MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Ethyol® may be confused with ethanol
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY
Adjuvant, Chemoprotective Agent (Cytoprotective)
Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy
For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:
The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:
Decrease of 20 mm Hg if baseline systolic blood pressure <100
Decrease of 25 mm Hg if baseline systolic blood pressure 100-119
Decrease of 30 mm Hg if baseline systolic blood pressure 120-139
Decrease of 40 mm Hg if baseline systolic blood pressure 140-179
Decrease of 50 mm Hg if baseline systolic blood pressure ≥ 180
If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction:
I.V.: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or
SubQ (unlabeled route): 500 mg once daily prior to radiation therapy
Prevention of radiation proctitis in rectal cancer (unlabeled use): I.V.: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (unlabeled) has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, ondansetron, pemetrexed, piperacillin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine HCl, prochlorperazine edisylate.
USE — Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiation proctitis in patients with rectal cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)
Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to aminothiol compounds or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation. Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available. Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation. Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects. Nausea/vomiting: The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events. Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
Concurrent drug therapy issues: Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.
DRUG INTERACTIONS
Antihypertensives: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CH, CN, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, IE, IL, IT, LU, MX, NI, NL, PA, PE, PH, PL, PT, SE, SV, TH, UY, VE)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: ~8-9 minutes
Excretion: Urine
Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
Wednesday, June 16, 2010
Amcinonide
PHARMACOLOGIC CATEGORY
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, miliaria, skin atrophy, striae, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, dryness, folliculitis, hypertrichosis, itching, irritation
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)
Cream (Amcinonide)
0.1% (15): $20.99
0.1% (30): $26.99
0.1% (60): $45.99
Cream (Cyclocort)
0.1% (30): $32.99
0.1% (60): $53.99
Lotion (Cyclocort)
0.1% (60): $47.99
Ointment (Amcinonide)
0.1% (60): $43.99
Ointment (Cyclocort)
0.1% (15): $24.99
0.1% (60): $53.99
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcinil (IT); Amicla (BE, LU, NL); Penticort (FR, IT); Visderm (AR, JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, miliaria, skin atrophy, striae, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, dryness, folliculitis, hypertrichosis, itching, irritation
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)
Cream (Amcinonide)
0.1% (15): $20.99
0.1% (30): $26.99
0.1% (60): $45.99
Cream (Cyclocort)
0.1% (30): $32.99
0.1% (60): $53.99
Lotion (Cyclocort)
0.1% (60): $47.99
Ointment (Amcinonide)
0.1% (60): $43.99
Ointment (Cyclocort)
0.1% (15): $24.99
0.1% (60): $53.99
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcinil (IT); Amicla (BE, LU, NL); Penticort (FR, IT); Visderm (AR, JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Amifostine
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Ethyol® may be confused with ethanol
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY
Adjuvant, Chemoprotective Agent (Cytoprotective)
Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy
For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:
The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:
Decrease of 20 mm Hg if baseline systolic blood pressure <100
Decrease of 25 mm Hg if baseline systolic blood pressure 100-119
Decrease of 30 mm Hg if baseline systolic blood pressure 120-139
Decrease of 40 mm Hg if baseline systolic blood pressure 140-179
Decrease of 50 mm Hg if baseline systolic blood pressure ≥ 180
If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction:
I.V.: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or
SubQ (unlabeled route): 500 mg once daily prior to radiation therapy
Prevention of radiation proctitis in rectal cancer (unlabeled use): I.V.: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (unlabeled) has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, ondansetron, pemetrexed, piperacillin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine HCl, prochlorperazine edisylate.
USE — Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiation proctitis in patients with rectal cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)
Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to aminothiol compounds or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation. Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available. Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation. Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects. Nausea/vomiting: The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events. Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
Concurrent drug therapy issues: Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.
DRUG INTERACTIONS
Antihypertensives: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CH, CN, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, IE, IL, IT, LU, MX, NI, NL, PA, PE, PH, PL, PT, SE, SV, TH, UY, VE)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: ~8-9 minutes
Excretion: Urine
Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
Sound-alike/look-alike issues:
Ethyol® may be confused with ethanol
U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY
Adjuvant, Chemoprotective Agent (Cytoprotective)
Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy
For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:
The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:
Decrease of 20 mm Hg if baseline systolic blood pressure <100
Decrease of 25 mm Hg if baseline systolic blood pressure 100-119
Decrease of 30 mm Hg if baseline systolic blood pressure 120-139
Decrease of 40 mm Hg if baseline systolic blood pressure 140-179
Decrease of 50 mm Hg if baseline systolic blood pressure ≥ 180
If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.
Xerostomia from head and neck cancer, reduction:
I.V.: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or
SubQ (unlabeled route): 500 mg once daily prior to radiation therapy
Prevention of radiation proctitis in rectal cancer (unlabeled use): I.V.: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 500 mg
Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — I.V.: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (unlabeled) has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, ondansetron, pemetrexed, piperacillin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine HCl, prochlorperazine edisylate.
USE — Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiation proctitis in patients with rectal cancer
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)
Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)
<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria
CONTRAINDICATIONS — Hypersensitivity to aminothiol compounds or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation. Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available. Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation. Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects. Nausea/vomiting: The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events. Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
Concurrent drug therapy issues: Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.
DRUG INTERACTIONS
Antihypertensives: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
MONITORING PARAMETERS — Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CH, CN, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HK, HN, IE, IL, IT, LU, MX, NI, NL, PA, PE, PH, PL, PT, SE, SV, TH, UY, VE)
MECHANISM OF ACTION — Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: ~8-9 minutes
Excretion: Urine
Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.
Amcinonide
PHARMACOLOGIC CATEGORY
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, miliaria, skin atrophy, striae, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, dryness, folliculitis, hypertrichosis, itching, irritation
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)
Cream (Amcinonide)
0.1% (15): $20.99
0.1% (30): $26.99
0.1% (60): $45.99
Cream (Cyclocort)
0.1% (30): $32.99
0.1% (60): $53.99
Lotion (Cyclocort)
0.1% (60): $47.99
Ointment (Amcinonide)
0.1% (60): $43.99
Ointment (Cyclocort)
0.1% (15): $24.99
0.1% (60): $53.99
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcinil (IT); Amicla (BE, LU, NL); Penticort (FR, IT); Visderm (AR, JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply in a thin film 2-3 times/day. Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream: 0.1% (15 g, 30 g, 60 g) [contains benzyl alcohol]
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g) [contains benzyl alcohol]
DOSAGE FORMS: CONCISE
Cream: 0.1% (15 g, 30 g, 60 g)
Lotion: 0.1% (60 mL)
Ointment: 0.1% (30 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (high potency corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, hypopigmentation, allergic dermatitis, maceration of the skin, miliaria, skin atrophy, striae, telangiectasia
Endocrine & metabolic: Cushing's syndrome, growth retardation (long-term use), HPA suppression, hyperglycemia; these reactions occur more frequently with occlusive dressings
Local: Burning, dryness, folliculitis, hypertrichosis, itching, irritation
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to amcinonide or any component of the formulation; use on the face, groin, or axilla
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Disease-related concerns: Infected/weeping lesions: Occlusive dressings should not be used in presence of infection or weeping lesions.
Special populations: Pediatrics: Chronic use of corticosteroids in children may interfere with growth and development.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)
Cream (Amcinonide)
0.1% (15): $20.99
0.1% (30): $26.99
0.1% (60): $45.99
Cream (Cyclocort)
0.1% (30): $32.99
0.1% (60): $53.99
Lotion (Cyclocort)
0.1% (60): $47.99
Ointment (Amcinonide)
0.1% (60): $43.99
Ointment (Cyclocort)
0.1% (15): $24.99
0.1% (60): $53.99
CANADIAN BRAND NAMES — Amcort®; Cyclocort®; ratio-Amcinonide; Taro-Amcinonide
INTERNATIONAL BRAND NAMES — Amciderm (DE, TH); Amcinil (IT); Amicla (BE, LU, NL); Penticort (FR, IT); Visderm (AR, JP)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Adequate through intact skin; increases with skin inflammation or occlusion
Metabolism: Hepatic
Excretion: Urine and feces
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Ambrisentan
U.S. BRAND NAMES — Letairis®
PHARMACOLOGIC CATEGORY
Endothelin Antagonist
Vasodilator
DOSING: ADULTS — Pulmonary arterial hypertension: Oral: Initial: 5 mg once daily; if tolerated, may increase to maximum 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment is required in mild-to-moderate renal impairment. No data available for use in severe renal impairment.
DOSING: HEPATIC IMPAIRMENT — Avoid use in patients with moderate-to-severe hepatic insufficiency. Dose reductions may be required in patients with mild hepatic insufficiency.
DOSING: ADJUSTMENT FOR TOXICITY — Modifications based on transaminase elevation:
If any elevation, regardless of degree, is accompanied by clinical symptoms of hepatic injury (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin >2 times ULN, treatment should be stopped and not reintroduced.
AST/ALT >3 but ≤ 5 times ULN: Confirm with additional test; if confirmed, reduce dose or interrupt treatment. Monitor transaminase levels at least every 2 weeks until levels are <3 times ULN. Reinitiate treatment as appropriate with return to pretreatment values and with more frequent checks of transaminase levels.
AST/ALT >5 but ≤ 8 times ULN: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels until they are <3 times ULN. May reintroduce treatment, as appropriate, at starting dose, following return to pretreatment values. More frequent checks of transaminase levels are required after resuming therapy.
AST/ALT >8 times ULN: Stop treatment and do not reintroduce.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Letairis®: 5 mg, 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Letairis®: 5 mg, 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Swallow tablet whole. Do not split, crush, or chew tablets. May be administered with or without food.
USE — Treatment of pulmonary artery hypertension (PAH) World Health Organization (WHO) Group I in patients with WHO Class II or III symptoms to improve exercise capacity and decrease the rate of clinical deterioration
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Peripheral edema (17%)
Central nervous system: Headache (15%)
1% to 10%:
Cardiovascular: Palpitation (5%), flushing (4%)
Gastrointestinal: Constipation (4%), abdominal pain (3%)
Hematologic: Hemoglobin decreased (7% to 10%)
Hepatic: Liver enzymes increased (1% to 3%)
Respiratory: Nasal congestion (6%), dyspnea (4%), nasopharyngitis (3%), sinusitis (3%)
Postmarketing and/or case reports: Fluid retention
CONTRAINDICATIONS — Pregnancy
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to ambrisentan or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Hepatic impairment: See "Disease-related concerns" below Letairis Education and Access Program (LEAP): See "Other Warnings/precautions" below Pregnancy: See "Special populations" below
Concerns related to adverse effects: Fluid retention/peripheral edema: Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur; a higher incidence is seen in elderly patients. There have also been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization). Further evaluation may be necessary to determine cause and appropriate treatment or discontinuation of therapy. Hematologic changes: A reduction in hematocrit/hemoglobin may be observed within the first few weeks of therapy with subsequent stabilization of levels. Hemoglobin reductions >15% have been observed in some patients. Measure hemoglobin prior to initiating therapy, at 1 month, and periodically thereafter. Significant decreases in hemoglobin in the absence of other causes may warrant the discontinuation of therapy. Spermatogenesis: Sperm count may be reduced in men during treatment (as observed with bosentan). No changes in sperm function or hormone levels have been noted. Fertility issues may require discussion with patient.
Disease-related concerns: Hepatic impairment: [U.S. Boxed Warning]: Avoid use in moderate-to-severe hepatic impairment. Has been associated with significant transaminase (ALT or AST) elevations (>3 times upper limit of normal [ULN]) in up to 3% of treated patients. Transaminase elevations are dose dependent. Avoid use in patients with elevated serum transaminases (>3 times ULN) at baseline. An increase in bilirubin may be observed as well. Monitor hepatic function closely (at least monthly) for the duration of treatment. Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Treatment should be stopped in patients who develop elevated transaminases >8 times ULN, elevated transaminases accompanied by symptoms of hepatic injury (unusual fatigue, jaundice, nausea, vomiting, abdominal pain, and/or fever) or elevated serum bilirubin >2 times ULN. Safety of reintroduction is unknown. Use caution in mild hepatic impairment. Dose reduction may be necessary. Pulmonary veno-occlusive disease (PVOD): Discontinue in any patient with pulmonary edema suggestive of PVOD.
Concurrent drug therapy issues: High potential for interactions: Use caution in patients taking strong inhibitors or inducers of CYP3A4 or CYP2C19, inhibitors of P-glycoprotein (eg, cyclosporine), or agents which affect glucuronidation metabolism via uridine 5'-diphosphate glucuronosyltransferase (UGT) enzymes.
Special populations: Pregnancy: [U.S. Boxed Warning]: Use in pregnancy is contraindicated; may cause birth defects. Exclude pregnancy prior to initiating therapy and monthly thereafter during therapy. Two reliable methods of contraception must be used during therapy and for one month after stopping treatment except in patients with tubal ligation or an implanted IUD (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients. A missed menses should be reported to healthcare provider and prompt immediate pregnancy testing.
Other warnings/precautions: Letairis Education and Access Program (LEAP): [U.S. Boxed Warning]: Because of the risks of hepatic impairment and the high likelihood of teratogenic effects, ambrisentan is only available through the LEAP restricted distribution program. Patients, prescribers, and pharmacies must be registered with and meet conditions of LEAP. Call 1-866-664-5327 for more information.
RESTRICTIONS — Ambrisentan (Letairis®) is only available through the limited distribution program (Letairis Education and Access Program [LEAP]). Only prescribers and pharmacies registered with LEAP may prescribe and dispense ambrisentan. Further information may be obtained from the manufacturer, Gilead Sciences, Inc (1-866-664-5327).
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major), 2C19 (major), P-glycoprotein
DRUG INTERACTIONS
CycloSPORINE: May increase the serum concentration of Ambrisentan. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Grapefruit/grapefruit juice may increase levels/effects of ambrisentan.
Herb/Nutraceutical: Avoid St John's wort (concurrent use may decrease levels/effects of ambrisentan).
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — [U.S. Boxed Warning]: Use in pregnancy is contraindicated. Based on animal studies, ambrisentan is likely to produce major birth defects if used by pregnant women. Pregnancy must be excluded prior to initiation of therapy and follow-up pregnancy tests should be obtained monthly. Two reliable methods of contraception must be used throughout treatment and for one month after stopping treatment unless the patient has undergone a tubal ligation or the insertion of an intrauterine device (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken with or without food. Avoid grapefruit and grapefruit juice.
MONITORING PARAMETERS — Serum transaminase (AST and ALT) and bilirubin should be determined prior to the initiation of therapy (baseline) and at monthly intervals thereafter. Monitor for clinical signs and symptoms of liver injury (eg, abdominal pain, fatigue, fever, jaundice, nausea, vomiting). Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Monitor levels every 2 weeks until they are <3>8 times ULN, elevated transaminases with accompanying symptoms of hepatic injury, or bilirubin >2 times ULN. Monitor for significant peripheral edema and evaluate etiology if it occurs.
A woman of childbearing potential must have a negative pregnancy test prior to the initiation of therapy and monthly thereafter. Hemoglobin and hematocrit should be measured at baseline, at 1 month, and periodically thereafter (generally stabilizes after the first few weeks of treatment).
CANADIAN BRAND NAMES — Volibris®
INTERNATIONAL BRAND NAMES — Volibris (CZ, EE, GB, IE, SE)
MECHANISM OF ACTION — Blocks endothelin receptor subtypes ETA and ETB on vascular endothelium and smooth muscle. Stimulation of these receptors in smooth muscle cells is associated with vasoconstriction. Simulation of ETB receptors in endothelial cells is associated with vasodilation and antiproliferative effects. Although ambrisentan blocks both ETA and ETB receptors, the affinity is greater for the A subtype. Improvement in symptoms of pulmonary artery hypertension and a decrease in the rate of clinical deterioration have been demonstrated in clinical trials.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid
Protein binding: 99%
Metabolism: Hepatic via CYP3A4, CYP2C19, and uridine 5'-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S; in vitro studies also suggest it is a substrate of organic anion transport protein (OATP) and P-glycoprotein (P-gp)
Half-life elimination: ~9 hours
Time to peak, plasma: ~2 hours
Excretion: Primarily nonrenal
PHARMACOLOGIC CATEGORY
Endothelin Antagonist
Vasodilator
DOSING: ADULTS — Pulmonary arterial hypertension: Oral: Initial: 5 mg once daily; if tolerated, may increase to maximum 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment is required in mild-to-moderate renal impairment. No data available for use in severe renal impairment.
DOSING: HEPATIC IMPAIRMENT — Avoid use in patients with moderate-to-severe hepatic insufficiency. Dose reductions may be required in patients with mild hepatic insufficiency.
DOSING: ADJUSTMENT FOR TOXICITY — Modifications based on transaminase elevation:
If any elevation, regardless of degree, is accompanied by clinical symptoms of hepatic injury (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin >2 times ULN, treatment should be stopped and not reintroduced.
AST/ALT >3 but ≤ 5 times ULN: Confirm with additional test; if confirmed, reduce dose or interrupt treatment. Monitor transaminase levels at least every 2 weeks until levels are <3 times ULN. Reinitiate treatment as appropriate with return to pretreatment values and with more frequent checks of transaminase levels.
AST/ALT >5 but ≤ 8 times ULN: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels until they are <3 times ULN. May reintroduce treatment, as appropriate, at starting dose, following return to pretreatment values. More frequent checks of transaminase levels are required after resuming therapy.
AST/ALT >8 times ULN: Stop treatment and do not reintroduce.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Letairis®: 5 mg, 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Letairis®: 5 mg, 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Swallow tablet whole. Do not split, crush, or chew tablets. May be administered with or without food.
USE — Treatment of pulmonary artery hypertension (PAH) World Health Organization (WHO) Group I in patients with WHO Class II or III symptoms to improve exercise capacity and decrease the rate of clinical deterioration
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Peripheral edema (17%)
Central nervous system: Headache (15%)
1% to 10%:
Cardiovascular: Palpitation (5%), flushing (4%)
Gastrointestinal: Constipation (4%), abdominal pain (3%)
Hematologic: Hemoglobin decreased (7% to 10%)
Hepatic: Liver enzymes increased (1% to 3%)
Respiratory: Nasal congestion (6%), dyspnea (4%), nasopharyngitis (3%), sinusitis (3%)
Postmarketing and/or case reports: Fluid retention
CONTRAINDICATIONS — Pregnancy
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to ambrisentan or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Hepatic impairment: See "Disease-related concerns" below Letairis Education and Access Program (LEAP): See "Other Warnings/precautions" below Pregnancy: See "Special populations" below
Concerns related to adverse effects: Fluid retention/peripheral edema: Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur; a higher incidence is seen in elderly patients. There have also been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization). Further evaluation may be necessary to determine cause and appropriate treatment or discontinuation of therapy. Hematologic changes: A reduction in hematocrit/hemoglobin may be observed within the first few weeks of therapy with subsequent stabilization of levels. Hemoglobin reductions >15% have been observed in some patients. Measure hemoglobin prior to initiating therapy, at 1 month, and periodically thereafter. Significant decreases in hemoglobin in the absence of other causes may warrant the discontinuation of therapy. Spermatogenesis: Sperm count may be reduced in men during treatment (as observed with bosentan). No changes in sperm function or hormone levels have been noted. Fertility issues may require discussion with patient.
Disease-related concerns: Hepatic impairment: [U.S. Boxed Warning]: Avoid use in moderate-to-severe hepatic impairment. Has been associated with significant transaminase (ALT or AST) elevations (>3 times upper limit of normal [ULN]) in up to 3% of treated patients. Transaminase elevations are dose dependent. Avoid use in patients with elevated serum transaminases (>3 times ULN) at baseline. An increase in bilirubin may be observed as well. Monitor hepatic function closely (at least monthly) for the duration of treatment. Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Treatment should be stopped in patients who develop elevated transaminases >8 times ULN, elevated transaminases accompanied by symptoms of hepatic injury (unusual fatigue, jaundice, nausea, vomiting, abdominal pain, and/or fever) or elevated serum bilirubin >2 times ULN. Safety of reintroduction is unknown. Use caution in mild hepatic impairment. Dose reduction may be necessary. Pulmonary veno-occlusive disease (PVOD): Discontinue in any patient with pulmonary edema suggestive of PVOD.
Concurrent drug therapy issues: High potential for interactions: Use caution in patients taking strong inhibitors or inducers of CYP3A4 or CYP2C19, inhibitors of P-glycoprotein (eg, cyclosporine), or agents which affect glucuronidation metabolism via uridine 5'-diphosphate glucuronosyltransferase (UGT) enzymes.
Special populations: Pregnancy: [U.S. Boxed Warning]: Use in pregnancy is contraindicated; may cause birth defects. Exclude pregnancy prior to initiating therapy and monthly thereafter during therapy. Two reliable methods of contraception must be used during therapy and for one month after stopping treatment except in patients with tubal ligation or an implanted IUD (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients. A missed menses should be reported to healthcare provider and prompt immediate pregnancy testing.
Other warnings/precautions: Letairis Education and Access Program (LEAP): [U.S. Boxed Warning]: Because of the risks of hepatic impairment and the high likelihood of teratogenic effects, ambrisentan is only available through the LEAP restricted distribution program. Patients, prescribers, and pharmacies must be registered with and meet conditions of LEAP. Call 1-866-664-5327 for more information.
RESTRICTIONS — Ambrisentan (Letairis®) is only available through the limited distribution program (Letairis Education and Access Program [LEAP]). Only prescribers and pharmacies registered with LEAP may prescribe and dispense ambrisentan. Further information may be obtained from the manufacturer, Gilead Sciences, Inc (1-866-664-5327).
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major), 2C19 (major), P-glycoprotein
DRUG INTERACTIONS
CycloSPORINE: May increase the serum concentration of Ambrisentan. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Grapefruit/grapefruit juice may increase levels/effects of ambrisentan.
Herb/Nutraceutical: Avoid St John's wort (concurrent use may decrease levels/effects of ambrisentan).
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — [U.S. Boxed Warning]: Use in pregnancy is contraindicated. Based on animal studies, ambrisentan is likely to produce major birth defects if used by pregnant women. Pregnancy must be excluded prior to initiation of therapy and follow-up pregnancy tests should be obtained monthly. Two reliable methods of contraception must be used throughout treatment and for one month after stopping treatment unless the patient has undergone a tubal ligation or the insertion of an intrauterine device (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken with or without food. Avoid grapefruit and grapefruit juice.
MONITORING PARAMETERS — Serum transaminase (AST and ALT) and bilirubin should be determined prior to the initiation of therapy (baseline) and at monthly intervals thereafter. Monitor for clinical signs and symptoms of liver injury (eg, abdominal pain, fatigue, fever, jaundice, nausea, vomiting). Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Monitor levels every 2 weeks until they are <3>8 times ULN, elevated transaminases with accompanying symptoms of hepatic injury, or bilirubin >2 times ULN. Monitor for significant peripheral edema and evaluate etiology if it occurs.
A woman of childbearing potential must have a negative pregnancy test prior to the initiation of therapy and monthly thereafter. Hemoglobin and hematocrit should be measured at baseline, at 1 month, and periodically thereafter (generally stabilizes after the first few weeks of treatment).
CANADIAN BRAND NAMES — Volibris®
INTERNATIONAL BRAND NAMES — Volibris (CZ, EE, GB, IE, SE)
MECHANISM OF ACTION — Blocks endothelin receptor subtypes ETA and ETB on vascular endothelium and smooth muscle. Stimulation of these receptors in smooth muscle cells is associated with vasoconstriction. Simulation of ETB receptors in endothelial cells is associated with vasodilation and antiproliferative effects. Although ambrisentan blocks both ETA and ETB receptors, the affinity is greater for the A subtype. Improvement in symptoms of pulmonary artery hypertension and a decrease in the rate of clinical deterioration have been demonstrated in clinical trials.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid
Protein binding: 99%
Metabolism: Hepatic via CYP3A4, CYP2C19, and uridine 5'-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S; in vitro studies also suggest it is a substrate of organic anion transport protein (OATP) and P-glycoprotein (P-gp)
Half-life elimination: ~9 hours
Time to peak, plasma: ~2 hours
Excretion: Primarily nonrenal
Ambrisentan
U.S. BRAND NAMES — Letairis®
PHARMACOLOGIC CATEGORY
Endothelin Antagonist
Vasodilator
DOSING: ADULTS — Pulmonary arterial hypertension: Oral: Initial: 5 mg once daily; if tolerated, may increase to maximum 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment is required in mild-to-moderate renal impairment. No data available for use in severe renal impairment.
DOSING: HEPATIC IMPAIRMENT — Avoid use in patients with moderate-to-severe hepatic insufficiency. Dose reductions may be required in patients with mild hepatic insufficiency.
DOSING: ADJUSTMENT FOR TOXICITY — Modifications based on transaminase elevation:
If any elevation, regardless of degree, is accompanied by clinical symptoms of hepatic injury (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin >2 times ULN, treatment should be stopped and not reintroduced.
AST/ALT >3 but ≤ 5 times ULN: Confirm with additional test; if confirmed, reduce dose or interrupt treatment. Monitor transaminase levels at least every 2 weeks until levels are <3 times ULN. Reinitiate treatment as appropriate with return to pretreatment values and with more frequent checks of transaminase levels.
AST/ALT >5 but ≤ 8 times ULN: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels until they are <3 times ULN. May reintroduce treatment, as appropriate, at starting dose, following return to pretreatment values. More frequent checks of transaminase levels are required after resuming therapy.
AST/ALT >8 times ULN: Stop treatment and do not reintroduce.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Letairis®: 5 mg, 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Letairis®: 5 mg, 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Swallow tablet whole. Do not split, crush, or chew tablets. May be administered with or without food.
USE — Treatment of pulmonary artery hypertension (PAH) World Health Organization (WHO) Group I in patients with WHO Class II or III symptoms to improve exercise capacity and decrease the rate of clinical deterioration
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Peripheral edema (17%)
Central nervous system: Headache (15%)
1% to 10%:
Cardiovascular: Palpitation (5%), flushing (4%)
Gastrointestinal: Constipation (4%), abdominal pain (3%)
Hematologic: Hemoglobin decreased (7% to 10%)
Hepatic: Liver enzymes increased (1% to 3%)
Respiratory: Nasal congestion (6%), dyspnea (4%), nasopharyngitis (3%), sinusitis (3%)
Postmarketing and/or case reports: Fluid retention
CONTRAINDICATIONS — Pregnancy
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to ambrisentan or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Hepatic impairment: See "Disease-related concerns" below Letairis Education and Access Program (LEAP): See "Other Warnings/precautions" below Pregnancy: See "Special populations" below
Concerns related to adverse effects: Fluid retention/peripheral edema: Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur; a higher incidence is seen in elderly patients. There have also been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization). Further evaluation may be necessary to determine cause and appropriate treatment or discontinuation of therapy. Hematologic changes: A reduction in hematocrit/hemoglobin may be observed within the first few weeks of therapy with subsequent stabilization of levels. Hemoglobin reductions >15% have been observed in some patients. Measure hemoglobin prior to initiating therapy, at 1 month, and periodically thereafter. Significant decreases in hemoglobin in the absence of other causes may warrant the discontinuation of therapy. Spermatogenesis: Sperm count may be reduced in men during treatment (as observed with bosentan). No changes in sperm function or hormone levels have been noted. Fertility issues may require discussion with patient.
Disease-related concerns: Hepatic impairment: [U.S. Boxed Warning]: Avoid use in moderate-to-severe hepatic impairment. Has been associated with significant transaminase (ALT or AST) elevations (>3 times upper limit of normal [ULN]) in up to 3% of treated patients. Transaminase elevations are dose dependent. Avoid use in patients with elevated serum transaminases (>3 times ULN) at baseline. An increase in bilirubin may be observed as well. Monitor hepatic function closely (at least monthly) for the duration of treatment. Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Treatment should be stopped in patients who develop elevated transaminases >8 times ULN, elevated transaminases accompanied by symptoms of hepatic injury (unusual fatigue, jaundice, nausea, vomiting, abdominal pain, and/or fever) or elevated serum bilirubin >2 times ULN. Safety of reintroduction is unknown. Use caution in mild hepatic impairment. Dose reduction may be necessary. Pulmonary veno-occlusive disease (PVOD): Discontinue in any patient with pulmonary edema suggestive of PVOD.
Concurrent drug therapy issues: High potential for interactions: Use caution in patients taking strong inhibitors or inducers of CYP3A4 or CYP2C19, inhibitors of P-glycoprotein (eg, cyclosporine), or agents which affect glucuronidation metabolism via uridine 5'-diphosphate glucuronosyltransferase (UGT) enzymes.
Special populations: Pregnancy: [U.S. Boxed Warning]: Use in pregnancy is contraindicated; may cause birth defects. Exclude pregnancy prior to initiating therapy and monthly thereafter during therapy. Two reliable methods of contraception must be used during therapy and for one month after stopping treatment except in patients with tubal ligation or an implanted IUD (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients. A missed menses should be reported to healthcare provider and prompt immediate pregnancy testing.
Other warnings/precautions: Letairis Education and Access Program (LEAP): [U.S. Boxed Warning]: Because of the risks of hepatic impairment and the high likelihood of teratogenic effects, ambrisentan is only available through the LEAP restricted distribution program. Patients, prescribers, and pharmacies must be registered with and meet conditions of LEAP. Call 1-866-664-5327 for more information.
RESTRICTIONS — Ambrisentan (Letairis®) is only available through the limited distribution program (Letairis Education and Access Program [LEAP]). Only prescribers and pharmacies registered with LEAP may prescribe and dispense ambrisentan. Further information may be obtained from the manufacturer, Gilead Sciences, Inc (1-866-664-5327).
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major), 2C19 (major), P-glycoprotein
DRUG INTERACTIONS
CycloSPORINE: May increase the serum concentration of Ambrisentan. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Grapefruit/grapefruit juice may increase levels/effects of ambrisentan.
Herb/Nutraceutical: Avoid St John's wort (concurrent use may decrease levels/effects of ambrisentan).
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — [U.S. Boxed Warning]: Use in pregnancy is contraindicated. Based on animal studies, ambrisentan is likely to produce major birth defects if used by pregnant women. Pregnancy must be excluded prior to initiation of therapy and follow-up pregnancy tests should be obtained monthly. Two reliable methods of contraception must be used throughout treatment and for one month after stopping treatment unless the patient has undergone a tubal ligation or the insertion of an intrauterine device (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken with or without food. Avoid grapefruit and grapefruit juice.
MONITORING PARAMETERS — Serum transaminase (AST and ALT) and bilirubin should be determined prior to the initiation of therapy (baseline) and at monthly intervals thereafter. Monitor for clinical signs and symptoms of liver injury (eg, abdominal pain, fatigue, fever, jaundice, nausea, vomiting). Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Monitor levels every 2 weeks until they are <3>8 times ULN, elevated transaminases with accompanying symptoms of hepatic injury, or bilirubin >2 times ULN. Monitor for significant peripheral edema and evaluate etiology if it occurs.
A woman of childbearing potential must have a negative pregnancy test prior to the initiation of therapy and monthly thereafter. Hemoglobin and hematocrit should be measured at baseline, at 1 month, and periodically thereafter (generally stabilizes after the first few weeks of treatment).
CANADIAN BRAND NAMES — Volibris®
INTERNATIONAL BRAND NAMES — Volibris (CZ, EE, GB, IE, SE)
MECHANISM OF ACTION — Blocks endothelin receptor subtypes ETA and ETB on vascular endothelium and smooth muscle. Stimulation of these receptors in smooth muscle cells is associated with vasoconstriction. Simulation of ETB receptors in endothelial cells is associated with vasodilation and antiproliferative effects. Although ambrisentan blocks both ETA and ETB receptors, the affinity is greater for the A subtype. Improvement in symptoms of pulmonary artery hypertension and a decrease in the rate of clinical deterioration have been demonstrated in clinical trials.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid
Protein binding: 99%
Metabolism: Hepatic via CYP3A4, CYP2C19, and uridine 5'-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S; in vitro studies also suggest it is a substrate of organic anion transport protein (OATP) and P-glycoprotein (P-gp)
Half-life elimination: ~9 hours
Time to peak, plasma: ~2 hours
Excretion: Primarily nonrenal
PHARMACOLOGIC CATEGORY
Endothelin Antagonist
Vasodilator
DOSING: ADULTS — Pulmonary arterial hypertension: Oral: Initial: 5 mg once daily; if tolerated, may increase to maximum 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment is required in mild-to-moderate renal impairment. No data available for use in severe renal impairment.
DOSING: HEPATIC IMPAIRMENT — Avoid use in patients with moderate-to-severe hepatic insufficiency. Dose reductions may be required in patients with mild hepatic insufficiency.
DOSING: ADJUSTMENT FOR TOXICITY — Modifications based on transaminase elevation:
If any elevation, regardless of degree, is accompanied by clinical symptoms of hepatic injury (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin >2 times ULN, treatment should be stopped and not reintroduced.
AST/ALT >3 but ≤ 5 times ULN: Confirm with additional test; if confirmed, reduce dose or interrupt treatment. Monitor transaminase levels at least every 2 weeks until levels are <3 times ULN. Reinitiate treatment as appropriate with return to pretreatment values and with more frequent checks of transaminase levels.
AST/ALT >5 but ≤ 8 times ULN: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels until they are <3 times ULN. May reintroduce treatment, as appropriate, at starting dose, following return to pretreatment values. More frequent checks of transaminase levels are required after resuming therapy.
AST/ALT >8 times ULN: Stop treatment and do not reintroduce.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Letairis®: 5 mg, 10 mg
DOSAGE FORMS: CONCISE
Tablet:
Letairis®: 5 mg, 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Swallow tablet whole. Do not split, crush, or chew tablets. May be administered with or without food.
USE — Treatment of pulmonary artery hypertension (PAH) World Health Organization (WHO) Group I in patients with WHO Class II or III symptoms to improve exercise capacity and decrease the rate of clinical deterioration
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Peripheral edema (17%)
Central nervous system: Headache (15%)
1% to 10%:
Cardiovascular: Palpitation (5%), flushing (4%)
Gastrointestinal: Constipation (4%), abdominal pain (3%)
Hematologic: Hemoglobin decreased (7% to 10%)
Hepatic: Liver enzymes increased (1% to 3%)
Respiratory: Nasal congestion (6%), dyspnea (4%), nasopharyngitis (3%), sinusitis (3%)
Postmarketing and/or case reports: Fluid retention
CONTRAINDICATIONS — Pregnancy
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to ambrisentan or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Hepatic impairment: See "Disease-related concerns" below Letairis Education and Access Program (LEAP): See "Other Warnings/precautions" below Pregnancy: See "Special populations" below
Concerns related to adverse effects: Fluid retention/peripheral edema: Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur; a higher incidence is seen in elderly patients. There have also been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization). Further evaluation may be necessary to determine cause and appropriate treatment or discontinuation of therapy. Hematologic changes: A reduction in hematocrit/hemoglobin may be observed within the first few weeks of therapy with subsequent stabilization of levels. Hemoglobin reductions >15% have been observed in some patients. Measure hemoglobin prior to initiating therapy, at 1 month, and periodically thereafter. Significant decreases in hemoglobin in the absence of other causes may warrant the discontinuation of therapy. Spermatogenesis: Sperm count may be reduced in men during treatment (as observed with bosentan). No changes in sperm function or hormone levels have been noted. Fertility issues may require discussion with patient.
Disease-related concerns: Hepatic impairment: [U.S. Boxed Warning]: Avoid use in moderate-to-severe hepatic impairment. Has been associated with significant transaminase (ALT or AST) elevations (>3 times upper limit of normal [ULN]) in up to 3% of treated patients. Transaminase elevations are dose dependent. Avoid use in patients with elevated serum transaminases (>3 times ULN) at baseline. An increase in bilirubin may be observed as well. Monitor hepatic function closely (at least monthly) for the duration of treatment. Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Treatment should be stopped in patients who develop elevated transaminases >8 times ULN, elevated transaminases accompanied by symptoms of hepatic injury (unusual fatigue, jaundice, nausea, vomiting, abdominal pain, and/or fever) or elevated serum bilirubin >2 times ULN. Safety of reintroduction is unknown. Use caution in mild hepatic impairment. Dose reduction may be necessary. Pulmonary veno-occlusive disease (PVOD): Discontinue in any patient with pulmonary edema suggestive of PVOD.
Concurrent drug therapy issues: High potential for interactions: Use caution in patients taking strong inhibitors or inducers of CYP3A4 or CYP2C19, inhibitors of P-glycoprotein (eg, cyclosporine), or agents which affect glucuronidation metabolism via uridine 5'-diphosphate glucuronosyltransferase (UGT) enzymes.
Special populations: Pregnancy: [U.S. Boxed Warning]: Use in pregnancy is contraindicated; may cause birth defects. Exclude pregnancy prior to initiating therapy and monthly thereafter during therapy. Two reliable methods of contraception must be used during therapy and for one month after stopping treatment except in patients with tubal ligation or an implanted IUD (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients. A missed menses should be reported to healthcare provider and prompt immediate pregnancy testing.
Other warnings/precautions: Letairis Education and Access Program (LEAP): [U.S. Boxed Warning]: Because of the risks of hepatic impairment and the high likelihood of teratogenic effects, ambrisentan is only available through the LEAP restricted distribution program. Patients, prescribers, and pharmacies must be registered with and meet conditions of LEAP. Call 1-866-664-5327 for more information.
RESTRICTIONS — Ambrisentan (Letairis®) is only available through the limited distribution program (Letairis Education and Access Program [LEAP]). Only prescribers and pharmacies registered with LEAP may prescribe and dispense ambrisentan. Further information may be obtained from the manufacturer, Gilead Sciences, Inc (1-866-664-5327).
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major), 2C19 (major), P-glycoprotein
DRUG INTERACTIONS
CycloSPORINE: May increase the serum concentration of Ambrisentan. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Grapefruit/grapefruit juice may increase levels/effects of ambrisentan.
Herb/Nutraceutical: Avoid St John's wort (concurrent use may decrease levels/effects of ambrisentan).
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — [U.S. Boxed Warning]: Use in pregnancy is contraindicated. Based on animal studies, ambrisentan is likely to produce major birth defects if used by pregnant women. Pregnancy must be excluded prior to initiation of therapy and follow-up pregnancy tests should be obtained monthly. Two reliable methods of contraception must be used throughout treatment and for one month after stopping treatment unless the patient has undergone a tubal ligation or the insertion of an intrauterine device (Copper T 380A or LNg 20). No other contraceptive measures are required for these patients.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken with or without food. Avoid grapefruit and grapefruit juice.
MONITORING PARAMETERS — Serum transaminase (AST and ALT) and bilirubin should be determined prior to the initiation of therapy (baseline) and at monthly intervals thereafter. Monitor for clinical signs and symptoms of liver injury (eg, abdominal pain, fatigue, fever, jaundice, nausea, vomiting). Reduce dose or interrupt therapy if transaminases >3 times ULN and ≤ 5 times ULN and discontinue therapy with levels >5 times ULN and ≤ 8 times ULN. Monitor levels every 2 weeks until they are <3>8 times ULN, elevated transaminases with accompanying symptoms of hepatic injury, or bilirubin >2 times ULN. Monitor for significant peripheral edema and evaluate etiology if it occurs.
A woman of childbearing potential must have a negative pregnancy test prior to the initiation of therapy and monthly thereafter. Hemoglobin and hematocrit should be measured at baseline, at 1 month, and periodically thereafter (generally stabilizes after the first few weeks of treatment).
CANADIAN BRAND NAMES — Volibris®
INTERNATIONAL BRAND NAMES — Volibris (CZ, EE, GB, IE, SE)
MECHANISM OF ACTION — Blocks endothelin receptor subtypes ETA and ETB on vascular endothelium and smooth muscle. Stimulation of these receptors in smooth muscle cells is associated with vasoconstriction. Simulation of ETB receptors in endothelial cells is associated with vasodilation and antiproliferative effects. Although ambrisentan blocks both ETA and ETB receptors, the affinity is greater for the A subtype. Improvement in symptoms of pulmonary artery hypertension and a decrease in the rate of clinical deterioration have been demonstrated in clinical trials.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid
Protein binding: 99%
Metabolism: Hepatic via CYP3A4, CYP2C19, and uridine 5'-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S; in vitro studies also suggest it is a substrate of organic anion transport protein (OATP) and P-glycoprotein (P-gp)
Half-life elimination: ~9 hours
Time to peak, plasma: ~2 hours
Excretion: Primarily nonrenal
Ambenonium
U.S. BRAND NAMES — Mytelase®
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, as chloride [scored]:
Mytelase®: 10 mg
DOSAGE FORMS: CONCISE
Caplet [scored]:
Mytelase®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of myasthenia gravis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing
Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia
Ocular: Small pupils, lacrimation
Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm
Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions
CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anticholinergic insensitivity: May develop for brief or prolonged periods; reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.
Disease-related concerns: Asthma: Use with caution in patients with asthma. Bradycardia: Use with caution in patients with bradycardia. Hyperthyroidism: Use with caution in patients with hyperthyroidism. Parkinson's disease: Use with caution in patients with Parkinson's disease. Peptic ulcer disease: Use with caution in patients with peptic ulcer disease. Seizures: Use with caution in patients with a history of seizures. Urinary tract obstruction: Use with caution in patients with urinary obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/not recommended
PRICING — (data from drugstore.com)
Tablets (Mytelase)
10 mg (100): $172.65
CANADIAN BRAND NAMES — Mytelase®
INTERNATIONAL BRAND NAMES — Mytelase (FI, HU, PL); Mytelase Chloride (BE, CZ, FR, HN, SE)
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, as chloride [scored]:
Mytelase®: 10 mg
DOSAGE FORMS: CONCISE
Caplet [scored]:
Mytelase®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of myasthenia gravis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing
Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia
Ocular: Small pupils, lacrimation
Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm
Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions
CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anticholinergic insensitivity: May develop for brief or prolonged periods; reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.
Disease-related concerns: Asthma: Use with caution in patients with asthma. Bradycardia: Use with caution in patients with bradycardia. Hyperthyroidism: Use with caution in patients with hyperthyroidism. Parkinson's disease: Use with caution in patients with Parkinson's disease. Peptic ulcer disease: Use with caution in patients with peptic ulcer disease. Seizures: Use with caution in patients with a history of seizures. Urinary tract obstruction: Use with caution in patients with urinary obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/not recommended
PRICING — (data from drugstore.com)
Tablets (Mytelase)
10 mg (100): $172.65
CANADIAN BRAND NAMES — Mytelase®
INTERNATIONAL BRAND NAMES — Mytelase (FI, HU, PL); Mytelase Chloride (BE, CZ, FR, HN, SE)
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