MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Albenza® may be confused with Aplenzin™ , Relenza®
International issues:
Albenza® may be confused with Avanza® which is a brand name for mirtazapine in Australia
U.S. BRAND NAMES — Albenza®
PHARMACOLOGIC CATEGORY
Anthelmintic
DOSING: ADULTS
Neurocysticercosis: Oral:
<60 kg: 15 mg/kg/day in 2 divided doses (maximum: 800 mg/day) for 8-30 days
≥ 60 kg: 800 mg/day in 2 divided doses for 8-30 days
Note: Give concurrent anticonvulsant and steroid therapy during first week.
Hydatid: Oral:
<60 kg: 15 mg/kg/day in 2 divided doses (maximum: 800 mg/day)
≥ 60 kg: 800 mg/day in 2 divided doses
Note: Administer dose for three 28-day cycles with a 14-day drug-free interval in between. The manufacturer recommends a total of 3 cycles.
Ancylostoma caninum, Ascaris lumbricoides(roundworm), Ancylostoma duodenale (hookworm), and Necator americanus(hookworm) (unlabeled use): Oral: 400 mg as a single dose
Clonorchis sinensis(Chinese liver fluke) (unlabeled use): Oral: 10 mg/kg for 7 days
Cutaneous larva migrans (unlabeled use): Oral: 400 mg once daily for 3 days
Enterobius vermicularis(pinworm) (unlabeled use): Oral: 400 mg as a single dose; may repeat in 2 weeks
Gnathostoma spinigerum (unlabeled use): Oral: 800 mg/day in 2 divided doses for 21 days
Gongylonemiasis (unlabeled use): Oral: 10 mg/kg/day for 3 days
Mansonella perstans(unlabeled use): Oral: 800 mg/day in 2 divided doses for 10 days
Visceral larva migrans (toxocariasis) (unlabeled use): Oral: 800 mg/day in 2 divided doses for 5 days
Cysticercus cellulosae(unlabeled use): Oral: 800 mg/day in 2 divided doses for 8-30 days; may be repeated as necessary
Disseminated microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses
Echinococcus granulosus(tapeworm) (unlabeled use): Oral: 800 mg/day in 2 divided doses for 1-6 months
Intestinal microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses for 21 days
Ocular microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses, in combination with fumagillin
DOSING: PEDIATRIC
(For additional information see "Albendazole: Pediatric drug information")
Neurocysticercosis: Oral: Refer to adult dosing.
Hydatid: Oral: Refer to adult dosing.
Cysticercus cellulosae(unlabeled use): Oral: 15 mg/kg/day (maximum: 800 mg/day) in 2 divided doses for 8-30 days; may be repeated as necessary
Echinococcus granulosus(tapeworm) (unlabeled use): Oral: 15 mg/kg/day (maximum: 800 mg) divided twice daily for 1-6 months
For the following unlabeled uses, refer to adult dosing:
Ancylostoma caninum, Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), Clonorchis sinensis, (Chinese liver fluke), cutaneous larva migrans, Enterobius vermicularis (pinworm), Gnathostoma spinigerum, gongylonemiasis, Mansonella perstans, Necator americanus (hookworm), visceral larva migrans (toxocariasis)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Albenza®: 200 mg
DOSAGE FORMS: CONCISE
Tablet:
Albenza®: 200 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Should be administered with a high-fat meal. Administer anticonvulsant and steroid therapy during first week of neurocysticercosis therapy. If patients have difficulty swallowing, tablets may be crushed or chewed, then swallowed with a drink of water.
USE — Treatment of parenchymal neurocysticercosis caused by Taenia solium and cystic hydatid disease of the liver, lung, and peritoneum caused by Echinococcus granulosus
USE - UNLABELED / INVESTIGATIONAL — Albendazole has activity against Ascaris lumbricoides (roundworm); Ancylostoma caninum; Ancylostoma duodenale and Necator americanus (hookworms); cutaneous larva migrans; Enterobius vermicularis (pinworm); Gnathostoma spinigerum; Gongylonema sp; Mansonella perstans (filariasis); Opisthorchis sinensis (liver fluke); visceral larva migrans (toxocariasis); activity has also been shown against the liver fluke Clonorchis sinensis, Giardia lamblia, Cysticercus cellulosae, and Echinococcus multilocularis. Albendazole has also been used for the treatment of intestinal microsporidiosis (Encephalitozoon intestinalis), disseminated microsporidiosis (E. hellem, E. cuniculi, E. intestinalis, Pleistophora sp, Trachipleistophora sp, Brachiola vesicularum), and ocular microsporidiosis (E. hellem, E. cuniculi, Vittaforma corneae).
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (11% neurocysticercosis; 1% hydatid)
Hepatic: LFTs increased (16% hydatid; <1% neurocysticercosis)
1% to 10%:
Central nervous system: Intracranial pressure increased (up to 2%), dizziness (≤ 1%), fever (≤ 1%), vertigo (≤ 1%), meningeal signs (1%)
Dermatologic: Alopecia (<1% to 2%)
Gastrointestinal: Abdominal pain (up to 6%), nausea/vomiting (4% to 6%)
<1% (Limited to important or life-threatening symptoms): Acute liver failure, acute renal failure, aplastic anemia, agranulocytosis, erythema multiforme, granulocytopenia, hepatitis, hypersensitivity reaction, leukopenia, neutropenia, pancytopenia, rash, Stevens-Johnson syndrome, thrombocytopenia, urticaria
CONTRAINDICATIONS — Hypersensitivity to albendazole, benzimidazoles, or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bone marrow suppression: Agranulocytosis, aplastic anemia, granulocytopenia, leukopenia, and pancytopenia have occurred leading to fatalities (rare); use with caution in patients with hepatic impairment (more susceptible to hematologic toxicity). Discontinue therapy in all patients who develop clinically significant decreases in blood cell counts. Transaminase elevations: Reversible elevations in hepatic enzymes have been reported. Patients with abnormal LFTs and hepatic echinococcosis are at an increased risk of hepatotoxicity. Discontinue therapy if LFT elevations are >2 times the upper limit of normal; may consider restarting treatment (with frequent monitoring of LFTs) when hepatic enzymes return to pretreatment values.
Disease-related concerns: Neurocysticercosis: Appropriate use: Corticosteroids should be administered before or upon initiation of albendazole therapy to minimize inflammatory reactions and prevent cerebral hypertension. Anticonvulsant therapy should be used concurrently during the first week of therapy to prevent seizures. If retinal lesions exist, weigh risk of further retinal damage due to albendazole-induced changes to the retinal lesion vs benefit of disease treatment.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP1A2, 3A4; Inhibits CYP1A2 (weak)
DRUG INTERACTIONS
Aminoquinolines (Antimalarial): May decrease the serum concentration of Anthelmintics. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Albendazole serum levels may be increased if taken with a fatty meal (increases the oral bioavailability by up to 5 times).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Albendazole has been shown to be teratogenic in laboratory animals and should not be used during pregnancy, if at all possible. Women should be advised to avoid pregnancy for at least 1 month following therapy. Discontinue if pregnancy occurs during treatment.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Should be taken with a high-fat meal.
PRICING — (data from drugstore.com)
Tablets (Albenza)
200 mg (12): $26.99
MONITORING PARAMETERS — Monitor fecal specimens for ova and parasites for 3 weeks after treatment; if positive, retreat; LFTs and CBC with differential at start of each 28-day cycle and every 2 weeks during therapy (more frequent monitoring for patients with liver disease); pregnancy test
INTERNATIONAL BRAND NAMES — ABZ (IN); Acure (PK); Albatel (TH); Alben (BR); Albenzol (EC); Albex (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Albezole (IN); Alfuca (TH); Almex (MY); Alminth (IN); Alzental (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SG, SY, YE); Alzol (TH); Bendex-400 (ZA); Benzol (PH); Bruzol (MX); Ceprazol (CN); Champs D-Worm 6 (MY); Ciclopar (CO); Dalben (HR); Digezanol (MX); Emanthal (IN); Eskasole (MX); Eskazole (AT, AU, DE, ES, GB, IL, JP, NL); Fintel (PE); Gascop (MX); Helmiben (UY); Helmidazole (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Labenda (TH); Lomsin (MX); Lurdex (MX); Mebenix (BR); Mesin-C (MY); Nemozole (IN); Pantex (PY); Paranthil (ZA); Parhel (CR, DO, GT, HN, NI, PA, SV); Rotopar (EC); Sioban (IN); Valbazen Vet (NO); Vastus (AR); Vemizol (MY); Vermin Plus (MX); Zeben (TH); Zela (TH); Zentab (TH); Zentel (AE, AU, BB, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CR, CY, CZ, DO, EG, ET, FR, GH, GM, GN, GR, GT, GY, HN, IL, IQ, IR, IT, JM, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PL, PR, PT, QA, SA, SC, SD, SL, SN, SR, SV, SY, TH, TN, TT, TZ, UG, VE, YE, ZA, ZM, ZW)
MECHANISM OF ACTION — Active metabolite, albendazole sulfoxide, causes selective degeneration of cytoplasmic microtubules in intestinal and tegmental cells of intestinal helminths and larvae; glycogen is depleted, glucose uptake and cholinesterase secretion are impaired, and desecratory substances accumulate intracellulary. ATP production decreases causing energy depletion, immobilization, and worm death.
PHARMACODYNAMICS / KINETICS
Absorption: Poor; may increase up to 5 times when administered with a fatty meal
Distribution: Well inside hydatid cysts and CSF
Protein binding: 70%
Metabolism: Hepatic; extensive first-pass effect; pathways include rapid sulfoxidation to active metabolite (albendazole sulfoxide [major]), hydrolysis, and oxidation
Half-life elimination: 8-12 hours
Time to peak, serum: 2-5 hours
Excretion: Urine (<1% as active metabolite); feces
Monday, May 24, 2010
Albendazole
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Albenza® may be confused with Aplenzin™ , Relenza®
International issues:
Albenza® may be confused with Avanza® which is a brand name for mirtazapine in Australia
U.S. BRAND NAMES — Albenza®
PHARMACOLOGIC CATEGORY
Anthelmintic
DOSING: ADULTS
Neurocysticercosis: Oral:
<60 kg: 15 mg/kg/day in 2 divided doses (maximum: 800 mg/day) for 8-30 days
≥ 60 kg: 800 mg/day in 2 divided doses for 8-30 days
Note: Give concurrent anticonvulsant and steroid therapy during first week.
Hydatid: Oral:
<60 kg: 15 mg/kg/day in 2 divided doses (maximum: 800 mg/day)
≥ 60 kg: 800 mg/day in 2 divided doses
Note: Administer dose for three 28-day cycles with a 14-day drug-free interval in between. The manufacturer recommends a total of 3 cycles.
Ancylostoma caninum, Ascaris lumbricoides(roundworm), Ancylostoma duodenale (hookworm), and Necator americanus(hookworm) (unlabeled use): Oral: 400 mg as a single dose
Clonorchis sinensis(Chinese liver fluke) (unlabeled use): Oral: 10 mg/kg for 7 days
Cutaneous larva migrans (unlabeled use): Oral: 400 mg once daily for 3 days
Enterobius vermicularis(pinworm) (unlabeled use): Oral: 400 mg as a single dose; may repeat in 2 weeks
Gnathostoma spinigerum (unlabeled use): Oral: 800 mg/day in 2 divided doses for 21 days
Gongylonemiasis (unlabeled use): Oral: 10 mg/kg/day for 3 days
Mansonella perstans(unlabeled use): Oral: 800 mg/day in 2 divided doses for 10 days
Visceral larva migrans (toxocariasis) (unlabeled use): Oral: 800 mg/day in 2 divided doses for 5 days
Cysticercus cellulosae(unlabeled use): Oral: 800 mg/day in 2 divided doses for 8-30 days; may be repeated as necessary
Disseminated microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses
Echinococcus granulosus(tapeworm) (unlabeled use): Oral: 800 mg/day in 2 divided doses for 1-6 months
Intestinal microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses for 21 days
Ocular microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses, in combination with fumagillin
DOSING: PEDIATRIC
(For additional information see "Albendazole: Pediatric drug information")
Neurocysticercosis: Oral: Refer to adult dosing.
Hydatid: Oral: Refer to adult dosing.
Cysticercus cellulosae(unlabeled use): Oral: 15 mg/kg/day (maximum: 800 mg/day) in 2 divided doses for 8-30 days; may be repeated as necessary
Echinococcus granulosus(tapeworm) (unlabeled use): Oral: 15 mg/kg/day (maximum: 800 mg) divided twice daily for 1-6 months
For the following unlabeled uses, refer to adult dosing:
Ancylostoma caninum, Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), Clonorchis sinensis, (Chinese liver fluke), cutaneous larva migrans, Enterobius vermicularis (pinworm), Gnathostoma spinigerum, gongylonemiasis, Mansonella perstans, Necator americanus (hookworm), visceral larva migrans (toxocariasis)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Albenza®: 200 mg
DOSAGE FORMS: CONCISE
Tablet:
Albenza®: 200 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Should be administered with a high-fat meal. Administer anticonvulsant and steroid therapy during first week of neurocysticercosis therapy. If patients have difficulty swallowing, tablets may be crushed or chewed, then swallowed with a drink of water.
USE — Treatment of parenchymal neurocysticercosis caused by Taenia solium and cystic hydatid disease of the liver, lung, and peritoneum caused by Echinococcus granulosus
USE - UNLABELED / INVESTIGATIONAL — Albendazole has activity against Ascaris lumbricoides (roundworm); Ancylostoma caninum; Ancylostoma duodenale and Necator americanus (hookworms); cutaneous larva migrans; Enterobius vermicularis (pinworm); Gnathostoma spinigerum; Gongylonema sp; Mansonella perstans (filariasis); Opisthorchis sinensis (liver fluke); visceral larva migrans (toxocariasis); activity has also been shown against the liver fluke Clonorchis sinensis, Giardia lamblia, Cysticercus cellulosae, and Echinococcus multilocularis. Albendazole has also been used for the treatment of intestinal microsporidiosis (Encephalitozoon intestinalis), disseminated microsporidiosis (E. hellem, E. cuniculi, E. intestinalis, Pleistophora sp, Trachipleistophora sp, Brachiola vesicularum), and ocular microsporidiosis (E. hellem, E. cuniculi, Vittaforma corneae).
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (11% neurocysticercosis; 1% hydatid)
Hepatic: LFTs increased (16% hydatid; <1% neurocysticercosis)
1% to 10%:
Central nervous system: Intracranial pressure increased (up to 2%), dizziness (≤ 1%), fever (≤ 1%), vertigo (≤ 1%), meningeal signs (1%)
Dermatologic: Alopecia (<1% to 2%)
Gastrointestinal: Abdominal pain (up to 6%), nausea/vomiting (4% to 6%)
<1% (Limited to important or life-threatening symptoms): Acute liver failure, acute renal failure, aplastic anemia, agranulocytosis, erythema multiforme, granulocytopenia, hepatitis, hypersensitivity reaction, leukopenia, neutropenia, pancytopenia, rash, Stevens-Johnson syndrome, thrombocytopenia, urticaria
CONTRAINDICATIONS — Hypersensitivity to albendazole, benzimidazoles, or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bone marrow suppression: Agranulocytosis, aplastic anemia, granulocytopenia, leukopenia, and pancytopenia have occurred leading to fatalities (rare); use with caution in patients with hepatic impairment (more susceptible to hematologic toxicity). Discontinue therapy in all patients who develop clinically significant decreases in blood cell counts. Transaminase elevations: Reversible elevations in hepatic enzymes have been reported. Patients with abnormal LFTs and hepatic echinococcosis are at an increased risk of hepatotoxicity. Discontinue therapy if LFT elevations are >2 times the upper limit of normal; may consider restarting treatment (with frequent monitoring of LFTs) when hepatic enzymes return to pretreatment values.
Disease-related concerns: Neurocysticercosis: Appropriate use: Corticosteroids should be administered before or upon initiation of albendazole therapy to minimize inflammatory reactions and prevent cerebral hypertension. Anticonvulsant therapy should be used concurrently during the first week of therapy to prevent seizures. If retinal lesions exist, weigh risk of further retinal damage due to albendazole-induced changes to the retinal lesion vs benefit of disease treatment.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP1A2, 3A4; Inhibits CYP1A2 (weak)
DRUG INTERACTIONS
Aminoquinolines (Antimalarial): May decrease the serum concentration of Anthelmintics. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Albendazole serum levels may be increased if taken with a fatty meal (increases the oral bioavailability by up to 5 times).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Albendazole has been shown to be teratogenic in laboratory animals and should not be used during pregnancy, if at all possible. Women should be advised to avoid pregnancy for at least 1 month following therapy. Discontinue if pregnancy occurs during treatment.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Should be taken with a high-fat meal.
PRICING — (data from drugstore.com)
Tablets (Albenza)
200 mg (12): $26.99
MONITORING PARAMETERS — Monitor fecal specimens for ova and parasites for 3 weeks after treatment; if positive, retreat; LFTs and CBC with differential at start of each 28-day cycle and every 2 weeks during therapy (more frequent monitoring for patients with liver disease); pregnancy test
INTERNATIONAL BRAND NAMES — ABZ (IN); Acure (PK); Albatel (TH); Alben (BR); Albenzol (EC); Albex (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Albezole (IN); Alfuca (TH); Almex (MY); Alminth (IN); Alzental (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SG, SY, YE); Alzol (TH); Bendex-400 (ZA); Benzol (PH); Bruzol (MX); Ceprazol (CN); Champs D-Worm 6 (MY); Ciclopar (CO); Dalben (HR); Digezanol (MX); Emanthal (IN); Eskasole (MX); Eskazole (AT, AU, DE, ES, GB, IL, JP, NL); Fintel (PE); Gascop (MX); Helmiben (UY); Helmidazole (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Labenda (TH); Lomsin (MX); Lurdex (MX); Mebenix (BR); Mesin-C (MY); Nemozole (IN); Pantex (PY); Paranthil (ZA); Parhel (CR, DO, GT, HN, NI, PA, SV); Rotopar (EC); Sioban (IN); Valbazen Vet (NO); Vastus (AR); Vemizol (MY); Vermin Plus (MX); Zeben (TH); Zela (TH); Zentab (TH); Zentel (AE, AU, BB, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CR, CY, CZ, DO, EG, ET, FR, GH, GM, GN, GR, GT, GY, HN, IL, IQ, IR, IT, JM, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PL, PR, PT, QA, SA, SC, SD, SL, SN, SR, SV, SY, TH, TN, TT, TZ, UG, VE, YE, ZA, ZM, ZW)
MECHANISM OF ACTION — Active metabolite, albendazole sulfoxide, causes selective degeneration of cytoplasmic microtubules in intestinal and tegmental cells of intestinal helminths and larvae; glycogen is depleted, glucose uptake and cholinesterase secretion are impaired, and desecratory substances accumulate intracellulary. ATP production decreases causing energy depletion, immobilization, and worm death.
PHARMACODYNAMICS / KINETICS
Absorption: Poor; may increase up to 5 times when administered with a fatty meal
Distribution: Well inside hydatid cysts and CSF
Protein binding: 70%
Metabolism: Hepatic; extensive first-pass effect; pathways include rapid sulfoxidation to active metabolite (albendazole sulfoxide [major]), hydrolysis, and oxidation
Half-life elimination: 8-12 hours
Time to peak, serum: 2-5 hours
Excretion: Urine (<1% as active metabolite); feces
Sound-alike/look-alike issues:
Albenza® may be confused with Aplenzin™ , Relenza®
International issues:
Albenza® may be confused with Avanza® which is a brand name for mirtazapine in Australia
U.S. BRAND NAMES — Albenza®
PHARMACOLOGIC CATEGORY
Anthelmintic
DOSING: ADULTS
Neurocysticercosis: Oral:
<60 kg: 15 mg/kg/day in 2 divided doses (maximum: 800 mg/day) for 8-30 days
≥ 60 kg: 800 mg/day in 2 divided doses for 8-30 days
Note: Give concurrent anticonvulsant and steroid therapy during first week.
Hydatid: Oral:
<60 kg: 15 mg/kg/day in 2 divided doses (maximum: 800 mg/day)
≥ 60 kg: 800 mg/day in 2 divided doses
Note: Administer dose for three 28-day cycles with a 14-day drug-free interval in between. The manufacturer recommends a total of 3 cycles.
Ancylostoma caninum, Ascaris lumbricoides(roundworm), Ancylostoma duodenale (hookworm), and Necator americanus(hookworm) (unlabeled use): Oral: 400 mg as a single dose
Clonorchis sinensis(Chinese liver fluke) (unlabeled use): Oral: 10 mg/kg for 7 days
Cutaneous larva migrans (unlabeled use): Oral: 400 mg once daily for 3 days
Enterobius vermicularis(pinworm) (unlabeled use): Oral: 400 mg as a single dose; may repeat in 2 weeks
Gnathostoma spinigerum (unlabeled use): Oral: 800 mg/day in 2 divided doses for 21 days
Gongylonemiasis (unlabeled use): Oral: 10 mg/kg/day for 3 days
Mansonella perstans(unlabeled use): Oral: 800 mg/day in 2 divided doses for 10 days
Visceral larva migrans (toxocariasis) (unlabeled use): Oral: 800 mg/day in 2 divided doses for 5 days
Cysticercus cellulosae(unlabeled use): Oral: 800 mg/day in 2 divided doses for 8-30 days; may be repeated as necessary
Disseminated microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses
Echinococcus granulosus(tapeworm) (unlabeled use): Oral: 800 mg/day in 2 divided doses for 1-6 months
Intestinal microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses for 21 days
Ocular microsporidiosis (unlabeled use): Oral: 800 mg/day in 2 divided doses, in combination with fumagillin
DOSING: PEDIATRIC
(For additional information see "Albendazole: Pediatric drug information")
Neurocysticercosis: Oral: Refer to adult dosing.
Hydatid: Oral: Refer to adult dosing.
Cysticercus cellulosae(unlabeled use): Oral: 15 mg/kg/day (maximum: 800 mg/day) in 2 divided doses for 8-30 days; may be repeated as necessary
Echinococcus granulosus(tapeworm) (unlabeled use): Oral: 15 mg/kg/day (maximum: 800 mg) divided twice daily for 1-6 months
For the following unlabeled uses, refer to adult dosing:
Ancylostoma caninum, Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), Clonorchis sinensis, (Chinese liver fluke), cutaneous larva migrans, Enterobius vermicularis (pinworm), Gnathostoma spinigerum, gongylonemiasis, Mansonella perstans, Necator americanus (hookworm), visceral larva migrans (toxocariasis)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Albenza®: 200 mg
DOSAGE FORMS: CONCISE
Tablet:
Albenza®: 200 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Should be administered with a high-fat meal. Administer anticonvulsant and steroid therapy during first week of neurocysticercosis therapy. If patients have difficulty swallowing, tablets may be crushed or chewed, then swallowed with a drink of water.
USE — Treatment of parenchymal neurocysticercosis caused by Taenia solium and cystic hydatid disease of the liver, lung, and peritoneum caused by Echinococcus granulosus
USE - UNLABELED / INVESTIGATIONAL — Albendazole has activity against Ascaris lumbricoides (roundworm); Ancylostoma caninum; Ancylostoma duodenale and Necator americanus (hookworms); cutaneous larva migrans; Enterobius vermicularis (pinworm); Gnathostoma spinigerum; Gongylonema sp; Mansonella perstans (filariasis); Opisthorchis sinensis (liver fluke); visceral larva migrans (toxocariasis); activity has also been shown against the liver fluke Clonorchis sinensis, Giardia lamblia, Cysticercus cellulosae, and Echinococcus multilocularis. Albendazole has also been used for the treatment of intestinal microsporidiosis (Encephalitozoon intestinalis), disseminated microsporidiosis (E. hellem, E. cuniculi, E. intestinalis, Pleistophora sp, Trachipleistophora sp, Brachiola vesicularum), and ocular microsporidiosis (E. hellem, E. cuniculi, Vittaforma corneae).
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Headache (11% neurocysticercosis; 1% hydatid)
Hepatic: LFTs increased (16% hydatid; <1% neurocysticercosis)
1% to 10%:
Central nervous system: Intracranial pressure increased (up to 2%), dizziness (≤ 1%), fever (≤ 1%), vertigo (≤ 1%), meningeal signs (1%)
Dermatologic: Alopecia (<1% to 2%)
Gastrointestinal: Abdominal pain (up to 6%), nausea/vomiting (4% to 6%)
<1% (Limited to important or life-threatening symptoms): Acute liver failure, acute renal failure, aplastic anemia, agranulocytosis, erythema multiforme, granulocytopenia, hepatitis, hypersensitivity reaction, leukopenia, neutropenia, pancytopenia, rash, Stevens-Johnson syndrome, thrombocytopenia, urticaria
CONTRAINDICATIONS — Hypersensitivity to albendazole, benzimidazoles, or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bone marrow suppression: Agranulocytosis, aplastic anemia, granulocytopenia, leukopenia, and pancytopenia have occurred leading to fatalities (rare); use with caution in patients with hepatic impairment (more susceptible to hematologic toxicity). Discontinue therapy in all patients who develop clinically significant decreases in blood cell counts. Transaminase elevations: Reversible elevations in hepatic enzymes have been reported. Patients with abnormal LFTs and hepatic echinococcosis are at an increased risk of hepatotoxicity. Discontinue therapy if LFT elevations are >2 times the upper limit of normal; may consider restarting treatment (with frequent monitoring of LFTs) when hepatic enzymes return to pretreatment values.
Disease-related concerns: Neurocysticercosis: Appropriate use: Corticosteroids should be administered before or upon initiation of albendazole therapy to minimize inflammatory reactions and prevent cerebral hypertension. Anticonvulsant therapy should be used concurrently during the first week of therapy to prevent seizures. If retinal lesions exist, weigh risk of further retinal damage due to albendazole-induced changes to the retinal lesion vs benefit of disease treatment.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP1A2, 3A4; Inhibits CYP1A2 (weak)
DRUG INTERACTIONS
Aminoquinolines (Antimalarial): May decrease the serum concentration of Anthelmintics. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Albendazole serum levels may be increased if taken with a fatty meal (increases the oral bioavailability by up to 5 times).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Albendazole has been shown to be teratogenic in laboratory animals and should not be used during pregnancy, if at all possible. Women should be advised to avoid pregnancy for at least 1 month following therapy. Discontinue if pregnancy occurs during treatment.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Should be taken with a high-fat meal.
PRICING — (data from drugstore.com)
Tablets (Albenza)
200 mg (12): $26.99
MONITORING PARAMETERS — Monitor fecal specimens for ova and parasites for 3 weeks after treatment; if positive, retreat; LFTs and CBC with differential at start of each 28-day cycle and every 2 weeks during therapy (more frequent monitoring for patients with liver disease); pregnancy test
INTERNATIONAL BRAND NAMES — ABZ (IN); Acure (PK); Albatel (TH); Alben (BR); Albenzol (EC); Albex (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Albezole (IN); Alfuca (TH); Almex (MY); Alminth (IN); Alzental (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SG, SY, YE); Alzol (TH); Bendex-400 (ZA); Benzol (PH); Bruzol (MX); Ceprazol (CN); Champs D-Worm 6 (MY); Ciclopar (CO); Dalben (HR); Digezanol (MX); Emanthal (IN); Eskasole (MX); Eskazole (AT, AU, DE, ES, GB, IL, JP, NL); Fintel (PE); Gascop (MX); Helmiben (UY); Helmidazole (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Labenda (TH); Lomsin (MX); Lurdex (MX); Mebenix (BR); Mesin-C (MY); Nemozole (IN); Pantex (PY); Paranthil (ZA); Parhel (CR, DO, GT, HN, NI, PA, SV); Rotopar (EC); Sioban (IN); Valbazen Vet (NO); Vastus (AR); Vemizol (MY); Vermin Plus (MX); Zeben (TH); Zela (TH); Zentab (TH); Zentel (AE, AU, BB, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CR, CY, CZ, DO, EG, ET, FR, GH, GM, GN, GR, GT, GY, HN, IL, IQ, IR, IT, JM, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PL, PR, PT, QA, SA, SC, SD, SL, SN, SR, SV, SY, TH, TN, TT, TZ, UG, VE, YE, ZA, ZM, ZW)
MECHANISM OF ACTION — Active metabolite, albendazole sulfoxide, causes selective degeneration of cytoplasmic microtubules in intestinal and tegmental cells of intestinal helminths and larvae; glycogen is depleted, glucose uptake and cholinesterase secretion are impaired, and desecratory substances accumulate intracellulary. ATP production decreases causing energy depletion, immobilization, and worm death.
PHARMACODYNAMICS / KINETICS
Absorption: Poor; may increase up to 5 times when administered with a fatty meal
Distribution: Well inside hydatid cysts and CSF
Protein binding: 70%
Metabolism: Hepatic; extensive first-pass effect; pathways include rapid sulfoxidation to active metabolite (albendazole sulfoxide [major]), hydrolysis, and oxidation
Half-life elimination: 8-12 hours
Time to peak, serum: 2-5 hours
Excretion: Urine (<1% as active metabolite); feces
Agalsidase beta
EDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Agalsidase beta may be confused with agalsidase alfa, alglucerase, alglucosidase alfa
International issues:
Agalsidase beta may be confused with agalsidase alfa, which is available in international markets
U.S. BRAND NAMES — Fabrazyme®
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Fabry disease: I.V.: 1 mg/kg every 2 weeks
DOSING: PEDIATRIC
(For additional information see "Agalsidase beta: Pediatric drug information")
Fabry disease: Children ≥ 8 years: I.V.: 1 mg/kg every 2 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSING: ADJUSTMENT FOR TOXICITY — Patient with IgE antibodies to agalsidase beta (rechallenge): 0.5 mg/kg every 2 weeks at an initial maximum infusion rate of 0.01 mg/minute; may gradually escalate dose (to maximum of 1 mg/kg every 2 weeks) and/or infusion rate (doubling the infusion rate every 30 minutes to a maximum rate of 0.25 mg/minute) as tolerated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Fabrazyme®: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg; derived from Chinese hamster cells]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Fabrazyme®: 5 mg, 35 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Antipyretics should be administered prior to infusion. Initial infusion rate should not exceed 0.25 mg/minute (15 mg/hour). Interrupt or decrease rate in the event of an infusion reaction; may be restarted after resolution of symptoms and/or after administration of antipyretics, antihistamines, and/or steroids. After patient tolerance to the infusion is established, rate may be increased in increments of 0.05-0.08 mg/minute (3-5 mg/hour) with each subsequent infusion. Maximum infusion rate: Patients <30 kg: 0.25 mg/minute; patients ≥ 30 kg: Infuse over at least 1.5 hours. An initial maximum infusion rate of 0.01 mg/minute should be used for rechallenge in patients with IgE antibodies; may increase infusion rate (doubling the infusion rate every 30 minutes) to a maximum rate of 0.25 mg/minute as tolerated. A 0.2 micron low protein-binding filter may be used during administration.
COMPATIBILITY — Stable in NS.
Compatibility when admixed: Do not mix with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include fever, tachycardia, hypertension, throat tightness, dyspnea, chills, abdominal pain, pruritus, urticaria, vomiting).
>10%:
Cardiovascular: Peripheral edema (21%)
Central nervous system: Chills (43%), headache (39%), fever (6% to 36%), fatigue (25%), dizziness (21%), pain (16%)
Gastrointestinal: Vomiting (24%)
Hematologic: Anemia (14%)
Neuromuscular & skeletal: Paresthesia (31%), limb pain (19%), back pain (16%)
Respiratory: Cough (33%), nasopharyngitis (28%), nasal congestion (19%), upper respiratory tract infection (19%), pharyngolaryngeal pain (16%), lower respiratory infection (11%)
Miscellaneous: IgG antibody formation (69% to 79%)
1% to 10%:
Cardiovascular: Hypertension (5% to 10%), chest discomfort (5%), tachycardia (5%), ventricular wall thickening (5%)
Central nervous system: Hypoesthesia (9%), insomnia (9%), anxiety (8%), depression (6%)
Dermatologic: Rash (10%), excoriation (9%), pruritus (8%), contact dermatitis (5%)
Endocrine & metabolic: Bicarbonate decreased (9%)
Gastrointestinal: Abdominal discomfort (6%), toothache (6%)
Neuromuscular & skeletal: Myalgia (8%), burning sensation (6%), muscle spasms (5%), neck pain (5%)
Otic: Tinnitus (8%), hearing impairment (5%)
Renal: Creatinine increased (9%), proteinuria (5%)
Respiratory: Sinusitis (9%), bronchitis (8%), congestion (8%), dyspnea (8%), pharyngitis (6%), wheezing (6%)
Miscellaneous: Feeling cold (10%), viral infection (5% to 6%), fungal infection (5%), infusion reactions (≥ 5%)
Other reported severe reactions (frequency not established): Abdominal pain, arrhythmia, ataxia, bradycardia, cardiac arrest, cardiac output decreased, chest pain, face edema, flushing, hypotension, nausea, nephrotic syndrome, pallor, stroke, throat tightness, urticaria, vertigo
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: Development of IgG antibodies is common, however some patients may also develop IgE antibodies; consider IgE testing in patients with allergic reaction. Rechallenge of patients with IgE-mediated reaction may be done with caution. Infusion reactions: Infusion-related reactions are common, and may be severe; pretreatment with antipyretics is advised. Medication for the treatment of reactions should be readily available.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease; may have increased risk of complications from infusion reactions; monitor closely.
Special populations: Pediatrics: Safety and efficacy have not been established in children <8 years of age.
Other warnings/precautions: Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (www.fabryregistry.com or 1-800-745-4447).
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not demonstrated adverse effects. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential are encouraged to enroll in Fabry registry.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Nursing mothers are encouraged to enroll in Fabry registry.
MONITORING PARAMETERS — Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer). Monitor for infusion-related reactions.
CANADIAN BRAND NAMES — Fabrazyme®
INTERNATIONAL BRAND NAMES — Fabrazyme (AT, AU, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IL, IT, KP, NL, NO, NZ, PL, PT, RU, SE, TR, TW)
MECHANISM OF ACTION — Agalsidase beta is a recombinant form of the enzyme alpha-galactosidase-A, which is required for the hydrolysis of GL-3 and other glycosphingolipids. The compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. In clinical trials of limited duration, agalsidase been noted to reduce tissue inclusions of a key sphingolipid (GL-3). It is believed that long-term enzyme replacement may reduce clinical manifestations of renal failure, cardiomyopathy, and stroke. However, the relationship to a reduction in clinical manifestations has not been established.
PHARMACODYNAMICS / KINETICS
Distribution: Vdss: Children: 247-1097 mL/kg; Adults: 112-570 mL/kg
Half-life elimination: Children: 86-151 minutes; Adults: 45-119 minutes
Sound-alike/look-alike issues:
Agalsidase beta may be confused with agalsidase alfa, alglucerase, alglucosidase alfa
International issues:
Agalsidase beta may be confused with agalsidase alfa, which is available in international markets
U.S. BRAND NAMES — Fabrazyme®
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Fabry disease: I.V.: 1 mg/kg every 2 weeks
DOSING: PEDIATRIC
(For additional information see "Agalsidase beta: Pediatric drug information")
Fabry disease: Children ≥ 8 years: I.V.: 1 mg/kg every 2 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSING: ADJUSTMENT FOR TOXICITY — Patient with IgE antibodies to agalsidase beta (rechallenge): 0.5 mg/kg every 2 weeks at an initial maximum infusion rate of 0.01 mg/minute; may gradually escalate dose (to maximum of 1 mg/kg every 2 weeks) and/or infusion rate (doubling the infusion rate every 30 minutes to a maximum rate of 0.25 mg/minute) as tolerated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Fabrazyme®: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg; derived from Chinese hamster cells]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Fabrazyme®: 5 mg, 35 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Antipyretics should be administered prior to infusion. Initial infusion rate should not exceed 0.25 mg/minute (15 mg/hour). Interrupt or decrease rate in the event of an infusion reaction; may be restarted after resolution of symptoms and/or after administration of antipyretics, antihistamines, and/or steroids. After patient tolerance to the infusion is established, rate may be increased in increments of 0.05-0.08 mg/minute (3-5 mg/hour) with each subsequent infusion. Maximum infusion rate: Patients <30 kg: 0.25 mg/minute; patients ≥ 30 kg: Infuse over at least 1.5 hours. An initial maximum infusion rate of 0.01 mg/minute should be used for rechallenge in patients with IgE antibodies; may increase infusion rate (doubling the infusion rate every 30 minutes) to a maximum rate of 0.25 mg/minute as tolerated. A 0.2 micron low protein-binding filter may be used during administration.
COMPATIBILITY — Stable in NS.
Compatibility when admixed: Do not mix with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include fever, tachycardia, hypertension, throat tightness, dyspnea, chills, abdominal pain, pruritus, urticaria, vomiting).
>10%:
Cardiovascular: Peripheral edema (21%)
Central nervous system: Chills (43%), headache (39%), fever (6% to 36%), fatigue (25%), dizziness (21%), pain (16%)
Gastrointestinal: Vomiting (24%)
Hematologic: Anemia (14%)
Neuromuscular & skeletal: Paresthesia (31%), limb pain (19%), back pain (16%)
Respiratory: Cough (33%), nasopharyngitis (28%), nasal congestion (19%), upper respiratory tract infection (19%), pharyngolaryngeal pain (16%), lower respiratory infection (11%)
Miscellaneous: IgG antibody formation (69% to 79%)
1% to 10%:
Cardiovascular: Hypertension (5% to 10%), chest discomfort (5%), tachycardia (5%), ventricular wall thickening (5%)
Central nervous system: Hypoesthesia (9%), insomnia (9%), anxiety (8%), depression (6%)
Dermatologic: Rash (10%), excoriation (9%), pruritus (8%), contact dermatitis (5%)
Endocrine & metabolic: Bicarbonate decreased (9%)
Gastrointestinal: Abdominal discomfort (6%), toothache (6%)
Neuromuscular & skeletal: Myalgia (8%), burning sensation (6%), muscle spasms (5%), neck pain (5%)
Otic: Tinnitus (8%), hearing impairment (5%)
Renal: Creatinine increased (9%), proteinuria (5%)
Respiratory: Sinusitis (9%), bronchitis (8%), congestion (8%), dyspnea (8%), pharyngitis (6%), wheezing (6%)
Miscellaneous: Feeling cold (10%), viral infection (5% to 6%), fungal infection (5%), infusion reactions (≥ 5%)
Other reported severe reactions (frequency not established): Abdominal pain, arrhythmia, ataxia, bradycardia, cardiac arrest, cardiac output decreased, chest pain, face edema, flushing, hypotension, nausea, nephrotic syndrome, pallor, stroke, throat tightness, urticaria, vertigo
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: Development of IgG antibodies is common, however some patients may also develop IgE antibodies; consider IgE testing in patients with allergic reaction. Rechallenge of patients with IgE-mediated reaction may be done with caution. Infusion reactions: Infusion-related reactions are common, and may be severe; pretreatment with antipyretics is advised. Medication for the treatment of reactions should be readily available.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease; may have increased risk of complications from infusion reactions; monitor closely.
Special populations: Pediatrics: Safety and efficacy have not been established in children <8 years of age.
Other warnings/precautions: Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (www.fabryregistry.com or 1-800-745-4447).
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not demonstrated adverse effects. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential are encouraged to enroll in Fabry registry.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Nursing mothers are encouraged to enroll in Fabry registry.
MONITORING PARAMETERS — Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer). Monitor for infusion-related reactions.
CANADIAN BRAND NAMES — Fabrazyme®
INTERNATIONAL BRAND NAMES — Fabrazyme (AT, AU, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IL, IT, KP, NL, NO, NZ, PL, PT, RU, SE, TR, TW)
MECHANISM OF ACTION — Agalsidase beta is a recombinant form of the enzyme alpha-galactosidase-A, which is required for the hydrolysis of GL-3 and other glycosphingolipids. The compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. In clinical trials of limited duration, agalsidase been noted to reduce tissue inclusions of a key sphingolipid (GL-3). It is believed that long-term enzyme replacement may reduce clinical manifestations of renal failure, cardiomyopathy, and stroke. However, the relationship to a reduction in clinical manifestations has not been established.
PHARMACODYNAMICS / KINETICS
Distribution: Vdss: Children: 247-1097 mL/kg; Adults: 112-570 mL/kg
Half-life elimination: Children: 86-151 minutes; Adults: 45-119 minutes
Agalsidase alfa
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Agalsidase alfa may be confused with agalsidase beta, alglucerase, alglucosidase alfa
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: I.V.: 0.2 mg/kg every 2 weeks
DOSING: PEDIATRIC — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment necessary.
DOSING: HEPATIC IMPAIRMENT — No data available.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 40 minutes using a dedicated I.V. line with filter. Do not infuse other agents through same I.V. line. Interrupt infusion in the presence of infusion-related reactions (eg, chills, flushing, dyspnea, rigors, tachycardia, urticaria). Infusion may be restarted after 5-10 minutes if symptoms subside or after administration of analgesics, antipyretics, antihistamines, and/or corticosteroids.
COMPATIBILITY — Stable in NS. Do not mix or infuse with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include chills, dyspnea, facial flushing, fever, hypertension, nausea, rigors, tachycardia, urticaria, and vomiting).
>10%:
Cardiovascular: Flushing (24%)
Central nervous system: Fever (20%), headache (11%)
Neuromuscular & skeletal: Rigors (20%)
Miscellaneous: IgG antibody formation (55%), infusion-related reactions (13%)
1% to 10%:
Cardiovascular: Chest tightness (7%), hypertension (4%), tachycardia (4%), chest pain (2%), edema (2%), peripheral coldness (2%), peripheral edema (2%)
Central nervous system: Dizziness (9%), fatigue (9%), fatigue aggravated (7%), hypersomnia (2%), hypoesthesia (2%), panic attack (2%), pain/discomfort (7%), somnolence (2%), vertigo (2%)
Dermatologic: Acne (9%), erythema (7%), mottled skin(4%), pruritus (4%), dry skin (2%), eczema (2%), rash (2%)
Gastrointestinal: Nausea (9%), dysgeusia (6%), diarrhea (4%), vomiting (4%), abdominal pain (2%), dyspepsia (2%), gastrointestinal upset (2%), stomach cramps (2%), stomach discomfort (2%)
Neuromuscular & skeletal: Myalgia (6%), neuropathic pain (6%), tremor (4%), musculoskeletal discomfort (2%), back pain (2%), limb pain (2%), paraesthesia (2%), weakness (2%)
Ocular: Lacrimation increased (2%), periorbital edema (2%)
Respiratory: Hoarseness (6%), throat tightness (6%), cough (4%), dyspnea (4%), nasopharyngitis (4%), pharyngitis (4%), nasal congestion (2%), snoring (2%), throat irritation (2%)
Miscellaneous: Feeling hot (4%), influenza-like syndrome(2%), parosmia (2%)
<1% (Limited to important or life-threatening): Chills, facial flushing, urticaria
CONTRAINDICATIONS — Hypersensitivity to agalsidase alfa or any component of the formulation; concomitant use with chloroquine, amiodarone, monobenzone, or gentamicin (these agents have the potential to inhibit intracellular agalsidase alfa activity)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: The presence IgG antibodies has been observed within 3 months from the onset of therapy in ~55% of treated patients. Approximately 60% of these patients are free of antibodies and >80% demonstrate immune tolerance, based on reduced titers of antibody within 12-18 months. Infusion reactions: Mild acute reactions (chills, facial flushing) are common and may occur during or within 1 hour after infusion. Severe reactions (nausea, pyrexia, rigors, tachycardia, urticaria, vomiting) are rare and usually occur within 2-4 months from the onset of therapy. Patients with a history of reactions may be premedicated with oral corticosteroids and antihistamines 1-3 hours prior to subsequent infusions.
Disease-related concerns: Fabry disease: Common symptoms observed in this patient population may be confused with adverse reactions related to treatment. Hepatic impairment: Safety and efficacy have not been established.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS
Amiodarone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Chloroquine: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Gentamicin: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Monobenzone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
PREGNANCY IMPLICATIONS — Adverse events were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. The benefits versus risks should be considered carefully before initiating agalsidase alfa therapy in pregnant women.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Creatinine clearance, ECG, echocardiography, Gb-3 levels (serum and urine)
CANADIAN BRAND NAMES — Replagal™
INTERNATIONAL BRAND NAMES — Replagal (AU, BE, CH, CZ, DK, EE, ES, FI, IL, NO, NZ, SE, TW)
MECHANISM OF ACTION — Agalsidase alfa is a recombinant form of the enzyme alpha-galactosidase-A, which catalyzes the hydrolysis of globotriaosylceramide (Gb-3) and other glycosphingolipids. These compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. Agalsidase has been noted to reduce cellular levels of Gb-3 within the liver, heart, kidney, blood vessels, and in plasma.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 17% of body weight
Metabolism: Plasma; via peptide hydrolysis
Half-life elimination: ~1.5-2 hours
Sound-alike/look-alike issues:
Agalsidase alfa may be confused with agalsidase beta, alglucerase, alglucosidase alfa
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: I.V.: 0.2 mg/kg every 2 weeks
DOSING: PEDIATRIC — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment necessary.
DOSING: HEPATIC IMPAIRMENT — No data available.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 40 minutes using a dedicated I.V. line with filter. Do not infuse other agents through same I.V. line. Interrupt infusion in the presence of infusion-related reactions (eg, chills, flushing, dyspnea, rigors, tachycardia, urticaria). Infusion may be restarted after 5-10 minutes if symptoms subside or after administration of analgesics, antipyretics, antihistamines, and/or corticosteroids.
COMPATIBILITY — Stable in NS. Do not mix or infuse with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include chills, dyspnea, facial flushing, fever, hypertension, nausea, rigors, tachycardia, urticaria, and vomiting).
>10%:
Cardiovascular: Flushing (24%)
Central nervous system: Fever (20%), headache (11%)
Neuromuscular & skeletal: Rigors (20%)
Miscellaneous: IgG antibody formation (55%), infusion-related reactions (13%)
1% to 10%:
Cardiovascular: Chest tightness (7%), hypertension (4%), tachycardia (4%), chest pain (2%), edema (2%), peripheral coldness (2%), peripheral edema (2%)
Central nervous system: Dizziness (9%), fatigue (9%), fatigue aggravated (7%), hypersomnia (2%), hypoesthesia (2%), panic attack (2%), pain/discomfort (7%), somnolence (2%), vertigo (2%)
Dermatologic: Acne (9%), erythema (7%), mottled skin(4%), pruritus (4%), dry skin (2%), eczema (2%), rash (2%)
Gastrointestinal: Nausea (9%), dysgeusia (6%), diarrhea (4%), vomiting (4%), abdominal pain (2%), dyspepsia (2%), gastrointestinal upset (2%), stomach cramps (2%), stomach discomfort (2%)
Neuromuscular & skeletal: Myalgia (6%), neuropathic pain (6%), tremor (4%), musculoskeletal discomfort (2%), back pain (2%), limb pain (2%), paraesthesia (2%), weakness (2%)
Ocular: Lacrimation increased (2%), periorbital edema (2%)
Respiratory: Hoarseness (6%), throat tightness (6%), cough (4%), dyspnea (4%), nasopharyngitis (4%), pharyngitis (4%), nasal congestion (2%), snoring (2%), throat irritation (2%)
Miscellaneous: Feeling hot (4%), influenza-like syndrome(2%), parosmia (2%)
<1% (Limited to important or life-threatening): Chills, facial flushing, urticaria
CONTRAINDICATIONS — Hypersensitivity to agalsidase alfa or any component of the formulation; concomitant use with chloroquine, amiodarone, monobenzone, or gentamicin (these agents have the potential to inhibit intracellular agalsidase alfa activity)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: The presence IgG antibodies has been observed within 3 months from the onset of therapy in ~55% of treated patients. Approximately 60% of these patients are free of antibodies and >80% demonstrate immune tolerance, based on reduced titers of antibody within 12-18 months. Infusion reactions: Mild acute reactions (chills, facial flushing) are common and may occur during or within 1 hour after infusion. Severe reactions (nausea, pyrexia, rigors, tachycardia, urticaria, vomiting) are rare and usually occur within 2-4 months from the onset of therapy. Patients with a history of reactions may be premedicated with oral corticosteroids and antihistamines 1-3 hours prior to subsequent infusions.
Disease-related concerns: Fabry disease: Common symptoms observed in this patient population may be confused with adverse reactions related to treatment. Hepatic impairment: Safety and efficacy have not been established.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS
Amiodarone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Chloroquine: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Gentamicin: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Monobenzone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
PREGNANCY IMPLICATIONS — Adverse events were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. The benefits versus risks should be considered carefully before initiating agalsidase alfa therapy in pregnant women.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Creatinine clearance, ECG, echocardiography, Gb-3 levels (serum and urine)
CANADIAN BRAND NAMES — Replagal™
INTERNATIONAL BRAND NAMES — Replagal (AU, BE, CH, CZ, DK, EE, ES, FI, IL, NO, NZ, SE, TW)
MECHANISM OF ACTION — Agalsidase alfa is a recombinant form of the enzyme alpha-galactosidase-A, which catalyzes the hydrolysis of globotriaosylceramide (Gb-3) and other glycosphingolipids. These compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. Agalsidase has been noted to reduce cellular levels of Gb-3 within the liver, heart, kidney, blood vessels, and in plasma.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 17% of body weight
Metabolism: Plasma; via peptide hydrolysis
Half-life elimination: ~1.5-2 hours
Agalsidase beta
EDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Agalsidase beta may be confused with agalsidase alfa, alglucerase, alglucosidase alfa
International issues:
Agalsidase beta may be confused with agalsidase alfa, which is available in international markets
U.S. BRAND NAMES — Fabrazyme®
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Fabry disease: I.V.: 1 mg/kg every 2 weeks
DOSING: PEDIATRIC
(For additional information see "Agalsidase beta: Pediatric drug information")
Fabry disease: Children ≥ 8 years: I.V.: 1 mg/kg every 2 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSING: ADJUSTMENT FOR TOXICITY — Patient with IgE antibodies to agalsidase beta (rechallenge): 0.5 mg/kg every 2 weeks at an initial maximum infusion rate of 0.01 mg/minute; may gradually escalate dose (to maximum of 1 mg/kg every 2 weeks) and/or infusion rate (doubling the infusion rate every 30 minutes to a maximum rate of 0.25 mg/minute) as tolerated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Fabrazyme®: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg; derived from Chinese hamster cells]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Fabrazyme®: 5 mg, 35 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Antipyretics should be administered prior to infusion. Initial infusion rate should not exceed 0.25 mg/minute (15 mg/hour). Interrupt or decrease rate in the event of an infusion reaction; may be restarted after resolution of symptoms and/or after administration of antipyretics, antihistamines, and/or steroids. After patient tolerance to the infusion is established, rate may be increased in increments of 0.05-0.08 mg/minute (3-5 mg/hour) with each subsequent infusion. Maximum infusion rate: Patients <30 kg: 0.25 mg/minute; patients ≥ 30 kg: Infuse over at least 1.5 hours. An initial maximum infusion rate of 0.01 mg/minute should be used for rechallenge in patients with IgE antibodies; may increase infusion rate (doubling the infusion rate every 30 minutes) to a maximum rate of 0.25 mg/minute as tolerated. A 0.2 micron low protein-binding filter may be used during administration.
COMPATIBILITY — Stable in NS.
Compatibility when admixed: Do not mix with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include fever, tachycardia, hypertension, throat tightness, dyspnea, chills, abdominal pain, pruritus, urticaria, vomiting).
>10%:
Cardiovascular: Peripheral edema (21%)
Central nervous system: Chills (43%), headache (39%), fever (6% to 36%), fatigue (25%), dizziness (21%), pain (16%)
Gastrointestinal: Vomiting (24%)
Hematologic: Anemia (14%)
Neuromuscular & skeletal: Paresthesia (31%), limb pain (19%), back pain (16%)
Respiratory: Cough (33%), nasopharyngitis (28%), nasal congestion (19%), upper respiratory tract infection (19%), pharyngolaryngeal pain (16%), lower respiratory infection (11%)
Miscellaneous: IgG antibody formation (69% to 79%)
1% to 10%:
Cardiovascular: Hypertension (5% to 10%), chest discomfort (5%), tachycardia (5%), ventricular wall thickening (5%)
Central nervous system: Hypoesthesia (9%), insomnia (9%), anxiety (8%), depression (6%)
Dermatologic: Rash (10%), excoriation (9%), pruritus (8%), contact dermatitis (5%)
Endocrine & metabolic: Bicarbonate decreased (9%)
Gastrointestinal: Abdominal discomfort (6%), toothache (6%)
Neuromuscular & skeletal: Myalgia (8%), burning sensation (6%), muscle spasms (5%), neck pain (5%)
Otic: Tinnitus (8%), hearing impairment (5%)
Renal: Creatinine increased (9%), proteinuria (5%)
Respiratory: Sinusitis (9%), bronchitis (8%), congestion (8%), dyspnea (8%), pharyngitis (6%), wheezing (6%)
Miscellaneous: Feeling cold (10%), viral infection (5% to 6%), fungal infection (5%), infusion reactions (≥ 5%)
Other reported severe reactions (frequency not established): Abdominal pain, arrhythmia, ataxia, bradycardia, cardiac arrest, cardiac output decreased, chest pain, face edema, flushing, hypotension, nausea, nephrotic syndrome, pallor, stroke, throat tightness, urticaria, vertigo
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: Development of IgG antibodies is common, however some patients may also develop IgE antibodies; consider IgE testing in patients with allergic reaction. Rechallenge of patients with IgE-mediated reaction may be done with caution. Infusion reactions: Infusion-related reactions are common, and may be severe; pretreatment with antipyretics is advised. Medication for the treatment of reactions should be readily available.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease; may have increased risk of complications from infusion reactions; monitor closely.
Special populations: Pediatrics: Safety and efficacy have not been established in children <8 years of age.
Other warnings/precautions: Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (www.fabryregistry.com or 1-800-745-4447).
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not demonstrated adverse effects. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential are encouraged to enroll in Fabry registry.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Nursing mothers are encouraged to enroll in Fabry registry.
MONITORING PARAMETERS — Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer). Monitor for infusion-related reactions.
CANADIAN BRAND NAMES — Fabrazyme®
INTERNATIONAL BRAND NAMES — Fabrazyme (AT, AU, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IL, IT, KP, NL, NO, NZ, PL, PT, RU, SE, TR, TW)
MECHANISM OF ACTION — Agalsidase beta is a recombinant form of the enzyme alpha-galactosidase-A, which is required for the hydrolysis of GL-3 and other glycosphingolipids. The compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. In clinical trials of limited duration, agalsidase been noted to reduce tissue inclusions of a key sphingolipid (GL-3). It is believed that long-term enzyme replacement may reduce clinical manifestations of renal failure, cardiomyopathy, and stroke. However, the relationship to a reduction in clinical manifestations has not been established.
PHARMACODYNAMICS / KINETICS
Distribution: Vdss: Children: 247-1097 mL/kg; Adults: 112-570 mL/kg
Half-life elimination: Children: 86-151 minutes; Adults: 45-119 minutes
Sound-alike/look-alike issues:
Agalsidase beta may be confused with agalsidase alfa, alglucerase, alglucosidase alfa
International issues:
Agalsidase beta may be confused with agalsidase alfa, which is available in international markets
U.S. BRAND NAMES — Fabrazyme®
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Fabry disease: I.V.: 1 mg/kg every 2 weeks
DOSING: PEDIATRIC
(For additional information see "Agalsidase beta: Pediatric drug information")
Fabry disease: Children ≥ 8 years: I.V.: 1 mg/kg every 2 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSING: ADJUSTMENT FOR TOXICITY — Patient with IgE antibodies to agalsidase beta (rechallenge): 0.5 mg/kg every 2 weeks at an initial maximum infusion rate of 0.01 mg/minute; may gradually escalate dose (to maximum of 1 mg/kg every 2 weeks) and/or infusion rate (doubling the infusion rate every 30 minutes to a maximum rate of 0.25 mg/minute) as tolerated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Fabrazyme®: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg; derived from Chinese hamster cells]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Fabrazyme®: 5 mg, 35 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Antipyretics should be administered prior to infusion. Initial infusion rate should not exceed 0.25 mg/minute (15 mg/hour). Interrupt or decrease rate in the event of an infusion reaction; may be restarted after resolution of symptoms and/or after administration of antipyretics, antihistamines, and/or steroids. After patient tolerance to the infusion is established, rate may be increased in increments of 0.05-0.08 mg/minute (3-5 mg/hour) with each subsequent infusion. Maximum infusion rate: Patients <30 kg: 0.25 mg/minute; patients ≥ 30 kg: Infuse over at least 1.5 hours. An initial maximum infusion rate of 0.01 mg/minute should be used for rechallenge in patients with IgE antibodies; may increase infusion rate (doubling the infusion rate every 30 minutes) to a maximum rate of 0.25 mg/minute as tolerated. A 0.2 micron low protein-binding filter may be used during administration.
COMPATIBILITY — Stable in NS.
Compatibility when admixed: Do not mix with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include fever, tachycardia, hypertension, throat tightness, dyspnea, chills, abdominal pain, pruritus, urticaria, vomiting).
>10%:
Cardiovascular: Peripheral edema (21%)
Central nervous system: Chills (43%), headache (39%), fever (6% to 36%), fatigue (25%), dizziness (21%), pain (16%)
Gastrointestinal: Vomiting (24%)
Hematologic: Anemia (14%)
Neuromuscular & skeletal: Paresthesia (31%), limb pain (19%), back pain (16%)
Respiratory: Cough (33%), nasopharyngitis (28%), nasal congestion (19%), upper respiratory tract infection (19%), pharyngolaryngeal pain (16%), lower respiratory infection (11%)
Miscellaneous: IgG antibody formation (69% to 79%)
1% to 10%:
Cardiovascular: Hypertension (5% to 10%), chest discomfort (5%), tachycardia (5%), ventricular wall thickening (5%)
Central nervous system: Hypoesthesia (9%), insomnia (9%), anxiety (8%), depression (6%)
Dermatologic: Rash (10%), excoriation (9%), pruritus (8%), contact dermatitis (5%)
Endocrine & metabolic: Bicarbonate decreased (9%)
Gastrointestinal: Abdominal discomfort (6%), toothache (6%)
Neuromuscular & skeletal: Myalgia (8%), burning sensation (6%), muscle spasms (5%), neck pain (5%)
Otic: Tinnitus (8%), hearing impairment (5%)
Renal: Creatinine increased (9%), proteinuria (5%)
Respiratory: Sinusitis (9%), bronchitis (8%), congestion (8%), dyspnea (8%), pharyngitis (6%), wheezing (6%)
Miscellaneous: Feeling cold (10%), viral infection (5% to 6%), fungal infection (5%), infusion reactions (≥ 5%)
Other reported severe reactions (frequency not established): Abdominal pain, arrhythmia, ataxia, bradycardia, cardiac arrest, cardiac output decreased, chest pain, face edema, flushing, hypotension, nausea, nephrotic syndrome, pallor, stroke, throat tightness, urticaria, vertigo
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: Development of IgG antibodies is common, however some patients may also develop IgE antibodies; consider IgE testing in patients with allergic reaction. Rechallenge of patients with IgE-mediated reaction may be done with caution. Infusion reactions: Infusion-related reactions are common, and may be severe; pretreatment with antipyretics is advised. Medication for the treatment of reactions should be readily available.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease; may have increased risk of complications from infusion reactions; monitor closely.
Special populations: Pediatrics: Safety and efficacy have not been established in children <8 years of age.
Other warnings/precautions: Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (www.fabryregistry.com or 1-800-745-4447).
DRUG INTERACTIONS — There are no known significant interactions.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not demonstrated adverse effects. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential are encouraged to enroll in Fabry registry.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Nursing mothers are encouraged to enroll in Fabry registry.
MONITORING PARAMETERS — Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer). Monitor for infusion-related reactions.
CANADIAN BRAND NAMES — Fabrazyme®
INTERNATIONAL BRAND NAMES — Fabrazyme (AT, AU, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IL, IT, KP, NL, NO, NZ, PL, PT, RU, SE, TR, TW)
MECHANISM OF ACTION — Agalsidase beta is a recombinant form of the enzyme alpha-galactosidase-A, which is required for the hydrolysis of GL-3 and other glycosphingolipids. The compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. In clinical trials of limited duration, agalsidase been noted to reduce tissue inclusions of a key sphingolipid (GL-3). It is believed that long-term enzyme replacement may reduce clinical manifestations of renal failure, cardiomyopathy, and stroke. However, the relationship to a reduction in clinical manifestations has not been established.
PHARMACODYNAMICS / KINETICS
Distribution: Vdss: Children: 247-1097 mL/kg; Adults: 112-570 mL/kg
Half-life elimination: Children: 86-151 minutes; Adults: 45-119 minutes
Agalsidase alfa
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Agalsidase alfa may be confused with agalsidase beta, alglucerase, alglucosidase alfa
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: I.V.: 0.2 mg/kg every 2 weeks
DOSING: PEDIATRIC — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment necessary.
DOSING: HEPATIC IMPAIRMENT — No data available.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 40 minutes using a dedicated I.V. line with filter. Do not infuse other agents through same I.V. line. Interrupt infusion in the presence of infusion-related reactions (eg, chills, flushing, dyspnea, rigors, tachycardia, urticaria). Infusion may be restarted after 5-10 minutes if symptoms subside or after administration of analgesics, antipyretics, antihistamines, and/or corticosteroids.
COMPATIBILITY — Stable in NS. Do not mix or infuse with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include chills, dyspnea, facial flushing, fever, hypertension, nausea, rigors, tachycardia, urticaria, and vomiting).
>10%:
Cardiovascular: Flushing (24%)
Central nervous system: Fever (20%), headache (11%)
Neuromuscular & skeletal: Rigors (20%)
Miscellaneous: IgG antibody formation (55%), infusion-related reactions (13%)
1% to 10%:
Cardiovascular: Chest tightness (7%), hypertension (4%), tachycardia (4%), chest pain (2%), edema (2%), peripheral coldness (2%), peripheral edema (2%)
Central nervous system: Dizziness (9%), fatigue (9%), fatigue aggravated (7%), hypersomnia (2%), hypoesthesia (2%), panic attack (2%), pain/discomfort (7%), somnolence (2%), vertigo (2%)
Dermatologic: Acne (9%), erythema (7%), mottled skin(4%), pruritus (4%), dry skin (2%), eczema (2%), rash (2%)
Gastrointestinal: Nausea (9%), dysgeusia (6%), diarrhea (4%), vomiting (4%), abdominal pain (2%), dyspepsia (2%), gastrointestinal upset (2%), stomach cramps (2%), stomach discomfort (2%)
Neuromuscular & skeletal: Myalgia (6%), neuropathic pain (6%), tremor (4%), musculoskeletal discomfort (2%), back pain (2%), limb pain (2%), paraesthesia (2%), weakness (2%)
Ocular: Lacrimation increased (2%), periorbital edema (2%)
Respiratory: Hoarseness (6%), throat tightness (6%), cough (4%), dyspnea (4%), nasopharyngitis (4%), pharyngitis (4%), nasal congestion (2%), snoring (2%), throat irritation (2%)
Miscellaneous: Feeling hot (4%), influenza-like syndrome(2%), parosmia (2%)
<1% (Limited to important or life-threatening): Chills, facial flushing, urticaria
CONTRAINDICATIONS — Hypersensitivity to agalsidase alfa or any component of the formulation; concomitant use with chloroquine, amiodarone, monobenzone, or gentamicin (these agents have the potential to inhibit intracellular agalsidase alfa activity)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: The presence IgG antibodies has been observed within 3 months from the onset of therapy in ~55% of treated patients. Approximately 60% of these patients are free of antibodies and >80% demonstrate immune tolerance, based on reduced titers of antibody within 12-18 months. Infusion reactions: Mild acute reactions (chills, facial flushing) are common and may occur during or within 1 hour after infusion. Severe reactions (nausea, pyrexia, rigors, tachycardia, urticaria, vomiting) are rare and usually occur within 2-4 months from the onset of therapy. Patients with a history of reactions may be premedicated with oral corticosteroids and antihistamines 1-3 hours prior to subsequent infusions.
Disease-related concerns: Fabry disease: Common symptoms observed in this patient population may be confused with adverse reactions related to treatment. Hepatic impairment: Safety and efficacy have not been established.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS
Amiodarone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Chloroquine: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Gentamicin: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Monobenzone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
PREGNANCY IMPLICATIONS — Adverse events were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. The benefits versus risks should be considered carefully before initiating agalsidase alfa therapy in pregnant women.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Creatinine clearance, ECG, echocardiography, Gb-3 levels (serum and urine)
CANADIAN BRAND NAMES — Replagal™
INTERNATIONAL BRAND NAMES — Replagal (AU, BE, CH, CZ, DK, EE, ES, FI, IL, NO, NZ, SE, TW)
MECHANISM OF ACTION — Agalsidase alfa is a recombinant form of the enzyme alpha-galactosidase-A, which catalyzes the hydrolysis of globotriaosylceramide (Gb-3) and other glycosphingolipids. These compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. Agalsidase has been noted to reduce cellular levels of Gb-3 within the liver, heart, kidney, blood vessels, and in plasma.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 17% of body weight
Metabolism: Plasma; via peptide hydrolysis
Half-life elimination: ~1.5-2 hours
Sound-alike/look-alike issues:
Agalsidase alfa may be confused with agalsidase beta, alglucerase, alglucosidase alfa
PHARMACOLOGIC CATEGORY
Enzyme
DOSING: ADULTS — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: I.V.: 0.2 mg/kg every 2 weeks
DOSING: PEDIATRIC — Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment necessary.
DOSING: HEPATIC IMPAIRMENT — No data available.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Injection, solution [preservative free]:
Replagal™ [CAN]: 1 mg/1mL (3.5 mL) [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 40 minutes using a dedicated I.V. line with filter. Do not infuse other agents through same I.V. line. Interrupt infusion in the presence of infusion-related reactions (eg, chills, flushing, dyspnea, rigors, tachycardia, urticaria). Infusion may be restarted after 5-10 minutes if symptoms subside or after administration of analgesics, antipyretics, antihistamines, and/or corticosteroids.
COMPATIBILITY — Stable in NS. Do not mix or infuse with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include chills, dyspnea, facial flushing, fever, hypertension, nausea, rigors, tachycardia, urticaria, and vomiting).
>10%:
Cardiovascular: Flushing (24%)
Central nervous system: Fever (20%), headache (11%)
Neuromuscular & skeletal: Rigors (20%)
Miscellaneous: IgG antibody formation (55%), infusion-related reactions (13%)
1% to 10%:
Cardiovascular: Chest tightness (7%), hypertension (4%), tachycardia (4%), chest pain (2%), edema (2%), peripheral coldness (2%), peripheral edema (2%)
Central nervous system: Dizziness (9%), fatigue (9%), fatigue aggravated (7%), hypersomnia (2%), hypoesthesia (2%), panic attack (2%), pain/discomfort (7%), somnolence (2%), vertigo (2%)
Dermatologic: Acne (9%), erythema (7%), mottled skin(4%), pruritus (4%), dry skin (2%), eczema (2%), rash (2%)
Gastrointestinal: Nausea (9%), dysgeusia (6%), diarrhea (4%), vomiting (4%), abdominal pain (2%), dyspepsia (2%), gastrointestinal upset (2%), stomach cramps (2%), stomach discomfort (2%)
Neuromuscular & skeletal: Myalgia (6%), neuropathic pain (6%), tremor (4%), musculoskeletal discomfort (2%), back pain (2%), limb pain (2%), paraesthesia (2%), weakness (2%)
Ocular: Lacrimation increased (2%), periorbital edema (2%)
Respiratory: Hoarseness (6%), throat tightness (6%), cough (4%), dyspnea (4%), nasopharyngitis (4%), pharyngitis (4%), nasal congestion (2%), snoring (2%), throat irritation (2%)
Miscellaneous: Feeling hot (4%), influenza-like syndrome(2%), parosmia (2%)
<1% (Limited to important or life-threatening): Chills, facial flushing, urticaria
CONTRAINDICATIONS — Hypersensitivity to agalsidase alfa or any component of the formulation; concomitant use with chloroquine, amiodarone, monobenzone, or gentamicin (these agents have the potential to inhibit intracellular agalsidase alfa activity)
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: The presence IgG antibodies has been observed within 3 months from the onset of therapy in ~55% of treated patients. Approximately 60% of these patients are free of antibodies and >80% demonstrate immune tolerance, based on reduced titers of antibody within 12-18 months. Infusion reactions: Mild acute reactions (chills, facial flushing) are common and may occur during or within 1 hour after infusion. Severe reactions (nausea, pyrexia, rigors, tachycardia, urticaria, vomiting) are rare and usually occur within 2-4 months from the onset of therapy. Patients with a history of reactions may be premedicated with oral corticosteroids and antihistamines 1-3 hours prior to subsequent infusions.
Disease-related concerns: Fabry disease: Common symptoms observed in this patient population may be confused with adverse reactions related to treatment. Hepatic impairment: Safety and efficacy have not been established.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS
Amiodarone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Chloroquine: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Gentamicin: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
Monobenzone: May inhibit the intracellular activity of agalsidase alfa; concomitant use is contraindicated.
PREGNANCY IMPLICATIONS — Adverse events were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. The benefits versus risks should be considered carefully before initiating agalsidase alfa therapy in pregnant women.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Creatinine clearance, ECG, echocardiography, Gb-3 levels (serum and urine)
CANADIAN BRAND NAMES — Replagal™
INTERNATIONAL BRAND NAMES — Replagal (AU, BE, CH, CZ, DK, EE, ES, FI, IL, NO, NZ, SE, TW)
MECHANISM OF ACTION — Agalsidase alfa is a recombinant form of the enzyme alpha-galactosidase-A, which catalyzes the hydrolysis of globotriaosylceramide (Gb-3) and other glycosphingolipids. These compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. Agalsidase has been noted to reduce cellular levels of Gb-3 within the liver, heart, kidney, blood vessels, and in plasma.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 17% of body weight
Metabolism: Plasma; via peptide hydrolysis
Half-life elimination: ~1.5-2 hours
Adenosine
MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Adenocard®; Adenoscan®
PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class IV
Diagnostic Agent
DOSING: ADULTS
Paroxysmal supraventricular tachycardia (Adenocard®): I.V. (rapid, over 1-2 seconds, via peripheral line): Initial: 6 mg; if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
Recommended dosage adjustment for adenosine when administered via central line or with concurrent carbamazepine or dipyridamole (ACLS, 2005): Initial dose: 3 mg
Pharmacologic stress testing (Adenoscan®): I.V.: Continuous I.V. infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or columetric infusion pump; total dose: 0.84 mg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.
Acute vasodilator testing in pulmonary artery hypertension (unlabeled use) (Adenoscan®): I.V.: Initial: 50 mcg/kg/minute increased by 50 mcg/kg/minute every 2 minutes to a maximum dose of 500 mcg/kg/minute (Schrader, 1992) or to a maximum dose of 250 mcg/kg/minute (McLaughlin, 2009); acutely assess vasodilator response
DOSING: PEDIATRIC — Rapid I.V. push (over 1-2 seconds) via peripheral line:
(For additional information see "Adenosine: Pediatric drug information")
Paroxysmal supraventricular tachycardia (Adenocard®): Infants and Children:
Manufacturer's recommendation:
Children <50 kg: Initial: 0.05-0.1 mg/kg (maximum initial dose: 6 mg). If conversion of PSVT does not occur within 1-2 minutes, may increase dose by 0.05-0.1 mg/kg. May repeat until sinus rhythm is established or to a maximum single dose of 0.3 mg/kg or 12 mg. Follow each dose with normal saline flush.
Children ≥ 50 kg: Refer to adult dosing.
Pediatric advanced life support (PALS, 2005): Treatment of SVT: I.V., I.O.: Initial: 0.1 mg/kg (maximum initial dose: 6 mg); if not effective within 1-2 minutes, administer 0.2 mg/kg; may repeat 0.2 mg/kg if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
DOSING: ELDERLY — Refer to adult dosing. Elderly may be more sensitive to effects of adenosine.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — For rapid bolus I.V. use only; administer I.V. push over 1-2 seconds at a peripheral I.V. site as proximal as possible to trunk (not in lower arm, hand, lower leg, or foot); follow each bolus with a rapid normal saline flush (≥ 5 mL). Use of 2 syringes (one with adenosine dose and the other with NS flush) connected to a T-connector or stopcock is recommended (ACLS, 2005). Note: If administered via central line in adults, reduce initial dose to 3 mg (ACLS, 2005).
COMPATIBILITY — Stable in D5LR, D5W, LR, NS.
USE
Adenocard®: Treatment of paroxysmal supraventricular tachycardia (PSVT) including that associated with accessory bypass tracts (Wolff-Parkinson-White syndrome); when clinically advisable, appropriate vagal maneuvers should be attempted prior to adenosine administration; not effective for conversion of atrial fibrillation, atrial flutter, or ventricular tachycardia
Adenoscan®: Pharmacologic stress agent used in myocardial perfusion thallium-201 scintigraphy
USE - UNLABELED / INVESTIGATIONAL
ACLS/PALS Guidelines (2005):
Stable, narrow-complex AV nodal or sinus nodal reentry tachycardias (eg, reentry SVT);
Unstable reentry SVT while preparations are made for synchronized direct-current cardioversion;
Undefined, stable, narrow-complex SVT as a combination therapeutic and diagnostic maneuver;
Stable, wide-complex tachycardias in patients with a recurrence of a known reentry pathway that has been previously defined
Adenoscan®: Acute vasodilator testing in pulmonary artery hypertension
ADVERSE REACTIONS SIGNIFICANT — Note: Frequency varies based on use; higher frequency of infusion-related effects, such as flushing and lightheadedness, were reported with continuous infusion (Adenoscan®).
>10%:
Cardiovascular: Facial flushing (18% to 44%)
Central nervous system: Headache (2% to 18%), lightheadedness (2% to 12%)
Gastrointestinal: GI discomfort (13%)
Neuromuscular & skeletal: Discomfort of neck, throat, jaw (<1% to 15%)
Respiratory: Chest pressure/discomfort (7% to 40%), dyspnea (12% to 28%)
1% to 10%:
Cardiovascular: AV block (infusion 6%; third degree <1%), ST segment depression (3%), hypotension (<1% to 2%), palpitation, chest pain
Central nervous system: Nervousness (2%), apprehension, dizziness
Gastrointestinal: Nausea (3%)
Neuromuscular & skeletal: Upper extremity discomfort (up to 4%), numbness (up to 2%), paresthesia (up to 2%)
Respiratory: Hyperventilation
Miscellaneous: Diaphoresis
<1% (Limited to important or life-threatening): Asystole (prolonged), atrial fibrillation (upon termination of PSVT), back discomfort, bradycardia, bronchospasm, burning sensation, blurred vision, hypertension (transient), injection site reaction, intracranial pressure increased, lower extremity discomfort, metallic taste, pressure in groin, respiratory arrest, seizure, torsade de pointes, ventricular fibrillation, ventricular tachycardia
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component of the formulation; second- or third-degree AV block or sick sinus syndrome (except in patients with a functioning artificial pacemaker); use in patients with atrial fibrillation/flutter with underlying Wolff-Parkinson-White (WPW) syndrome is considered to be contraindicated (Fuster, 2006)
In addition to the above, Adenoscan® should be avoided in patients with known or suspected bronchoconstrictive or bronchospastic lung disease.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Atrial fibrillation/flutter: There have been reports of atrial fibrillation/flutter when administered to patients with paroxysmal supraventricular tachycardia (PSVT) and may be especially problematic in patients with PSVT and underlying Wolff-Parkinson-White syndrome. Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with pre-existing S-A nodal dysfunction may experience prolonged sinus pauses after adenosine; use caution in patients with first-degree AV block or bundle branch block; avoid use of adenosine for pharmacologic stress testing in patients with high-grade AV block or sinus node dysfunction (unless a functional pacemaker is in place). Rare, prolonged episodes of asystole have been reported, with fatal outcomes in some cases. Hypotension: May produce profound vasodilation with subsequent hypotension. When used as a bolus dose (PSVT), effects are generally self-limiting (due to the short half-life of adenosine). However, when used as a continuous infusion (pharmacologic stress testing), effects may be more pronounced and persistent, corresponding to continued exposure. Use infusions with caution in patients with autonomic dysfunction, carotid stenosis (with cerebrovascular insufficiency), uncorrected hypovolemia, pericarditis, pleural effusion and/or stenotic valvular heart disease. Proarrhythmic effects: Monitor for proarrhythmic effects (eg, polymorphic ventricular tachycardia) during and shortly after administration/termination of arrhythmia. The benign transient occurrence of atrial and ventricular ectopy is common upon termination of arrhythmia.
Disease-related concerns: Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Heart transplant recipients: Use with extreme caution in heart transplant recipients; adenosine may cause prolonged asystole; reduction of initial adenosine dose is recommended (ACLS, 2005); considered by some to be contraindicated in this setting (Delacretaz, 2006). Pulmonary artery hypertension: Acute vasodilator testing (not an approved use): Use with extreme caution in patients with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; significant decompensation has occurred with other highly selective pulmonary vasodilators resulting in acute pulmonary edema. Respiratory disease: Avoid use in patients with bronchoconstriction or bronchospasm (eg, asthma); mild-to-moderate exacerbations have been reported following use in a limited number of patients with asthma. Use caution in patients with obstructive lung disease not associated with bronchoconstriction (eg, emphysema, bronchitis); respiratory compromise has occurred during use. Wolff-Parkinson-White (WPW) syndrome: Use in patients with atrial fibrillation/flutter with underlying WPW syndrome is considered to be contraindicated since ventricular fibrillation may result (Fuster, 2006).
Concurrent drug therapy issues: Caffeine: Pharmacologic stress testing: Since caffeine antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use; avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing. Carbamazepine: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Dipyridamole: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Drugs which slow AV node conduction: Use with caution in patients receiving other drugs which slow AV node conduction (eg, digoxin, verapamil). Theophylline: Pharmacologic stress testing: Since theophylline antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use whenever possible.
Special populations: Elderly: Use with caution in the elderly; may be at increased risk of hemodynamic effects, bradycardia, and/or AV block.
Dosage form specific issues: Adenocard®: Transient AV block is expected. When used in PSVT, at the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the ECG. Administer as a rapid bolus, either directly into a vein or (if administered into an I.V. line), as close to the patient as possible (followed by saline flush).
Other warnings/precautions: Appropriate use: ECG monitoring is required during use. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Adenosine does not convert atrial fibrillation/flutter to normal sinus rhythm; however, may be used diagnostically in these settings if the underlying rhythm is not apparent.
DRUG INTERACTIONS
CarBAMazepine: May enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Consider using a lower initial dose of adenosine in patients who are receiving carbamazepine. Risk D: Consider therapy modification
Dipyridamole: May enhance the therapeutic effect of Adenosine. Dose reduction of adenosine may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Risk D: Consider therapy modification
Nicotine: May enhance the AV-blocking effect of Adenosine. Nicotine may enhance the tachycardic effect of Adenosine. Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Adenosine. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Avoid food or drugs with caffeine. Adenosine's therapeutic effect may be decreased if used concurrently with caffeine. Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reports of administration during pregnancy have indicated no adverse effects on fetus or newborn attributable to adenosine.
LACTATION — Excretion in breast milk unknown
DIETARY CONSIDERATIONS — Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
MONITORING PARAMETERS — ECG, heart rate, blood pressure
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
INTERNATIONAL BRAND NAMES — Adenocard (BR); Adenocor (AU, BE, BG, CZ, DK, EE, EG, ES, FI, GB, HN, HU, IE, IL, KP, LU, MY, NO, PE, PL, PT, SE, TH, TW, UY, VE, ZA); Adenocur (NL); Adenoject (IN); Adenoscan (ES, HK); Adenosin Ebewe (PL); Adenosina Biol (AR, PY); Adenozer (TW); Adrekar (AT, DE); Cardiovert (PH); Fosfobion (PL); Krenosin (FR, IT, LU, MX); Krenosine (CH); Soladen (PL); Tricor (CN)
MECHANISM OF ACTION — Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: Very brief
Metabolism: Blood and tissue to inosine then to adenosine monophosphate (AMP) and hypoxanthine
Half-life elimination: <10 seconds
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Adenocard®; Adenoscan®
PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class IV
Diagnostic Agent
DOSING: ADULTS
Paroxysmal supraventricular tachycardia (Adenocard®): I.V. (rapid, over 1-2 seconds, via peripheral line): Initial: 6 mg; if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
Recommended dosage adjustment for adenosine when administered via central line or with concurrent carbamazepine or dipyridamole (ACLS, 2005): Initial dose: 3 mg
Pharmacologic stress testing (Adenoscan®): I.V.: Continuous I.V. infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or columetric infusion pump; total dose: 0.84 mg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.
Acute vasodilator testing in pulmonary artery hypertension (unlabeled use) (Adenoscan®): I.V.: Initial: 50 mcg/kg/minute increased by 50 mcg/kg/minute every 2 minutes to a maximum dose of 500 mcg/kg/minute (Schrader, 1992) or to a maximum dose of 250 mcg/kg/minute (McLaughlin, 2009); acutely assess vasodilator response
DOSING: PEDIATRIC — Rapid I.V. push (over 1-2 seconds) via peripheral line:
(For additional information see "Adenosine: Pediatric drug information")
Paroxysmal supraventricular tachycardia (Adenocard®): Infants and Children:
Manufacturer's recommendation:
Children <50 kg: Initial: 0.05-0.1 mg/kg (maximum initial dose: 6 mg). If conversion of PSVT does not occur within 1-2 minutes, may increase dose by 0.05-0.1 mg/kg. May repeat until sinus rhythm is established or to a maximum single dose of 0.3 mg/kg or 12 mg. Follow each dose with normal saline flush.
Children ≥ 50 kg: Refer to adult dosing.
Pediatric advanced life support (PALS, 2005): Treatment of SVT: I.V., I.O.: Initial: 0.1 mg/kg (maximum initial dose: 6 mg); if not effective within 1-2 minutes, administer 0.2 mg/kg; may repeat 0.2 mg/kg if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
DOSING: ELDERLY — Refer to adult dosing. Elderly may be more sensitive to effects of adenosine.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — For rapid bolus I.V. use only; administer I.V. push over 1-2 seconds at a peripheral I.V. site as proximal as possible to trunk (not in lower arm, hand, lower leg, or foot); follow each bolus with a rapid normal saline flush (≥ 5 mL). Use of 2 syringes (one with adenosine dose and the other with NS flush) connected to a T-connector or stopcock is recommended (ACLS, 2005). Note: If administered via central line in adults, reduce initial dose to 3 mg (ACLS, 2005).
COMPATIBILITY — Stable in D5LR, D5W, LR, NS.
USE
Adenocard®: Treatment of paroxysmal supraventricular tachycardia (PSVT) including that associated with accessory bypass tracts (Wolff-Parkinson-White syndrome); when clinically advisable, appropriate vagal maneuvers should be attempted prior to adenosine administration; not effective for conversion of atrial fibrillation, atrial flutter, or ventricular tachycardia
Adenoscan®: Pharmacologic stress agent used in myocardial perfusion thallium-201 scintigraphy
USE - UNLABELED / INVESTIGATIONAL
ACLS/PALS Guidelines (2005):
Stable, narrow-complex AV nodal or sinus nodal reentry tachycardias (eg, reentry SVT);
Unstable reentry SVT while preparations are made for synchronized direct-current cardioversion;
Undefined, stable, narrow-complex SVT as a combination therapeutic and diagnostic maneuver;
Stable, wide-complex tachycardias in patients with a recurrence of a known reentry pathway that has been previously defined
Adenoscan®: Acute vasodilator testing in pulmonary artery hypertension
ADVERSE REACTIONS SIGNIFICANT — Note: Frequency varies based on use; higher frequency of infusion-related effects, such as flushing and lightheadedness, were reported with continuous infusion (Adenoscan®).
>10%:
Cardiovascular: Facial flushing (18% to 44%)
Central nervous system: Headache (2% to 18%), lightheadedness (2% to 12%)
Gastrointestinal: GI discomfort (13%)
Neuromuscular & skeletal: Discomfort of neck, throat, jaw (<1% to 15%)
Respiratory: Chest pressure/discomfort (7% to 40%), dyspnea (12% to 28%)
1% to 10%:
Cardiovascular: AV block (infusion 6%; third degree <1%), ST segment depression (3%), hypotension (<1% to 2%), palpitation, chest pain
Central nervous system: Nervousness (2%), apprehension, dizziness
Gastrointestinal: Nausea (3%)
Neuromuscular & skeletal: Upper extremity discomfort (up to 4%), numbness (up to 2%), paresthesia (up to 2%)
Respiratory: Hyperventilation
Miscellaneous: Diaphoresis
<1% (Limited to important or life-threatening): Asystole (prolonged), atrial fibrillation (upon termination of PSVT), back discomfort, bradycardia, bronchospasm, burning sensation, blurred vision, hypertension (transient), injection site reaction, intracranial pressure increased, lower extremity discomfort, metallic taste, pressure in groin, respiratory arrest, seizure, torsade de pointes, ventricular fibrillation, ventricular tachycardia
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component of the formulation; second- or third-degree AV block or sick sinus syndrome (except in patients with a functioning artificial pacemaker); use in patients with atrial fibrillation/flutter with underlying Wolff-Parkinson-White (WPW) syndrome is considered to be contraindicated (Fuster, 2006)
In addition to the above, Adenoscan® should be avoided in patients with known or suspected bronchoconstrictive or bronchospastic lung disease.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Atrial fibrillation/flutter: There have been reports of atrial fibrillation/flutter when administered to patients with paroxysmal supraventricular tachycardia (PSVT) and may be especially problematic in patients with PSVT and underlying Wolff-Parkinson-White syndrome. Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with pre-existing S-A nodal dysfunction may experience prolonged sinus pauses after adenosine; use caution in patients with first-degree AV block or bundle branch block; avoid use of adenosine for pharmacologic stress testing in patients with high-grade AV block or sinus node dysfunction (unless a functional pacemaker is in place). Rare, prolonged episodes of asystole have been reported, with fatal outcomes in some cases. Hypotension: May produce profound vasodilation with subsequent hypotension. When used as a bolus dose (PSVT), effects are generally self-limiting (due to the short half-life of adenosine). However, when used as a continuous infusion (pharmacologic stress testing), effects may be more pronounced and persistent, corresponding to continued exposure. Use infusions with caution in patients with autonomic dysfunction, carotid stenosis (with cerebrovascular insufficiency), uncorrected hypovolemia, pericarditis, pleural effusion and/or stenotic valvular heart disease. Proarrhythmic effects: Monitor for proarrhythmic effects (eg, polymorphic ventricular tachycardia) during and shortly after administration/termination of arrhythmia. The benign transient occurrence of atrial and ventricular ectopy is common upon termination of arrhythmia.
Disease-related concerns: Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Heart transplant recipients: Use with extreme caution in heart transplant recipients; adenosine may cause prolonged asystole; reduction of initial adenosine dose is recommended (ACLS, 2005); considered by some to be contraindicated in this setting (Delacretaz, 2006). Pulmonary artery hypertension: Acute vasodilator testing (not an approved use): Use with extreme caution in patients with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; significant decompensation has occurred with other highly selective pulmonary vasodilators resulting in acute pulmonary edema. Respiratory disease: Avoid use in patients with bronchoconstriction or bronchospasm (eg, asthma); mild-to-moderate exacerbations have been reported following use in a limited number of patients with asthma. Use caution in patients with obstructive lung disease not associated with bronchoconstriction (eg, emphysema, bronchitis); respiratory compromise has occurred during use. Wolff-Parkinson-White (WPW) syndrome: Use in patients with atrial fibrillation/flutter with underlying WPW syndrome is considered to be contraindicated since ventricular fibrillation may result (Fuster, 2006).
Concurrent drug therapy issues: Caffeine: Pharmacologic stress testing: Since caffeine antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use; avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing. Carbamazepine: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Dipyridamole: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Drugs which slow AV node conduction: Use with caution in patients receiving other drugs which slow AV node conduction (eg, digoxin, verapamil). Theophylline: Pharmacologic stress testing: Since theophylline antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use whenever possible.
Special populations: Elderly: Use with caution in the elderly; may be at increased risk of hemodynamic effects, bradycardia, and/or AV block.
Dosage form specific issues: Adenocard®: Transient AV block is expected. When used in PSVT, at the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the ECG. Administer as a rapid bolus, either directly into a vein or (if administered into an I.V. line), as close to the patient as possible (followed by saline flush).
Other warnings/precautions: Appropriate use: ECG monitoring is required during use. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Adenosine does not convert atrial fibrillation/flutter to normal sinus rhythm; however, may be used diagnostically in these settings if the underlying rhythm is not apparent.
DRUG INTERACTIONS
CarBAMazepine: May enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Consider using a lower initial dose of adenosine in patients who are receiving carbamazepine. Risk D: Consider therapy modification
Dipyridamole: May enhance the therapeutic effect of Adenosine. Dose reduction of adenosine may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Risk D: Consider therapy modification
Nicotine: May enhance the AV-blocking effect of Adenosine. Nicotine may enhance the tachycardic effect of Adenosine. Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Adenosine. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Avoid food or drugs with caffeine. Adenosine's therapeutic effect may be decreased if used concurrently with caffeine. Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reports of administration during pregnancy have indicated no adverse effects on fetus or newborn attributable to adenosine.
LACTATION — Excretion in breast milk unknown
DIETARY CONSIDERATIONS — Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.
MONITORING PARAMETERS — ECG, heart rate, blood pressure
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
INTERNATIONAL BRAND NAMES — Adenocard (BR); Adenocor (AU, BE, BG, CZ, DK, EE, EG, ES, FI, GB, HN, HU, IE, IL, KP, LU, MY, NO, PE, PL, PT, SE, TH, TW, UY, VE, ZA); Adenocur (NL); Adenoject (IN); Adenoscan (ES, HK); Adenosin Ebewe (PL); Adenosina Biol (AR, PY); Adenozer (TW); Adrekar (AT, DE); Cardiovert (PH); Fosfobion (PL); Krenosin (FR, IT, LU, MX); Krenosine (CH); Soladen (PL); Tricor (CN)
MECHANISM OF ACTION — Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm
PHARMACODYNAMICS / KINETICS
Onset of action: Rapid
Duration: Very brief
Metabolism: Blood and tissue to inosine then to adenosine monophosphate (AMP) and hypoxanthine
Half-life elimination: <10 seconds
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