MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
AMILoride may be confused with amiodarone, amLODIPine, amrinone
PHARMACOLOGIC CATEGORY
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
Tablets (Midamor)
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
Wednesday, June 16, 2010
Amiloride
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
AMILoride may be confused with amiodarone, amLODIPine, amrinone
PHARMACOLOGIC CATEGORY
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
Tablets (Midamor)
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
Sound-alike/look-alike issues:
AMILoride may be confused with amiodarone, amLODIPine, amrinone
PHARMACOLOGIC CATEGORY
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
Tablets (Midamor)
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
Amikacin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
Amikacin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
Amifostine
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Ethyol® may be confused with ethanol
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY
Adjuvant, Chemoprotective Agent (Cytoprotective)
Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy
For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:
The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:
Decrease of 20 mm Hg if baseline systolic blood pressure <100
Decrease of 25 mm Hg if baseline systolic blood pressure 100-119
Decrease of 30 mm Hg if baseline systolic blood pressure 120-139
Decrease of 40 mm Hg if baseline systolic blood pressure 140-179
Decrease of 50 mm Hg if baseline systolic blood pressure ≥ 180
If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction:
I.V.: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or
SubQ (unlabeled route): 500 mg once daily prior to radiation therapy
Prevention of radiation proctitis in rectal cancer (unlabeled use): I.V.: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (unlabeled) has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, ondansetron, pemetrexed, piperacillin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine HCl, prochlorperazine edisylate.
USE — Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiation proctitis in patients with rectal cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)
Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to aminothiol compounds or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation. Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available. Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation. Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects. Nausea/vomiting: The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events. Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
Concurrent drug therapy issues: Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.
DRUG INTERACTIONS
Antihypertensives: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CH, CN, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, IE, IL, IT, LU, MX, NI, NL, PA, PE, PH, PL, PT, SE, SV, TH, UY, VE)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: ~8-9 minutes
Excretion: Urine
Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
Sound-alike/look-alike issues:
Ethyol® may be confused with ethanol
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY
Adjuvant, Chemoprotective Agent (Cytoprotective)
Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy
For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:
The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:
Decrease of 20 mm Hg if baseline systolic blood pressure <100
Decrease of 25 mm Hg if baseline systolic blood pressure 100-119
Decrease of 30 mm Hg if baseline systolic blood pressure 120-139
Decrease of 40 mm Hg if baseline systolic blood pressure 140-179
Decrease of 50 mm Hg if baseline systolic blood pressure ≥ 180
If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction:
I.V.: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or
SubQ (unlabeled route): 500 mg once daily prior to radiation therapy
Prevention of radiation proctitis in rectal cancer (unlabeled use): I.V.: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (unlabeled) has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, ondansetron, pemetrexed, piperacillin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine HCl, prochlorperazine edisylate.
USE — Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiation proctitis in patients with rectal cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)
Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to aminothiol compounds or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation. Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available. Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation. Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects. Nausea/vomiting: The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events. Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
Concurrent drug therapy issues: Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.
DRUG INTERACTIONS
Antihypertensives: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CH, CN, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, IE, IL, IT, LU, MX, NI, NL, PA, PE, PH, PL, PT, SE, SV, TH, UY, VE)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: ~8-9 minutes
Excretion: Urine
Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
Amcinonide
PHARMACOLOGIC CATEGORY
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, miliaria, skin atrophy, striae, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, dryness, folliculitis, hypertrichosis, itching, irritation
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)
Cream (Amcinonide)
0.1% (15): $20.99
0.1% (30): $26.99
0.1% (60): $45.99
Cream (Cyclocort)
0.1% (30): $32.99
0.1% (60): $53.99
Lotion (Cyclocort)
0.1% (60): $47.99
Ointment (Amcinonide)
0.1% (60): $43.99
Ointment (Cyclocort)
0.1% (15): $24.99
0.1% (60): $53.99
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcinil (IT); Amicla (BE, LU, NL); Penticort (FR, IT); Visderm (AR, JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, miliaria, skin atrophy, striae, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, dryness, folliculitis, hypertrichosis, itching, irritation
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)
Cream (Amcinonide)
0.1% (15): $20.99
0.1% (30): $26.99
0.1% (60): $45.99
Cream (Cyclocort)
0.1% (30): $32.99
0.1% (60): $53.99
Lotion (Cyclocort)
0.1% (60): $47.99
Ointment (Amcinonide)
0.1% (60): $43.99
Ointment (Cyclocort)
0.1% (15): $24.99
0.1% (60): $53.99
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcinil (IT); Amicla (BE, LU, NL); Penticort (FR, IT); Visderm (AR, JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Amifostine
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Ethyol® may be confused with ethanol
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY
Adjuvant, Chemoprotective Agent (Cytoprotective)
Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy
For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:
The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:
Decrease of 20 mm Hg if baseline systolic blood pressure <100
Decrease of 25 mm Hg if baseline systolic blood pressure 100-119
Decrease of 30 mm Hg if baseline systolic blood pressure 120-139
Decrease of 40 mm Hg if baseline systolic blood pressure 140-179
Decrease of 50 mm Hg if baseline systolic blood pressure ≥ 180
If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction:
I.V.: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or
SubQ (unlabeled route): 500 mg once daily prior to radiation therapy
Prevention of radiation proctitis in rectal cancer (unlabeled use): I.V.: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (unlabeled) has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, ondansetron, pemetrexed, piperacillin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine HCl, prochlorperazine edisylate.
USE — Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiation proctitis in patients with rectal cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)
Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to aminothiol compounds or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation. Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available. Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation. Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects. Nausea/vomiting: The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events. Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
Concurrent drug therapy issues: Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.
DRUG INTERACTIONS
Antihypertensives: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CH, CN, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, IE, IL, IT, LU, MX, NI, NL, PA, PE, PH, PL, PT, SE, SV, TH, UY, VE)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: ~8-9 minutes
Excretion: Urine
Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
Sound-alike/look-alike issues:
Ethyol® may be confused with ethanol
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY
Adjuvant, Chemoprotective Agent (Cytoprotective)
Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy
For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:
The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:
Decrease of 20 mm Hg if baseline systolic blood pressure <100
Decrease of 25 mm Hg if baseline systolic blood pressure 100-119
Decrease of 30 mm Hg if baseline systolic blood pressure 120-139
Decrease of 40 mm Hg if baseline systolic blood pressure 140-179
Decrease of 50 mm Hg if baseline systolic blood pressure ≥ 180
If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction:
I.V.: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or
SubQ (unlabeled route): 500 mg once daily prior to radiation therapy
Prevention of radiation proctitis in rectal cancer (unlabeled use): I.V.: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (unlabeled) has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, ondansetron, pemetrexed, piperacillin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine HCl, prochlorperazine edisylate.
USE — Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiation proctitis in patients with rectal cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)
Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to aminothiol compounds or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation. Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available. Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation. Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects. Nausea/vomiting: The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events. Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
Concurrent drug therapy issues: Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.
DRUG INTERACTIONS
Antihypertensives: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CH, CN, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, IE, IL, IT, LU, MX, NI, NL, PA, PE, PH, PL, PT, SE, SV, TH, UY, VE)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: ~8-9 minutes
Excretion: Urine
Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
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