MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Drysol™ may be confused with Drisdol®
U.S. BRAND NAMES — Certain Dri® [OTC]; Drysol™ ; Hypercare™ ; Xerac AC™
PHARMACOLOGIC CATEGORY
Topical Skin Product
DOSING: ADULTS — Hyperhidrosis: Topical: Apply once daily at bedtime; once excessive sweating has stopped, may decrease to once or twice weekly, or as needed. Wash treated area in the morning.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, topical:
Certain Dri®: 12% (36 mL)
Drysol™ : 20% (35 mL, 37.5 mL, 60 mL) [contains ethanol 93%]
Hypercare™ : 20% (35 mL, 37.5 mL, 60 mL) [contains ethanol 93%]
Xerac AC™ : 6.25% (35 mL, 60 mL) [contains ethanol 96%]
DOSAGE FORMS: CONCISE
Solution, topical:
Certain Dri® [OTC]: 12% (36 mL)
Drysol™ , Hypercare™ : 20% (35 mL, 37.5 mL, 60 mL)
Xerac AC™ : 6.25% (35 mL, 60 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Topical: Apply to dry skin. Area may be covered with plastic wrap held in place with snug-fitting T-shirt. Do not hold in place with tape.
USE — Astringent in the management of hyperhidrosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Skin irritation
Local: Burning sensation, prickling sensation, transient itching or stinging
CONTRAINDICATIONS — Hypersensitivity to any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Skin irritation: Discontinue if skin irritation occurs.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with eyes. Do not apply to broken or recently shaved skin. May be harmful to certain metals or fabrics.
DRUG INTERACTIONS — There are no known significant interactions.
PRICING — (data from drugstore.com)
Solution (Drysol)
20% (35): $17.99
20% (37.5): $16.99
20% (60): $20.66
Solution (Hypercare)
20% (35): $16.99
20% (37.5): $15.99
20% (60): $18.99
Solution (Xerac AC)
6.25% (35): $16.99
6.25% (60): $18.99
INTERNATIONAL BRAND NAMES — Anhydrol Forte (GB, IE, IL); Driclor (AU, GB, HK, IE, KP, PH, SG); Drysol (CN, MX)
PATIENT INFORMATION — For external use only. Product may discolor clothing if not completely dry. Discontinue if rash develops.
Wednesday, June 16, 2010
Aluminum chloride hexahydrate
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Drysol™ may be confused with Drisdol®
U.S. BRAND NAMES — Certain Dri® [OTC]; Drysol™ ; Hypercare™ ; Xerac AC™
PHARMACOLOGIC CATEGORY
Topical Skin Product
DOSING: ADULTS — Hyperhidrosis: Topical: Apply once daily at bedtime; once excessive sweating has stopped, may decrease to once or twice weekly, or as needed. Wash treated area in the morning.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, topical:
Certain Dri®: 12% (36 mL)
Drysol™ : 20% (35 mL, 37.5 mL, 60 mL) [contains ethanol 93%]
Hypercare™ : 20% (35 mL, 37.5 mL, 60 mL) [contains ethanol 93%]
Xerac AC™ : 6.25% (35 mL, 60 mL) [contains ethanol 96%]
DOSAGE FORMS: CONCISE
Solution, topical:
Certain Dri® [OTC]: 12% (36 mL)
Drysol™ , Hypercare™ : 20% (35 mL, 37.5 mL, 60 mL)
Xerac AC™ : 6.25% (35 mL, 60 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Topical: Apply to dry skin. Area may be covered with plastic wrap held in place with snug-fitting T-shirt. Do not hold in place with tape.
USE — Astringent in the management of hyperhidrosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Skin irritation
Local: Burning sensation, prickling sensation, transient itching or stinging
CONTRAINDICATIONS — Hypersensitivity to any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Skin irritation: Discontinue if skin irritation occurs.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with eyes. Do not apply to broken or recently shaved skin. May be harmful to certain metals or fabrics.
DRUG INTERACTIONS — There are no known significant interactions.
PRICING — (data from drugstore.com)
Solution (Drysol)
20% (35): $17.99
20% (37.5): $16.99
20% (60): $20.66
Solution (Hypercare)
20% (35): $16.99
20% (37.5): $15.99
20% (60): $18.99
Solution (Xerac AC)
6.25% (35): $16.99
6.25% (60): $18.99
INTERNATIONAL BRAND NAMES — Anhydrol Forte (GB, IE, IL); Driclor (AU, GB, HK, IE, KP, PH, SG); Drysol (CN, MX)
PATIENT INFORMATION — For external use only. Product may discolor clothing if not completely dry. Discontinue if rash develops.
Sound-alike/look-alike issues:
Drysol™ may be confused with Drisdol®
U.S. BRAND NAMES — Certain Dri® [OTC]; Drysol™ ; Hypercare™ ; Xerac AC™
PHARMACOLOGIC CATEGORY
Topical Skin Product
DOSING: ADULTS — Hyperhidrosis: Topical: Apply once daily at bedtime; once excessive sweating has stopped, may decrease to once or twice weekly, or as needed. Wash treated area in the morning.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, topical:
Certain Dri®: 12% (36 mL)
Drysol™ : 20% (35 mL, 37.5 mL, 60 mL) [contains ethanol 93%]
Hypercare™ : 20% (35 mL, 37.5 mL, 60 mL) [contains ethanol 93%]
Xerac AC™ : 6.25% (35 mL, 60 mL) [contains ethanol 96%]
DOSAGE FORMS: CONCISE
Solution, topical:
Certain Dri® [OTC]: 12% (36 mL)
Drysol™ , Hypercare™ : 20% (35 mL, 37.5 mL, 60 mL)
Xerac AC™ : 6.25% (35 mL, 60 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Topical: Apply to dry skin. Area may be covered with plastic wrap held in place with snug-fitting T-shirt. Do not hold in place with tape.
USE — Astringent in the management of hyperhidrosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Skin irritation
Local: Burning sensation, prickling sensation, transient itching or stinging
CONTRAINDICATIONS — Hypersensitivity to any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Skin irritation: Discontinue if skin irritation occurs.
Other warnings/precautions: Appropriate use: For external use only; avoid contact with eyes. Do not apply to broken or recently shaved skin. May be harmful to certain metals or fabrics.
DRUG INTERACTIONS — There are no known significant interactions.
PRICING — (data from drugstore.com)
Solution (Drysol)
20% (35): $17.99
20% (37.5): $16.99
20% (60): $20.66
Solution (Hypercare)
20% (35): $16.99
20% (37.5): $15.99
20% (60): $18.99
Solution (Xerac AC)
6.25% (35): $16.99
6.25% (60): $18.99
INTERNATIONAL BRAND NAMES — Anhydrol Forte (GB, IE, IL); Driclor (AU, GB, HK, IE, KP, PH, SG); Drysol (CN, MX)
PATIENT INFORMATION — For external use only. Product may discolor clothing if not completely dry. Discontinue if rash develops.
Aluminum chloride (dental)
U.S. BRAND NAMES — Hemodent™
PHARMACOLOGIC CATEGORY
Astringent
Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Apply retraction cord as directed
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
DOSAGE FORMS: CONCISE
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
GENERIC EQUIVALENT AVAILABLE — No
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS
Other warnings/precautions: Application: Since large amounts of astringents may cause tissue irritation and possible damage, only small amounts should be applied.
DRUG INTERACTIONS — There are no known significant interactions.
MECHANISM OF ACTION — Precipitates tissue and blood proteins causing a mechanical obstruction to hemorrhage from injured blood vessels
PHARMACOLOGIC CATEGORY
Astringent
Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Apply retraction cord as directed
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
DOSAGE FORMS: CONCISE
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
GENERIC EQUIVALENT AVAILABLE — No
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS
Other warnings/precautions: Application: Since large amounts of astringents may cause tissue irritation and possible damage, only small amounts should be applied.
DRUG INTERACTIONS — There are no known significant interactions.
MECHANISM OF ACTION — Precipitates tissue and blood proteins causing a mechanical obstruction to hemorrhage from injured blood vessels
Aluminum chloride (dental)
U.S. BRAND NAMES — Hemodent™
PHARMACOLOGIC CATEGORY
Astringent
Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Apply retraction cord as directed
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
DOSAGE FORMS: CONCISE
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
GENERIC EQUIVALENT AVAILABLE — No
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS
Other warnings/precautions: Application: Since large amounts of astringents may cause tissue irritation and possible damage, only small amounts should be applied.
DRUG INTERACTIONS — There are no known significant interactions.
MECHANISM OF ACTION — Precipitates tissue and blood proteins causing a mechanical obstruction to hemorrhage from injured blood vessels
PHARMACOLOGIC CATEGORY
Astringent
Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Apply retraction cord as directed
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
DOSAGE FORMS: CONCISE
Liquid:
Hemodent™ : 21% (10 mL, 20 mL, 40 mL)
Retraction cord [impregnated with 21% solution]:
Hemodent™ : Braided cord, thin (7 ft); braided cord medium thin (7 ft); twisted cord #3 (7 ft); twisted cord #9 (7ft)
GENERIC EQUIVALENT AVAILABLE — No
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS
Other warnings/precautions: Application: Since large amounts of astringents may cause tissue irritation and possible damage, only small amounts should be applied.
DRUG INTERACTIONS — There are no known significant interactions.
MECHANISM OF ACTION — Precipitates tissue and blood proteins causing a mechanical obstruction to hemorrhage from injured blood vessels
Altretamine
MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
International issues:
Hexalen®: Brand name for hexetidine in Greece
U.S. BRAND NAMES — Hexalen®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
DOSING: ADULTS — Refer to individual protocols.
Ovarian cancer: Oral: 260 mg/m2/day in 4 divided doses for 14 or 21 days of a 28-day cycle
Alternatively (unlabeled use): 4-12 mg/kg/day in 3-4 divided doses for 21-90 days
Alternatively (unlabeled use): 240-320 mg/m2/day in 3-4 divided doses for 21 days, repeated every 6 weeks
Alternatively (unlabeled use): 150 mg/m2/day in 3-4 divided doses for 14 days of a 28-day cycle
DOSING: ELDERLY — Refer to adult dosing.
DOSING: ADJUSTMENT FOR TOXICITY — Temporarily withhold for 14 days or longer, and resume dose at 200 mg/m2/day for any of the following:
Platelet count <75,000/mm3
White blood cell count <2000/mm3 or granulocyte count <1000/mm3
Progressive neurotoxicity
Gastrointestinal intolerance not responsive to antiemetic regimens
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gelcap:
Hexalen®: 50 mg
DOSAGE FORMS: CONCISE
Gelcap:
Hexalen®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer total daily dose as 3-4 divided doses after meals and at bedtime.
USE — Palliative treatment of persistent or recurrent ovarian cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Peripheral sensory neuropathy (31%; moderate-to-severe 9%), neurotoxicity (21%; may be progressive and dose limiting)
Gastrointestinal: Nausea/vomiting (33% to 70%; severe 1%), diarrhea (48%)
Hematologic: Anemia (33%), leukopenia (5% to 15%; grade 4: 1%), neutropenia
1% to 10%:
Central nervous system: Fatigue (1%), seizure (1%)
Gastrointestinal: Stomach cramps, anorexia (1%)
Hematologic: Thrombocytopenia (9%)
Hepatic: Alkaline phosphatase increased (9%)
<1% (Limited to important or life-threatening): Alopecia, ataxia, depression, dizziness, hepatotoxicity, mood disorders, pruritus, rash, tremor, vertigo
CONTRAINDICATIONS — Hypersensitivity to altretamine or any component of the formulation; pre-existing severe bone marrow suppression or severe neurologic toxicity; pregnancy
WARNINGS / PRECAUTIONS
Boxed warnings: Bone marrow suppression: . Experienced physician: . Neurotoxicity: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Bone marrow suppression: [U.S. Boxed Warning]: Peripheral blood counts should be done routinely before and after drug therapy; bone marrow suppression is common. Use with caution in patients previously treated with other myelosuppressive drugs. Neurotoxicity: [U.S. Boxed Warning]: Neurologic examinations should be done routinely before and after drug therapy; neurotoxicity is common. USe with caution in patients with pre-existing neurotoxicity.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
MAO Inhibitors: Altretamine may enhance the orthostatic effect of MAO Inhibitors. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pyridoxine: May diminish the therapeutic effect of Altretamine. Specifically when altretamine is used in combination with Cisplatin the response duration may be diminished. Risk D: Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Tricyclic Antidepressants: Altretamine may enhance the orthostatic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should avoid becoming pregnant while on therapy.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential toxicity in the nursing infant, breast-feeding is not recommended.
DIETARY CONSIDERATIONS — Should be taken after meals at bedtime.
PRICING — (data from drugstore.com)
Capsules (Hexalen)
50 mg (100): $1167.31
MONITORING PARAMETERS — CBC with differential, liver function tests; neurologic examination
CANADIAN BRAND NAMES — Hexalen®
INTERNATIONAL BRAND NAMES — Hexalen (AU, BG, GB, IL, JP, NO, NZ, SE, TH); Hexastat (AR, FR, IT, PT); Hexinawas (ES)
MECHANISM OF ACTION — Although altretamine's clinical antitumor spectrum resembles that of alkylating agents, the drug has demonstrated activity in alkylator-resistant patients. The drug selectively inhibits the incorporation of radioactive thymidine and uridine into DNA and RNA, inhibiting DNA and RNA synthesis; reactive intermediates covalently bind to microsomal proteins and DNA; can spontaneously degrade to demethylated melamines and formaldehyde which are also cytotoxic.
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed (75% to 89%)
Distribution: Highly concentrated hepatically and renally; low in other organs
Protein binding: 50% to 94%
Metabolism: Hepatic; rapid and extensive demethylation to active metabolites (pentamethylmelamine and tetramethylmelamine)
Half-life elimination: 13 hours
Time to peak, plasma: 0.5-3 hours
Excretion: Urine (90%, <1% as unchanged drug)
PATIENT INFORMATION — Report any numbness or tingling in extremities. Nausea and vomiting may occur.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
International issues:
Hexalen®: Brand name for hexetidine in Greece
U.S. BRAND NAMES — Hexalen®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
DOSING: ADULTS — Refer to individual protocols.
Ovarian cancer: Oral: 260 mg/m2/day in 4 divided doses for 14 or 21 days of a 28-day cycle
Alternatively (unlabeled use): 4-12 mg/kg/day in 3-4 divided doses for 21-90 days
Alternatively (unlabeled use): 240-320 mg/m2/day in 3-4 divided doses for 21 days, repeated every 6 weeks
Alternatively (unlabeled use): 150 mg/m2/day in 3-4 divided doses for 14 days of a 28-day cycle
DOSING: ELDERLY — Refer to adult dosing.
DOSING: ADJUSTMENT FOR TOXICITY — Temporarily withhold for 14 days or longer, and resume dose at 200 mg/m2/day for any of the following:
Platelet count <75,000/mm3
White blood cell count <2000/mm3 or granulocyte count <1000/mm3
Progressive neurotoxicity
Gastrointestinal intolerance not responsive to antiemetic regimens
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gelcap:
Hexalen®: 50 mg
DOSAGE FORMS: CONCISE
Gelcap:
Hexalen®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer total daily dose as 3-4 divided doses after meals and at bedtime.
USE — Palliative treatment of persistent or recurrent ovarian cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Peripheral sensory neuropathy (31%; moderate-to-severe 9%), neurotoxicity (21%; may be progressive and dose limiting)
Gastrointestinal: Nausea/vomiting (33% to 70%; severe 1%), diarrhea (48%)
Hematologic: Anemia (33%), leukopenia (5% to 15%; grade 4: 1%), neutropenia
1% to 10%:
Central nervous system: Fatigue (1%), seizure (1%)
Gastrointestinal: Stomach cramps, anorexia (1%)
Hematologic: Thrombocytopenia (9%)
Hepatic: Alkaline phosphatase increased (9%)
<1% (Limited to important or life-threatening): Alopecia, ataxia, depression, dizziness, hepatotoxicity, mood disorders, pruritus, rash, tremor, vertigo
CONTRAINDICATIONS — Hypersensitivity to altretamine or any component of the formulation; pre-existing severe bone marrow suppression or severe neurologic toxicity; pregnancy
WARNINGS / PRECAUTIONS
Boxed warnings: Bone marrow suppression: . Experienced physician: . Neurotoxicity: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Bone marrow suppression: [U.S. Boxed Warning]: Peripheral blood counts should be done routinely before and after drug therapy; bone marrow suppression is common. Use with caution in patients previously treated with other myelosuppressive drugs. Neurotoxicity: [U.S. Boxed Warning]: Neurologic examinations should be done routinely before and after drug therapy; neurotoxicity is common. USe with caution in patients with pre-existing neurotoxicity.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
MAO Inhibitors: Altretamine may enhance the orthostatic effect of MAO Inhibitors. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pyridoxine: May diminish the therapeutic effect of Altretamine. Specifically when altretamine is used in combination with Cisplatin the response duration may be diminished. Risk D: Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Tricyclic Antidepressants: Altretamine may enhance the orthostatic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should avoid becoming pregnant while on therapy.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential toxicity in the nursing infant, breast-feeding is not recommended.
DIETARY CONSIDERATIONS — Should be taken after meals at bedtime.
PRICING — (data from drugstore.com)
Capsules (Hexalen)
50 mg (100): $1167.31
MONITORING PARAMETERS — CBC with differential, liver function tests; neurologic examination
CANADIAN BRAND NAMES — Hexalen®
INTERNATIONAL BRAND NAMES — Hexalen (AU, BG, GB, IL, JP, NO, NZ, SE, TH); Hexastat (AR, FR, IT, PT); Hexinawas (ES)
MECHANISM OF ACTION — Although altretamine's clinical antitumor spectrum resembles that of alkylating agents, the drug has demonstrated activity in alkylator-resistant patients. The drug selectively inhibits the incorporation of radioactive thymidine and uridine into DNA and RNA, inhibiting DNA and RNA synthesis; reactive intermediates covalently bind to microsomal proteins and DNA; can spontaneously degrade to demethylated melamines and formaldehyde which are also cytotoxic.
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed (75% to 89%)
Distribution: Highly concentrated hepatically and renally; low in other organs
Protein binding: 50% to 94%
Metabolism: Hepatic; rapid and extensive demethylation to active metabolites (pentamethylmelamine and tetramethylmelamine)
Half-life elimination: 13 hours
Time to peak, plasma: 0.5-3 hours
Excretion: Urine (90%, <1% as unchanged drug)
PATIENT INFORMATION — Report any numbness or tingling in extremities. Nausea and vomiting may occur.
Altretamine
MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
International issues:
Hexalen®: Brand name for hexetidine in Greece
U.S. BRAND NAMES — Hexalen®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
DOSING: ADULTS — Refer to individual protocols.
Ovarian cancer: Oral: 260 mg/m2/day in 4 divided doses for 14 or 21 days of a 28-day cycle
Alternatively (unlabeled use): 4-12 mg/kg/day in 3-4 divided doses for 21-90 days
Alternatively (unlabeled use): 240-320 mg/m2/day in 3-4 divided doses for 21 days, repeated every 6 weeks
Alternatively (unlabeled use): 150 mg/m2/day in 3-4 divided doses for 14 days of a 28-day cycle
DOSING: ELDERLY — Refer to adult dosing.
DOSING: ADJUSTMENT FOR TOXICITY — Temporarily withhold for 14 days or longer, and resume dose at 200 mg/m2/day for any of the following:
Platelet count <75,000/mm3
White blood cell count <2000/mm3 or granulocyte count <1000/mm3
Progressive neurotoxicity
Gastrointestinal intolerance not responsive to antiemetic regimens
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gelcap:
Hexalen®: 50 mg
DOSAGE FORMS: CONCISE
Gelcap:
Hexalen®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer total daily dose as 3-4 divided doses after meals and at bedtime.
USE — Palliative treatment of persistent or recurrent ovarian cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Peripheral sensory neuropathy (31%; moderate-to-severe 9%), neurotoxicity (21%; may be progressive and dose limiting)
Gastrointestinal: Nausea/vomiting (33% to 70%; severe 1%), diarrhea (48%)
Hematologic: Anemia (33%), leukopenia (5% to 15%; grade 4: 1%), neutropenia
1% to 10%:
Central nervous system: Fatigue (1%), seizure (1%)
Gastrointestinal: Stomach cramps, anorexia (1%)
Hematologic: Thrombocytopenia (9%)
Hepatic: Alkaline phosphatase increased (9%)
<1% (Limited to important or life-threatening): Alopecia, ataxia, depression, dizziness, hepatotoxicity, mood disorders, pruritus, rash, tremor, vertigo
CONTRAINDICATIONS — Hypersensitivity to altretamine or any component of the formulation; pre-existing severe bone marrow suppression or severe neurologic toxicity; pregnancy
WARNINGS / PRECAUTIONS
Boxed warnings: Bone marrow suppression: . Experienced physician: . Neurotoxicity: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Bone marrow suppression: [U.S. Boxed Warning]: Peripheral blood counts should be done routinely before and after drug therapy; bone marrow suppression is common. Use with caution in patients previously treated with other myelosuppressive drugs. Neurotoxicity: [U.S. Boxed Warning]: Neurologic examinations should be done routinely before and after drug therapy; neurotoxicity is common. USe with caution in patients with pre-existing neurotoxicity.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
MAO Inhibitors: Altretamine may enhance the orthostatic effect of MAO Inhibitors. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pyridoxine: May diminish the therapeutic effect of Altretamine. Specifically when altretamine is used in combination with Cisplatin the response duration may be diminished. Risk D: Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Tricyclic Antidepressants: Altretamine may enhance the orthostatic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should avoid becoming pregnant while on therapy.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential toxicity in the nursing infant, breast-feeding is not recommended.
DIETARY CONSIDERATIONS — Should be taken after meals at bedtime.
PRICING — (data from drugstore.com)
Capsules (Hexalen)
50 mg (100): $1167.31
MONITORING PARAMETERS — CBC with differential, liver function tests; neurologic examination
CANADIAN BRAND NAMES — Hexalen®
INTERNATIONAL BRAND NAMES — Hexalen (AU, BG, GB, IL, JP, NO, NZ, SE, TH); Hexastat (AR, FR, IT, PT); Hexinawas (ES)
MECHANISM OF ACTION — Although altretamine's clinical antitumor spectrum resembles that of alkylating agents, the drug has demonstrated activity in alkylator-resistant patients. The drug selectively inhibits the incorporation of radioactive thymidine and uridine into DNA and RNA, inhibiting DNA and RNA synthesis; reactive intermediates covalently bind to microsomal proteins and DNA; can spontaneously degrade to demethylated melamines and formaldehyde which are also cytotoxic.
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed (75% to 89%)
Distribution: Highly concentrated hepatically and renally; low in other organs
Protein binding: 50% to 94%
Metabolism: Hepatic; rapid and extensive demethylation to active metabolites (pentamethylmelamine and tetramethylmelamine)
Half-life elimination: 13 hours
Time to peak, plasma: 0.5-3 hours
Excretion: Urine (90%, <1% as unchanged drug)
PATIENT INFORMATION — Report any numbness or tingling in extremities. Nausea and vomiting may occur.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
International issues:
Hexalen®: Brand name for hexetidine in Greece
U.S. BRAND NAMES — Hexalen®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
DOSING: ADULTS — Refer to individual protocols.
Ovarian cancer: Oral: 260 mg/m2/day in 4 divided doses for 14 or 21 days of a 28-day cycle
Alternatively (unlabeled use): 4-12 mg/kg/day in 3-4 divided doses for 21-90 days
Alternatively (unlabeled use): 240-320 mg/m2/day in 3-4 divided doses for 21 days, repeated every 6 weeks
Alternatively (unlabeled use): 150 mg/m2/day in 3-4 divided doses for 14 days of a 28-day cycle
DOSING: ELDERLY — Refer to adult dosing.
DOSING: ADJUSTMENT FOR TOXICITY — Temporarily withhold for 14 days or longer, and resume dose at 200 mg/m2/day for any of the following:
Platelet count <75,000/mm3
White blood cell count <2000/mm3 or granulocyte count <1000/mm3
Progressive neurotoxicity
Gastrointestinal intolerance not responsive to antiemetic regimens
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gelcap:
Hexalen®: 50 mg
DOSAGE FORMS: CONCISE
Gelcap:
Hexalen®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer total daily dose as 3-4 divided doses after meals and at bedtime.
USE — Palliative treatment of persistent or recurrent ovarian cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Peripheral sensory neuropathy (31%; moderate-to-severe 9%), neurotoxicity (21%; may be progressive and dose limiting)
Gastrointestinal: Nausea/vomiting (33% to 70%; severe 1%), diarrhea (48%)
Hematologic: Anemia (33%), leukopenia (5% to 15%; grade 4: 1%), neutropenia
1% to 10%:
Central nervous system: Fatigue (1%), seizure (1%)
Gastrointestinal: Stomach cramps, anorexia (1%)
Hematologic: Thrombocytopenia (9%)
Hepatic: Alkaline phosphatase increased (9%)
<1% (Limited to important or life-threatening): Alopecia, ataxia, depression, dizziness, hepatotoxicity, mood disorders, pruritus, rash, tremor, vertigo
CONTRAINDICATIONS — Hypersensitivity to altretamine or any component of the formulation; pre-existing severe bone marrow suppression or severe neurologic toxicity; pregnancy
WARNINGS / PRECAUTIONS
Boxed warnings: Bone marrow suppression: . Experienced physician: . Neurotoxicity: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Bone marrow suppression: [U.S. Boxed Warning]: Peripheral blood counts should be done routinely before and after drug therapy; bone marrow suppression is common. Use with caution in patients previously treated with other myelosuppressive drugs. Neurotoxicity: [U.S. Boxed Warning]: Neurologic examinations should be done routinely before and after drug therapy; neurotoxicity is common. USe with caution in patients with pre-existing neurotoxicity.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
MAO Inhibitors: Altretamine may enhance the orthostatic effect of MAO Inhibitors. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pyridoxine: May diminish the therapeutic effect of Altretamine. Specifically when altretamine is used in combination with Cisplatin the response duration may be diminished. Risk D: Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Tricyclic Antidepressants: Altretamine may enhance the orthostatic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should avoid becoming pregnant while on therapy.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential toxicity in the nursing infant, breast-feeding is not recommended.
DIETARY CONSIDERATIONS — Should be taken after meals at bedtime.
PRICING — (data from drugstore.com)
Capsules (Hexalen)
50 mg (100): $1167.31
MONITORING PARAMETERS — CBC with differential, liver function tests; neurologic examination
CANADIAN BRAND NAMES — Hexalen®
INTERNATIONAL BRAND NAMES — Hexalen (AU, BG, GB, IL, JP, NO, NZ, SE, TH); Hexastat (AR, FR, IT, PT); Hexinawas (ES)
MECHANISM OF ACTION — Although altretamine's clinical antitumor spectrum resembles that of alkylating agents, the drug has demonstrated activity in alkylator-resistant patients. The drug selectively inhibits the incorporation of radioactive thymidine and uridine into DNA and RNA, inhibiting DNA and RNA synthesis; reactive intermediates covalently bind to microsomal proteins and DNA; can spontaneously degrade to demethylated melamines and formaldehyde which are also cytotoxic.
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed (75% to 89%)
Distribution: Highly concentrated hepatically and renally; low in other organs
Protein binding: 50% to 94%
Metabolism: Hepatic; rapid and extensive demethylation to active metabolites (pentamethylmelamine and tetramethylmelamine)
Half-life elimination: 13 hours
Time to peak, plasma: 0.5-3 hours
Excretion: Urine (90%, <1% as unchanged drug)
PATIENT INFORMATION — Report any numbness or tingling in extremities. Nausea and vomiting may occur.
Saturday, June 12, 2010
Alteplase
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Activase® may be confused with Cathflo® Activase®, TNKase®
Alteplase may be confused with Altace®
"tPA" abbreviation should not be used when writing orders for this medication; has been misread as TNKase (tenecteplase)
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (I.V.) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Activase®; Cathflo® Activase®
PHARMACOLOGIC CATEGORY
Thrombolytic Agent
DOSING: ADULTS
ST-elevation myocardial infarction (STEMI): I.V. (Activase®): Front loading dose (weight-based):
Patients >67 kg: Total dose: 100 mg over 1.5 hours; infuse 15 mg over 1-2 minutes. Infuse 50 mg over 30 minutes. Infuse remaining 35 mg of alteplase over the next hour. See "Note."
Patients ≤ 67 kg: Infuse 15 mg I.V. bolus over 1-2 minutes, then infuse 0.75 mg/kg (not to exceed 50 mg) over next 30 minutes, followed by 0.5 mg/kg over next 60 minutes (not to exceed 35 mg). See "Note."
Note: All patients should receive 162-325 mg of chewable nonenteric coated aspirin as soon as possible and then daily. Administer concurrently with heparin 60 units/kg bolus (maximum: 4000 units) followed by continuous infusion of 12 units/kg/hour (maximum: 1000 units/hour) and adjust to aPTT target of 50-70 seconds (or 1.5-2 times the upper limit of control).
Acute pulmonary embolism: I.V. (Activase®): 100 mg over 2 hours.
Acute ischemic stroke: I.V. (Activase®): Within 3 hours of the onset of symptom onset (labeled use) or within 3-4.5 hours of symptom onset (unlabeled use; del Zoppo, 2009; Hacke, 2008): Note: Initiation of anticoagulants (eg, heparin) or antiplatelet agents (eg, aspirin) within 24 hours after starting alteplase is not recommended; however, initiation of aspirin between 24-48 hours after stroke onset is recommended (Adams, 2007). Initiation of SubQ heparin (≤ 10,000 units) or equivalent doses of low molecular weight heparin for prevention of DVT during the first 24 hours of the 3-4.5 hour window trial did not increase incidence of intracerebral hemorrhage (Hacke, 2008).
Recommended total dose: 0.9 mg/kg (maximum total dose: 90 mg)
Patients ≤ 100 kg: Load with 0.09 mg/kg (10% of 0.9 mg/kg dose) as an I.V. bolus over 1 minute, followed by 0.81 mg/kg (90% of 0.9 mg/kg dose) as a continuous infusion over 60 minutes.
Patients >100 kg: Load with 9 mg (10% of 90 mg) as an I.V. bolus over 1 minute, followed by 81 mg (90% of 90 mg) as a continuous infusion over 60 minutes.
Central venous catheter clearance: Intracatheter (Cathflo® Activase® 1 mg/mL):
Patients <30 kg: 110% of the internal lumen volume of the catheter, not to exceed 2 mg/2 mL; retain in catheter for 0.5-2 hours; may instill a second dose if catheter remains occluded
Patients ≥ 30 kg: 2 mg (2 mL); retain in catheter for 0.5-2 hours; may instill a second dose if catheter remains occluded
Acute peripheral arterial occlusive disease (unlabeled use): Intra-arterial: 0.02-0.1 mg/kg/hour for up to 36 hours
Advisory Panel to the Society for Cardiovascular and Interventional Radiology on Thrombolytic Therapy recommendation: ≤ 2 mg/hour and subtherapeutic heparin (aPTT <1.5 times baseline)
DOSING: PEDIATRIC — Central venous catheter clearance: Intracatheter: Patients <30 kg: 110% of the internal lumen volume of the catheter, not to exceed 2 mg/2 mL; retain in catheter for 0.5-2 hours; may instill a second dose if catheter remains occluded
(For additional information see "Alteplase: Pediatric drug information")
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, recombinant:
Activase®: 50 mg [29 million int. units; contains polysorbate 80; packaged with diluent]; 100 mg [58 million int. units; contains polysorbate 80; packaged with diluent and transfer device]
Cathflo® Activase®: 2 mg [contains polysorbate 80]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution, recombinant:
Activase®: 50 mg [29 million int. units]; 100 mg [58 million int. units]
Cathflo® Activase®: 2 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION
Activase®: ST-elevation MI: Accelerated infusion: Bolus dose may be prepared by one of three methods:
1) Removal of 15 mL reconstituted (1 mg/mL) solution from vial
2) Removal of 15 mL from a port on the infusion line after priming
3) Programming an infusion pump to deliver a 15 mL bolus at the initiation of infusion
Activase®: Acute ischemic stroke: Bolus dose (10% of total dose) may be prepared by one of three methods:
1) Removal of the appropriate volume from reconstituted solution (1 mg/mL)
2) Removal of the appropriate volume from a port on the infusion line after priming
3) Programming an infusion pump to deliver the appropriate volume at the initiation of infusion
Note: Remaining dose for STEMI, AIS, or total dose for acute pulmonary embolism may be administered as follows: Any quantity of drug not to be administered to the patient must be removed from vial(s) prior to administration of remaining dose.
50 mg vial: Either PVC bag or glass vial and infusion set
100 mg vial: Insert spike end of the infusion set through the same puncture site created by transfer device and infuse from vial
If further dilution is desired, may be diluted in equal volume of 0.9% sodium chloride or D5W to yield a final concentration of 0.5 mg/mL.
Cathflo® Activase®: Intracatheter: Instill dose into occluded catheter. Do not force solution into catheter. After a 30-minute dwell time, assess catheter function by attempting to aspirate blood. If catheter is functional, aspirate 4-5 mL of blood in patients ≥ 10 kg or 3 mL in patients <10 kg to remove Cathflo® Activase® and residual clots. Gently irrigate the catheter with NS. If catheter remains nonfunctional, let Cathflo® Activase® dwell for another 90 minutes (total dwell time: 120 minutes) and reassess function. If catheter function is not restored, a second dose may be instilled.
COMPATIBILITY — Stable in NS, sterile water for injection; incompatible with bacteriostatic water; variable stability (consult detailed reference) in D5W.
Y-site administration: Compatible: Lidocaine, metoprolol, propranolol. Incompatible: Dobutamine, dopamine, heparin, nitroglycerin.
Compatibility when admixed: Compatible: Lidocaine, morphine, nitroglycerin. Incompatible: Dobutamine, dopamine, heparin.
USE — Management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in coronary arteries; management of acute ischemic stroke (AIS); management of acute pulmonary embolism
Recommended criteria for treatment:
STEMI: Chest pain ≥ 20 minutes duration, onset of chest pain within 12 hours of treatment (or within prior 12-24 hours in patients with continuing ischemic symptoms), and ST-segment elevation >0.1 mV in at least two contiguous precordial leads or two adjacent limb leads on ECG or new or presumably new left bundle branch block (LBBB)
AIS: Onset of stroke symptoms within 3 hours of treatment
Acute pulmonary embolism: Age ≤ 75 years: Documented massive pulmonary embolism by pulmonary angiography or echocardiography or high probability lung scan with clinical shock
Cathflo® Activase®: Restoration of central venous catheter function
USE - UNLABELED / INVESTIGATIONAL — Acute ischemic stroke presenting 3-4.5 hours after symptom onset; acute peripheral arterial occlusive disease
ADVERSE REACTIONS SIGNIFICANT — As with all drugs which may affect hemostasis, bleeding is the major adverse effect associated with alteplase. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the dosage administered, concurrent use of multiple agents which alter hemostasis, and patient predisposition. Rapid lysis of coronary artery thrombi by thrombolytic agents may be associated with reperfusion-related atrial and/or ventricular arrhythmia. Note: Lowest rate of bleeding complications expected with dose used to restore catheter function.
1% to 10%:
Cardiovascular: Hypotension
Central nervous system: Fever
Dermatologic: Bruising (1%)
Gastrointestinal: GI hemorrhage (5%), nausea, vomiting
Genitourinary: GU hemorrhage (4%)
Hematologic: Bleeding (0.5% major, 7% minor: GUSTO trial)
Local: Bleeding at catheter puncture site (15.3%, accelerated administration)
<1% (Limited to important or life-threatening): Allergic reactions: Anaphylaxis, anaphylactoid reactions, laryngeal edema, rash, and urticaria (<0.02%); epistaxis; gingival hemorrhage; intracranial hemorrhage (0.4% to 0.87% when dose is ≤ 100 mg); pericardial hemorrhage; retroperitoneal hemorrhage
Additional cardiovascular events associated with use in STEMI: AV block, cardiogenic shock, heart failure, cardiac arrest, recurrent ischemia/infarction, myocardial rupture, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, thromboembolism, pulmonary edema, asystole, ventricular tachycardia, bradycardia, ruptured intracranial AV malformation, seizure, hemorrhagic bursitis, cholesterol crystal embolization
Additional events associated with use in pulmonary embolism: Pulmonary re-embolization, pulmonary edema, pleural effusion, thromboembolism
Additional events associated with use in stroke: Cerebral edema, cerebral herniation, seizure, new ischemic stroke
CONTRAINDICATIONS — Hypersensitivity to alteplase or any component of the formulation
Treatment of STEMI or PE: Active internal bleeding; history of CVA; recent intracranial or intraspinal surgery or trauma; intracranial neoplasm; arteriovenous malformation or aneurysm; known bleeding diathesis; severe uncontrolled hypertension; suspected aortic dissection
Treatment of acute ischemic stroke: Evidence of intracranial hemorrhage or suspicion of subarachnoid hemorrhage on pretreatment evaluation; intracranial or intraspinal surgery within 3 months; stroke or serious head injury within 3 months; history of intracranial hemorrhage; uncontrolled hypertension at time of treatment (eg, >185 mm Hg systolic or >110 mm Hg diastolic); seizure at the onset of stroke; active internal bleeding; intracranial neoplasm; arteriovenous malformation or aneurysm; multilobar cerebral infarction (hypodensity >1/3 cerebral hemisphere; Adams, 2007); clinical presentation suggesting post-MI pericarditis; known bleeding diathesis including but not limited to current use of oral anticoagulants producing an INR >1.7, an INR >1.7, administration of heparin within 48 hours preceding the onset of stroke with an elevated aPTT at presentation, platelet count <100,000/mm3.
Additional exclusion criteria within clinical trials:
Presentation <3>400 mg/dL, and arterial puncture at a noncompressible site or lumbar puncture within 1 week.
Presentation 3-4.5 hours after initial symptoms (ECASS-III; Hacke, 2008): Age >80 years, time of symptom onset unknown, rapidly improving or minor symptoms, current use of anticoagulants regardless of INR, glucose level <50>400 mg/dL, aggressive intravenous treatment required to lower blood pressure, major surgery or severe trauma within 3 months, baseline National Institutes of Health Stroke Scale (NIHSS) score >25, and history of both stroke and diabetes.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Arrhythmias: Coronary thrombolysis may result in reperfusion arrhythmias. Bleeding: Do not use doses >150 mg; associated with increased risk of intracranial hemorrhage. The total dose should not exceed 90 mg for acute ischemic stroke or 100 mg for acute myocardial infarction or pulmonary embolism. Monitor all potential bleeding sites; if serious bleeding occurs, the infusion of alteplase and heparin should be stopped.
Disease-related concerns: Conditions that increase bleeding risk: For the following conditions, the risk of bleeding is higher with use of thrombolytics and should be weighed against the benefits of therapy: Recent (within 10 days) major surgery (eg, CABG, obstetrical delivery, organ biopsy, pregnancy, previous puncture of noncompressible vessels), prolonged CPR with evidence of thoracic trauma, lumbar puncture within 1 week, cerebrovascular disease, recent gastrointestinal or genitourinary bleeding, recent trauma, hypertension (systolic BP >175 mm Hg and/or diastolic BP >110 mm Hg), high likelihood of left heart thrombus (eg, mitral stenosis with atrial fibrillation), acute pericarditis, subacute bacterial endocarditis, hemostatic defects including ones caused by severe renal or hepatic dysfunction, significant hepatic dysfunction, diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions, septic thrombophlebitis or occluded AV cannula at seriously infected site and/or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of location. ST-elevation myocardial infarction (STEMI): Appropriate use: Follow standard management for STEMI while infusing alteplase. Stroke: Appropriate use: Patients who present within 3 hours of stroke symptom onset should be treated with alteplase unless contraindications exist. A longer time window (3-4.5 hours after symptom onset) has now been formally evaluated and shown to be safe and efficacious for select individuals (del Zoppo, 2009; Hacke, 2008).Treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended.
Concurrent drug therapy issues: Anticoagulants: Use with caution in patients receiving oral anticoagulants; increased risk of bleeding. In the treatment of acute ischemic stroke, the current use of oral anticoagulants producing an INR >1.7 is a contraindication. Aspirin: In the treatment of acute ischemic stroke, avoid aspirin for 24 hours following administration of alteplase; administration within 24 hours increases the risk of hemorrhagic transformation. Heparin: Concurrent heparin anticoagulation may contribute to bleeding. In the treatment of acute ischemic stroke, concurrent use of anticoagulants was not permitted during the initial 24 hours of the <3 hour window trial (NINDS, 1995). Initiation of SubQ heparin (≤ 10,000 units) or equivalent doses of low molecular weight heparin for prevention of DVT during the first 24 hours of the 3-4.5 hour window trial was permitted and did not increase the incidence of intracerebral hemorrhage (Hacke, 2008).
Special populations: Elderly: Use with caution in patients with advanced age (eg, >75 years); increased risk of bleeding. Acute ischemic stroke (within 3-4.5 hours after symptom onset): Patients >80 years were excluded from the clinical trial (Hacke, 2008). Pregnancy: Use with caution in pregnancy; increased risk of bleeding.
Dosage form specific issues: Cathflo® Activase®: When used to restore catheter function, use Cathflo® cautiously in those patients with known or suspected catheter infections. Evaluate catheter for other causes of dysfunction before use. Avoid excessive pressure when instilling into catheter.
Other warnings/precautions: Administration: Intramuscular injections and nonessential handling of the patient should be avoided. Venipunctures should be performed carefully and only when necessary. If arterial puncture is necessary, use an upper extremity vessel that can be manually compressed.
DRUG INTERACTIONS
Anticoagulants: Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. Risk D: Consider therapy modification
Drotrecogin Alfa: Thrombolytic Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Risk D: Consider therapy modification
Nitroglycerin: May decrease the serum concentration of Alteplase. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Salicylates: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, ginkgo (all have additional antiplatelet activity).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. The risk of bleeding may be increased in pregnant women. Use during pregnancy is limited; administer to pregnant women only if the potential benefits justify the risk to the fetus.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS
Acute ischemic stroke: In addition to monitoring for bleeding complications, the 2007 AHA/ASA Guidelines for the early management of acute ischemic stroke recommends the following:
Perform neurological assessments every 15 minutes during infusion and every 30 minutes thereafter for the next 6 hours, then hourly until 24 hours after treatment.
If severe headache, acute hypertension, nausea, or vomiting occurs, discontinue the infusion and obtain emergency CT scan.
Measure BP every 15 minutes for the first 2 hours then every 30 minutes for the next 6 hours, then hourly until 24 hours after initiation of alteplase. Increase frequency if a systolic BP is ≥ 180 mm Hg or if a diastolic BP is ≥ 105 mm Hg; administer antihypertensive medications to maintain BP at or below these levels.
Obtain a follow-up CT scan at 24 hours before starting anticoagulants or antiplatelet agents.
Central venous catheter clearance: Assess catheter function by attempting to aspirate blood.
ST-elevation MI: Assess for evidence of cardiac reperfusion through resolution of chest pain, resolution of baseline ECG changes, preserved left ventricular function, cardiac enzyme washout phenomenon, and/or the appearance of reperfusion arrhythmias; assess for bleeding potential through clinical evidence of GI bleeding, hematuria, gingival bleeding, fibrinogen levels, fibrinogen degradation products, prothrombin times, and partial thromboplastin times.
REFERENCE RANGE
Not routinely measured; literature supports therapeutic levels of 0.52-1.8 mcg/mL
Fibrinogen: 200-400 mg/dL
Activated partial thromboplastin time (aPTT): 22.5-38.7 seconds
Prothrombin time (PT): 10.9-12.2 seconds
CANADIAN BRAND NAMES — Activase® rt-PA; Cathflo® Activase®
INTERNATIONAL BRAND NAMES — Actilyse (AE, AR, AT, AU, BD, BE, BF, BG, BH, BJ, BR, CH, CI, CL, CN, CO, CY, CZ, DE, DK, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HK, HN, HU, ID, IE, IL, IN, IQ, IR, IT, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, NO, OM, PH, PK, PL, PT, PY, QA, SA, SC, SD, SE, SG, SL, SN, SY, TH, TN, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Activacin (JP)
MECHANISM OF ACTION — Initiates local fibrinolysis by binding to fibrin in a thrombus (clot) and converts entrapped plasminogen to plasmin
PHARMACODYNAMICS / KINETICS
Duration: >50% present in plasma cleared ~5 minutes after infusion terminated, ~80% cleared within 10 minutes
Excretion: Clearance: Rapidly from circulating plasma (550-650 mL/minute), primarily hepatic; >50% present in plasma is cleared within 5 minutes after the infusion is terminated, ~80% cleared within 10 minutes
Sound-alike/look-alike issues:
Activase® may be confused with Cathflo® Activase®, TNKase®
Alteplase may be confused with Altace®
"tPA" abbreviation should not be used when writing orders for this medication; has been misread as TNKase (tenecteplase)
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (I.V.) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Activase®; Cathflo® Activase®
PHARMACOLOGIC CATEGORY
Thrombolytic Agent
DOSING: ADULTS
ST-elevation myocardial infarction (STEMI): I.V. (Activase®): Front loading dose (weight-based):
Patients >67 kg: Total dose: 100 mg over 1.5 hours; infuse 15 mg over 1-2 minutes. Infuse 50 mg over 30 minutes. Infuse remaining 35 mg of alteplase over the next hour. See "Note."
Patients ≤ 67 kg: Infuse 15 mg I.V. bolus over 1-2 minutes, then infuse 0.75 mg/kg (not to exceed 50 mg) over next 30 minutes, followed by 0.5 mg/kg over next 60 minutes (not to exceed 35 mg). See "Note."
Note: All patients should receive 162-325 mg of chewable nonenteric coated aspirin as soon as possible and then daily. Administer concurrently with heparin 60 units/kg bolus (maximum: 4000 units) followed by continuous infusion of 12 units/kg/hour (maximum: 1000 units/hour) and adjust to aPTT target of 50-70 seconds (or 1.5-2 times the upper limit of control).
Acute pulmonary embolism: I.V. (Activase®): 100 mg over 2 hours.
Acute ischemic stroke: I.V. (Activase®): Within 3 hours of the onset of symptom onset (labeled use) or within 3-4.5 hours of symptom onset (unlabeled use; del Zoppo, 2009; Hacke, 2008): Note: Initiation of anticoagulants (eg, heparin) or antiplatelet agents (eg, aspirin) within 24 hours after starting alteplase is not recommended; however, initiation of aspirin between 24-48 hours after stroke onset is recommended (Adams, 2007). Initiation of SubQ heparin (≤ 10,000 units) or equivalent doses of low molecular weight heparin for prevention of DVT during the first 24 hours of the 3-4.5 hour window trial did not increase incidence of intracerebral hemorrhage (Hacke, 2008).
Recommended total dose: 0.9 mg/kg (maximum total dose: 90 mg)
Patients ≤ 100 kg: Load with 0.09 mg/kg (10% of 0.9 mg/kg dose) as an I.V. bolus over 1 minute, followed by 0.81 mg/kg (90% of 0.9 mg/kg dose) as a continuous infusion over 60 minutes.
Patients >100 kg: Load with 9 mg (10% of 90 mg) as an I.V. bolus over 1 minute, followed by 81 mg (90% of 90 mg) as a continuous infusion over 60 minutes.
Central venous catheter clearance: Intracatheter (Cathflo® Activase® 1 mg/mL):
Patients <30 kg: 110% of the internal lumen volume of the catheter, not to exceed 2 mg/2 mL; retain in catheter for 0.5-2 hours; may instill a second dose if catheter remains occluded
Patients ≥ 30 kg: 2 mg (2 mL); retain in catheter for 0.5-2 hours; may instill a second dose if catheter remains occluded
Acute peripheral arterial occlusive disease (unlabeled use): Intra-arterial: 0.02-0.1 mg/kg/hour for up to 36 hours
Advisory Panel to the Society for Cardiovascular and Interventional Radiology on Thrombolytic Therapy recommendation: ≤ 2 mg/hour and subtherapeutic heparin (aPTT <1.5 times baseline)
DOSING: PEDIATRIC — Central venous catheter clearance: Intracatheter: Patients <30 kg: 110% of the internal lumen volume of the catheter, not to exceed 2 mg/2 mL; retain in catheter for 0.5-2 hours; may instill a second dose if catheter remains occluded
(For additional information see "Alteplase: Pediatric drug information")
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, recombinant:
Activase®: 50 mg [29 million int. units; contains polysorbate 80; packaged with diluent]; 100 mg [58 million int. units; contains polysorbate 80; packaged with diluent and transfer device]
Cathflo® Activase®: 2 mg [contains polysorbate 80]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution, recombinant:
Activase®: 50 mg [29 million int. units]; 100 mg [58 million int. units]
Cathflo® Activase®: 2 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION
Activase®: ST-elevation MI: Accelerated infusion: Bolus dose may be prepared by one of three methods:
1) Removal of 15 mL reconstituted (1 mg/mL) solution from vial
2) Removal of 15 mL from a port on the infusion line after priming
3) Programming an infusion pump to deliver a 15 mL bolus at the initiation of infusion
Activase®: Acute ischemic stroke: Bolus dose (10% of total dose) may be prepared by one of three methods:
1) Removal of the appropriate volume from reconstituted solution (1 mg/mL)
2) Removal of the appropriate volume from a port on the infusion line after priming
3) Programming an infusion pump to deliver the appropriate volume at the initiation of infusion
Note: Remaining dose for STEMI, AIS, or total dose for acute pulmonary embolism may be administered as follows: Any quantity of drug not to be administered to the patient must be removed from vial(s) prior to administration of remaining dose.
50 mg vial: Either PVC bag or glass vial and infusion set
100 mg vial: Insert spike end of the infusion set through the same puncture site created by transfer device and infuse from vial
If further dilution is desired, may be diluted in equal volume of 0.9% sodium chloride or D5W to yield a final concentration of 0.5 mg/mL.
Cathflo® Activase®: Intracatheter: Instill dose into occluded catheter. Do not force solution into catheter. After a 30-minute dwell time, assess catheter function by attempting to aspirate blood. If catheter is functional, aspirate 4-5 mL of blood in patients ≥ 10 kg or 3 mL in patients <10 kg to remove Cathflo® Activase® and residual clots. Gently irrigate the catheter with NS. If catheter remains nonfunctional, let Cathflo® Activase® dwell for another 90 minutes (total dwell time: 120 minutes) and reassess function. If catheter function is not restored, a second dose may be instilled.
COMPATIBILITY — Stable in NS, sterile water for injection; incompatible with bacteriostatic water; variable stability (consult detailed reference) in D5W.
Y-site administration: Compatible: Lidocaine, metoprolol, propranolol. Incompatible: Dobutamine, dopamine, heparin, nitroglycerin.
Compatibility when admixed: Compatible: Lidocaine, morphine, nitroglycerin. Incompatible: Dobutamine, dopamine, heparin.
USE — Management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in coronary arteries; management of acute ischemic stroke (AIS); management of acute pulmonary embolism
Recommended criteria for treatment:
STEMI: Chest pain ≥ 20 minutes duration, onset of chest pain within 12 hours of treatment (or within prior 12-24 hours in patients with continuing ischemic symptoms), and ST-segment elevation >0.1 mV in at least two contiguous precordial leads or two adjacent limb leads on ECG or new or presumably new left bundle branch block (LBBB)
AIS: Onset of stroke symptoms within 3 hours of treatment
Acute pulmonary embolism: Age ≤ 75 years: Documented massive pulmonary embolism by pulmonary angiography or echocardiography or high probability lung scan with clinical shock
Cathflo® Activase®: Restoration of central venous catheter function
USE - UNLABELED / INVESTIGATIONAL — Acute ischemic stroke presenting 3-4.5 hours after symptom onset; acute peripheral arterial occlusive disease
ADVERSE REACTIONS SIGNIFICANT — As with all drugs which may affect hemostasis, bleeding is the major adverse effect associated with alteplase. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the dosage administered, concurrent use of multiple agents which alter hemostasis, and patient predisposition. Rapid lysis of coronary artery thrombi by thrombolytic agents may be associated with reperfusion-related atrial and/or ventricular arrhythmia. Note: Lowest rate of bleeding complications expected with dose used to restore catheter function.
1% to 10%:
Cardiovascular: Hypotension
Central nervous system: Fever
Dermatologic: Bruising (1%)
Gastrointestinal: GI hemorrhage (5%), nausea, vomiting
Genitourinary: GU hemorrhage (4%)
Hematologic: Bleeding (0.5% major, 7% minor: GUSTO trial)
Local: Bleeding at catheter puncture site (15.3%, accelerated administration)
<1% (Limited to important or life-threatening): Allergic reactions: Anaphylaxis, anaphylactoid reactions, laryngeal edema, rash, and urticaria (<0.02%); epistaxis; gingival hemorrhage; intracranial hemorrhage (0.4% to 0.87% when dose is ≤ 100 mg); pericardial hemorrhage; retroperitoneal hemorrhage
Additional cardiovascular events associated with use in STEMI: AV block, cardiogenic shock, heart failure, cardiac arrest, recurrent ischemia/infarction, myocardial rupture, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, thromboembolism, pulmonary edema, asystole, ventricular tachycardia, bradycardia, ruptured intracranial AV malformation, seizure, hemorrhagic bursitis, cholesterol crystal embolization
Additional events associated with use in pulmonary embolism: Pulmonary re-embolization, pulmonary edema, pleural effusion, thromboembolism
Additional events associated with use in stroke: Cerebral edema, cerebral herniation, seizure, new ischemic stroke
CONTRAINDICATIONS — Hypersensitivity to alteplase or any component of the formulation
Treatment of STEMI or PE: Active internal bleeding; history of CVA; recent intracranial or intraspinal surgery or trauma; intracranial neoplasm; arteriovenous malformation or aneurysm; known bleeding diathesis; severe uncontrolled hypertension; suspected aortic dissection
Treatment of acute ischemic stroke: Evidence of intracranial hemorrhage or suspicion of subarachnoid hemorrhage on pretreatment evaluation; intracranial or intraspinal surgery within 3 months; stroke or serious head injury within 3 months; history of intracranial hemorrhage; uncontrolled hypertension at time of treatment (eg, >185 mm Hg systolic or >110 mm Hg diastolic); seizure at the onset of stroke; active internal bleeding; intracranial neoplasm; arteriovenous malformation or aneurysm; multilobar cerebral infarction (hypodensity >1/3 cerebral hemisphere; Adams, 2007); clinical presentation suggesting post-MI pericarditis; known bleeding diathesis including but not limited to current use of oral anticoagulants producing an INR >1.7, an INR >1.7, administration of heparin within 48 hours preceding the onset of stroke with an elevated aPTT at presentation, platelet count <100,000/mm3.
Additional exclusion criteria within clinical trials:
Presentation <3>400 mg/dL, and arterial puncture at a noncompressible site or lumbar puncture within 1 week.
Presentation 3-4.5 hours after initial symptoms (ECASS-III; Hacke, 2008): Age >80 years, time of symptom onset unknown, rapidly improving or minor symptoms, current use of anticoagulants regardless of INR, glucose level <50>400 mg/dL, aggressive intravenous treatment required to lower blood pressure, major surgery or severe trauma within 3 months, baseline National Institutes of Health Stroke Scale (NIHSS) score >25, and history of both stroke and diabetes.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Arrhythmias: Coronary thrombolysis may result in reperfusion arrhythmias. Bleeding: Do not use doses >150 mg; associated with increased risk of intracranial hemorrhage. The total dose should not exceed 90 mg for acute ischemic stroke or 100 mg for acute myocardial infarction or pulmonary embolism. Monitor all potential bleeding sites; if serious bleeding occurs, the infusion of alteplase and heparin should be stopped.
Disease-related concerns: Conditions that increase bleeding risk: For the following conditions, the risk of bleeding is higher with use of thrombolytics and should be weighed against the benefits of therapy: Recent (within 10 days) major surgery (eg, CABG, obstetrical delivery, organ biopsy, pregnancy, previous puncture of noncompressible vessels), prolonged CPR with evidence of thoracic trauma, lumbar puncture within 1 week, cerebrovascular disease, recent gastrointestinal or genitourinary bleeding, recent trauma, hypertension (systolic BP >175 mm Hg and/or diastolic BP >110 mm Hg), high likelihood of left heart thrombus (eg, mitral stenosis with atrial fibrillation), acute pericarditis, subacute bacterial endocarditis, hemostatic defects including ones caused by severe renal or hepatic dysfunction, significant hepatic dysfunction, diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions, septic thrombophlebitis or occluded AV cannula at seriously infected site and/or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of location. ST-elevation myocardial infarction (STEMI): Appropriate use: Follow standard management for STEMI while infusing alteplase. Stroke: Appropriate use: Patients who present within 3 hours of stroke symptom onset should be treated with alteplase unless contraindications exist. A longer time window (3-4.5 hours after symptom onset) has now been formally evaluated and shown to be safe and efficacious for select individuals (del Zoppo, 2009; Hacke, 2008).Treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended.
Concurrent drug therapy issues: Anticoagulants: Use with caution in patients receiving oral anticoagulants; increased risk of bleeding. In the treatment of acute ischemic stroke, the current use of oral anticoagulants producing an INR >1.7 is a contraindication. Aspirin: In the treatment of acute ischemic stroke, avoid aspirin for 24 hours following administration of alteplase; administration within 24 hours increases the risk of hemorrhagic transformation. Heparin: Concurrent heparin anticoagulation may contribute to bleeding. In the treatment of acute ischemic stroke, concurrent use of anticoagulants was not permitted during the initial 24 hours of the <3 hour window trial (NINDS, 1995). Initiation of SubQ heparin (≤ 10,000 units) or equivalent doses of low molecular weight heparin for prevention of DVT during the first 24 hours of the 3-4.5 hour window trial was permitted and did not increase the incidence of intracerebral hemorrhage (Hacke, 2008).
Special populations: Elderly: Use with caution in patients with advanced age (eg, >75 years); increased risk of bleeding. Acute ischemic stroke (within 3-4.5 hours after symptom onset): Patients >80 years were excluded from the clinical trial (Hacke, 2008). Pregnancy: Use with caution in pregnancy; increased risk of bleeding.
Dosage form specific issues: Cathflo® Activase®: When used to restore catheter function, use Cathflo® cautiously in those patients with known or suspected catheter infections. Evaluate catheter for other causes of dysfunction before use. Avoid excessive pressure when instilling into catheter.
Other warnings/precautions: Administration: Intramuscular injections and nonessential handling of the patient should be avoided. Venipunctures should be performed carefully and only when necessary. If arterial puncture is necessary, use an upper extremity vessel that can be manually compressed.
DRUG INTERACTIONS
Anticoagulants: Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. Risk D: Consider therapy modification
Drotrecogin Alfa: Thrombolytic Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Risk D: Consider therapy modification
Nitroglycerin: May decrease the serum concentration of Alteplase. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Salicylates: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, ginkgo (all have additional antiplatelet activity).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. The risk of bleeding may be increased in pregnant women. Use during pregnancy is limited; administer to pregnant women only if the potential benefits justify the risk to the fetus.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS
Acute ischemic stroke: In addition to monitoring for bleeding complications, the 2007 AHA/ASA Guidelines for the early management of acute ischemic stroke recommends the following:
Perform neurological assessments every 15 minutes during infusion and every 30 minutes thereafter for the next 6 hours, then hourly until 24 hours after treatment.
If severe headache, acute hypertension, nausea, or vomiting occurs, discontinue the infusion and obtain emergency CT scan.
Measure BP every 15 minutes for the first 2 hours then every 30 minutes for the next 6 hours, then hourly until 24 hours after initiation of alteplase. Increase frequency if a systolic BP is ≥ 180 mm Hg or if a diastolic BP is ≥ 105 mm Hg; administer antihypertensive medications to maintain BP at or below these levels.
Obtain a follow-up CT scan at 24 hours before starting anticoagulants or antiplatelet agents.
Central venous catheter clearance: Assess catheter function by attempting to aspirate blood.
ST-elevation MI: Assess for evidence of cardiac reperfusion through resolution of chest pain, resolution of baseline ECG changes, preserved left ventricular function, cardiac enzyme washout phenomenon, and/or the appearance of reperfusion arrhythmias; assess for bleeding potential through clinical evidence of GI bleeding, hematuria, gingival bleeding, fibrinogen levels, fibrinogen degradation products, prothrombin times, and partial thromboplastin times.
REFERENCE RANGE
Not routinely measured; literature supports therapeutic levels of 0.52-1.8 mcg/mL
Fibrinogen: 200-400 mg/dL
Activated partial thromboplastin time (aPTT): 22.5-38.7 seconds
Prothrombin time (PT): 10.9-12.2 seconds
CANADIAN BRAND NAMES — Activase® rt-PA; Cathflo® Activase®
INTERNATIONAL BRAND NAMES — Actilyse (AE, AR, AT, AU, BD, BE, BF, BG, BH, BJ, BR, CH, CI, CL, CN, CO, CY, CZ, DE, DK, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HK, HN, HU, ID, IE, IL, IN, IQ, IR, IT, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, NO, OM, PH, PK, PL, PT, PY, QA, SA, SC, SD, SE, SG, SL, SN, SY, TH, TN, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Activacin (JP)
MECHANISM OF ACTION — Initiates local fibrinolysis by binding to fibrin in a thrombus (clot) and converts entrapped plasminogen to plasmin
PHARMACODYNAMICS / KINETICS
Duration: >50% present in plasma cleared ~5 minutes after infusion terminated, ~80% cleared within 10 minutes
Excretion: Clearance: Rapidly from circulating plasma (550-650 mL/minute), primarily hepatic; >50% present in plasma is cleared within 5 minutes after the infusion is terminated, ~80% cleared within 10 minutes
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