Aminolevulinic acid

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aminolevulinic acid may be confused with methyl aminolevulinate

U.S. BRAND NAMES — Levulan® Kerastick®

PHARMACOLOGIC CATEGORY
Photosensitizing Agent, Topical
Topical Skin Product

DOSING: ADULTS — Actinic keratoses: Topical: Apply to actinic keratoses (not perilesional skin) followed 14-18 hours later by blue light illumination. Application/treatment may be repeated at a treatment site (once) after 8 weeks.

DOSING: ELDERLY — Refer to adult dosing.

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

Powder for topical solution:
Levulan® Kerastick®: 20% (1s, 6s) [2-component system containing aminolevulinic acid hydrochloride 354 mg (powder) and diluent containing ethanol 48% (1.5 mL) packaged together in an applicator tube]

DOSAGE FORMS: CONCISE
Powder for topical solution:
Levulan® Kerastick®: 20% (1s, 6s)

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Dab lesion gently with wet applicator tip (apply enough to uniformly wet lesion without excess running or dripping). Only apply to affected skin. Do not apply to periorbital area, ocular tissue, or mucosal surfaces. Allow to dry, then reapply to same lesion. Apply to either scalp or facial lesions, but not to both simultaneously. Follow application with blue light exposure in 14-18 hours. Do not wash the application area during the time between application and photosensitization; after photosensitization, gently rinse actinic keratosis with water and pat dry. Stinging or burning may occur during blue light treatment. Following blue light treatment, the lesion will temporarily redden, swell and/or scale, which should resolve within 4 weeks after treatment.

USE — Treatment of minimally to moderately thick actinic keratoses (grade 1 or 2) of the face or scalp; to be used in conjunction with blue light illumination

USE - UNLABELED / INVESTIGATIONAL — Photodynamic treatment of low-risk superficial basal cell skin cancer and low-risk squamous cell skin cancer in situ (Bowen's disease)

ADVERSE REACTIONS SIGNIFICANT — Transient stinging, burning, itching, erythema, and edema result from the photosensitizing properties of this agent. Symptoms subside between 1 minute and 24 hours after turning off the blue light illuminator. Severe stinging or burning was reported in at least 50% of patients from at least 1 lesional site during treatment.

>10%: Dermatologic: Stinging or burning (most patients; severe: ≥ 50%), erythema (99%), scaling/crusted skin (64% to 71%), hyper-/hypopigmentation (22% to 36%), edematous lesions (35%), itching (14% to 25%), erosion (2% to 14%), skin disorder (5% to 12%)

1% to 10%:
Central nervous system: Dysesthesia (≤ 2%)
Dermatologic: Vesiculation (4% to 5%), skin ulceration (2% to 4%), pustular drug eruption (≤ 4%)
Hematologic: Bleeding/hemorrhage (2% to 4%)
Local: Wheal/flare (2% to 7%), scabbing (≤ 2%), tenderness (1% to 2%), edema (≤ 1%), excoriation (≤ 1%), local pain (≤ 1%), oozing (≤ 1%)

CONTRAINDICATIONS — Hypersensitivity to aminolevulinic acid or any component of the formulation; individuals with cutaneous photosensitivity at wavelengths of 400-450 nm; porphyria; allergy to porphyrins

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Photosensitivity: Treatment site will become photosensitive following application. Patients should be instructed to avoid exposure to sunlight, bright indoor lights, or tanning beds during the period prior to blue light treatment. Exposure may result in lesion burning, edema, erythema, and/or stinging. Sunscreen will not protect against visible light; head should be covered with light-opaque material or wide-brimmed hat. If unable to return the next day for blue light treatment, avoid sunlight/bright light exposure to treated lesions for at least 40 hours. Skin irritation: Excessive irritation may occur if applied under occlusion.

Disease-related concerns: Coagulation defects: Has not been tested in individuals with coagulation defects (acquired or inherited).

Concurrent drug therapy issues: Photosensitizing agents: Concomitant use of other known photosensitizing agents may increase the degree of photosensitivity reaction.

Other warnings/precautions: Appropriate use: For external use only. Do not apply to eyes or mucous membranes. Application should involve either scalp or face lesions, although not simultaneously. Should be applied by a qualified health professional to avoid application to perilesional skin.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted, and 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

CANADIAN BRAND NAMES — Levulan® Kerastick®

INTERNATIONAL BRAND NAMES — Metvix (AR, AU, BE, BR, CH, CN, CZ, DE, DK, FI, GB, IE, NO, NZ, SE, SG)

MECHANISM OF ACTION — Aminolevulinic acid is a metabolic precursor of the photosensitizer protoporphyrin IX (PpIX). Photosensitization following local application of aminolevulinic acid occurs through the metabolic conversion to PpIX. When exposed to light of appropriate wavelength and energy, accumulated PpIX produces a photodynamic reaction resulting in local cytotoxicity. Precancerous and cancerous cells exhibit a higher rate of porphyrin induction compared to normal cells.

PHARMACODYNAMICS / KINETICS
Peak fluorescence intensity of protoporphyrin IX (PpIX): Actinic keratosis: 11 hours +/- 1 hour; Perilesional skin: 12 hours +/- 1 hour

Half-life elimination: Mean fluorescence clearance half-life of PpIX for lesions: 30 +/- 10 hours

PATIENT INFORMATION — Solution will be applied by prescriber. Once solution is applied, affected skin will be sensitive to light. Wear protective clothing when exposed to light and avoid bright lights (including tanning beds) and sunlight. Sunscreens will not prevent phototoxic reactions. Solution will be applied directly to lesions; blue light exposure should follow 14-18 hours later. Do not wash solution off skin during this time. If you are not able to return for blue light therapy, avoid sunlight and other bright light for at least 40 hours following application of solution.

Aminolevulinic acid

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aminolevulinic acid may be confused with methyl aminolevulinate

U.S. BRAND NAMES — Levulan® Kerastick®

PHARMACOLOGIC CATEGORY
Photosensitizing Agent, Topical
Topical Skin Product

DOSING: ADULTS — Actinic keratoses: Topical: Apply to actinic keratoses (not perilesional skin) followed 14-18 hours later by blue light illumination. Application/treatment may be repeated at a treatment site (once) after 8 weeks.

DOSING: ELDERLY — Refer to adult dosing.

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

Powder for topical solution:
Levulan® Kerastick®: 20% (1s, 6s) [2-component system containing aminolevulinic acid hydrochloride 354 mg (powder) and diluent containing ethanol 48% (1.5 mL) packaged together in an applicator tube]

DOSAGE FORMS: CONCISE
Powder for topical solution:
Levulan® Kerastick®: 20% (1s, 6s)

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Dab lesion gently with wet applicator tip (apply enough to uniformly wet lesion without excess running or dripping). Only apply to affected skin. Do not apply to periorbital area, ocular tissue, or mucosal surfaces. Allow to dry, then reapply to same lesion. Apply to either scalp or facial lesions, but not to both simultaneously. Follow application with blue light exposure in 14-18 hours. Do not wash the application area during the time between application and photosensitization; after photosensitization, gently rinse actinic keratosis with water and pat dry. Stinging or burning may occur during blue light treatment. Following blue light treatment, the lesion will temporarily redden, swell and/or scale, which should resolve within 4 weeks after treatment.

USE — Treatment of minimally to moderately thick actinic keratoses (grade 1 or 2) of the face or scalp; to be used in conjunction with blue light illumination

USE - UNLABELED / INVESTIGATIONAL — Photodynamic treatment of low-risk superficial basal cell skin cancer and low-risk squamous cell skin cancer in situ (Bowen's disease)

ADVERSE REACTIONS SIGNIFICANT — Transient stinging, burning, itching, erythema, and edema result from the photosensitizing properties of this agent. Symptoms subside between 1 minute and 24 hours after turning off the blue light illuminator. Severe stinging or burning was reported in at least 50% of patients from at least 1 lesional site during treatment.

>10%: Dermatologic: Stinging or burning (most patients; severe: ≥ 50%), erythema (99%), scaling/crusted skin (64% to 71%), hyper-/hypopigmentation (22% to 36%), edematous lesions (35%), itching (14% to 25%), erosion (2% to 14%), skin disorder (5% to 12%)

1% to 10%:
Central nervous system: Dysesthesia (≤ 2%)
Dermatologic: Vesiculation (4% to 5%), skin ulceration (2% to 4%), pustular drug eruption (≤ 4%)
Hematologic: Bleeding/hemorrhage (2% to 4%)
Local: Wheal/flare (2% to 7%), scabbing (≤ 2%), tenderness (1% to 2%), edema (≤ 1%), excoriation (≤ 1%), local pain (≤ 1%), oozing (≤ 1%)

CONTRAINDICATIONS — Hypersensitivity to aminolevulinic acid or any component of the formulation; individuals with cutaneous photosensitivity at wavelengths of 400-450 nm; porphyria; allergy to porphyrins

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Photosensitivity: Treatment site will become photosensitive following application. Patients should be instructed to avoid exposure to sunlight, bright indoor lights, or tanning beds during the period prior to blue light treatment. Exposure may result in lesion burning, edema, erythema, and/or stinging. Sunscreen will not protect against visible light; head should be covered with light-opaque material or wide-brimmed hat. If unable to return the next day for blue light treatment, avoid sunlight/bright light exposure to treated lesions for at least 40 hours. Skin irritation: Excessive irritation may occur if applied under occlusion.

Disease-related concerns: Coagulation defects: Has not been tested in individuals with coagulation defects (acquired or inherited).

Concurrent drug therapy issues: Photosensitizing agents: Concomitant use of other known photosensitizing agents may increase the degree of photosensitivity reaction.

Other warnings/precautions: Appropriate use: For external use only. Do not apply to eyes or mucous membranes. Application should involve either scalp or face lesions, although not simultaneously. Should be applied by a qualified health professional to avoid application to perilesional skin.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted, and 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

CANADIAN BRAND NAMES — Levulan® Kerastick®

INTERNATIONAL BRAND NAMES — Metvix (AR, AU, BE, BR, CH, CN, CZ, DE, DK, FI, GB, IE, NO, NZ, SE, SG)

MECHANISM OF ACTION — Aminolevulinic acid is a metabolic precursor of the photosensitizer protoporphyrin IX (PpIX). Photosensitization following local application of aminolevulinic acid occurs through the metabolic conversion to PpIX. When exposed to light of appropriate wavelength and energy, accumulated PpIX produces a photodynamic reaction resulting in local cytotoxicity. Precancerous and cancerous cells exhibit a higher rate of porphyrin induction compared to normal cells.

PHARMACODYNAMICS / KINETICS
Peak fluorescence intensity of protoporphyrin IX (PpIX): Actinic keratosis: 11 hours +/- 1 hour; Perilesional skin: 12 hours +/- 1 hour

Half-life elimination: Mean fluorescence clearance half-life of PpIX for lesions: 30 +/- 10 hours

PATIENT INFORMATION — Solution will be applied by prescriber. Once solution is applied, affected skin will be sensitive to light. Wear protective clothing when exposed to light and avoid bright lights (including tanning beds) and sunlight. Sunscreens will not prevent phototoxic reactions. Solution will be applied directly to lesions; blue light exposure should follow 14-18 hours later. Do not wash solution off skin during this time. If you are not able to return for blue light therapy, avoid sunlight and other bright light for at least 40 hours following application of solution.

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

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

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®