MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Adenocard®; Adenoscan®
PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class IV
Diagnostic Agent
DOSING: ADULTS
Paroxysmal supraventricular tachycardia (Adenocard®): I.V. (rapid, over 1-2 seconds, via peripheral line): Initial: 6 mg; if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
Recommended dosage adjustment for adenosine when administered via central line or with concurrent carbamazepine or dipyridamole (ACLS, 2005): Initial dose: 3 mg
Pharmacologic stress testing (Adenoscan®): I.V.: Continuous I.V. infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or columetric infusion pump; total dose: 0.84 mg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.
Acute vasodilator testing in pulmonary artery hypertension (unlabeled use) (Adenoscan®): I.V.: Initial: 50 mcg/kg/minute increased by 50 mcg/kg/minute every 2 minutes to a maximum dose of 500 mcg/kg/minute (Schrader, 1992) or to a maximum dose of 250 mcg/kg/minute (McLaughlin, 2009); acutely assess vasodilator response
DOSING: PEDIATRIC — Rapid I.V. push (over 1-2 seconds) via peripheral line:
(For additional information see "Adenosine: Pediatric drug information")
Paroxysmal supraventricular tachycardia (Adenocard®): Infants and Children:
Manufacturer's recommendation:
Children <50 kg: Initial: 0.05-0.1 mg/kg (maximum initial dose: 6 mg). If conversion of PSVT does not occur within 1-2 minutes, may increase dose by 0.05-0.1 mg/kg. May repeat until sinus rhythm is established or to a maximum single dose of 0.3 mg/kg or 12 mg. Follow each dose with normal saline flush.
Children ≥ 50 kg: Refer to adult dosing.
Pediatric advanced life support (PALS, 2005): Treatment of SVT: I.V., I.O.: Initial: 0.1 mg/kg (maximum initial dose: 6 mg); if not effective within 1-2 minutes, administer 0.2 mg/kg; may repeat 0.2 mg/kg if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
DOSING: ELDERLY — Refer to adult dosing. Elderly may be more sensitive to effects of adenosine.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — For rapid bolus I.V. use only; administer I.V. push over 1-2 seconds at a peripheral I.V. site as proximal as possible to trunk (not in lower arm, hand, lower leg, or foot); follow each bolus with a rapid normal saline flush (≥ 5 mL). Use of 2 syringes (one with adenosine dose and the other with NS flush) connected to a T-connector or stopcock is recommended (ACLS, 2005). Note: If administered via central line in adults, reduce initial dose to 3 mg (ACLS, 2005).
COMPATIBILITY — Stable in D5LR, D5W, LR, NS.
USE
Adenocard®: Treatment of paroxysmal supraventricular tachycardia (PSVT) including that associated with accessory bypass tracts (Wolff-Parkinson-White syndrome); when clinically advisable, appropriate vagal maneuvers should be attempted prior to adenosine administration; not effective for conversion of atrial fibrillation, atrial flutter, or ventricular tachycardia
Adenoscan®: Pharmacologic stress agent used in myocardial perfusion thallium-201 scintigraphy
USE - UNLABELED / INVESTIGATIONAL
ACLS/PALS Guidelines (2005):
Stable, narrow-complex AV nodal or sinus nodal reentry tachycardias (eg, reentry SVT);
Unstable reentry SVT while preparations are made for synchronized direct-current cardioversion;
Undefined, stable, narrow-complex SVT as a combination therapeutic and diagnostic maneuver;
Stable, wide-complex tachycardias in patients with a recurrence of a known reentry pathway that has been previously defined
Adenoscan®: Acute vasodilator testing in pulmonary artery hypertension
ADVERSE REACTIONS SIGNIFICANT — Note: Frequency varies based on use; higher frequency of infusion-related effects, such as flushing and lightheadedness, were reported with continuous infusion (Adenoscan®).
>10%:
Cardiovascular: Facial flushing (18% to 44%)
Central nervous system: Headache (2% to 18%), lightheadedness (2% to 12%)
Gastrointestinal: GI discomfort (13%)
Neuromuscular & skeletal: Discomfort of neck, throat, jaw (<1% to 15%)
Respiratory: Chest pressure/discomfort (7% to 40%), dyspnea (12% to 28%)
1% to 10%:
Cardiovascular: AV block (infusion 6%; third degree <1%), ST segment depression (3%), hypotension (<1% to 2%), palpitation, chest pain
Central nervous system: Nervousness (2%), apprehension, dizziness
Gastrointestinal: Nausea (3%)
Neuromuscular & skeletal: Upper extremity discomfort (up to 4%), numbness (up to 2%), paresthesia (up to 2%)
Respiratory: Hyperventilation
Miscellaneous: Diaphoresis
<1% (Limited to important or life-threatening): Asystole (prolonged), atrial fibrillation (upon termination of PSVT), back discomfort, bradycardia, bronchospasm, burning sensation, blurred vision, hypertension (transient), injection site reaction, intracranial pressure increased, lower extremity discomfort, metallic taste, pressure in groin, respiratory arrest, seizure, torsade de pointes, ventricular fibrillation, ventricular tachycardia
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component of the formulation; second- or third-degree AV block or sick sinus syndrome (except in patients with a functioning artificial pacemaker); use in patients with atrial fibrillation/flutter with underlying Wolff-Parkinson-White (WPW) syndrome is considered to be contraindicated (Fuster, 2006)
In addition to the above, Adenoscan® should be avoided in patients with known or suspected bronchoconstrictive or bronchospastic lung disease.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Atrial fibrillation/flutter: There have been reports of atrial fibrillation/flutter when administered to patients with paroxysmal supraventricular tachycardia (PSVT) and may be especially problematic in patients with PSVT and underlying Wolff-Parkinson-White syndrome. Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with pre-existing S-A nodal dysfunction may experience prolonged sinus pauses after adenosine; use caution in patients with first-degree AV block or bundle branch block; avoid use of adenosine for pharmacologic stress testing in patients with high-grade AV block or sinus node dysfunction (unless a functional pacemaker is in place). Rare, prolonged episodes of asystole have been reported, with fatal outcomes in some cases. Hypotension: May produce profound vasodilation with subsequent hypotension. When used as a bolus dose (PSVT), effects are generally self-limiting (due to the short half-life of adenosine). However, when used as a continuous infusion (pharmacologic stress testing), effects may be more pronounced and persistent, corresponding to continued exposure. Use infusions with caution in patients with autonomic dysfunction, carotid stenosis (with cerebrovascular insufficiency), uncorrected hypovolemia, pericarditis, pleural effusion and/or stenotic valvular heart disease. Proarrhythmic effects: Monitor for proarrhythmic effects (eg, polymorphic ventricular tachycardia) during and shortly after administration/termination of arrhythmia. The benign transient occurrence of atrial and ventricular ectopy is common upon termination of arrhythmia.
Disease-related concerns: Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Heart transplant recipients: Use with extreme caution in heart transplant recipients; adenosine may cause prolonged asystole; reduction of initial adenosine dose is recommended (ACLS, 2005); considered by some to be contraindicated in this setting (Delacretaz, 2006). Pulmonary artery hypertension: Acute vasodilator testing (not an approved use): Use with extreme caution in patients with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; significant decompensation has occurred with other highly selective pulmonary vasodilators resulting in acute pulmonary edema. Respiratory disease: Avoid use in patients with bronchoconstriction or bronchospasm (eg, asthma); mild-to-moderate exacerbations have been reported following use in a limited number of patients with asthma. Use caution in patients with obstructive lung disease not associated with bronchoconstriction (eg, emphysema, bronchitis); respiratory compromise has occurred during use. Wolff-Parkinson-White (WPW) syndrome: Use in patients with atrial fibrillation/flutter with underlying WPW syndrome is considered to be contraindicated since ventricular fibrillation may result (Fuster, 2006).
Concurrent drug therapy issues: Caffeine: Pharmacologic stress testing: Since caffeine antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use; avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing. Carbamazepine: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Dipyridamole: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Drugs which slow AV node conduction: Use with caution in patients receiving other drugs which slow AV node conduction (eg, digoxin, verapamil). Theophylline: Pharmacologic stress testing: Since theophylline antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use whenever possible.
Special populations: Elderly: Use with caution in the elderly; may be at increased risk of hemodynamic effects, bradycardia, and/or AV block.
Dosage form specific issues: Adenocard®: Transient AV block is expected. When used in PSVT, at the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the ECG. Administer as a rapid bolus, either directly into a vein or (if administered into an I.V. line), as close to the patient as possible (followed by saline flush).
Other warnings/precautions: Appropriate use: ECG monitoring is required during use. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Adenosine does not convert atrial fibrillation/flutter to normal sinus rhythm; however, may be used diagnostically in these settings if the underlying rhythm is not apparent.
DRUG INTERACTIONS
CarBAMazepine: May enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Consider using a lower initial dose of adenosine in patients who are receiving carbamazepine. Risk D: Consider therapy modification
Dipyridamole: May enhance the therapeutic effect of Adenosine. Dose reduction of adenosine may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Risk D: Consider therapy modification
Nicotine: May enhance the AV-blocking effect of Adenosine. Nicotine may enhance the tachycardic effect of Adenosine. Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Adenosine. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Avoid food or drugs with caffeine. Adenosine's therapeutic effect may be decreased if used concurrently with caffeine. Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reports of administration during pregnancy have indicated no adverse effects on fetus or newborn attributable to adenosine.
LACTATION — Excretion in breast milk unknown
DIETARY CONSIDERATIONS — Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
MONITORING PARAMETERS — ECG, heart rate, blood pressure
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
INTERNATIONAL BRAND NAMES — Adenocard (BR); Adenocor (AU, BE, BG, CZ, DK, EE, EG, ES, FI, GB, HN, HU, IE, IL, KP, LU, MY, NO, PE, PL, PT, SE, TH, TW, UY, VE, ZA); Adenocur (NL); Adenoject (IN); Adenoscan (ES, HK); Adenosin Ebewe (PL); Adenosina Biol (AR, PY); Adenozer (TW); Adrekar (AT, DE); Cardiovert (PH); Fosfobion (PL); Krenosin (FR, IT, LU, MX); Krenosine (CH); Soladen (PL); Tricor (CN)
MECHANISM OF ACTION — Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: Very brief
Metabolism: Blood and tissue to inosine then to adenosine monophosphate (AMP) and hypoxanthine
Half-life elimination: <10 seconds
Monday, May 24, 2010
Adenosine
MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Adenocard®; Adenoscan®
PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class IV
Diagnostic Agent
DOSING: ADULTS
Paroxysmal supraventricular tachycardia (Adenocard®): I.V. (rapid, over 1-2 seconds, via peripheral line): Initial: 6 mg; if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
Recommended dosage adjustment for adenosine when administered via central line or with concurrent carbamazepine or dipyridamole (ACLS, 2005): Initial dose: 3 mg
Pharmacologic stress testing (Adenoscan®): I.V.: Continuous I.V. infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or columetric infusion pump; total dose: 0.84 mg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.
Acute vasodilator testing in pulmonary artery hypertension (unlabeled use) (Adenoscan®): I.V.: Initial: 50 mcg/kg/minute increased by 50 mcg/kg/minute every 2 minutes to a maximum dose of 500 mcg/kg/minute (Schrader, 1992) or to a maximum dose of 250 mcg/kg/minute (McLaughlin, 2009); acutely assess vasodilator response
DOSING: PEDIATRIC — Rapid I.V. push (over 1-2 seconds) via peripheral line:
(For additional information see "Adenosine: Pediatric drug information")
Paroxysmal supraventricular tachycardia (Adenocard®): Infants and Children:
Manufacturer's recommendation:
Children <50 kg: Initial: 0.05-0.1 mg/kg (maximum initial dose: 6 mg). If conversion of PSVT does not occur within 1-2 minutes, may increase dose by 0.05-0.1 mg/kg. May repeat until sinus rhythm is established or to a maximum single dose of 0.3 mg/kg or 12 mg. Follow each dose with normal saline flush.
Children ≥ 50 kg: Refer to adult dosing.
Pediatric advanced life support (PALS, 2005): Treatment of SVT: I.V., I.O.: Initial: 0.1 mg/kg (maximum initial dose: 6 mg); if not effective within 1-2 minutes, administer 0.2 mg/kg; may repeat 0.2 mg/kg if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
DOSING: ELDERLY — Refer to adult dosing. Elderly may be more sensitive to effects of adenosine.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — For rapid bolus I.V. use only; administer I.V. push over 1-2 seconds at a peripheral I.V. site as proximal as possible to trunk (not in lower arm, hand, lower leg, or foot); follow each bolus with a rapid normal saline flush (≥ 5 mL). Use of 2 syringes (one with adenosine dose and the other with NS flush) connected to a T-connector or stopcock is recommended (ACLS, 2005). Note: If administered via central line in adults, reduce initial dose to 3 mg (ACLS, 2005).
COMPATIBILITY — Stable in D5LR, D5W, LR, NS.
USE
Adenocard®: Treatment of paroxysmal supraventricular tachycardia (PSVT) including that associated with accessory bypass tracts (Wolff-Parkinson-White syndrome); when clinically advisable, appropriate vagal maneuvers should be attempted prior to adenosine administration; not effective for conversion of atrial fibrillation, atrial flutter, or ventricular tachycardia
Adenoscan®: Pharmacologic stress agent used in myocardial perfusion thallium-201 scintigraphy
USE - UNLABELED / INVESTIGATIONAL
ACLS/PALS Guidelines (2005):
Stable, narrow-complex AV nodal or sinus nodal reentry tachycardias (eg, reentry SVT);
Unstable reentry SVT while preparations are made for synchronized direct-current cardioversion;
Undefined, stable, narrow-complex SVT as a combination therapeutic and diagnostic maneuver;
Stable, wide-complex tachycardias in patients with a recurrence of a known reentry pathway that has been previously defined
Adenoscan®: Acute vasodilator testing in pulmonary artery hypertension
ADVERSE REACTIONS SIGNIFICANT — Note: Frequency varies based on use; higher frequency of infusion-related effects, such as flushing and lightheadedness, were reported with continuous infusion (Adenoscan®).
>10%:
Cardiovascular: Facial flushing (18% to 44%)
Central nervous system: Headache (2% to 18%), lightheadedness (2% to 12%)
Gastrointestinal: GI discomfort (13%)
Neuromuscular & skeletal: Discomfort of neck, throat, jaw (<1% to 15%)
Respiratory: Chest pressure/discomfort (7% to 40%), dyspnea (12% to 28%)
1% to 10%:
Cardiovascular: AV block (infusion 6%; third degree <1%), ST segment depression (3%), hypotension (<1% to 2%), palpitation, chest pain
Central nervous system: Nervousness (2%), apprehension, dizziness
Gastrointestinal: Nausea (3%)
Neuromuscular & skeletal: Upper extremity discomfort (up to 4%), numbness (up to 2%), paresthesia (up to 2%)
Respiratory: Hyperventilation
Miscellaneous: Diaphoresis
<1% (Limited to important or life-threatening): Asystole (prolonged), atrial fibrillation (upon termination of PSVT), back discomfort, bradycardia, bronchospasm, burning sensation, blurred vision, hypertension (transient), injection site reaction, intracranial pressure increased, lower extremity discomfort, metallic taste, pressure in groin, respiratory arrest, seizure, torsade de pointes, ventricular fibrillation, ventricular tachycardia
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component of the formulation; second- or third-degree AV block or sick sinus syndrome (except in patients with a functioning artificial pacemaker); use in patients with atrial fibrillation/flutter with underlying Wolff-Parkinson-White (WPW) syndrome is considered to be contraindicated (Fuster, 2006)
In addition to the above, Adenoscan® should be avoided in patients with known or suspected bronchoconstrictive or bronchospastic lung disease.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Atrial fibrillation/flutter: There have been reports of atrial fibrillation/flutter when administered to patients with paroxysmal supraventricular tachycardia (PSVT) and may be especially problematic in patients with PSVT and underlying Wolff-Parkinson-White syndrome. Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with pre-existing S-A nodal dysfunction may experience prolonged sinus pauses after adenosine; use caution in patients with first-degree AV block or bundle branch block; avoid use of adenosine for pharmacologic stress testing in patients with high-grade AV block or sinus node dysfunction (unless a functional pacemaker is in place). Rare, prolonged episodes of asystole have been reported, with fatal outcomes in some cases. Hypotension: May produce profound vasodilation with subsequent hypotension. When used as a bolus dose (PSVT), effects are generally self-limiting (due to the short half-life of adenosine). However, when used as a continuous infusion (pharmacologic stress testing), effects may be more pronounced and persistent, corresponding to continued exposure. Use infusions with caution in patients with autonomic dysfunction, carotid stenosis (with cerebrovascular insufficiency), uncorrected hypovolemia, pericarditis, pleural effusion and/or stenotic valvular heart disease. Proarrhythmic effects: Monitor for proarrhythmic effects (eg, polymorphic ventricular tachycardia) during and shortly after administration/termination of arrhythmia. The benign transient occurrence of atrial and ventricular ectopy is common upon termination of arrhythmia.
Disease-related concerns: Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Heart transplant recipients: Use with extreme caution in heart transplant recipients; adenosine may cause prolonged asystole; reduction of initial adenosine dose is recommended (ACLS, 2005); considered by some to be contraindicated in this setting (Delacretaz, 2006). Pulmonary artery hypertension: Acute vasodilator testing (not an approved use): Use with extreme caution in patients with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; significant decompensation has occurred with other highly selective pulmonary vasodilators resulting in acute pulmonary edema. Respiratory disease: Avoid use in patients with bronchoconstriction or bronchospasm (eg, asthma); mild-to-moderate exacerbations have been reported following use in a limited number of patients with asthma. Use caution in patients with obstructive lung disease not associated with bronchoconstriction (eg, emphysema, bronchitis); respiratory compromise has occurred during use. Wolff-Parkinson-White (WPW) syndrome: Use in patients with atrial fibrillation/flutter with underlying WPW syndrome is considered to be contraindicated since ventricular fibrillation may result (Fuster, 2006).
Concurrent drug therapy issues: Caffeine: Pharmacologic stress testing: Since caffeine antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use; avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing. Carbamazepine: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Dipyridamole: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Drugs which slow AV node conduction: Use with caution in patients receiving other drugs which slow AV node conduction (eg, digoxin, verapamil). Theophylline: Pharmacologic stress testing: Since theophylline antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use whenever possible.
Special populations: Elderly: Use with caution in the elderly; may be at increased risk of hemodynamic effects, bradycardia, and/or AV block.
Dosage form specific issues: Adenocard®: Transient AV block is expected. When used in PSVT, at the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the ECG. Administer as a rapid bolus, either directly into a vein or (if administered into an I.V. line), as close to the patient as possible (followed by saline flush).
Other warnings/precautions: Appropriate use: ECG monitoring is required during use. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Adenosine does not convert atrial fibrillation/flutter to normal sinus rhythm; however, may be used diagnostically in these settings if the underlying rhythm is not apparent.
DRUG INTERACTIONS
CarBAMazepine: May enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Consider using a lower initial dose of adenosine in patients who are receiving carbamazepine. Risk D: Consider therapy modification
Dipyridamole: May enhance the therapeutic effect of Adenosine. Dose reduction of adenosine may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Risk D: Consider therapy modification
Nicotine: May enhance the AV-blocking effect of Adenosine. Nicotine may enhance the tachycardic effect of Adenosine. Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Adenosine. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Avoid food or drugs with caffeine. Adenosine's therapeutic effect may be decreased if used concurrently with caffeine. Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reports of administration during pregnancy have indicated no adverse effects on fetus or newborn attributable to adenosine.
LACTATION — Excretion in breast milk unknown
DIETARY CONSIDERATIONS — Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
MONITORING PARAMETERS — ECG, heart rate, blood pressure
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
INTERNATIONAL BRAND NAMES — Adenocard (BR); Adenocor (AU, BE, BG, CZ, DK, EE, EG, ES, FI, GB, HN, HU, IE, IL, KP, LU, MY, NO, PE, PL, PT, SE, TH, TW, UY, VE, ZA); Adenocur (NL); Adenoject (IN); Adenoscan (ES, HK); Adenosin Ebewe (PL); Adenosina Biol (AR, PY); Adenozer (TW); Adrekar (AT, DE); Cardiovert (PH); Fosfobion (PL); Krenosin (FR, IT, LU, MX); Krenosine (CH); Soladen (PL); Tricor (CN)
MECHANISM OF ACTION — Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: Very brief
Metabolism: Blood and tissue to inosine then to adenosine monophosphate (AMP) and hypoxanthine
Half-life elimination: <10 seconds
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Adenocard®; Adenoscan®
PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class IV
Diagnostic Agent
DOSING: ADULTS
Paroxysmal supraventricular tachycardia (Adenocard®): I.V. (rapid, over 1-2 seconds, via peripheral line): Initial: 6 mg; if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
Recommended dosage adjustment for adenosine when administered via central line or with concurrent carbamazepine or dipyridamole (ACLS, 2005): Initial dose: 3 mg
Pharmacologic stress testing (Adenoscan®): I.V.: Continuous I.V. infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or columetric infusion pump; total dose: 0.84 mg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.
Acute vasodilator testing in pulmonary artery hypertension (unlabeled use) (Adenoscan®): I.V.: Initial: 50 mcg/kg/minute increased by 50 mcg/kg/minute every 2 minutes to a maximum dose of 500 mcg/kg/minute (Schrader, 1992) or to a maximum dose of 250 mcg/kg/minute (McLaughlin, 2009); acutely assess vasodilator response
DOSING: PEDIATRIC — Rapid I.V. push (over 1-2 seconds) via peripheral line:
(For additional information see "Adenosine: Pediatric drug information")
Paroxysmal supraventricular tachycardia (Adenocard®): Infants and Children:
Manufacturer's recommendation:
Children <50 kg: Initial: 0.05-0.1 mg/kg (maximum initial dose: 6 mg). If conversion of PSVT does not occur within 1-2 minutes, may increase dose by 0.05-0.1 mg/kg. May repeat until sinus rhythm is established or to a maximum single dose of 0.3 mg/kg or 12 mg. Follow each dose with normal saline flush.
Children ≥ 50 kg: Refer to adult dosing.
Pediatric advanced life support (PALS, 2005): Treatment of SVT: I.V., I.O.: Initial: 0.1 mg/kg (maximum initial dose: 6 mg); if not effective within 1-2 minutes, administer 0.2 mg/kg; may repeat 0.2 mg/kg if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
DOSING: ELDERLY — Refer to adult dosing. Elderly may be more sensitive to effects of adenosine.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — For rapid bolus I.V. use only; administer I.V. push over 1-2 seconds at a peripheral I.V. site as proximal as possible to trunk (not in lower arm, hand, lower leg, or foot); follow each bolus with a rapid normal saline flush (≥ 5 mL). Use of 2 syringes (one with adenosine dose and the other with NS flush) connected to a T-connector or stopcock is recommended (ACLS, 2005). Note: If administered via central line in adults, reduce initial dose to 3 mg (ACLS, 2005).
COMPATIBILITY — Stable in D5LR, D5W, LR, NS.
USE
Adenocard®: Treatment of paroxysmal supraventricular tachycardia (PSVT) including that associated with accessory bypass tracts (Wolff-Parkinson-White syndrome); when clinically advisable, appropriate vagal maneuvers should be attempted prior to adenosine administration; not effective for conversion of atrial fibrillation, atrial flutter, or ventricular tachycardia
Adenoscan®: Pharmacologic stress agent used in myocardial perfusion thallium-201 scintigraphy
USE - UNLABELED / INVESTIGATIONAL
ACLS/PALS Guidelines (2005):
Stable, narrow-complex AV nodal or sinus nodal reentry tachycardias (eg, reentry SVT);
Unstable reentry SVT while preparations are made for synchronized direct-current cardioversion;
Undefined, stable, narrow-complex SVT as a combination therapeutic and diagnostic maneuver;
Stable, wide-complex tachycardias in patients with a recurrence of a known reentry pathway that has been previously defined
Adenoscan®: Acute vasodilator testing in pulmonary artery hypertension
ADVERSE REACTIONS SIGNIFICANT — Note: Frequency varies based on use; higher frequency of infusion-related effects, such as flushing and lightheadedness, were reported with continuous infusion (Adenoscan®).
>10%:
Cardiovascular: Facial flushing (18% to 44%)
Central nervous system: Headache (2% to 18%), lightheadedness (2% to 12%)
Gastrointestinal: GI discomfort (13%)
Neuromuscular & skeletal: Discomfort of neck, throat, jaw (<1% to 15%)
Respiratory: Chest pressure/discomfort (7% to 40%), dyspnea (12% to 28%)
1% to 10%:
Cardiovascular: AV block (infusion 6%; third degree <1%), ST segment depression (3%), hypotension (<1% to 2%), palpitation, chest pain
Central nervous system: Nervousness (2%), apprehension, dizziness
Gastrointestinal: Nausea (3%)
Neuromuscular & skeletal: Upper extremity discomfort (up to 4%), numbness (up to 2%), paresthesia (up to 2%)
Respiratory: Hyperventilation
Miscellaneous: Diaphoresis
<1% (Limited to important or life-threatening): Asystole (prolonged), atrial fibrillation (upon termination of PSVT), back discomfort, bradycardia, bronchospasm, burning sensation, blurred vision, hypertension (transient), injection site reaction, intracranial pressure increased, lower extremity discomfort, metallic taste, pressure in groin, respiratory arrest, seizure, torsade de pointes, ventricular fibrillation, ventricular tachycardia
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component of the formulation; second- or third-degree AV block or sick sinus syndrome (except in patients with a functioning artificial pacemaker); use in patients with atrial fibrillation/flutter with underlying Wolff-Parkinson-White (WPW) syndrome is considered to be contraindicated (Fuster, 2006)
In addition to the above, Adenoscan® should be avoided in patients with known or suspected bronchoconstrictive or bronchospastic lung disease.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Atrial fibrillation/flutter: There have been reports of atrial fibrillation/flutter when administered to patients with paroxysmal supraventricular tachycardia (PSVT) and may be especially problematic in patients with PSVT and underlying Wolff-Parkinson-White syndrome. Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with pre-existing S-A nodal dysfunction may experience prolonged sinus pauses after adenosine; use caution in patients with first-degree AV block or bundle branch block; avoid use of adenosine for pharmacologic stress testing in patients with high-grade AV block or sinus node dysfunction (unless a functional pacemaker is in place). Rare, prolonged episodes of asystole have been reported, with fatal outcomes in some cases. Hypotension: May produce profound vasodilation with subsequent hypotension. When used as a bolus dose (PSVT), effects are generally self-limiting (due to the short half-life of adenosine). However, when used as a continuous infusion (pharmacologic stress testing), effects may be more pronounced and persistent, corresponding to continued exposure. Use infusions with caution in patients with autonomic dysfunction, carotid stenosis (with cerebrovascular insufficiency), uncorrected hypovolemia, pericarditis, pleural effusion and/or stenotic valvular heart disease. Proarrhythmic effects: Monitor for proarrhythmic effects (eg, polymorphic ventricular tachycardia) during and shortly after administration/termination of arrhythmia. The benign transient occurrence of atrial and ventricular ectopy is common upon termination of arrhythmia.
Disease-related concerns: Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Heart transplant recipients: Use with extreme caution in heart transplant recipients; adenosine may cause prolonged asystole; reduction of initial adenosine dose is recommended (ACLS, 2005); considered by some to be contraindicated in this setting (Delacretaz, 2006). Pulmonary artery hypertension: Acute vasodilator testing (not an approved use): Use with extreme caution in patients with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; significant decompensation has occurred with other highly selective pulmonary vasodilators resulting in acute pulmonary edema. Respiratory disease: Avoid use in patients with bronchoconstriction or bronchospasm (eg, asthma); mild-to-moderate exacerbations have been reported following use in a limited number of patients with asthma. Use caution in patients with obstructive lung disease not associated with bronchoconstriction (eg, emphysema, bronchitis); respiratory compromise has occurred during use. Wolff-Parkinson-White (WPW) syndrome: Use in patients with atrial fibrillation/flutter with underlying WPW syndrome is considered to be contraindicated since ventricular fibrillation may result (Fuster, 2006).
Concurrent drug therapy issues: Caffeine: Pharmacologic stress testing: Since caffeine antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use; avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing. Carbamazepine: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Dipyridamole: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Drugs which slow AV node conduction: Use with caution in patients receiving other drugs which slow AV node conduction (eg, digoxin, verapamil). Theophylline: Pharmacologic stress testing: Since theophylline antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use whenever possible.
Special populations: Elderly: Use with caution in the elderly; may be at increased risk of hemodynamic effects, bradycardia, and/or AV block.
Dosage form specific issues: Adenocard®: Transient AV block is expected. When used in PSVT, at the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the ECG. Administer as a rapid bolus, either directly into a vein or (if administered into an I.V. line), as close to the patient as possible (followed by saline flush).
Other warnings/precautions: Appropriate use: ECG monitoring is required during use. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Adenosine does not convert atrial fibrillation/flutter to normal sinus rhythm; however, may be used diagnostically in these settings if the underlying rhythm is not apparent.
DRUG INTERACTIONS
CarBAMazepine: May enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Consider using a lower initial dose of adenosine in patients who are receiving carbamazepine. Risk D: Consider therapy modification
Dipyridamole: May enhance the therapeutic effect of Adenosine. Dose reduction of adenosine may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Risk D: Consider therapy modification
Nicotine: May enhance the AV-blocking effect of Adenosine. Nicotine may enhance the tachycardic effect of Adenosine. Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Adenosine. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Avoid food or drugs with caffeine. Adenosine's therapeutic effect may be decreased if used concurrently with caffeine. Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reports of administration during pregnancy have indicated no adverse effects on fetus or newborn attributable to adenosine.
LACTATION — Excretion in breast milk unknown
DIETARY CONSIDERATIONS — Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
MONITORING PARAMETERS — ECG, heart rate, blood pressure
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
INTERNATIONAL BRAND NAMES — Adenocard (BR); Adenocor (AU, BE, BG, CZ, DK, EE, EG, ES, FI, GB, HN, HU, IE, IL, KP, LU, MY, NO, PE, PL, PT, SE, TH, TW, UY, VE, ZA); Adenocur (NL); Adenoject (IN); Adenoscan (ES, HK); Adenosin Ebewe (PL); Adenosina Biol (AR, PY); Adenozer (TW); Adrekar (AT, DE); Cardiovert (PH); Fosfobion (PL); Krenosin (FR, IT, LU, MX); Krenosine (CH); Soladen (PL); Tricor (CN)
MECHANISM OF ACTION — Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: Very brief
Metabolism: Blood and tissue to inosine then to adenosine monophosphate (AMP) and hypoxanthine
Half-life elimination: <10 seconds
Adefovir
U.S. BRAND NAMES — Hepsera™
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — Hepatitis B (chronic): Oral: 10 mg once daily. Note: Usual treatment duration is at least 1 year and varies with HBeAg status, consult current guidelines and literature.
DOSING: PEDIATRIC — Hepatitis B (chronic): Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Adult recommendations only (no dosage adjustment recommendations available for patients <18 years with renal impairment):
Clcr ≥ 50 mL/minute: No dosage adjustment necessary
Clcr 30-49 mL/minute: 10 mg every 48 hours
Clcr 10-29 mL/minute: 10 mg every 72 hours
Hemodialysis: 10 mg every 7 days (following dialysis)
DOSING: HEPATIC IMPAIRMENT — No adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as dipivoxil:
Hepsera®: 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Hepsera®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered without regard to food.
USE — Treatment of chronic hepatitis B with evidence of active viral replication (based on persistent elevation of ALT/AST or histologic evidence), including patients with lamivudine-resistant hepatitis B
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (24% to 25%)
Gastrointestinal: Abdominal pain (15% to 18%), diarrhea (up to 13%)
Hepatic: Hepatitis exacerbation (up to 25% within 12 weeks of adefovir discontinuation)
Neuromuscular & skeletal: Weakness (13% to 25%)
Renal: Hematuria (grade ≥ 3: 11%)
1% to 10%:
Dermatologic: Rash, pruritus
Endocrine & metabolic: Hypophosphatemia (<2 mg/dL: 1% and 3% in pre-/post-liver transplant patients, respectively)
Gastrointestinal: Flatulence (up to 8%), dyspepsia (5% to 9%), nausea, vomiting
Renal: Serum creatinine increased (≥ 0.5 mg/dL: 2% to 3% in compensated liver disease; incidence may be higher in patients with decompensated cirrhosis or in liver transplant recipients), renal failure
Note: In liver transplant patients with baseline renal dysfunction, frequency of increased serum creatinine has been observed to be as high as 32% to 51% at 48 and 96 weeks post-transplantation, respectively; considering the concomitant use of other potentially nephrotoxic medications, baseline renal insufficiency, and predisposing comorbidities, the role of adefovir in these changes could not be established.
Respiratory: Cough (6% to 8%), rhinitis (up to 5%)
Postmarketing and/or case reports: Fanconi syndrome, hepatitis, myopathy, nephrotoxicity, osteomalacia
CONTRAINDICATIONS — Hypersensitivity to adefovir or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: . Human immunodeficiency virus (HIV): . Lactic acidosis/hepatomegaly: . Renal impairment: .
Concerns related to adverse effects: Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Exacerbations may occur in up to 25% of patients and usually within 12 weeks and may be self-limited or resolve upon resuming treatment; risk may be increased with advanced liver disease or cirrhosis. Monitor liver function several months after stopping treatment; reinitiation of antihepatitis B therapy may be required.
Resistant hepatitis B virus (HBV): In patients with lamivudine-resistant HBV, switching to adefovir was associated with a higher risk of adefovir-resistance compared to adding adefovir to lamivudine therapy (Lok, 2007).
Nonresponse to adefovir monotherapy (<2 log drop in HBV DNA after 6 months of treatment): Consider alternative treatment (Lok, 2007). HIV: [U.S. Boxed Warning]:May cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Determine HIV status prior to initiating treatment with adefovir. Renal impairment: [U.S. Boxed Warning]: Use with caution in patients with renal dysfunction or in patients at risk of renal toxicity (including concurrent nephrotoxic agents or NSAIDs). Chronic administration may result in nephrotoxicity. Dosage adjustment is required in adult patients with renal dysfunction or in patients who develop renal dysfunction during therapy; no data available for use in children ≥ 12 years or adolescents with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Tenofovir: Adefovir may diminish the therapeutic effect of Tenofovir. Specifically, adefovir-associated mutations in Hepatitis B viral reverse transcriptase may decrease viral susceptibility to tenofovir. Tenofovir may increase the serum concentration of Adefovir. Similarly, Adefovir may increase the concentration of Tenofovir. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Should be avoided in hepatitis B infection due to potential hepatic toxicity.
Food: Does not have a significant effect on adefovir absorption.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use in pregnancy only when clearly needed. Pregnant women exposed to adefovir should be registered with the pregnancy registry (800-258-4263).
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken without regard to food.
PRICING — (data from drugstore.com)
Tablets (Hepsera)
10 mg (30): $882.35
MONITORING PARAMETERS — HIV status (prior to initiation of therapy); serum creatinine (prior to initiation and during therapy; every 3 months in patients with medical conditions which predispose to renal insufficiency and in all patients treated for >1 year; more frequent monitoring required if preexisting real insufficiency detected [Lok, 2007]); viral load; LFTs for several months following discontinuation of adefovir
CANADIAN BRAND NAMES — Hepsera™
INTERNATIONAL BRAND NAMES — Adesera (IN); Hepsera (AR, AT, AU, BE, BG, BR, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, HK, HN, ID, IE, IL, IT, KP, NI, NL, NO, PA, PE, PH, PK, PL, PT, RU, SE, SG, SV, TH, TR, TW, VE); Youheding (CL)
MECHANISM OF ACTION — Acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Distribution: 0.35-0.39 L/kg
Protein binding: ≤ 4%
Metabolism: Prodrug; rapidly converted to adefovir (active metabolite) in intestine
Bioavailability: 59%
Half-life elimination: 7.5 hours; prolonged in renal impairment
Time to peak: 1.75 hours
Excretion: Urine (45% as active metabolite within 24 hours)
PATIENT INFORMATION — Not a cure for hepatitis B, nor will it reduce the risk of transmission. Report persistent lethargy, acute headache, severe nausea or vomiting, difficulty breathing, loss of sensation, or rash. Do not discontinue unless instructed by prescriber; additional monitoring is required after discontinuation to ensure the disease does not recur.
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — Hepatitis B (chronic): Oral: 10 mg once daily. Note: Usual treatment duration is at least 1 year and varies with HBeAg status, consult current guidelines and literature.
DOSING: PEDIATRIC — Hepatitis B (chronic): Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Adult recommendations only (no dosage adjustment recommendations available for patients <18 years with renal impairment):
Clcr ≥ 50 mL/minute: No dosage adjustment necessary
Clcr 30-49 mL/minute: 10 mg every 48 hours
Clcr 10-29 mL/minute: 10 mg every 72 hours
Hemodialysis: 10 mg every 7 days (following dialysis)
DOSING: HEPATIC IMPAIRMENT — No adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as dipivoxil:
Hepsera®: 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Hepsera®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered without regard to food.
USE — Treatment of chronic hepatitis B with evidence of active viral replication (based on persistent elevation of ALT/AST or histologic evidence), including patients with lamivudine-resistant hepatitis B
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (24% to 25%)
Gastrointestinal: Abdominal pain (15% to 18%), diarrhea (up to 13%)
Hepatic: Hepatitis exacerbation (up to 25% within 12 weeks of adefovir discontinuation)
Neuromuscular & skeletal: Weakness (13% to 25%)
Renal: Hematuria (grade ≥ 3: 11%)
1% to 10%:
Dermatologic: Rash, pruritus
Endocrine & metabolic: Hypophosphatemia (<2 mg/dL: 1% and 3% in pre-/post-liver transplant patients, respectively)
Gastrointestinal: Flatulence (up to 8%), dyspepsia (5% to 9%), nausea, vomiting
Renal: Serum creatinine increased (≥ 0.5 mg/dL: 2% to 3% in compensated liver disease; incidence may be higher in patients with decompensated cirrhosis or in liver transplant recipients), renal failure
Note: In liver transplant patients with baseline renal dysfunction, frequency of increased serum creatinine has been observed to be as high as 32% to 51% at 48 and 96 weeks post-transplantation, respectively; considering the concomitant use of other potentially nephrotoxic medications, baseline renal insufficiency, and predisposing comorbidities, the role of adefovir in these changes could not be established.
Respiratory: Cough (6% to 8%), rhinitis (up to 5%)
Postmarketing and/or case reports: Fanconi syndrome, hepatitis, myopathy, nephrotoxicity, osteomalacia
CONTRAINDICATIONS — Hypersensitivity to adefovir or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: . Human immunodeficiency virus (HIV): . Lactic acidosis/hepatomegaly: . Renal impairment: .
Concerns related to adverse effects: Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Exacerbations may occur in up to 25% of patients and usually within 12 weeks and may be self-limited or resolve upon resuming treatment; risk may be increased with advanced liver disease or cirrhosis. Monitor liver function several months after stopping treatment; reinitiation of antihepatitis B therapy may be required.
Resistant hepatitis B virus (HBV): In patients with lamivudine-resistant HBV, switching to adefovir was associated with a higher risk of adefovir-resistance compared to adding adefovir to lamivudine therapy (Lok, 2007).
Nonresponse to adefovir monotherapy (<2 log drop in HBV DNA after 6 months of treatment): Consider alternative treatment (Lok, 2007). HIV: [U.S. Boxed Warning]:May cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Determine HIV status prior to initiating treatment with adefovir. Renal impairment: [U.S. Boxed Warning]: Use with caution in patients with renal dysfunction or in patients at risk of renal toxicity (including concurrent nephrotoxic agents or NSAIDs). Chronic administration may result in nephrotoxicity. Dosage adjustment is required in adult patients with renal dysfunction or in patients who develop renal dysfunction during therapy; no data available for use in children ≥ 12 years or adolescents with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Tenofovir: Adefovir may diminish the therapeutic effect of Tenofovir. Specifically, adefovir-associated mutations in Hepatitis B viral reverse transcriptase may decrease viral susceptibility to tenofovir. Tenofovir may increase the serum concentration of Adefovir. Similarly, Adefovir may increase the concentration of Tenofovir. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Should be avoided in hepatitis B infection due to potential hepatic toxicity.
Food: Does not have a significant effect on adefovir absorption.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use in pregnancy only when clearly needed. Pregnant women exposed to adefovir should be registered with the pregnancy registry (800-258-4263).
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken without regard to food.
PRICING — (data from drugstore.com)
Tablets (Hepsera)
10 mg (30): $882.35
MONITORING PARAMETERS — HIV status (prior to initiation of therapy); serum creatinine (prior to initiation and during therapy; every 3 months in patients with medical conditions which predispose to renal insufficiency and in all patients treated for >1 year; more frequent monitoring required if preexisting real insufficiency detected [Lok, 2007]); viral load; LFTs for several months following discontinuation of adefovir
CANADIAN BRAND NAMES — Hepsera™
INTERNATIONAL BRAND NAMES — Adesera (IN); Hepsera (AR, AT, AU, BE, BG, BR, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, HK, HN, ID, IE, IL, IT, KP, NI, NL, NO, PA, PE, PH, PK, PL, PT, RU, SE, SG, SV, TH, TR, TW, VE); Youheding (CL)
MECHANISM OF ACTION — Acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Distribution: 0.35-0.39 L/kg
Protein binding: ≤ 4%
Metabolism: Prodrug; rapidly converted to adefovir (active metabolite) in intestine
Bioavailability: 59%
Half-life elimination: 7.5 hours; prolonged in renal impairment
Time to peak: 1.75 hours
Excretion: Urine (45% as active metabolite within 24 hours)
PATIENT INFORMATION — Not a cure for hepatitis B, nor will it reduce the risk of transmission. Report persistent lethargy, acute headache, severe nausea or vomiting, difficulty breathing, loss of sensation, or rash. Do not discontinue unless instructed by prescriber; additional monitoring is required after discontinuation to ensure the disease does not recur.
Adefovir
U.S. BRAND NAMES — Hepsera™
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — Hepatitis B (chronic): Oral: 10 mg once daily. Note: Usual treatment duration is at least 1 year and varies with HBeAg status, consult current guidelines and literature.
DOSING: PEDIATRIC — Hepatitis B (chronic): Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Adult recommendations only (no dosage adjustment recommendations available for patients <18 years with renal impairment):
Clcr ≥ 50 mL/minute: No dosage adjustment necessary
Clcr 30-49 mL/minute: 10 mg every 48 hours
Clcr 10-29 mL/minute: 10 mg every 72 hours
Hemodialysis: 10 mg every 7 days (following dialysis)
DOSING: HEPATIC IMPAIRMENT — No adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as dipivoxil:
Hepsera®: 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Hepsera®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered without regard to food.
USE — Treatment of chronic hepatitis B with evidence of active viral replication (based on persistent elevation of ALT/AST or histologic evidence), including patients with lamivudine-resistant hepatitis B
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (24% to 25%)
Gastrointestinal: Abdominal pain (15% to 18%), diarrhea (up to 13%)
Hepatic: Hepatitis exacerbation (up to 25% within 12 weeks of adefovir discontinuation)
Neuromuscular & skeletal: Weakness (13% to 25%)
Renal: Hematuria (grade ≥ 3: 11%)
1% to 10%:
Dermatologic: Rash, pruritus
Endocrine & metabolic: Hypophosphatemia (<2 mg/dL: 1% and 3% in pre-/post-liver transplant patients, respectively)
Gastrointestinal: Flatulence (up to 8%), dyspepsia (5% to 9%), nausea, vomiting
Renal: Serum creatinine increased (≥ 0.5 mg/dL: 2% to 3% in compensated liver disease; incidence may be higher in patients with decompensated cirrhosis or in liver transplant recipients), renal failure
Note: In liver transplant patients with baseline renal dysfunction, frequency of increased serum creatinine has been observed to be as high as 32% to 51% at 48 and 96 weeks post-transplantation, respectively; considering the concomitant use of other potentially nephrotoxic medications, baseline renal insufficiency, and predisposing comorbidities, the role of adefovir in these changes could not be established.
Respiratory: Cough (6% to 8%), rhinitis (up to 5%)
Postmarketing and/or case reports: Fanconi syndrome, hepatitis, myopathy, nephrotoxicity, osteomalacia
CONTRAINDICATIONS — Hypersensitivity to adefovir or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: . Human immunodeficiency virus (HIV): . Lactic acidosis/hepatomegaly: . Renal impairment: .
Concerns related to adverse effects: Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Exacerbations may occur in up to 25% of patients and usually within 12 weeks and may be self-limited or resolve upon resuming treatment; risk may be increased with advanced liver disease or cirrhosis. Monitor liver function several months after stopping treatment; reinitiation of antihepatitis B therapy may be required.
Resistant hepatitis B virus (HBV): In patients with lamivudine-resistant HBV, switching to adefovir was associated with a higher risk of adefovir-resistance compared to adding adefovir to lamivudine therapy (Lok, 2007).
Nonresponse to adefovir monotherapy (<2 log drop in HBV DNA after 6 months of treatment): Consider alternative treatment (Lok, 2007). HIV: [U.S. Boxed Warning]:May cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Determine HIV status prior to initiating treatment with adefovir. Renal impairment: [U.S. Boxed Warning]: Use with caution in patients with renal dysfunction or in patients at risk of renal toxicity (including concurrent nephrotoxic agents or NSAIDs). Chronic administration may result in nephrotoxicity. Dosage adjustment is required in adult patients with renal dysfunction or in patients who develop renal dysfunction during therapy; no data available for use in children ≥ 12 years or adolescents with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Tenofovir: Adefovir may diminish the therapeutic effect of Tenofovir. Specifically, adefovir-associated mutations in Hepatitis B viral reverse transcriptase may decrease viral susceptibility to tenofovir. Tenofovir may increase the serum concentration of Adefovir. Similarly, Adefovir may increase the concentration of Tenofovir. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Should be avoided in hepatitis B infection due to potential hepatic toxicity.
Food: Does not have a significant effect on adefovir absorption.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use in pregnancy only when clearly needed. Pregnant women exposed to adefovir should be registered with the pregnancy registry (800-258-4263).
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken without regard to food.
PRICING — (data from drugstore.com)
Tablets (Hepsera)
10 mg (30): $882.35
MONITORING PARAMETERS — HIV status (prior to initiation of therapy); serum creatinine (prior to initiation and during therapy; every 3 months in patients with medical conditions which predispose to renal insufficiency and in all patients treated for >1 year; more frequent monitoring required if preexisting real insufficiency detected [Lok, 2007]); viral load; LFTs for several months following discontinuation of adefovir
CANADIAN BRAND NAMES — Hepsera™
INTERNATIONAL BRAND NAMES — Adesera (IN); Hepsera (AR, AT, AU, BE, BG, BR, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, HK, HN, ID, IE, IL, IT, KP, NI, NL, NO, PA, PE, PH, PK, PL, PT, RU, SE, SG, SV, TH, TR, TW, VE); Youheding (CL)
MECHANISM OF ACTION — Acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Distribution: 0.35-0.39 L/kg
Protein binding: ≤ 4%
Metabolism: Prodrug; rapidly converted to adefovir (active metabolite) in intestine
Bioavailability: 59%
Half-life elimination: 7.5 hours; prolonged in renal impairment
Time to peak: 1.75 hours
Excretion: Urine (45% as active metabolite within 24 hours)
PATIENT INFORMATION — Not a cure for hepatitis B, nor will it reduce the risk of transmission. Report persistent lethargy, acute headache, severe nausea or vomiting, difficulty breathing, loss of sensation, or rash. Do not discontinue unless instructed by prescriber; additional monitoring is required after discontinuation to ensure the disease does not recur.
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — Hepatitis B (chronic): Oral: 10 mg once daily. Note: Usual treatment duration is at least 1 year and varies with HBeAg status, consult current guidelines and literature.
DOSING: PEDIATRIC — Hepatitis B (chronic): Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Adult recommendations only (no dosage adjustment recommendations available for patients <18 years with renal impairment):
Clcr ≥ 50 mL/minute: No dosage adjustment necessary
Clcr 30-49 mL/minute: 10 mg every 48 hours
Clcr 10-29 mL/minute: 10 mg every 72 hours
Hemodialysis: 10 mg every 7 days (following dialysis)
DOSING: HEPATIC IMPAIRMENT — No adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as dipivoxil:
Hepsera®: 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Hepsera®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered without regard to food.
USE — Treatment of chronic hepatitis B with evidence of active viral replication (based on persistent elevation of ALT/AST or histologic evidence), including patients with lamivudine-resistant hepatitis B
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (24% to 25%)
Gastrointestinal: Abdominal pain (15% to 18%), diarrhea (up to 13%)
Hepatic: Hepatitis exacerbation (up to 25% within 12 weeks of adefovir discontinuation)
Neuromuscular & skeletal: Weakness (13% to 25%)
Renal: Hematuria (grade ≥ 3: 11%)
1% to 10%:
Dermatologic: Rash, pruritus
Endocrine & metabolic: Hypophosphatemia (<2 mg/dL: 1% and 3% in pre-/post-liver transplant patients, respectively)
Gastrointestinal: Flatulence (up to 8%), dyspepsia (5% to 9%), nausea, vomiting
Renal: Serum creatinine increased (≥ 0.5 mg/dL: 2% to 3% in compensated liver disease; incidence may be higher in patients with decompensated cirrhosis or in liver transplant recipients), renal failure
Note: In liver transplant patients with baseline renal dysfunction, frequency of increased serum creatinine has been observed to be as high as 32% to 51% at 48 and 96 weeks post-transplantation, respectively; considering the concomitant use of other potentially nephrotoxic medications, baseline renal insufficiency, and predisposing comorbidities, the role of adefovir in these changes could not be established.
Respiratory: Cough (6% to 8%), rhinitis (up to 5%)
Postmarketing and/or case reports: Fanconi syndrome, hepatitis, myopathy, nephrotoxicity, osteomalacia
CONTRAINDICATIONS — Hypersensitivity to adefovir or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: . Human immunodeficiency virus (HIV): . Lactic acidosis/hepatomegaly: . Renal impairment: .
Concerns related to adverse effects: Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Exacerbations may occur in up to 25% of patients and usually within 12 weeks and may be self-limited or resolve upon resuming treatment; risk may be increased with advanced liver disease or cirrhosis. Monitor liver function several months after stopping treatment; reinitiation of antihepatitis B therapy may be required.
Resistant hepatitis B virus (HBV): In patients with lamivudine-resistant HBV, switching to adefovir was associated with a higher risk of adefovir-resistance compared to adding adefovir to lamivudine therapy (Lok, 2007).
Nonresponse to adefovir monotherapy (<2 log drop in HBV DNA after 6 months of treatment): Consider alternative treatment (Lok, 2007). HIV: [U.S. Boxed Warning]:May cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Determine HIV status prior to initiating treatment with adefovir. Renal impairment: [U.S. Boxed Warning]: Use with caution in patients with renal dysfunction or in patients at risk of renal toxicity (including concurrent nephrotoxic agents or NSAIDs). Chronic administration may result in nephrotoxicity. Dosage adjustment is required in adult patients with renal dysfunction or in patients who develop renal dysfunction during therapy; no data available for use in children ≥ 12 years or adolescents with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Tenofovir: Adefovir may diminish the therapeutic effect of Tenofovir. Specifically, adefovir-associated mutations in Hepatitis B viral reverse transcriptase may decrease viral susceptibility to tenofovir. Tenofovir may increase the serum concentration of Adefovir. Similarly, Adefovir may increase the concentration of Tenofovir. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Should be avoided in hepatitis B infection due to potential hepatic toxicity.
Food: Does not have a significant effect on adefovir absorption.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use in pregnancy only when clearly needed. Pregnant women exposed to adefovir should be registered with the pregnancy registry (800-258-4263).
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken without regard to food.
PRICING — (data from drugstore.com)
Tablets (Hepsera)
10 mg (30): $882.35
MONITORING PARAMETERS — HIV status (prior to initiation of therapy); serum creatinine (prior to initiation and during therapy; every 3 months in patients with medical conditions which predispose to renal insufficiency and in all patients treated for >1 year; more frequent monitoring required if preexisting real insufficiency detected [Lok, 2007]); viral load; LFTs for several months following discontinuation of adefovir
CANADIAN BRAND NAMES — Hepsera™
INTERNATIONAL BRAND NAMES — Adesera (IN); Hepsera (AR, AT, AU, BE, BG, BR, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, HK, HN, ID, IE, IL, IT, KP, NI, NL, NO, PA, PE, PH, PK, PL, PT, RU, SE, SG, SV, TH, TR, TW, VE); Youheding (CL)
MECHANISM OF ACTION — Acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Distribution: 0.35-0.39 L/kg
Protein binding: ≤ 4%
Metabolism: Prodrug; rapidly converted to adefovir (active metabolite) in intestine
Bioavailability: 59%
Half-life elimination: 7.5 hours; prolonged in renal impairment
Time to peak: 1.75 hours
Excretion: Urine (45% as active metabolite within 24 hours)
PATIENT INFORMATION — Not a cure for hepatitis B, nor will it reduce the risk of transmission. Report persistent lethargy, acute headache, severe nausea or vomiting, difficulty breathing, loss of sensation, or rash. Do not discontinue unless instructed by prescriber; additional monitoring is required after discontinuation to ensure the disease does not recur.
Adapalene and benzoyl peroxide
U.S. BRAND NAMES — Epiduo™
PHARMACOLOGIC CATEGORY
Acne Products
Topical Skin Product
Topical Skin Product, Acne
DOSING: ADULTS — Acne vulgaris: Topical: Apply once daily to affected areas after skin has been cleaned and dried
DOSING: PEDIATRIC — Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
DOSAGE FORMS: CONCISE
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Apply a pea-sized amount for each area of the face (eg, forehead, chin, each cheek). Skin should be clean and dry before applying. For external use only; avoid applying to eyes and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT
>10%: Dermatologic: Dry skin (<1% to 14%)
1% to 10%: Dermatologic: Scaling (<1% to 9%), erythema (1% to 8%), burning (1% to 7%), stinging (1% to 7%), contact dermatitis (3%), skin irritation (1%)
CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bleaching effects: May bleach hair or colored fabric. Photosensitivity: Use is associated with increased suspectibility/sensitivity to UV light; avoid sunlamps or excessive sunlight exposure. Daily sunscreen use and other protective measures are recommended. Skin irritation: Certain cutaneous signs and symptoms (eg, erythema, dryness, scaling, burning/stinging) may occur during treatment; these are most likely to occur during the first 4 weeks and usually lessen with continued use. Use of moisturizer, decreased use, or discontinuation may be recommended.
Concurrent drug therapy issues: Topical acne product: Use concomitant topical acne therapy with caution; cumulative irritancy may occur.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with abraded skin, mucous membranes, and eyes.
DRUG INTERACTIONS
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
MECHANISM OF ACTION
Benzoyl peroxide releases free-radical oxygen which oxidizes bacterial proteins in the sebaceous follicles decreasing the number of anaerobic bacteria and decreasing irritating-type free fatty acids.
Adapalene is a retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris.
PHARMACODYNAMICS / KINETICS
Absorption: Via the skin
Metabolism: Benzoyl peroxide: Converted to benzoic acid in skin
Excretion: Adapalene: Primarily through bile; Benzoyl peroxide: Urine
PHARMACOLOGIC CATEGORY
Acne Products
Topical Skin Product
Topical Skin Product, Acne
DOSING: ADULTS — Acne vulgaris: Topical: Apply once daily to affected areas after skin has been cleaned and dried
DOSING: PEDIATRIC — Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
DOSAGE FORMS: CONCISE
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Apply a pea-sized amount for each area of the face (eg, forehead, chin, each cheek). Skin should be clean and dry before applying. For external use only; avoid applying to eyes and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT
>10%: Dermatologic: Dry skin (<1% to 14%)
1% to 10%: Dermatologic: Scaling (<1% to 9%), erythema (1% to 8%), burning (1% to 7%), stinging (1% to 7%), contact dermatitis (3%), skin irritation (1%)
CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bleaching effects: May bleach hair or colored fabric. Photosensitivity: Use is associated with increased suspectibility/sensitivity to UV light; avoid sunlamps or excessive sunlight exposure. Daily sunscreen use and other protective measures are recommended. Skin irritation: Certain cutaneous signs and symptoms (eg, erythema, dryness, scaling, burning/stinging) may occur during treatment; these are most likely to occur during the first 4 weeks and usually lessen with continued use. Use of moisturizer, decreased use, or discontinuation may be recommended.
Concurrent drug therapy issues: Topical acne product: Use concomitant topical acne therapy with caution; cumulative irritancy may occur.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with abraded skin, mucous membranes, and eyes.
DRUG INTERACTIONS
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
MECHANISM OF ACTION
Benzoyl peroxide releases free-radical oxygen which oxidizes bacterial proteins in the sebaceous follicles decreasing the number of anaerobic bacteria and decreasing irritating-type free fatty acids.
Adapalene is a retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris.
PHARMACODYNAMICS / KINETICS
Absorption: Via the skin
Metabolism: Benzoyl peroxide: Converted to benzoic acid in skin
Excretion: Adapalene: Primarily through bile; Benzoyl peroxide: Urine
Adapalene and benzoyl peroxide
U.S. BRAND NAMES — Epiduo™
PHARMACOLOGIC CATEGORY
Acne Products
Topical Skin Product
Topical Skin Product, Acne
DOSING: ADULTS — Acne vulgaris: Topical: Apply once daily to affected areas after skin has been cleaned and dried
DOSING: PEDIATRIC — Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
DOSAGE FORMS: CONCISE
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Apply a pea-sized amount for each area of the face (eg, forehead, chin, each cheek). Skin should be clean and dry before applying. For external use only; avoid applying to eyes and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT
>10%: Dermatologic: Dry skin (<1% to 14%)
1% to 10%: Dermatologic: Scaling (<1% to 9%), erythema (1% to 8%), burning (1% to 7%), stinging (1% to 7%), contact dermatitis (3%), skin irritation (1%)
CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bleaching effects: May bleach hair or colored fabric. Photosensitivity: Use is associated with increased suspectibility/sensitivity to UV light; avoid sunlamps or excessive sunlight exposure. Daily sunscreen use and other protective measures are recommended. Skin irritation: Certain cutaneous signs and symptoms (eg, erythema, dryness, scaling, burning/stinging) may occur during treatment; these are most likely to occur during the first 4 weeks and usually lessen with continued use. Use of moisturizer, decreased use, or discontinuation may be recommended.
Concurrent drug therapy issues: Topical acne product: Use concomitant topical acne therapy with caution; cumulative irritancy may occur.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with abraded skin, mucous membranes, and eyes.
DRUG INTERACTIONS
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
MECHANISM OF ACTION
Benzoyl peroxide releases free-radical oxygen which oxidizes bacterial proteins in the sebaceous follicles decreasing the number of anaerobic bacteria and decreasing irritating-type free fatty acids.
Adapalene is a retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris.
PHARMACODYNAMICS / KINETICS
Absorption: Via the skin
Metabolism: Benzoyl peroxide: Converted to benzoic acid in skin
Excretion: Adapalene: Primarily through bile; Benzoyl peroxide: Urine
PHARMACOLOGIC CATEGORY
Acne Products
Topical Skin Product
Topical Skin Product, Acne
DOSING: ADULTS — Acne vulgaris: Topical: Apply once daily to affected areas after skin has been cleaned and dried
DOSING: PEDIATRIC — Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
DOSAGE FORMS: CONCISE
Gel, topical:
Epiduo™ : Adapalene 0.1% and benzoyl peroxide 2.5% (45 g)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Apply a pea-sized amount for each area of the face (eg, forehead, chin, each cheek). Skin should be clean and dry before applying. For external use only; avoid applying to eyes and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT
>10%: Dermatologic: Dry skin (<1% to 14%)
1% to 10%: Dermatologic: Scaling (<1% to 9%), erythema (1% to 8%), burning (1% to 7%), stinging (1% to 7%), contact dermatitis (3%), skin irritation (1%)
CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bleaching effects: May bleach hair or colored fabric. Photosensitivity: Use is associated with increased suspectibility/sensitivity to UV light; avoid sunlamps or excessive sunlight exposure. Daily sunscreen use and other protective measures are recommended. Skin irritation: Certain cutaneous signs and symptoms (eg, erythema, dryness, scaling, burning/stinging) may occur during treatment; these are most likely to occur during the first 4 weeks and usually lessen with continued use. Use of moisturizer, decreased use, or discontinuation may be recommended.
Concurrent drug therapy issues: Topical acne product: Use concomitant topical acne therapy with caution; cumulative irritancy may occur.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with abraded skin, mucous membranes, and eyes.
DRUG INTERACTIONS
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
MECHANISM OF ACTION
Benzoyl peroxide releases free-radical oxygen which oxidizes bacterial proteins in the sebaceous follicles decreasing the number of anaerobic bacteria and decreasing irritating-type free fatty acids.
Adapalene is a retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris.
PHARMACODYNAMICS / KINETICS
Absorption: Via the skin
Metabolism: Benzoyl peroxide: Converted to benzoic acid in skin
Excretion: Adapalene: Primarily through bile; Benzoyl peroxide: Urine
Adapalene
U.S. BRAND NAMES — Differin®
PHARMACOLOGIC CATEGORY
Acne Products
Topical Skin Product, Acne
DOSING: ADULTS — Acne: Topical: Apply once daily before bedtime; results appear after 8-12 weeks of therapy.
DOSING: PEDIATRIC — Children >12 years: Refer to adult dosing.
(For additional information see "Adapalene: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, topical:
Differin®: 0.1% (15 g, 45 g)
Gel, topical:
Differin®: 0.1% (15 g, 45 g) [alcohol free]; 0.3% (45 g) [alcohol free]
DOSAGE FORMS: CONCISE
Cream, topical:
Differin®: 0.1% (15 g, 45 g)
Gel, topical:
Differin®: 0.1% (15 g, 45 g); 0.3% (45 g)
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT
>10%: Dermatologic: Erythema, scaling, dryness, pruritus, burning, pruritus or burning immediately after application
<1% (Limited to important or life-threatening): Acne flares, conjunctivitis, contact dermatitis, dermatitis, eczema, eyelid edema, skin discoloration, skin irritation, stinging, sunburn, rash (topical cream)
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component in the vehicle gel
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Photosensitivity: Use is associated with increased susceptibility/sensitivity to UV light; avoid sunlamps or excessive sunlight exposure. Daily sunscreen use and other protective measures recommended. Skin irritation: Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning, or pruritus may occur during treatment; these are most likely to occur during the first 2-4 weeks and will usually lessen with continued use.
Disease-related concerns: Eczema: Use with caution in patients with eczema.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with abraded skin, mucous membranes, eyes, mouth, angles of the nose.
DRUG INTERACTIONS
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Cream (Differin)
0.1% (45): $189.50
Gel (Differin)
0.1% (45): $185.59
0.3% (45): $177.06
CANADIAN BRAND NAMES — Differin®; Differin® XP
INTERNATIONAL BRAND NAMES — Aclene (KP); Acure (TW); Adaferin (CR, DO, GT, HN, IN, MX, NI, PA, SV); Adaferin Gel (IL); Beautyface (TW); Butipalen (KP); Deriva (MY); Differin (AR, AU, BR, CL, CN, EE, FI, HK, HN, KP, MY, NO, PE, PH, PL, PY, SG, TH, TW, UY, VE, ZA); Differin Gel (AT, BE, CH, DE, GB, IE, IL, IT, SE); Differine (CZ, ES, FR); Elibel (KP); Evalen (ID); Klenzit (PH); Panalene (AR); Pindome (TW); Redap (DK); Rozac (IN)
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS / KINETICS
Absorption: Topical: Minimal
Excretion: Bile
PATIENT INFORMATION — Thoroughly wash hands after applying. Avoid hydration of skin immediately before application. Minimize exposure to sunlight. Avoid washing face more frequently than 2-3 times/day. If severe irritation occurs, discontinue medication temporarily and adjust dose when irritation subsides. Avoid using topical preparations with high alcoholic content during treatment period. Do not exceed prescribed dose.
PHARMACOLOGIC CATEGORY
Acne Products
Topical Skin Product, Acne
DOSING: ADULTS — Acne: Topical: Apply once daily before bedtime; results appear after 8-12 weeks of therapy.
DOSING: PEDIATRIC — Children >12 years: Refer to adult dosing.
(For additional information see "Adapalene: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, topical:
Differin®: 0.1% (15 g, 45 g)
Gel, topical:
Differin®: 0.1% (15 g, 45 g) [alcohol free]; 0.3% (45 g) [alcohol free]
DOSAGE FORMS: CONCISE
Cream, topical:
Differin®: 0.1% (15 g, 45 g)
Gel, topical:
Differin®: 0.1% (15 g, 45 g); 0.3% (45 g)
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT
>10%: Dermatologic: Erythema, scaling, dryness, pruritus, burning, pruritus or burning immediately after application
<1% (Limited to important or life-threatening): Acne flares, conjunctivitis, contact dermatitis, dermatitis, eczema, eyelid edema, skin discoloration, skin irritation, stinging, sunburn, rash (topical cream)
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component in the vehicle gel
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Photosensitivity: Use is associated with increased susceptibility/sensitivity to UV light; avoid sunlamps or excessive sunlight exposure. Daily sunscreen use and other protective measures recommended. Skin irritation: Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning, or pruritus may occur during treatment; these are most likely to occur during the first 2-4 weeks and will usually lessen with continued use.
Disease-related concerns: Eczema: Use with caution in patients with eczema.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with abraded skin, mucous membranes, eyes, mouth, angles of the nose.
DRUG INTERACTIONS
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Cream (Differin)
0.1% (45): $189.50
Gel (Differin)
0.1% (45): $185.59
0.3% (45): $177.06
CANADIAN BRAND NAMES — Differin®; Differin® XP
INTERNATIONAL BRAND NAMES — Aclene (KP); Acure (TW); Adaferin (CR, DO, GT, HN, IN, MX, NI, PA, SV); Adaferin Gel (IL); Beautyface (TW); Butipalen (KP); Deriva (MY); Differin (AR, AU, BR, CL, CN, EE, FI, HK, HN, KP, MY, NO, PE, PH, PL, PY, SG, TH, TW, UY, VE, ZA); Differin Gel (AT, BE, CH, DE, GB, IE, IL, IT, SE); Differine (CZ, ES, FR); Elibel (KP); Evalen (ID); Klenzit (PH); Panalene (AR); Pindome (TW); Redap (DK); Rozac (IN)
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS / KINETICS
Absorption: Topical: Minimal
Excretion: Bile
PATIENT INFORMATION — Thoroughly wash hands after applying. Avoid hydration of skin immediately before application. Minimize exposure to sunlight. Avoid washing face more frequently than 2-3 times/day. If severe irritation occurs, discontinue medication temporarily and adjust dose when irritation subsides. Avoid using topical preparations with high alcoholic content during treatment period. Do not exceed prescribed dose.
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