in 2–4 divided doses; may be ↑ as needed (usual range for maintenance dose is 2–4 mg/kg/day in 2 divided doses).

PO (Children 5 wk–5 mo): Infantile hemangioma– 0.6 mg/kg twice daily (at least 9 hr apart); after 1 wk, ↑ to 1.1 mg/kg twice daily; after another wk, ↑ to 1.7 mg/kg twice daily and maintain for 6 mo.

IV (Adults): Antiarrhythmic– 1–3 mg; may be repeated after 2 min and again in 4 hr if needed.

IV Children: Antiarrhythmic– 10–100 mcg (0.01–0.1 mg)/kg (up to 1 mg/dose); may be repeated every 6–8 hr if needed.

Availability (generic available)

Oral solution: 20 mg/5 mL, 40 mg/5 mL

Oral solution (Hemangeol): 4.28 mg/mL

Tablets: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg

Extended-release capsules: 60 mg, 80 mg, 120 mg, 160 mg

Solution for injection: 1 mg/mL

In Combination with: hydrochlorothiazide (generic only).

Assessment

  • Monitor BP and pulse frequently during dose adjustment period and periodically during therapy.

    • Abrupt withdrawal of propranolol may precipitate life-threatening arrhythmias, hypertension, or myocardial ischemia. Drug should be tapered over a 2-wk period before discontinuation. Assess patient carefully during tapering and after medication is discontinued. Consider that patients taking propranolol for non-cardiac indications may have undiagnosed cardiac disease. Abrupt discontinuation or withdrawal over too-short a period of time (less than 9 days) should be avoided.
    • Pedi:  Assess pediatric patients for signs and symptoms of hypoglycemia, particularly when oral foods and fluids are restricted.
    • Patients receiving propranolol IV must have continuous ECG monitoring and may have pulmonary capillary wedge pressure (PCWP) or central venous pressure (CVP) monitoring during and for several hrs after administration.
  • Assess for orthostatic hypotension when assisting patient up from supine position.
  • Monitor intake and output ratios and daily weight. Assess patient routinely for evidence of fluid overload (peripheral edema, dyspnea, rales/crackles, fatigue, weight gain, jugular venous distention).
  • Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
  • Angina: Assess frequency and characteristics of anginal attacks periodically during therapy.
  • Vascular Headache Prophylaxis: Assess frequency, severity, characteristics, and location of vascular headaches periodically during therapy.
  • PTSD: Assess frequency of symptoms (flashbacks, nightmares, efforts to avoid thoughts or activities that may trigger memories of the trauma, and hypervigilance) periodically throughout therapy.
  • Infantile Hemangioma: Monitor heart rate and BP for 2 hrs after propranolol initiation or dose increases. May worsen bradycardia or hypotension. Discontinue if severe (<80 beats per min) or symptomatic bradycardia or hypotension (systolic BP <50 mmHg) occurs.

Lab Test Considerations:

May cause ↑ BUN, serum lipoprotein, potassium, triglyceride, and uric acid levels.

  • May cause ↑ ANA titers.
  • May cause ↓ or ↑ in blood glucose levels. In labile diabetic patients, hypoglycemia may be accompanied by precipitous ↑ of BP.

Toxicity Overdose:

Monitor patients receiving beta blockers for signs of overdose (bradycardia, severe dizziness or fainting, severe drowsiness, dyspnea, bluish fingernails or palms, seizures). Notify health care professional immediately if these signs occur.

  • Hypotension may be treated with modified Trendelenburg position and IV fluids unless contraindicated. Vasopressors (epinephrine, norepinephrine, dopamine, dobutamine) may also be used. Hypotension does not respond to beta agonists.
  • Glucagon has been used to treat bradycardia and hypotension.

Potential Diagnoses

Implementation

  • High Alert: IV vasoactive medications are inherently dangerous. Before administering intravenously, have second practitioner independently check the original order, dose calculations, and infusion pump settings. Also, patient harm or fatalities have occurred when switching from oral to IV  propranolol ; oral and parenteral doses are not interchangeable. IV dose is 1/10 of the oral dose. Change to oral therapy as soon as possible.
  • High Alert: Do not confuse propranolol with Pravachol. Do not confuse Inderal (propranolol) with Adderall (an amphetamine/dextroamphetamine combination drug).
  • PO 

    Take apical pulse prior to administering. If <50 bpm or if arrhythmia occurs, withhold medication and notify physician or other health care professional.

    • Administer with meals or directly after eating to enhance absorption.
    • Swallow extended release tablets whole; do not crush, break, or chew.  Propranolol tablets  may be crushed and mixed with food.
    • Mix propranolol oral solution with liquid or semisolid food (water, juices, applesauce, puddings). To ensure entire dose is taken, rinse glass with more liquid or have patient consume all of the applesauce or pudding. Do not store after mixing.
    • Administer  Hemangeol  during or right after a feeding to prevent hypoglycemia. Skip dose if child is not eating or vomiting. Administer using oral syringe provided; if necessary may be diluted in small amount of milk or fruit juice and given in baby's bottle.

IV Administration

  • IV Push:   Diluent:  Administer undiluted or dilute each 1 mg in 10 mL of D5W for injection. Concentration: Undiluted: 1 mg/mL. Diluted in 10 mL of D5W: 0.1 mg/mL.
  • Rate: Administer at 0.5 mg/ min for adults to avoid hypotension and cardiac arrest; do not exceed 1 mg/min. Pedi:  Administer over 10 min.
  • Intermittent Infusion:   Diluent:  May be diluted in 50 mL of 0.9% NaCl, D5W, D5/0.45% NaCl, D5/0.9% NaCl, or lactated Ringer's injection. Concentration: Depends on dose.
  • Rate: Infuse over 10–15 min.
  • Y-Site Compatibility
    • acyclovir
    • alemtuzumab
    • alfentanil
    • alteplase
    • amikacin
    • aminocaproic acid
    • aminophylline
    • amiodarone
    • anidulafungin
    • argatroban
    • ascorbic acid
    • atropine
    • azathioprine
    • aztreonam
    • benztropine
    • bivalirudin
    • bleomycin
    • bumetanide
    • buprenorphine
    • butorphanol
    • calcium chloride
    • calcium gluconate
    • carboplatin
    • carmustine
    • caspofungin
    • cefazolin
    • cefotetan
    • ceftazidime
    • ceftriaxone
    • cefuroxime
    • chloramphenicol
    • chlorpromazine
    • cisplatin
    • clindamycin
    • cyanocobalamin
    • cyclophosphamide
    • cyclosporine
    • cytarabine
    • dactinomycin
    • daptomycin
    • daptomycin
    • daunorubicin hydrochloride
    • dexamethasone
    • dexmedetomidine
    • dexrazoxane
    • digoxin
    • diltiazem
    • diphenhydramine
    • dobutamine
    • docetaxel
    • dopamine
    • doxorubicin
    • doxorubicin liposomal
    • doxycycline
    • enalaprilat
    • ephedrine
    • epinephrine
    • epirubicin
    • epoetin alfa
    • eptifibatide
    • ertapenem
    • erythromycin
    • esmolol
    • etoposide
    • etoposide phosphate
    • famotidine
    • fenoldopam
    • fentanyl
    • fluconazole
    • fludarabine
    • fluorouracil
    • folic acid
    • foscarnet
    • fosphenytoin
    • furosemide
    • ganciclovir
    • gemcitabine
    • gentamicin
    • glycopyrrolate
    • granisetron
    • heparin
    • hydrocortisone
    • hydromorphone
    • idarubicin
    • ifosfamide
    • imipenem/cilastatin
    • isoproterenol
    • ketorolac
    • labetalol
    • leucovorin
    • levofloxacin
    • lidocaine
    • linezolid
    • lorazepam
    • magnesium sulfate
    • mannitol
    • meperidine
    • mesna
    • methotrexate
    • methylprednisolone
    • metoclopramide
    • metoprolol
    • metronidazole
    • midazolam
    • milrinone
    • mitoxantrone
    • morphine
    • moxifloxacin
    • multivitamins
    • mycophenolate
    • nafcillin
    • nalbuphine
    • naloxone
    • nicardipine
    • nitroglycerin
    • nitroprusside
    • norepinephrine
    • octreotide
    • ondansetron
    • oxacillin
    • oxaliplatin
    • oxytocin
    • palonosetron
    • pamidronate
    • pancuronium
    • papaverine
    • pemetrexed
    • penicillin G
    • pentamidine
    • pentobarbital
    • phenobarbital
    • phenylephrine
    • phytonadione
    • potassium acetate
    • potassium chloride
    • procainamide
    • prochlorperazine
    • promazine
    • promethazine
    • propofol
    • protamine
    • pyridoxine
    • quinupristin/dalfopristin
    • rocuronium
    • sodium acetate
    • sodium bicarbonate
    • streptokinase
    • succinylcholine
    • sufentanil
    • tacrolimus
    • theophylline
    • thiamine
    • thiotepa
    • tigecycline
    • tirofiban
    • tobramycin
    • topotecan
    • vancomycin
    • vasopressin
    • vecuronium
    • verapamil
    • vinblastine
    • vincristine
    • vinorelbine
    • vitamin B complex with C
    • voriconazole
    • zoledronic acid
  • Y-Site Incompatibility
    • amphotericin B deoxycholate
    • amphotericin B lipid complex
    • amphotericin B liposome
    • dantrolene
    • diazepam
    • diazoxide
    • indomethacin
    • insulin
    • mitomycin
    • paclitaxel
    • pantoprazole
    • phenytoin
    • piperacillin/tazobactam
    • trimethoprim/sulfamethoxazole

Patient/Family Teaching

  • Instruct patient to take medication as directed, at the same time each day, even if feeling well; do not skip or double up on missed doses. Take missed doses as soon as possible up to 4 hr before next dose (8 hr with extended-release propranolol). Inform patient that abrupt withdrawal can cause life-threatening arrhythmias, hypertension, or myocardial ischemia. Advise parent to read medication guide prior to starting and with each Rx refill in case of changes in  Hemangeol. 
  • Advise patient to make sure enough medication is available for weekends, holidays, and vacations. A written prescription may be kept in wallet in case of emergency.
  • Teach patient and family how to check pulse daily and BP biweekly. Advise patient to hold dose and contact health care professional if pulse is <50 bpm or BP changes significantly.
  • May cause drowsiness or dizziness. Caution patients to avoid driving or other activities that require alertness until response to the drug is known.
  • Advise patients to change positions slowly to minimize orthostatic hypotension, especially during initiation of therapy or when dose is increased.
  • Caution patient that this medication may increase sensitivity to cold.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products, especially NSAIDs and cold preparations, concurrently with this medication.
  • Advise diabetic patients to closely monitor blood sugar, especially if weakness, malaise, irritability, or fatigue occurs. Medication may mask some signs of hypoglycemia, but dizziness and sweating may still occur. Acute hypertension may occur following insulin-induced hypoglycemia in patients receiving propranolol. Instruct parents/caregivers of children receiving  Hemangeol  how to recognize signs of hypoglycemia, and to notify health care professional and take child to nearest emergency department if hypoglycemia is suspected.
  • Advise patient to notify health care professional if slow pulse, difficulty breathing, wheezing, cold hands and feet, dizziness, light-headedness, confusion, depression, rash, fever, sore throat, unusual bleeding, or bruising occurs.
  • Instruct patient to inform health care professional of medication regimen prior to treatment or surgery.
  • Advise patient to carry identification describing disease process and medication regimen at all times.
  • Hypertension: Reinforce the need to continue additional therapies for hypertension (weight loss, sodium restriction, stress reduction, regular exercise, moderation of alcohol consumption, and smoking cessation). Medication controls but does not cure hypertension.
  • Angina: Caution patient to avoid overexertion with decrease in chest pain.
  • Vascular Headache Prophylaxis: Caution patient that sharing this medication may be dangerous.
  • PTSD: Advise patient that medication may relieve distressing symptoms but that psychotherapy is the primary treatment for the disorder. Refer patient and family to a PTSD support group.

Evaluation/Desired Outcomes

  • Decrease in BP.
  • Control of arrhythmias without appearance of detrimental side effects.
  • Reduction in frequency of anginal attacks.
  • Increase in activity tolerance.
  • Prevention of MI.
  • Prevention of vascular headaches.
  • Management of thyrotoxicosis.
  • Management of pheochromocytoma.
  • Decrease in tremors.
  • Management of hypertrophic cardiomyopathy.
  • Decrease in symptoms associated with PTSD.
  • Resolution of Infantile hemangioma (propranolol only)

propranololis the The Washington Manual Word of the day!