Thursday, June 17, 2010

Aminocaproic acid

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amicar® may be confused with amikacin, Amikin®, Omacor®

U.S. BRAND NAMES — Amicar®

PHARMACOLOGIC CATEGORY
Antifibrinolytic Agent
Antihemophilic Agent
Hemostatic Agent
Lysine Analog

DOSING: ADULTS
Acute bleeding syndrome: Oral, I.V.: Loading dose: 4-5 g during the first hour, followed by 1 g/hour for 8 hours (or 1.25 g/hour using oral solution) or until bleeding controlled (maximum daily dose: 30 g)

Control of bleeding in thrombocytopenia (unlabeled use):
Initial: I.V.: 100 mg/kg over 30-60 minutes
Maintenance: Oral: 1-3 g every 6 hours

Control of oral bleeding in congenital and acquired coagulation disorder (unlabeled use): Oral: 50-60 mg/kg every 4 hours

Prevention of dental procedure bleeding in patients on oral anticoagulant therapy (unlabeled use): Oral rinse: Hold 4 g/10 mL in mouth for 2 minutes then spit out. Repeat every 6 hours for 2 days after procedure (Souto, 1996). Concentration and frequency may vary by institution and product availability.

Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 10 g over 20-30 minutes prior to skin incision, followed by 1-2.5 g/hour (usual dose 2 g/hour) until the end of operation (may continue infusion for 4 hours after protamine reversal of heparin). May add 10 g to cardiopulmonary bypass circuit priming solution.
or
10 g over 20-30 minutes prior to skin incision, followed by 10 g after heparin administration then 10 g at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin

Traumatic hyphema (unlabeled use): Oral: 100 mg/kg/dose every 4 hours (maximum daily dose: 30 g)

DOSING: PEDIATRIC

(For additional information see "Aminocaproic acid: Pediatric drug information")
Acute bleeding syndrome (unlabeled use): Oral, I.V.: Loading dose: 100-200 mg/kg during the first hour, followed by continuous infusion at 33.3 mg/kg/hour (I.V.) or 100 mg/kg (oral or I.V.) every 6 hours

Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 100 mg/kg given over 20-30 minutes after induction and prior to incision, 100 mg/kg during cardiopulmonary bypass, and 100 mg/kg after protamine reversal of heparin

Traumatic hyphema (unlabeled use): Oral: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — May accumulate in patients with decreased renal function.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution: 250 mg/mL (20 mL)

Solution, oral: 1.25 g/5 mL (240 mL, 480 mL)

Syrup:
Amicar®: 1.25 g/5 mL (480 mL) [raspberry flavor]

Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg

DOSAGE FORMS: CONCISE
Injection, solution: 250 mg/mL (20 mL)

Solution, oral: 1.25 g/5 mL (480 mL)

Syrup:
Amicar®: 1.25 g/5 mL

Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Rapid I.V. injection (IVP) of undiluted solution is not recommended due to possible hypotension, bradycardia, and arrhythmia.

I.V.: Acute bleeding syndrome: Administer loading dose over 1 hour, followed by a continuous infusion

I.V.: Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): Administer loading dose over 20-30 minutes prior to skin incision, followed by a continuous infusion until the end of operation or as 2 additional bolus doses (over 20-30 minutes) given after heparin administration and at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin.

COMPATIBILITY — Stable in D5W, NS, Ringer's injection

USE — To enhance hemostasis when fibrinolysis contributes to bleeding (causes may include cardiac surgery, hematologic disorders, neoplastic disorders, abruption placentae, hepatic cirrhosis, and urinary fibrinolysis)

USE - UNLABELED / INVESTIGATIONAL — Treatment of traumatic hyphema; control bleeding in thrombocytopenia; control oral bleeding in congenital and acquired coagulation disorders; topical treatment (mouth rinse) of bleeding associated with dental procedures in patients on oral anticoagulant therapy; prevention of perioperative bleeding associated with cardiac surgery

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.

Cardiovascular: Arrhythmia, bradycardia, edema, hypotension, intracranial hypertension, peripheral ischemia, syncope, thrombosis

Central nervous system: Confusion, delirium, dizziness, fatigue, hallucinations, headache, malaise, seizure, stroke

Dermatologic: Rash, pruritus

Gastrointestinal: Abdominal pain, anorexia, cramps, diarrhea, GI irritation, nausea, vomiting

Genitourinary: Dry ejaculation

Hematologic: Agranulocytosis, bleeding time increased, leukopenia, thrombocytopenia

Local: Injection site necrosis, injection site pain, injectionsite reactions

Neuromuscular & skeletal: CPK increased, myalgia, myositis, myopathy, rhabdomyolysis (rare), weakness

Ophthalmic: Vision decreased, watery eyes

Otic: Tinnitus

Renal: BUN increased, intrarenal obstruction (glomerular capillary thrombosis), myoglobinuria (rare), renal failure (rare)

Respiratory: Dyspnea, nasal congestion, pulmonary embolism

Miscellaneous: Allergic reaction, anaphylactoid reaction, anaphylaxis

Postmarketing and/or case reports: Hepatic lesion, myocardial lesion

CONTRAINDICATIONS — Disseminated intravascular coagulation (without heparin); evidence of an active intravascular clotting process

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Intrarenal obstruction: May occur secondary to glomerular capillary thrombosis or clots in the renal pelvis and ureters; do not use in hematuria of upper urinary tract origin unless possible benefits outweigh risks. Skeletal muscle weakness: Ranging from mild myalgias and fatigue to severe myopathy with rhabdomyolysis and acute renal failure has been reported with prolonged use. Monitor CPK; discontinue treatment with a rise in CPK.

Disease-related concerns: Renal impairment: Use with caution in patients with renal impairment; may accumulate.

Concurrent drug therapy issues: Blood products: Do not administer with factor IX complex concentrates or anti-inhibitor coagulant complexes; may increase risk for thrombosis.

Dosage form specific issues: Benzyl alcohol: Injection contains benzyl alcohol which has been associated with "gasping syndrome" in neonates.

Other warnings/precautions: Appropriate use: Do not administer without a definite diagnosis of laboratory findings indicative of hyperfibrinolysis. Inhibition of fibrinolysis may promote clotting or thrombosis; more likely due to the presence of DIC. I.V. administration: Avoid rapid I.V. administration; may induce hypotension, bradycardia, or arrhythmia; rapid injection of undiluted solution is not recommended.

DRUG INTERACTIONS
Anti-inhibitor Coagulant Complex: Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex. Risk X: Avoid combination

Factor IX: Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX. Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination

Factor IX Complex (Human): Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX Complex (Human). Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination

Fibrinogen Concentrate (Human): Antifibrinolytic Agents may enhance the adverse/toxic effect of Fibrinogen Concentrate (Human). Specifically, the risk for thrombosis may be increased. Fibrinogen Concentrate (Human) may enhance the adverse/toxic effect of Antifibrinolytic Agents. Specifically, the risk for thrombosis may be increased. Risk C: Monitor therapy

Tretinoin (Oral): May enhance the thrombogenic effect of Antifibrinolytic Agents. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Animal reproductive studies have not been conducted.

LACTATION — Excretion in breast milk unknown/use caution

PRICING — (data from drugstore.com)
Tablets (Amicar)
500 mg (30): $103.40

Tablets (Aminocaproic Acid)
500 mg (100): $177.59

MONITORING PARAMETERS — Fibrinogen, fibrin split products, creatine phosphokinase (with long-term therapy), BUN, creatinine

INTERNATIONAL BRAND NAMES — Acepramin (HU); Acidum e-aminocapronicum (PL); Amicar (AE, AU, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE, ZA); Caproamin (ES, VE); Caproamin Fides (ES); Caprolest (NL); Caprolisin (IT); EAC (DE); Epsamon (CH); Epsicaprom (PT); Epsilon (FI); Hamostat (IN); Hemocaprol (ES); Hexalense (FR); Ipron (TW); Ipsilon (AR, BR, JP, PY, UY); Resplamin (JP); Syrop acidi e-aminocapronici (PL)

MECHANISM OF ACTION — Binds competitively to plasminogen; blocking the binding of plasminogen to fibrin and the subsequent conversion to plasmin, resulting in inhibition of fibrin degradation (fibrinolysis).

PHARMACODYNAMICS / KINETICS
Onset of action: ~1-72 hours

Distribution: Widely through intravascular and extravascular compartments
Vd: Oral: 23 L, I.V.: 30 L

Metabolism: Minimally hepatic

Half-life elimination: ~2 hours

Time to peak: Oral: Within 2 hours

Excretion: Urine (65% as unchanged drug, 11% as metabolite)

PATIENT INFORMATION — Report any signs of bleeding; change positions slowly to minimize dizziness

Amiloride and hydrochlorothiazide

PHARMACOLOGIC CATEGORY
Diuretic, Combination

DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose

DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day

DOSING: RENAL IMPAIRMENT — See individual agents.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg

DOSAGE FORMS: CONCISE
Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg

GENERIC EQUIVALENT AVAILABLE — Yes

USE — Potassium-sparing diuretic; antihypertensive

ADVERSE REACTIONS SIGNIFICANT — See individual agents.

WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.

Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. 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. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.

Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy

ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. 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

Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification

Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy

Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. 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

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination

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

Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification

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 therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy

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

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.

LACTATION — Excretion in breast milk unknown/contraindicated

DIETARY CONSIDERATIONS — May be taken with food.

PRICING — (data from drugstore.com)
Tablets (Amiloride-Hydrochlorothiazide)
5-50 mg (100): $27.99

CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide

INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, TW); Amuretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (MY); Biduret (IN); Bildiuretic (TH); Co-Amilozide (AU, GB); Hydrozide (NZ); Hyperetic (TH); Kaluril (IL); Lorinid Mite (ID); Mengdaqing (CL); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, EE, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PE, PK, PT, PY, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moure-M (TH); Mourinate (TH); Sefaretic (HK); Sparkal (DK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)

PHARMACODYNAMICS / KINETICS — See individual agents.

Amino acid injection

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
TrophAmine® may be confused with tromethamine

U.S. BRAND NAMES — Aminosyn®; Aminosyn® II; Aminosyn®-HBC; Aminosyn®-PF; Aminosyn®-RF; BranchAmin®; Clinisol®; FreAmine®; FreAmine® HBC®; FreAmine® III; HepatAmine®; Hepatasol®; NephrAmine®; PremaSol™ ; Prosol; Renamin®; Travasol®; TrophAmine®

PHARMACOLOGIC CATEGORY
Intravenous Nutritional Therapy

DOSING: ADULTS — Protein as amino acids: I.V. (as a component of parenteral nutrition):

Maintenance: 0.8-1 g/kg/day

Normal/mild stress level: 1-1.2 g/kg/day

Moderate stress level: 1.2-1.5 g/kg/day

Severe stress level: 1.5-2 g/kg/day

Burn patients (severe): Increase protein until significant wound healing achieved

Solid organ transplant: Perioperative: 1.5-2 g/kg/day

Renal failure:
Acute (severely malnourished or hypercatabolic): 1.5-1.8 g/kg/day
Chronic, with dialysis: 1.2-1.3 g/kg/day
Chronic, without dialysis: 0.6-0.8 g/kg/day
Continuous hemofiltration: ≥ 1 g/kg/day

Hepatic failure:
Acute management when other treatments have failed:
With encephalopathy: 0.6-1 g/kg/day
Without encephalopathy: 1-1.5 g/kg/day
Chronic encephalopathy: Use branch chain amino acid enriched diets only if unresponsive to pharmacotherapy

Pregnant women in second or third trimester: Add an additional 10-14 g/day

DOSING: PEDIATRIC — Protein as amino acids: I.V. (as a component of parenteral nutrition):

Term: Initial: 2.5 g/kg/day; Goal: 3 g/kg/day

Extremely (<1000 g) and very (<1500 g) low-birth-weight (stable): Initial: 1-1.5 g/kg/day; Goal: 3.5-3.85 g/kg/day to promote utero growth rates

Sepsis, hypoxia: Initial: 1 g/kg/day; goal: 3-3.85 g/kg/day

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.

Injection, solution [branched chain]:
Aminosyn®-HBC: 7% (500 mL, 1000 mL) [contains aluminum]
BranchAmin®: 4% (500 mL) [contains alumnium]
FreAmine® HBC: 6.9% (750 mL) [contains aluminum, sodium bisulfate]

Injection, solution [crystalline]:
Aminosyn®: 3.5% (1000 mL) [contains aluminum]; 5% (500 mL, 1000 mL) [contains aluminum]; 7% (500 mL, 1000 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 7% (500 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 10% (2000 mL) [contains aluminum, sodium hydrosulfite]; 15% (2000 mL) [contains aluminum, sodium hydrosulfite]
Clinisol®: 15% (500 mL, 2000 mL) [contains aluminum]
FreAmine® III: 8.5% (500 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
PremaSol™ : 6% (500 mL); 10% (500 mL, 1000 mL, 2000 mL)
Prosol: 20% (2000 mL) [contains aluminum]
Travasol®: 10% (500 mL, 1000 mL, 2000 mL)

Injection, solution [hepatic]:
Aminosyn®-HF: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
HepatAmine®: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
Hepatasol®: 8% (500 mL) [contains aluminum]

Injection, solution [pediatric]:
Aminosyn®-PF: 7% (500 mL) [contains aluminum]; 10% (1000 mL) [contains aluminum]
TrophAmine®: 6% (500 mL); 10% (500 mL) [contains aluminum, sodium metabisulfate]

Injection, solution [renal]:
Aminosyn®-RF: 5.2% (500 mL) [contains aluminum]
NephrAmine®: 5.4% (250 mL) [contains aluminum, sodium hydrosulfite]
Renamin®: 6.5% (500 mL) [contains aluminum, sodium hydrosulfite]

DOSAGE FORMS: CONCISE — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.

Injection, solution [branched chain]:
Aminosyn®-HBC: 7%
BranchAmin®: 4%
FreAmine® HBC: 6.9%

Injection, solution [crystalline]:
Aminosyn®: 3.5%, 5%, 7%, 8.5%, 10%
Aminosyn® ll: 7%, 8.5%, 10%, 15%
Clinisol®: 15%
FreAmine® III: 8.5%, 10%
PremaSol™ : 6%, 10%
Prosol: 20%
Travasol®: 10%

Injection, solution [hepatic]:
Aminosyn®-HF, HepatAmine®, Hepatasol®: 8%

Injection, solution [pediatric]:
Aminosyn®-PF: 7%, 10%
TrophAmine®: 6%, 10%

Injection, solution [renal]:
Aminosyn®-RF: 5.2%
NephrAmine®: 5.4%
Renamin®: 6.5%

ADMINISTRATION — Administered as a component of peripheral parenteral or total parenteral nutrition. Peripheral administration of nutrition is dependent upon osmolality of solution. Total parenteral nutrition must be administered via central venous access.

USE — As part of parenteral nutrition to prevent nitrogen loss or treat negative nitrogen balance when alimentary tract cannot be used (eg, GI absorption is impaired, bowel rest is needed). Specialty amino acid formulas may be considered only in certain instances.

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.

Endocrine & metabolic: Fluid, electrolyte imbalance

Local: Erythema, phlebitis, thrombosis

Renal: Azotemia

CONTRAINDICATIONS — Inborn errors of amino acid metabolism

WARNINGS / PRECAUTIONS
Disease-related concerns: Heart failure: Use with caution in patients sensitive to volume overload (eg, heart failure, hepatic failure); consider concentrated total parenteral nutrition formula. Hepatic impairment: Use caution in protein delivery especially in patients with hepatic encephalopathy; dosage adjustments may be necessary. Consider volume status in patients with hepatic failure, may require concentrated total parenteral nutrition formula. Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustments may be necessary depending upon renal replacement therapy options. It is essential to provide adequate calories in a minimal amount of fluid. Monitor fluid balance closely.

Dosage form specific issues: Aluminum: Solutions may contain aluminum; toxic levels may occur following prolonged administration in premature neonates or patients with renal impairment. Sulfites: Some products contain sulfites as preservatives.

Other warning/precautions: Monitoring: Monitor fluid and electrolyte status.

PREGNANCY RISK FACTOR — C (show table)

LACTATION — Excretion in breast milk unknown/use caution

MONITORING PARAMETERS — General patient monitoring during I.V. nutritional therapy

Bone densitometry: Perform upon initiation of long-term therapy.

Efficacy: Nutrition and outcome parameters should be measured serially.

Electrolytes: Sodium, potassium, chloride, and bicarbonate should be monitored frequently upon initiation and until stable; phosphate should be monitored closely in patients with pulmonary disease.

Glucose: In patients with diabetes or patients with glucose intolerance risk factors, monitor closely. Monitor frequently upon initiation of therapy and with any changes in insulin dose or renal function.

Line site: Monitor for signs and symptoms of infection.

Liver function tests: Monitor periodically.

Neonates: Sodium, calcium, and phosphate should be monitored closely. Frequent (some advise

Refeeding syndrome: Patients at risk should have phosphorus, magnesium, potassium, and glucose levels monitored closely at initiation.

Triglycerides: Before initiation of lipid therapy and at least weekly during therapy.

Vitamin A status: Should be carefully monitored in patients with chronic renal failure.

CANADIAN BRAND NAMES — Aminosyn; Aminosyn-PF; Aminosyn-RF; Primene®

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.

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

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.

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.

Ambrisentan

U.S. BRAND NAMES — Letairis®

PHARMACOLOGIC CATEGORY
Endothelin Antagonist
Vasodilator

DOSING: ADULTS — Pulmonary arterial hypertension: Oral: Initial: 5 mg once daily; if tolerated, may increase to maximum 10 mg once daily

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — No dosage adjustment is required in mild-to-moderate renal impairment. No data available for use in severe renal impairment.

DOSING: HEPATIC IMPAIRMENT — Avoid use in patients with moderate-to-severe hepatic insufficiency. Dose reductions may be required in patients with mild hepatic insufficiency.

DOSING: ADJUSTMENT FOR TOXICITY — Modifications based on transaminase elevation:

If any elevation, regardless of degree, is accompanied by clinical symptoms of hepatic injury (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin >2 times ULN, treatment should be stopped and not reintroduced.

AST/ALT >3 but ≤ 5 times ULN: Confirm with additional test; if confirmed, reduce dose or interrupt treatment. Monitor transaminase levels at least every 2 weeks until levels are <3 times ULN. Reinitiate treatment as appropriate with return to pretreatment values and with more frequent checks of transaminase levels.

AST/ALT >5 but ≤ 8 times ULN: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels until they are <3 times ULN. May reintroduce treatment, as appropriate, at starting dose, following return to pretreatment values. More frequent checks of transaminase levels are required after resuming therapy.

AST/ALT >8 times ULN: Stop treatment and do not reintroduce.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:
Letairis®: 5 mg, 10 mg

DOSAGE FORMS: CONCISE
Tablet:
Letairis®: 5 mg, 10 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Swallow tablet whole. Do not split, crush, or chew tablets. May be administered with or without food.

USE — Treatment of pulmonary artery hypertension (PAH) World Health Organization (WHO) Group I in patients with WHO Class II or III symptoms to improve exercise capacity and decrease the rate of clinical deterioration

ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Peripheral edema (17%)
Central nervous system: Headache (15%)

1% to 10%:
Cardiovascular: Palpitation (5%), flushing (4%)
Gastrointestinal: Constipation (4%), abdominal pain (3%)
Hematologic: Hemoglobin decreased (7% to 10%)
Hepatic: Liver enzymes increased (1% to 3%)
Respiratory: Nasal congestion (6%), dyspnea (4%), nasopharyngitis (3%), sinusitis (3%)

Postmarketing and/or case reports: Fluid retention

CONTRAINDICATIONS — Pregnancy

Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to ambrisentan or any component of the formulation

WARNINGS / PRECAUTIONS
Boxed warnings: Hepatic impairment: See "Disease-related concerns" below Letairis Education and Access Program (LEAP): See "Other Warnings/precautions" below Pregnancy: See "Special populations" below

Concerns related to adverse effects: Fluid retention/peripheral edema: Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur; a higher incidence is seen in elderly patients. There have also been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization). Further evaluation may be necessary to determine cause and appropriate treatment or discontinuation of therapy. Hematologic changes: A reduction in hematocrit/hemoglobin may be observed within the first few weeks of therapy with subsequent stabilization of levels. Hemoglobin reductions >15% have been observed in some patients. Measure hemoglobin prior to initiating therapy, at 1 month, and periodically thereafter. Significant decreases in hemoglobin in the absence of other causes may warrant the discontinuation of therapy. Spermatogenesis: Sperm count may be reduced in men during treatment (as observed with bosentan). No changes in sperm function or hormone levels have been noted. Fertility issues may require discussion with patient.

Disease-related concerns: Hepatic impairment: [U.S. Boxed Warning]: Avoid use in moderate-to-severe hepatic impairment. Has been associated with significant transaminase (ALT or AST) elevations (>3 times upper limit of normal [ULN]) in up to 3% of treated patients. Transaminase elevations are dose dependent. Avoid use in patients with elevated serum transaminases (>3 times ULN) at baseline. An increase in bilirubin may be observed as well. Monitor hepatic function closely (at least monthly) for the duration of treatment. Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Treatment should be stopped in patients who develop elevated transaminases >8 times ULN, elevated transaminases accompanied by symptoms of hepatic injury (unusual fatigue, jaundice, nausea, vomiting, abdominal pain, and/or fever) or elevated serum bilirubin >2 times ULN. Safety of reintroduction is unknown. Use caution in mild hepatic impairment. Dose reduction may be necessary. Pulmonary veno-occlusive disease (PVOD): Discontinue in any patient with pulmonary edema suggestive of PVOD.

Concurrent drug therapy issues: High potential for interactions: Use caution in patients taking strong inhibitors or inducers of CYP3A4 or CYP2C19, inhibitors of P-glycoprotein (eg, cyclosporine), or agents which affect glucuronidation metabolism via uridine 5'-diphosphate glucuronosyltransferase (UGT) enzymes.

Special populations: Pregnancy: [U.S. Boxed Warning]: Use in pregnancy is contraindicated; may cause birth defects. Exclude pregnancy prior to initiating therapy and monthly thereafter during therapy. Two reliable methods of contraception must be used during therapy and for one month after stopping treatment except in patients with tubal ligation or an implanted IUD (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients. A missed menses should be reported to healthcare provider and prompt immediate pregnancy testing.

Other warnings/precautions: Letairis Education and Access Program (LEAP): [U.S. Boxed Warning]: Because of the risks of hepatic impairment and the high likelihood of teratogenic effects, ambrisentan is only available through the LEAP restricted distribution program. Patients, prescribers, and pharmacies must be registered with and meet conditions of LEAP. Call 1-866-664-5327 for more information.

RESTRICTIONS — Ambrisentan (Letairis®) is only available through the limited distribution program (Letairis Education and Access Program [LEAP]). Only prescribers and pharmacies registered with LEAP may prescribe and dispense ambrisentan. Further information may be obtained from the manufacturer, Gilead Sciences, Inc (1-866-664-5327).

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major), 2C19 (major), P-glycoprotein

DRUG INTERACTIONS
CycloSPORINE: May increase the serum concentration of Ambrisentan. Risk C: Monitor therapy

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy

CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy

CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Grapefruit/grapefruit juice may increase levels/effects of ambrisentan.

Herb/Nutraceutical: Avoid St John's wort (concurrent use may decrease levels/effects of ambrisentan).

PREGNANCY RISK FACTOR — X (show table)

PREGNANCY IMPLICATIONS — [U.S. Boxed Warning]: Use in pregnancy is contraindicated. Based on animal studies, ambrisentan is likely to produce major birth defects if used by pregnant women. Pregnancy must be excluded prior to initiation of therapy and follow-up pregnancy tests should be obtained monthly. Two reliable methods of contraception must be used throughout treatment and for one month after stopping treatment unless the patient has undergone a tubal ligation or the insertion of an intrauterine device (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients.

LACTATION — Excretion in breast milk unknown/not recommended

DIETARY CONSIDERATIONS — May be taken with or without food. Avoid grapefruit and grapefruit juice.

MONITORING PARAMETERS — Serum transaminase (AST and ALT) and bilirubin should be determined prior to the initiation of therapy (baseline) and at monthly intervals thereafter. Monitor for clinical signs and symptoms of liver injury (eg, abdominal pain, fatigue, fever, jaundice, nausea, vomiting). Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Monitor levels every 2 weeks until they are <3>8 times ULN, elevated transaminases with accompanying symptoms of hepatic injury, or bilirubin >2 times ULN. Monitor for significant peripheral edema and evaluate etiology if it occurs.

A woman of childbearing potential must have a negative pregnancy test prior to the initiation of therapy and monthly thereafter. Hemoglobin and hematocrit should be measured at baseline, at 1 month, and periodically thereafter (generally stabilizes after the first few weeks of treatment).

CANADIAN BRAND NAMES — Volibris®

INTERNATIONAL BRAND NAMES — Volibris (CZ, EE, GB, IE, SE)

MECHANISM OF ACTION — Blocks endothelin receptor subtypes ETA and ETB on vascular endothelium and smooth muscle. Stimulation of these receptors in smooth muscle cells is associated with vasoconstriction. Simulation of ETB receptors in endothelial cells is associated with vasodilation and antiproliferative effects. Although ambrisentan blocks both ETA and ETB receptors, the affinity is greater for the A subtype. Improvement in symptoms of pulmonary artery hypertension and a decrease in the rate of clinical deterioration have been demonstrated in clinical trials.

PHARMACODYNAMICS / KINETICS
Absorption: Rapid

Protein binding: 99%

Metabolism: Hepatic via CYP3A4, CYP2C19, and uridine 5'-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S; in vitro studies also suggest it is a substrate of organic anion transport protein (OATP) and P-glycoprotein (P-gp)

Half-life elimination: ~9 hours

Time to peak, plasma: ~2 hours

Excretion: Primarily nonrenal

Ambenonium

U.S. BRAND NAMES — Mytelase®

PHARMACOLOGIC CATEGORY
Cholinergic Agonist

DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Caplet, as chloride [scored]:
Mytelase®: 10 mg

DOSAGE FORMS: CONCISE
Caplet [scored]:
Mytelase®: 10 mg

GENERIC EQUIVALENT AVAILABLE — No

USE — Treatment of myasthenia gravis

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.

Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing

Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache

Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria

Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence

Genitourinary: Urinary urgency

Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia

Ocular: Small pupils, lacrimation

Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm

Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions

CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anticholinergic insensitivity: May develop for brief or prolonged periods; reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.

Disease-related concerns: Asthma: Use with caution in patients with asthma. Bradycardia: Use with caution in patients with bradycardia. Hyperthyroidism: Use with caution in patients with hyperthyroidism. Parkinson's disease: Use with caution in patients with Parkinson's disease. Peptic ulcer disease: Use with caution in patients with peptic ulcer disease. Seizures: Use with caution in patients with a history of seizures. Urinary tract obstruction: Use with caution in patients with urinary obstruction.

Special populations: Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Appropriate use: Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized.

DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — C (show table)

LACTATION — Excretion in breast milk unknown/not recommended

PRICING — (data from drugstore.com)
Tablets (Mytelase)
10 mg (100): $172.65

CANADIAN BRAND NAMES — Mytelase®

INTERNATIONAL BRAND NAMES — Mytelase (FI, HU, PL); Mytelase Chloride (BE, CZ, FR, HN, SE)

Alvimopan

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Alvimopan may be confused with almotriptan

U.S. BRAND NAMES — Entereg®

PHARMACOLOGIC CATEGORY
Gastrointestinal Agent, Miscellaneous
Opioid Antagonist, Peripherally-Acting

DOSING: ADULTS — Note: For hospital use only.

Management of postoperative ileus: Oral:
Initial: 12 mg administered 30 minutes to 5 hours prior to surgery
Maintenance: 12 mg twice daily beginning the day after surgery for a maximum of 7 days or until discharged from hospital (maximum total treatment doses: 15 doses)

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Mild-to-severe impairment: No adjustment needed; use caution.

ESRD: Use not recommended.

DOSING: HEPATIC IMPAIRMENT
Mild-to-moderate impairment (Child-Pugh class A and B): No adjustment needed; use caution.

Severe impairment (Child-Pugh class C): Use not recommended.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics ); consult specific product labeling.

Capsule:
Entereg®: 12 mg

DOSAGE FORMS: CONCISE
Capsule:
Entereg®: 12 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Patient must be hospitalized. Initial dose should be administered 30 minutes to 5 hours prior to surgery.

USE — Accelerate the time to upper and lower GI recovery following partial large or small bowel resection surgery with primary anastomosis

ADVERSE REACTIONS SIGNIFICANT — Note: Incidence reported limited to bowel resection patients only. 1% to 10%:

Endocrine & metabolic: Hypokalemia (10%)

Gastrointestinal: Dyspepsia (7%)

Genitourinary: Urinary retention (3%)

Hematologic: Anemia (5%)

Neuromuscular & skeletal: Back pain (3%)

CONTRAINDICATIONS — Patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan

WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below.

Concerns related to adverse effects: Cardiovascular effects: A trend towards an increased incidence of MI was observed in alvimopan (low dose) treated patients compared to placebo in a 12-month study in patients treated with opioids for chronic pain. MI was generally observed more frequently in the initial 1-4 months of treatment. Other studies have not observed this trend and a causal relationship has not been found.

Disease-related concerns: Complete bowel obstruction: Use not recommended in patients undergoing surgery for complete bowel obstruction. Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment (Child-Pugh classes A and B); use not recommended with severe impairment (Child-Pugh class C). Renal impairment: Use with caution in patients with renal impairment; use not recommended in patients with ESRD.

Concurrent drug therapy issues: Opioids: Use with caution in patients recently exposed to opioids; may be more sensitive to gastrointestinal adverse effects (eg, abdominal pain, diarrhea, nausea and vomiting). Contraindicated in patients who have received therapeutic opioids for >7 consecutive days immediately prior to use.

Special populations: Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: For short-term (≤ 15 doses) hospital use only. Only hospitals that have registered through the ENTEREG Access Support and Education (E.A.S.E.™ ) Program and met all requirements may use. It will not be dispensed to patients who have been discharged from the hospital.

RESTRICTIONS — Only hospitals enrolled in the ENTEREG Access Support and Education (E.A.S.E.™ ) Program may administer this medication. Hospital staff must be educated on need to limit to short-term (no more than 15 doses) and inpatient use. Hospitals may contact the E.A.S.E.™ program at 1-866-423-6567 (1-866-4ADOLOR).

METABOLISM / TRANSPORT EFFECTS — Substrate of P-glycoprotein

DRUG INTERACTIONS
Analgesics (Opioid): May enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification

ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with a high-fat meal, extent and rate of absorption may be reduced (Cmax and AUC decreased by ~38% and 21%, respectively).

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Animal studies have not shown teratogenic effects to the fetus. However, there are no adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.

LACTATION — Excretion in breast milk unknown/use caution

DIETARY CONSIDERATIONS — Take with or without food; high-fat meals may decrease the rate and extent of absorption

MECHANISM OF ACTION — An opioid receptor antagonist which blocks opioid binding at the mu receptor; alvimopan has restricted ability to cross the blood-brain barrier at therapeutic doses. It selectively and competitively binds to the GI tract mu opioid receptors and antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms.

PHARMACODYNAMICS / KINETICS
Distribution: Vd: 20-40 L

Protein binding: Parent drug: 80%; metabolite: 94% (both primarily to albumin)

Metabolism: Hydrolyzed to an amide hydrolysis compound (active metabolite) by gut microflora; further metabolism of active metabolite to glucuronide conjugates and other minor metabolites.

Bioavailability: ~6% (range: 1% to 19%)

Half-life elimination: 10-18 hours

Time to peak, plasma: ~2 hours

Excretion: Urine (35% as unchanged drug and metabolites); feces (via biliary excretion)

Amantadine

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amantadine may be confused with ranitidine, rimantadine
Symmetrel® may be confused with Synthroid®

International issues:
Symmetrel® may be confused with Somatrel® which is a brand name for somatorelin in Denmark

SPECIAL ALERTS
CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - September 2009

The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:
(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.
(2) Treatment with oseltamivir or zanamivir is generally recommended for patients who are at higher risk for influenza-related complications (eg, children <5 years of age, adults ≥ 65 years of age, pregnant women, immunosuppressed patients, patients <19 years of age receiving long-term aspirin therapy, and persons with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).
(3) Any suspected influenza patient with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy.
(4) Treatment, when indicated, should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit.
(5) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.
(6) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):
- Persons at higher risk of influenza complications
- Healthcare and public health workers or first responders
(7) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.
(8) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.

CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:
http://www.cdc.gov/h1n1flu/recommendations.htm
http://www.cdc.gov/h1n1flu/guidance/

U.S. BRAND NAMES — Symmetrel®

PHARMACOLOGIC CATEGORY
Anti-Parkinson's Agent, Dopamine Agonist
Antiviral Agent
Antiviral Agent, Adamantane

DOSING: ADULTS
Influenza A treatment/prophylaxis:Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling:
Influenza A treatment: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects); Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days).
Influenza A prophylaxis: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects). Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.

Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300 mg/day in divided doses, if needed

Parkinson's disease: Oral: Usual dose: 100 mg twice daily as monotherapy; may increase to 400 mg/day in divided doses, if needed, with close monitoring. Note: Patients with a serious concomitant illness or those receiving high doses of other anti-parkinson drugs should be started at 100 mg/day; may increase to 100 mg twice daily, if needed, after one to several weeks.

DOSING: PEDIATRIC

(For additional information see "Amantadine: Pediatric drug information")
Influenza A treatment/prophylaxis: Oral: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling and past ACIP dosing recommendations:
Influenza A treatment:
1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day
≥ 10 years and <40 kg: 5 mg/kg/day in 2 divided doses; maximum dose: 150 mg/day (CDC, 2003)
≥ 10 years and ≥ 40 kg: 100 mg twice daily (CDC, 2003)
Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days)
Influenza A prophylaxis: Refer to "Influenza A treatment" dosing. Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose).

DOSING: ELDERLY — Patients ≥ 65 years: Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).

Influenza A treatment/prophylaxis: 100 mg once daily

DOSING: RENAL IMPAIRMENT
Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day

Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days

Clcr <15 mL/minute: Administer 200 mg every 7 days

Hemodialysis: Administer 200 mg every 7 days

Peritoneal dialysis: No supplemental dose is needed

Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, as hydrochloride: 100 mg

Capsule, softgel, as hydrochloride: 100 mg

Solution, oral, as hydrochloride: 50 mg/5 mL (473 mL)

Syrup, oral, as hydrochloride: 50 mg/5 mL (10 mL, 480 mL)

Tablet, as hydrochloride: 100 mg
Symmetrel®: 100 mg

DOSAGE FORMS: CONCISE
Capsule: 100 mg

Capsule, softgel: 100 mg

Solution, oral: 50 mg/5 mL

Syrup, oral: 50 mg/5 mL

Tablet: 100 mg
Symmetrel®: 100 mg

GENERIC EQUIVALENT AVAILABLE — Yes

USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current ACIP guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms

Note: In certain circumstances, the ACIP recommends use of amantadine in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when resistance to oseltamivir is suspected.

ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Cardiovascular: Orthostatic hypotension, peripheral edema
Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, lightheadedness, nervousness, somnolence
Dermatologic: Livedo reticularis
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia
Respiratory: Dry nose

<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, amnesia, anaphylaxis, arrhythmia, bilirubin increased, BUN increased, cardiac arrest, coma, CPK increased, creatinine increased, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, GGT increased, heart failure, hyperkinesis, LDH increased, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)

CONTRAINDICATIONS — Hypersensitivity to amantadine or any component of the formulation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Impulse control disorders: Dopamine agonists used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases. Melanoma: Risk for melanoma development is increased in Parkinson's disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed. Neuroleptic malignant syndrome: Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Suicidal ideation: There have been reports of suicidal ideation/attempt in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness.

Disease-related concerns: Cardiovascular disease: Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dosage reduction may be required. Eczema: Use with caution in patients with a history of recurrent and eczematoid dermatitis. Glaucoma: Avoid in untreated angle closure glaucoma. Hepatic impairment: Use with caution in patients with hepatic impairment; rarely, elevations in transaminases have been reported. Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established. Parkinson's disease: Appropriate use: When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Psychosis: Use with caution in patients with uncontrolled psychosis or severe psychoneurosis. Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended. Seizure disorder: Use with caution in patients with a history of seizure disorder.

Concurrent drug therapy issues: CNS stimulants: Use with caution in patients receiving CNS stimulant drugs.

Special populations: Elderly: Use with caution in the elderly; may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). These patients may require dosage reductions based on renal function. Pediatrics: Safety and efficacy have not been established in children <1 year of age.

Other warnings/precautions: Withdrawal syndrome: May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.

DRUG INTERACTIONS
Antipsychotics (Atypical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification

Antipsychotics (Typical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification

Influenza Virus Vaccine: Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine. This only pertains to live, attentuated influenza virus vaccine. Risk D: Consider therapy modification

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy

Trimethoprim: May enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.

LACTATION — Enters breast milk/not recommended

PRICING — (data from drugstore.com)
Capsules (Amantadine HCl)
100 mg (30): $21.99

Syrup (Amantadine HCl)
50 mg/5 mL (120): $15.98

Tablets (Amantadine HCl)
100 mg (30): $33.99

MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure

CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®

INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amanta (KP); Amantadin (EE); Amantadin-ratiopharm (PL); Amantadina Juventus (ES); Amantadina Llorente (ES); Amantan (BE, LU); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (CL, FI); Boidan (JP); Enzil (TW); Hofcomant (AT, FI); Influ (TW); Influ-A (IL); Mantadan (IT); Mantadix (FR, LU); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CN, CR, CY, CZ, DE, DO, EE, EG, ET, GH, GM, GN, GT, HK, HN, HU, IL, IQ, IR, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Prayanol (CN); Symmetrel (AE, AT, AU, BH, CH, CY, EG, GB, GR, HR, IE, IL, IQ, IR, JO, KW, LB, LY, NL, NO, OM, QA, SA, SY, VE, YE); Viregyt-K (BG, HU, PL); Virofral (DK); Virosol (AR)

MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers

PHARMACODYNAMICS / KINETICS
Onset of action: Antidyskinetic: Within 48 hours

Absorption: Well absorbed

Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier

Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%

Metabolism: Not appreciable; small amounts of an acetyl metabolite identified

Bioavailability: 86% to 90%

Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); Healthy, older (≥ 60 years) males: 29 hours (range: 20-41 hours); End-stage renal disease: 7-10 days

Time to peak, plasma: 2-4 hours

Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion

PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.