propranolol (Inderal, Inderal LA, InnoPran XL, Hemangeol)
Classes: Antidysrhythmics, II; Beta-Blockers, Nonselective; Antianginal Agents; Antimigraine Agents
Dosing and uses of Inderal, Inderal LA (propranolol)
Adult dosage forms and strengths
oral solution
- 20mg/5mL
- 40mg/5mL
injectable solution
- 1mg/mL
tablet
- 10mg
- 20mg
- 40mg
- 60mg
- 80mg
capsule, extended-release
- 60mg
- 80mg
- 120mg
- 160mg
Hypertension
Immediate release
- 40 mg PO q12hr initially, increasing every 3-7 days; maintenance: 80-240 mg PO q8-12hr; not to exceed 640 mg/day
Inderal LA
- 80 mg/day PO initially; maintenance: 120-160 mg/day; not to exceed 640 mg/day
InnoPran XL
- 80 mg/day PO initially; may be increased every 2-3 weeks until response achieved; maintenance: not to exceed 120 mg/day PO
Migraine
Prophylaxis
80 mg/day PO divided q6-8hr initially; may be increased by 20-40 mg/day every 3-4 weeks; not to exceed 160-240 mg/day divided q6-8hr
Inderal LA: 80 mg/day PO; maintenance: 160-240 mg/day
Withdraw therapy if satisfactory response not seen after 6 weeks
Angina
80-320 mg/day PO divided q6-12hr
Inderal LA: 80 mg/day PO; not to exceed 320 mg/day
Pheochromocytoma
30-60 mg/day PO in divided doses
Hypertrophic Subaortic Stenosis
20-40 mg PO q6-8hr
Supraventricular Arrhythmia
PO: 10-30 mg q6-8hr
IV: 1-3 mg at 1 mg/min initially; repeat q2-5min to total of 5 mg
Once response or maximum dose achieved, do not give additional dose for at least 4 hours
Portal Hypertension
Prevention of variceal bleeding
10-60 mg PO q6-8hr; 10 mg PO q8hr initially; titrate dose to reduce resting heart rate by 25%
Essential Tremor
40 mg PO q12hr initially; maintenance: 120-320 mg/day PO divided q8-12hr
Antipsychotic-Induced Akathisia
30-120 mg PO q8-12hr
Malignant Glioma (Orphan)
Orphan designation for treatment of malignant glioma (plus etodolac)
Sponsor
- Vicus Therapeutics, LLC; 55 Madison Avenue, Suite 400; Morristown, NJ 07960
Esophageal Variceal Bleeding (Off-label)
20-180 mg PO q12hr; adjust to maximum tolerated dose
Panic Disorder (Off-label)
40-320 mg/day PO
Aggressive Behavior (Off-label)
80-300 mg/day PO
Pediatric dosage forms and strengths
oral solution
- 4.28mg/mL (Hemangeol)
- 20mg/5mL
- 40mg/5mL
injectable solution
- 1mg/mL
tablet
- 10mg
- 20mg
- 40mg
- 60mg
- 80mg
capsule, extended-release
- 60mg
- 80mg
- 120mg
- 160mg
Infantile Hemangiomas
Hemangeol: Indicated for treatment of proliferating hemangioma requiring systemic therapy
Initiate treatment at aged 5 weeks to 5 months
Starting dose: 0.6 mg/kg (0.15 mL/kg) PO BID for 1 week, THEN increase dose to 1.1 mg/kg (0.3 mL/kg) BID; after 2 more weeks, increase to maintenance dose of 1.7 mg/kg (0.4 mL/kg) BId
Administration (infantile hemangiomas)
- Use supplied oral dosing syringe for administration and give directly into the child’s mouth; if necessary, the product may be diluted in a small quantity of milk or fruit juice and given in a baby’s bottle
- Administer doses at least 9 hr apart during or after feedings
- To reduce the risk of hypoglycemia, administer during or right after a feeding; skip the dose if the child is not eating or is vomiting
- Readjust dose periodically as the child's weight increases
- Monitor HR and BP for 2 hr after initial dose and after increasing dose
- If hemangiomas recur, treatment may be reinitiated
Hypertension (Off-label)
0.5-1 mg/kg/day PO divided q6-12hr initially; increase gradually every 5-7 days; usual range: 2-4 mg/kg/day PO divided q12hr
Arrhythmias (Off-label)
PO: 0.5-1 mg/kg/day divided q6-8hr; may be increased every 3-7 days; usual range: 2-6 mg/kg/day; not to exceed 16 mg/kg/day or 60 mg/day
IV: 0.01-0.1 mg/kg over 10 minutes; repeat q6-8hr PRN; not to exceed 1 mg for infants or 3 mg for children
Hypercyanotic Spells (Off-label)
PO: 1 mg/kg/day divided q6hr; after 1 week, may be increased by 1 mg/kg/day to maximum of 10-15 mg/kg/day if patient refractory; allow 24 hours between dosing changes
IV: 0.01-0.2 mg/kg over 10 minutes; not to exceed 5 mg
Thyrotoxicosis (Off-label)
10-40 mg PO q6hr; adjust dose to effect
Geriatric dosage forms and strengths
Hypertension
Immediate-release: 40 mg PO q12hr initially, increased every 3-7 days; maintenance: 80-240 mg PO q8-12hr; not to exceed 640 mg/day
Inderal LA: 80 mg/day PO initially; maintenance: 120-160 mg/day; not to exceed 640 mg/day
InnoPran XL: 80 mg/day PO initially; may be increased every 2-3 weeks until response achieved; maintenance: not to exceed 120 mg/day PO
Consider lower initial dose
Supraventricular Arrhythmia
PO: 10 mg q6-8hr; may be increased every 3-7 days
IV: 1-3 mg at 1 mg/min initially; repeat q2-5min to total of 5 mg
Once response or maximum dose achieved, do not give additional dose for at least 4 hours
Inderal, Inderal LA (propranolol) adverse (side) effects
Frequency not defined
Aggravated congestive heart failure
Bradycardia
Hypotension
Arthropathy
Raynaud phenomenon
Hyper/hypoglycemia
Depression
Fatigue
Insomnia
Paresthesia
Psychotic disorder
Pruritus
Nausea
Vomiting
Hyperlipidemia
Hyperkalemia
Cramping
Bronchospasm
Dyspnea
Pulmonary edema
Respiratory distress
Wheezing
Postmarketing Reports
Allergic: Hypersensitivity reactions, including anaphylactic/anaphylactoid; agranulocytosis, erythematous rash, fever with sore throat
Skin: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, urticaria
Musculoskeletal: Myopathy, myotonia
Warnings
Black box warnings
May exacerbate ischemic heart disease after abrupt withdrawaL
Hypersensitivity to catecholamines has been observed during withdrawaL
Exacerbation of angina and, in some cases, myocardial infarction occurrence after abrupt discontinuance
When discontinuing long-term administration of beta blockers (particularly with ischemic heart disease), gradually reduce dose over 1-2 weeks and carefully monitor
If angina markedly worsens or acute coronary insufficiency develops, reinstate beta-blocker administration promptly, at least temporarily (in addition to other measures appropriate for unstable angina)
Warn patients against interruption or discontinuance of beta-blocker therapy without physician advice
Because coronary artery disease is common and may be unrecognized, slowly discontinue beta-blocker therapy, even in patients treated only for hypertension
Contraindications
Asthma, COPd
Severe sinus bradycardia or 2°/3° heart block (except in patients with functioning artificial pacemaker)
Cardiogenic shock
Uncompensated congestive heart failure
Hypersensitivity
Overt heart failure
Sick sinus syndrome without permanent pacemaker
Infantile hemangioma
- Premature infants with corrected age <5 weeks
- Infants weighing <2 kg
- Hypersensitivity
- Asthma or history of bronchospasm
- Heart rate <80 bpm
- Greater than first-degree heart block
- Decompensated heart failure
- Blood pressure <50/30 mm Hg
- Pheochromocytoma
Cautions
Do not use InnoPran XL in pediatric patients
Long-term beta blocker therapy should not be routinely discontinued before 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
Use caution in bronchospastic disease, cerebrovascular insufficiency, congestive heart failure, diabetes mellitus, hyperthyroidism/thyrotoxicosis, liver disease, renal impairment, peripheral vascular disease, myasthenic conditions
Sudden discontinuance can exacerbate angina and lead to myocardial infarction
Use in pheochromocytoma
Increased risk of stroke after surgery
Hypersensitivity reactions, including anaphylactic and anaphylactoid reactions, have been reported
Cutaneous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, and urticaria, have been reported
Exacerbation of myopathy and myotonia has been reported
Less effective than thiazide diuretics in black and geriatric patients
May worsen bradycardia or hypotension; monitor HR and Bp
Avoid beta blockers without alpha1-adrenergic receptor blocking activity in patients with prinzmetal variant angina; unopposed alpha-1 adrenergic receptors may worsen anginal symptoms
May induce or exacerbate psoriasis; cause and effect not established
Prevents the response of endogenous catecholamines to correct hypoglycemia and masks the adrenergic warning signs of hypoglycemia, particularly tachycardia, palpitations, and sweating May cause or worsen bradycardia or hypotension
Infantile hemangiomas and PHACE syndrome
- By dropping blood pressure, propranolol may increase the risk of stroke in patients with PHACE syndrome who have severe cerebrovascular anomalies
- Investigate infants with large facial infantile hemangioma for potential arteriopathy associated with PHACE syndrome before therapy
Pregnancy and lactation
Pregnancy category: C; intrauterine growth retardation, small placentas, and congenital abnormalities reported, but no adequate and well-controlled studies conducted
Lactation: Use is controversial; an insignificant amount is excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Inderal, Inderal LA (propranolol)
Mechanism of action
Nonselective beta adrenergic receptor blocker; competitive beta1 and beta2 receptor inhibition results in decreases in heart rate, myocardial contractility, myocardial oxygen demand, and blood pressure
Class 2 antidysrhythmic
Absorption
Bioavailability: 30-70% (food increases bioavailability)
Onset: Hypertension, 2-3 wk; beta blockade, 2-10 min (IV) or 1-2 hr (PO)
Duration: 6-12 hr (immediate release); 24-27 hr (extended release)
Peak plasma time: 1-4 hr (immediate release); 6-14 hr (extended release)
Distribution
Protein bound: 68% (newborns); 90% (adults)
Vd: 4 L/kg in adults
Metabolism
Metabolized by hepatic P450 enzymes CYP2D6 and CYP1A2
Metabolites: 4-hydroxypropranolol (active)
Elimination
Half-life: Children, 3.9-6.4 hr; adults, 3.9-6.4 hr (immediate release) or 8-10 hr (extended release)
Excretion: Urine (96-99%)
Dialyzable: HD: No
Administration
IV Incompatibilities
Additive: Bicarbonate
Syringe: Bicarbonate
Y-site: Amphotericin B cholesteryl sulfate, diazoxide
IV Compatibilities
Solution: Most common solvents
Additive: Dobutamine, verapamiL
Syringe: Inamrinone, milrinone
Y-site: Alteplase, fenoldopam, gatifloxacin, heparin, hydrocortisone, sodium succinate, inamrinone, linezolid, meperidine, milrinone, morphine, potassium chloride, propofol, tacrolimus, tirofiban, vitamins B and C
IV Administration
IV administration rate should not exceed 1 mg/min
IV dose is much smaller than oral dose
Give by direct injection into large vessel or into tubing of free-flowing compatible IV solution
Continuous IV infusion generally is not recommended
Storage
Protect injection from light