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Drug overview for EXJADE (deferasirox):
Generic name: DEFERASIROX (deaf-ur-ES-ur-ox)
Drug class: Iron Chelating Agents
Therapeutic class: Antidotes and other Reversal Agents
Deferasirox is a heavy metal antagonist that chelates iron.
No enhanced Uses information available for this drug.
Generic name: DEFERASIROX (deaf-ur-ES-ur-ox)
Drug class: Iron Chelating Agents
Therapeutic class: Antidotes and other Reversal Agents
Deferasirox is a heavy metal antagonist that chelates iron.
No enhanced Uses information available for this drug.
DRUG IMAGES
EXJADE 125 MG TABLET
EXJADE 250 MG TABLET
EXJADE 500 MG TABLET
The following indications for EXJADE (deferasirox) have been approved by the FDA:
Indications:
Chronic iron overload due to repeated blood transfusions
Chronic iron overload in patient with non-transfusion-dependent thalassemia (NTDT)
Professional Synonyms:
Secondary iron overload from multiple blood transfusions
Transfusion hemosiderosis
Transfusion-induced iron overload
Transfusional hemosiderosis
Transfusional iron overload
Indications:
Chronic iron overload due to repeated blood transfusions
Chronic iron overload in patient with non-transfusion-dependent thalassemia (NTDT)
Professional Synonyms:
Secondary iron overload from multiple blood transfusions
Transfusion hemosiderosis
Transfusion-induced iron overload
Transfusional hemosiderosis
Transfusional iron overload
The following dosing information is available for EXJADE (deferasirox):
For patients currently receiving deferasirox tablets for oral suspension (e.g., Exjade(R)) for chelation therapy, when converting to film-coated tablets or granules (e.g., Jadenu(R)) the dosage should be reduced by about 30%, rounded to the nearest whole tablet or whole sachet dosage strength (Table 1).
Table 1. Conversion from Deferasirox Tablets for Oral Suspension to Deferasirox Film-Coated Tablets or Granules for Oral Use
Dosage of Deferasirox Dosage of Deferasirox Tablets for Oral Tablets or Granules for Suspension Oral Use Transfusion-Dependent Iron Overload Starting Dose 20 mg/kg per day 14 mg/kg per day Titration Increments 5-10 mg/kg 3.5-7 mg/kg Maximum Dose 40 mg/kg per day 28 mg/kg per day Non-Transfusion-Dependen t Thalassemia Syndrome Starting Dose 10 mg/kg per day 7 mg/kg per day Titration Increments 5-10 mg/kg 3.5-7 mg/kg Maximum Dose 20 mg/kg per day 14 mg/kg per day
Concomitant use of deferasirox with bile acid sequestrants (e.g., cholestyramine, colesevelam, colestipol) or potent UGT inducers (e.g., phenobarbital, phenytoin, rifampin, ritonavir) should be avoided. If such concomitant use cannot be avoided, consider an increase in the initial deferasirox dosage by 50%. Further dosage adjustments should be made according to the patient's clinical response and serum ferritin concentrations.
Table 1. Conversion from Deferasirox Tablets for Oral Suspension to Deferasirox Film-Coated Tablets or Granules for Oral Use
Dosage of Deferasirox Dosage of Deferasirox Tablets for Oral Tablets or Granules for Suspension Oral Use Transfusion-Dependent Iron Overload Starting Dose 20 mg/kg per day 14 mg/kg per day Titration Increments 5-10 mg/kg 3.5-7 mg/kg Maximum Dose 40 mg/kg per day 28 mg/kg per day Non-Transfusion-Dependen t Thalassemia Syndrome Starting Dose 10 mg/kg per day 7 mg/kg per day Titration Increments 5-10 mg/kg 3.5-7 mg/kg Maximum Dose 20 mg/kg per day 14 mg/kg per day
Concomitant use of deferasirox with bile acid sequestrants (e.g., cholestyramine, colesevelam, colestipol) or potent UGT inducers (e.g., phenobarbital, phenytoin, rifampin, ritonavir) should be avoided. If such concomitant use cannot be avoided, consider an increase in the initial deferasirox dosage by 50%. Further dosage adjustments should be made according to the patient's clinical response and serum ferritin concentrations.
Deferasirox is administered orally as tablets for oral suspension (e.g., Exjade(R)), as film-coated tablets for oral use (e.g., Jadenu(R)), and as granules for oral use (e.g., Jadenu(R) Sprinkle). Dosing conversion is required when switching between deferasirox formulations. In patients currently receiving chelation therapy with deferasirox tablets for oral suspension (e.g., Exjade(R)), conversion to film-coated tablets use (e.g., Jadenu(R)) or granules for oral use (e.g., Jadenu(R) Sprinkle) requires a decrease in dosage.
Administer deferasirox tablets for oral suspension (e.g., Exjade(R)) and film-coated tablets or granules (e.g., Jadenu(R)) once daily on an empty stomach (at least 30 minutes before eating), preferably at the same time each day. Film-coated tablet and granule preparations may also be administered with a light meal (containing less than 7% fat and approximately 250 calories). Store all deferasirox preparations between 20-25degreesC (excursions permitted between 15-30degreesC). Protect from moisture.
Administer deferasirox tablets for oral suspension (e.g., Exjade(R)) and film-coated tablets or granules (e.g., Jadenu(R)) once daily on an empty stomach (at least 30 minutes before eating), preferably at the same time each day. Film-coated tablet and granule preparations may also be administered with a light meal (containing less than 7% fat and approximately 250 calories). Store all deferasirox preparations between 20-25degreesC (excursions permitted between 15-30degreesC). Protect from moisture.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| EXJADE 125 MG TABLET | Maintenance | Adults take 1 tablet (125 mg) by oral route once daily on an empty stomach. Dissolve tablets in water, orange juice or apple juice and swallow. |
| EXJADE 250 MG TABLET | Maintenance | Adults take 1 tablet (250 mg) by oral route once daily on an empty stomach. Dissolve tablets in water, orange juice or apple juice and swallow. |
| EXJADE 500 MG TABLET | Maintenance | Adults take 1 tablet (500 mg) by oral route once daily on an empty stomach. Dissolve tablets in water, orange juice or apple juice and swallow. |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| DEFERASIROX 125 MG TB FOR SUSP | Maintenance | Adults take 1 tablet (125 mg) by oral route once daily on an empty stomach. Dissolve tablets in water, orange juice or apple juice and swallow. |
| DEFERASIROX 250 MG TB FOR SUSP | Maintenance | Adults take 1 tablet (250 mg) by oral route once daily on an empty stomach. Dissolve tablets in water, orange juice or apple juice and swallow. |
| DEFERASIROX 500 MG TB FOR SUSP | Maintenance | Adults take 1 tablet (500 mg) by oral route once daily on an empty stomach. Dissolve tablets in water, orange juice or apple juice and swallow. |
The following drug interaction information is available for EXJADE (deferasirox):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Fezolinetant/CYP1A2 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Inhibitors of CYP1A2 may inhibit the metabolism of fezolinetant.(1) CLINICAL EFFECTS: Concurrent use of a CYP1A2 inhibitor may increase levels of and adverse effects from fezolinetant.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of fezolinetant states that concurrent use with CYP1A2 inhibitors is contraindicated.(1) DISCUSSION: In a study, fluvoxamine, a strong CYP1A2 inhibitor, increased fezolinetant maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 840%, respectively. Mexiletine (400 mg every 8 hours), a moderate CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 40% and 360%, respectively. Cimetidine (300 mg every 6 hours), a weak CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 30% and 100%, respectively.(1) Strong CYP1A2 inhibitors linked to this monograph include angelica root, ciprofloxacin, enasidenib, enoxacin, fluvoxamine, and rofecoxib. Moderate CYP1A2 inhibitors linked to this monograph include capmatinib, dipyrone, fexinidazole, genistein, hormonal contraceptives, methoxsalen, mexiletine, osilodrostat, phenylpropanolamine, pipemidic acid, rucaparib, troleandomycin, vemurafenib, and viloxazine. Weak CYP1A2 inhibitors linked to this monograph include allopurinol, artemisinin, caffeine, cannabidiol, cimetidine, curcumin, dan-shen, deferasirox, disulfiram, Echinacea, famotidine, ginseng, norfloxacin, obeticholic acid, parsley, piperine, propafenone, propranolol, ribociclib, simeprevir, thiabendazole, ticlopidine, triclabendazole, verapamil, zileuton.(2-4) |
VEOZAH |
There are 8 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Deferasirox/Aluminum Salts SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Decreased absorption of deferasirox possibly from complex formation with the aluminum salt. CLINICAL EFFECTS: The therapeutic effects of deferasirox may be reduced. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of deferasirox states patients taking deferasirox should not take aluminum salts or aluminum-containing antacid products. DISCUSSION: Simultaneous administration of deferasirox and aluminum has not been studied. Even though deferasirox has a lower affinity for aluminum than iron, it should not be taken with aluminum-containing products. |
ALUMINUM HYDROXIDE, ATTAPULGITE, CARAFATE, KAOLIN, SUCRALFATE |
| Deferasirox/Strong UGT Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong inducers of UDP-glucuronosyltransferase (UGT) may induce the metabolism of deferasirox.(1) CLINICAL EFFECTS: Concurrent use of carbamazepine, efavirenz, etravirine, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin, or ritonavir may result in decreased levels and effectiveness of deferasirox.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of strong UGT inducers with deferasirox. If concurrent therapy is warranted, consider increasing the initial dose of deferasirox by 50%. Further dosage adjustments should be made based upon serum ferritin levels and clinical response. Doses above 40 mg/kg are not recommended.(1) DISCUSSION: In a study in healthy subjects, administration of rifampin (600 mg/day for 9 days) decreased the area-under-curve (AUC) of a single dose of deferasirox (30 mg/kg) by 44%.(1) Other strong inducers of UGT, such as carbamazepine, efavirenz, etravirine, fosphenytoin, phenobarbital, phenytoin, primidone, and ritonavir are expected to produce similar results.(1) |
CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EPITOL, EQUETRO, ETRAVIRINE, FOSPHENYTOIN SODIUM, INTELENCE, KALETRA, LOPINAVIR-RITONAVIR, MYSOLINE, NORVIR, PAXLOVID, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIMIDONE, RIFADIN, RIFAMPIN, RITONAVIR, SEZABY, SYMFI, SYMFI LO, TEGRETOL, TEGRETOL XR |
| Deferasirox/Bile Acid Sequestrants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bile acid sequestrants may interfere with the enterohepatic recycling of deferasirox.(1) CLINICAL EFFECTS: Concurrent use of bile acid sequestrants may result in decreased levels and effectiveness of deferasirox, even when the administration times are separated.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of bile acid sequestrants with deferasirox. If concurrent therapy is warranted, consider increasing the initial dose of deferasirox by 50%. Further dosage adjustments should be made based upon serum ferritin levels and clinical response. Doses above 40 mg/kg are not recommended.(1) DISCUSSION: In a study in healthy subjects, administration of cholestyramine (12 g twice daily, 4 and 10 hours after deferasirox) decreased the area-under-curve (AUC) of a single dose of deferasirox (dosage not stated) by 45%.(1) |
CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESEVELAM HCL, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT, WELCHOL |
| Theophylline;Tizanidine/Deferasirox SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Deferasirox may inhibit the metabolism of theophylline or tizanidine by CYP1A2.(1-3) CLINICAL EFFECTS: Concurrent use of deferasirox may result in elevated levels of and increased effects of theophylline or tizanidine.(1) PREDISPOSING FACTORS: With tizanidine, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(4) PATIENT MANAGEMENT: Patients receiving theophylline or tizanidine may need their dose reduced when deferasirox is started. Theophylline AUC and elimination half-life may double. Monitor theophylline concentrations and adjust dose accordingly.(1) Patients already receiving deferasirox when theophylline or tizanidine is started may be more susceptible to adverse effects. A lower than usual dose of theophylline or tizanidine may be needed. The US manufacturer of deferasirox recommends avoiding concomitant therapy with theophylline or CYP1A2 narrow therapeutic range substrates such as tizanidine.(1) The US manufacturer of tizanidine recommends avoiding concomitant therapy with CYP1A2 inhibitors. If concurrent therapy is necessary, tizanidine should be initiated at 2 mg dose and increased in 2-4 mg steps daily based on patient response to therapy. If adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue tizanidine therapy.(3) DISCUSSION: In a study with healthy volunteers, deferasirox dosage of 30mg/kg/day (duration not stated) and a single dose of theophylline 120 mg led to an approximate doubling of the theophylline area-under-curve (AUC) and elimination half-life. Although a deferasirox - tizanidine interaction has not been specifically studied, the FDA has designated tizanidine as a CYP1A2 narrow therapeutic range substrate(2); when the combination is required close monitoring would be prudent. |
AMINOPHYLLINE, ELIXOPHYLLIN, THEO-24, THEOPHYLLINE, THEOPHYLLINE ANHYDROUS, THEOPHYLLINE ER, THEOPHYLLINE ETHYLENEDIAMINE, TIZANIDINE HCL, ZANAFLEX |
| Busulfan/Deferasirox SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Deferasirox may increase the plasma concentrations of busulfan.(1-3) The exact mechanism is unknown but may involve competitive inhibition of glucuronidation enzymes.(2) CLINICAL EFFECTS: Concurrent use of deferasirox may result in elevated levels of and toxicity from busulfan.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy should be closely monitored for toxicity. The dosage of busulfan may need to be adjusted.(1-3) DISCUSSION: In a case report, co-administration of deferasirox with busulfan led to a 1.5-fold increase in area under the curve (AUC) and 37% decrease in drug clearance (CL).(2) In another case report, concomitant use of busulfan and deferasirox led to a 2-fold increase in AUC and 46% decrease in CL.(3) In both reports, the dose of busulfan when used with concomitant deferasirox was approximately half of the dose required with busulfan alone. |
BUSULFAN, BUSULFEX, MYLERAN |
| Hormonal Contraceptives/Deferasirox SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Deferasirox may induce the CYP3A4 mediated metabolism of hormonal contraceptives.(1) CLINICAL EFFECTS: Concurrent use of deferasirox may reduce the effectiveness of hormonal contraceptives.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Women of reproductive age should be counseled not to rely on hormonal contraception (including oral contraceptives, patches, implants, and/or IUDs) for contraception. Women should use a non-hormonal method of birth control during deferasirox therapy.(1) For emergency contraception, the UK's Medicines & Healthcare Products Regulatory Agency (MHRA) recommends that women who have used a CYP3A4 inducer in the previous 4 weeks should consider a non-hormonal emergency contraceptive (i.e., a copper IUD). If a non-hormonal emergency contraceptive is not an option, double the usual dose of levonorgestrel from 1.5 to 3 mg. Advise the patient to have a pregnancy test to exclude pregnancy after use and to seek medical advice if she does become pregnant.(2) DISCUSSION: Deferasirox may induce the CYP3A4 mediated metabolism of hormonal contraceptives. Deferasirox may decrease the effectiveness of hormonal contraceptives, including oral contraceptives, patches, implants, and/or IUDs. Women should use a non-hormonal method of birth control during deferasirox therapy.(1) |
2-METHOXYESTRADIOL, AFIRMELLE, ALTAVERA, ALYACEN, AMETHIA, AMETHYST, ANNOVERA, APRI, ARANELLE, ASHLYNA, AUBRA, AUBRA EQ, AUROVELA, AUROVELA 24 FE, AUROVELA FE, AVIANE, AYUNA, AZURETTE, BALCOLTRA, BALZIVA, BEYAZ, BLISOVI 24 FE, BLISOVI FE, BRIELLYN, CAMILA, CAMRESE, CAMRESE LO, CAZIANT, CHARLOTTE 24 FE, CHATEAL EQ, CRYSELLE, CYRED, CYRED EQ, DASETTA, DAYSEE, DEBLITANE, DEPO-PROVERA, DEPO-SUBQ PROVERA 104, DESOGESTR-ETH ESTRAD ETH ESTRA, DIETHYLSTILBESTROL, DOLISHALE, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, ELINEST, ELLA, ELURYNG, EMZAHH, ENILLORING, ENPRESSE, ENSKYCE, ERRIN, ESTARYLLA, ESTRADIOL, ESTRADIOL BENZOATE, ESTRADIOL CYPIONATE, ESTRADIOL HEMIHYDRATE, ESTRADIOL HEMIHYDRATE MICRO, ESTRADIOL MICRONIZED, ESTRADIOL VALERATE, ESTRIOL, ESTRIOL MICRONIZED, ESTRONE, ETHINYL ESTRADIOL, ETHYNODIOL-ETHINYL ESTRADIOL, ETONOGESTREL-ETHINYL ESTRADIOL, FALMINA, FEIRZA, FEMLYV, FINZALA, GEMMILY, HAILEY, HAILEY 24 FE, HAILEY FE, HALOETTE, HEATHER, ICLEVIA, INCASSIA, ISIBLOOM, JAIMIESS, JASMIEL, JENCYCLA, JOLESSA, JOYEAUX, JULEBER, JUNEL, JUNEL FE, JUNEL FE 24, KAITLIB FE, KALLIGA, KARIVA, KELNOR 1-35, KELNOR 1-50, KURVELO, LARIN, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEENA, LESSINA, LEVONEST, LEVONORG-ETH ESTRAD ETH ESTRAD, LEVONORG-ETH ESTRAD-FE BISGLYC, LEVONORGESTREL-ETH ESTRADIOL, LEVORA-28, LO LOESTRIN FE, LO-ZUMANDIMINE, LOESTRIN, LOESTRIN FE, LOJAIMIESS, LORYNA, LOW-OGESTREL, LUTERA, LYLEQ, LYZA, MARLISSA, MEDROXYPROGESTERONE ACETATE, MERZEE, MIBELAS 24 FE, MICROGESTIN, MICROGESTIN FE, MILI, MINZOYA, MONO-LINYAH, NATAZIA, NECON, NEXPLANON, NEXTSTELLIS, NIKKI, NORA-BE, NORELGESTROMIN-ETH ESTRADIOL, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRON-ETHINYL ESTRADIOL, NORETHINDRONE, NORETHINDRONE-E.ESTRADIOL-IRON, NORGESTIMATE-ETHINYL ESTRADIOL, NORTREL, NUVARING, NYLIA, OCELLA, ORTHO TRI-CYCLEN, ORTHO-NOVUM, PHILITH, PIMTREA, PORTIA, RECLIPSEN, RIVELSA, SAFYRAL, SETLAKIN, SHAROBEL, SIMLIYA, SIMPESSE, SLYND, SPRINTEC, SRONYX, SYEDA, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-ESTARYLLA, TRI-LEGEST FE, TRI-LINYAH, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, TRI-VYLIBRA LO, TRIVORA-28, TULANA, TURQOZ, TWIRLA, TYBLUME, VALTYA, VELIVET, VESTURA, VIENVA, VIORELE, VOLNEA, VYFEMLA, VYLIBRA, WERA, WYMZYA FE, XARAH FE, XELRIA FE, XULANE, YASMIN 28, YAZ, ZAFEMY, ZARAH, ZOVIA 1-35, ZUMANDIMINE |
| Exagamglogene Autotemcel/Iron Chelators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Treatment with exagamglogene autotemcel requires hematopoietic stem cell (HSC) mobilization which can suppress the immune system. CLINICAL EFFECTS: Iron chelators should be held prior to and after infusion with exagamglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Iron chelators should be discontinued 7 days prior to initiation of mobilization or conditioning. Avoid myelosuppressive iron chelators for six months after exagamglogene autotemcel infusion. Avoid non-myelosuppressive iron chelators for three months after exagamglogene autotemcel infusion. If iron chelation is needed, consider phlebotomy in lieu of iron chelation when appropriate.(1) DISCUSSION: In preparation for infusion of exagamglogene autotemcel, iron chelation should be discontinued 7 days prior to initiation of mobilization or conditioning.(1) |
CASGEVY |
| Tovorafenib/Moderate CYP2C8 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inhibitors of CYP2C8 may inhibit the metabolism of tovorafenib.(1) CLINICAL EFFECTS: Concomitant use of a moderate CYP2C8 inhibitor may increase tovorafenib plasma concentrations, which may increase the risk of tovorafenib toxicity, including hepatotoxicity, bleeding, and photosensitivity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of tovorafenib recommends avoiding concomitant use of tovorafenib with moderate CYP2C8 inhibitors.(1) DISCUSSION: Moderate CYP2C8 inhibitors are predicted to increase tovorafenib exposure.(1) Moderate CYP2C8 inhibitors linked to this monograph include clopidogrel, deferasirox, leflunomide, letermovir, mifepristone (chronic therapy), and teriflunomide.(2) |
OJEMDA |
There are 6 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Repaglinide/Deferasirox SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Deferasirox may inhibit the metabolism of repaglinide by CYP2C8.(1) CLINICAL EFFECTS: Concurrent use of deferasirox may result in elevated levels of and increased effects of repaglinide.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy with deferasirox and repaglinide closely. Consider decreasing the dosage of repaglinide.(1) DISCUSSION: In a study in healthy subjects, administration of deferasirox (30 mg/kg/day for 4 days) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of repaglinide (0.5 mg) by 2.3-fold and 62%, respectively.(1) |
REPAGLINIDE |
| Paclitaxel/Selected Strong and Moderate CYP2C8 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of CYP2C8 may inhibit paclitaxel metabolism by this pathway. Clopidogrel and gemfibrozil are strong inhibitors of CYP2C8. Deferasirox is a moderate inhibitor of CYP2C8.(1-3) CLINICAL EFFECTS: Concurrent use of CYP2C8 inhibitors and paclitaxel may result in elevated levels and clinical effects of paclitaxel.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturers of paclitaxel recommend combination use CYP2C8 inhibitors with caution. If concomitant use is necessary, paclitaxel dose reduction may be required.(1,2) DISCUSSION: The US manufacturer of paclitaxel recommends use with CYP2C8 inhibitors with caution.(1,2) |
ABRAXANE, PACLITAXEL, PACLITAXEL PROTEIN-BOUND |
| Selexipag/Moderate CYP2C8 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate CYP2C8 inhibitors may inhibit the metabolism of selexipag.(1) CLINICAL EFFECTS: Concurrent use of a moderate CYP2C8 inhibitor may increase levels and effects of selexipag, including headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, flushing, decreased hemoglobin, and hyperthyroidism.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When co-administered with a moderate inhibitor of CYP2C8, reduce the dose of selexipag to once daily. If the moderate CYP2C8 inhibitor is discontinued, increase the dose of selexipag to twice daily.(1) If concurrent use is warranted, monitor patients closely for increased effects of selexipag, including headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, flushing, decreased hemoglobin, and hyperthyroidism. DISCUSSION: Clopidogrel (300 mg for 1 day then 75 mg daily, a moderate CYP2C8 inhibitor) had no effect on exposure to selexipag but increased the area-under-curve (AUC) of selexipag's active metabolite by 2.7-fold.(1) A study in healthy subjects evaluated concurrent therapy with selexipag 200 mcg twice daily with clopidogrel 300 mg single does or 75 mg daily. The AUC and the maximum concentration (Cmax) of ACT-333679, the major contributor to the drug effect, increased 2.25-fold (90% confidence interval (CI) 2.06, 2.46) and 1.69-fold (90% CI 1.55, 1.84), respectively with clopidogrel 300 mg and 2.70-fold (90% CI 2.45, 2.96) and 1.90-fold (90% CI 1.72, 2.11), respectively with clopidogrel 75 mg.(2) Moderate CYP2C8 inhibitors linked include: clopidogrel, deferasirox, leflunomide, letermovir, selpercatinib, and teriflunomide.(3-4) |
UPTRAVI |
| Etrasimod/Strong and Moderate CYP2C8 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong and moderate inhibitors of CYP2C8 may impair the CYP2C8-mediated metabolism of etrasimod.(1) Etrasimod is metabolized by CYP2C8, CYP2C9, and CYP3A4.(1) CLINICAL EFFECTS: In patients who are poor metabolizers of CYP2C9, concurrent use of a strong or moderate inhibitor of CYP2C8 may result in elevated levels of and clinical effects from etrasimod including immunosuppression, decreased lung function, bradycardia, and AV conduction delays. PREDISPOSING FACTORS: CYP2C9 poor metabolizers (e.g., *2/*3, *3/*3) may have decreased clearance of etrasimod when etrasimod is used concomitantly with strong or moderate inhibitors of CYP2C8.(1) PATIENT MANAGEMENT: Concomitant use of etrasimod with strong or moderate CYP2C8 inhibitors in patients who are CYP2C9 poor metabolizers is not recommended.(1) DISCUSSION: CYP2C9 activity is decreased in individuals with genetic variants such as CYP2C9*2 and CYP2C9*3 alleles. The impact of CYP2C9 genetic variants on the pharmacokinetics of etrasimod has not been directly evaluated. Increased exposure of etrasimod in patients who are CYP2C9 poor metabolizers is expected with concomitant use of strong or moderate inhibitors of CYP2C8.(1) Concomitant use of etrasimod with steady-state fluconazole (a moderate CYP2C9 and CYP3A4 inhibitor) increased etrasimod area-under-curve (AUC) by 84%.(1) Strong inhibitors of CYP2C8 include: clopidogrel and gemfibrozil.(2,3) Moderate inhibitors of CYP2C8 include: deferasirox.(2,3) |
VELSIPITY |
| Lovotibeglogene Autotemcel/Iron Chelators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Treatment with lovotibeglogene autotemcel requires hematopoietic stem cell (HSC) mobilization which can suppress the immune system. CLINICAL EFFECTS: Iron chelators should be held prior to and after infusion with lovotibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Iron chelators should be discontinued 7 days prior to initiation of mobilization or conditioning. Avoid myelosuppressive iron chelators for six months after lovotibeglogene autotemcel infusion. Avoid non-myelosuppressive iron chelators for three months after lovotibeglogene autotemcel infusion. If iron chelation is needed, consider phlebotomy in lieu of iron chelation when appropriate.(1) DISCUSSION: In preparation for infusion of lovotibeglogene autotemcel, iron chelation should be discontinued 7 days prior to initiation of mobilization or conditioning.(1) |
LYFGENIA |
| Resmetirom/Moderate CYP2C8 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate inhibitors of CYP2C8 may inhibit the metabolism of resmetirom.(1) CLINICAL EFFECTS: Concomitant use of a moderate CYP2C8 inhibitor may increase resmetirom plasma concentrations, which may increase the risk of resmetirom toxicity, including hepatotoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concomitant use of resmetirom with moderate CYP2C8 inhibitors is not recommended. If concurrent use is warranted, reduce the dose of resmetirom based on the patient's weight. -If <100 kg, reduce the dose of resmetirom to 60 mg once daily; -If >=100 kg, reduce the dose of resmetirom to 80 mg once daily.(1) DISCUSSION: Multiple doses of resmetirom 100 mg daily were given with clopidogrel, a moderate CYP2C8 inhibitor, and the resmetirom area-under-curve (AUC) and maximum concentration (Cmax) increased 1.7-fold and 1.3-fold, respectively.(1) Moderate CYP2C8 inhibitors linked to this monograph include: clopidogrel, deferasirox, leflunomide, mifepristone (chronic therapy), pirtobrutinib, selpercatinib, and teriflunomide.(2) |
REZDIFFRA |
The following contraindication information is available for EXJADE (deferasirox):
Drug contraindication overview.
*eGFR less than 40 mL/minute per 1.73 m2 *Poor performance status *High-risk myelodysplastic syndrome *Advanced malignancy *Platelet counts less than 50,000/mm3 *Known hypersensitivity to deferasirox or any ingredient in the formulation
*eGFR less than 40 mL/minute per 1.73 m2 *Poor performance status *High-risk myelodysplastic syndrome *Advanced malignancy *Platelet counts less than 50,000/mm3 *Known hypersensitivity to deferasirox or any ingredient in the formulation
There are 6 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Acute renal failure |
| Child-pugh class C hepatic impairment |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Lactation |
There are 13 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Child-pugh class B hepatic impairment |
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| Dehydration |
| Disease of liver |
| Hyperbilirubinemia |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Malignancy |
| Multiple organ failure |
| Myelodysplastic syndrome |
| Neutropenic disorder |
| Ocular hypertension |
| Pregnancy |
| Thrombocytopenic disorder |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Anemia |
| Cataracts |
| Hearing loss |
| Proteinuria |
The following adverse reaction information is available for EXJADE (deferasirox):
Adverse reaction overview.
Adverse effects reported in more than 5% of patients receiving deferasirox with transfusional iron overload include diarrhea, vomiting, nausea, abdominal pain, rash, and increases in serum creatinine concentration. Adverse effects reported in more than 5% of patients receiving deferasirox with NTDT syndromes include diarrhea, rash, and nausea.
Adverse effects reported in more than 5% of patients receiving deferasirox with transfusional iron overload include diarrhea, vomiting, nausea, abdominal pain, rash, and increases in serum creatinine concentration. Adverse effects reported in more than 5% of patients receiving deferasirox with NTDT syndromes include diarrhea, rash, and nausea.
There are 36 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Kidney disease with reduction in glomerular filtration rate (GFr) |
Urticaria |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acute renal failure Agranulocytosis Anaphylaxis Anemia Angioedema Biliary calculus Cataracts DRESS syndrome Erythema multiforme Fanconi syndrome Gastritis Gastrointestinal hemorrhage Gastrointestinal perforation Gastrointestinal ulcer Hearing loss Hepatic failure Hepatitis Hyperbilirubinemia Hypersensitivity angiitis Hypersensitivity drug reaction IgA vasculitis Increased alanine transaminase Increased aspartate transaminase Interstitial nephritis Maculopathy Neutropenic disorder Ocular hypertension Optic neuritis Pancreatitis Renal failure Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis |
There are 23 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Diarrhea Nausea Pharyngitis Proteinuria Skin rash Vomiting |
Dysmenorrhea Increased defecation frequency Insomnia Lymphadenopathy Sleep disorder Upper respiratory infection Vertigo |
| Rare/Very Rare |
|---|
|
Alopecia Dizziness Dyschromia Edema Esophagitis Fatigue Fever Hyperkinesis Symptoms of anxiety |
The following precautions are available for EXJADE (deferasirox):
Safety and efficacy for transfusional iron overload have not been established in children younger than 2 years of age. Use of deferasirox for transfusional iron overload is based on data from 292 pediatric patients ranging from 2 to less than 16 years of age with various congenital and acquired anemias. Safety and efficacy for chronic iron overload in non-transfusion-dependent thalassemia (NTDT) syndromes have not been established in children younger than 10 years of age.
Use of deferasirox for chronic iron overload in NTDT is based on data from 16 pediatric patients with chronic iron overload and NTDT who were 10 to less than 16 years of age with a liver iron concentration (LIC) of at least 5 mg Fe/g dry weight and a serum ferritin concentration of more than 300 mcg/L. Additional data from well-designed pediatric and adult studies support this use. Systemic exposure of deferasirox in children less than 6 years of age is lower than that in adults.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Use of deferasirox for chronic iron overload in NTDT is based on data from 16 pediatric patients with chronic iron overload and NTDT who were 10 to less than 16 years of age with a liver iron concentration (LIC) of at least 5 mg Fe/g dry weight and a serum ferritin concentration of more than 300 mcg/L. Additional data from well-designed pediatric and adult studies support this use. Systemic exposure of deferasirox in children less than 6 years of age is lower than that in adults.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
No data are available to inform the drug-associated risk of deferasirox use in pregnancy. Animal reproductive studies demonstrated decreases in offspring viability and increases in renal anomalies at doses less than or similar to the equivalent human dose. Use deferasirox during pregnancy only if benefits clearly outweigh the potential risks of treatment.
Deferasirox is distributed into milk in rats; it is not known whether the drug is distributed into human milk. The effects of deferasirox on milk production, and the effects on the breastfed infant are not known. Consider the benefits of breastfeeding along with the potential for adverse effects from deferasirox exposure to the breast-fed infant, along with the mother's clinical need for the drug. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
The manufacturer makes no specific dosage recommendations in geriatric patients; however, in clinical trials, geriatric patients experienced a higher frequency of adverse reactions compared to younger adult patients. Due to decreased hepatic, renal, and cardiac function, in addition to the presence of other coexisting conditions, careful selection of the dosage of deferasirox is necessary in geriatric patients, and dosing is usually initiated at the lower end of the dosing range. Deferasirox should be used with caution in geriatric patients because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.
Geriatric patients receiving deferasirox should be monitored closely for early signs and/or symptoms of adverse reactions that may require dosage adjustment. Select the dose cautiously in geriatric patients. In clinical studies of deferasirox, geriatric patients 65 years of age or older experienced a higher incidence of adverse reactions than younger adults. The majority of these geriatric patients had myelodysplastic syndrome (MDS).
Geriatric patients receiving deferasirox should be monitored closely for early signs and/or symptoms of adverse reactions that may require dosage adjustment. Select the dose cautiously in geriatric patients. In clinical studies of deferasirox, geriatric patients 65 years of age or older experienced a higher incidence of adverse reactions than younger adults. The majority of these geriatric patients had myelodysplastic syndrome (MDS).
The following prioritized warning is available for EXJADE (deferasirox):
WARNING: Deferasirox may rarely cause serious (even fatal) kidney disease, liver disease, and stomach/intestinal bleeding (see also Side Effects section). Kidney disease may be more likely to occur in people with kidney problems and in people with serious blood diseases. Liver disease may be more likely to occur in people with liver problems (such as cirrhosis) and in older adults.
Stomach/intestinal bleeding may be more likely to occur in older adults with serious blood diseases (including blood cancers). Consult your doctor for more details. Your doctor will monitor you closely while you are taking this medication. Keep all regular medical and lab appointments.
WARNING: Deferasirox may rarely cause serious (even fatal) kidney disease, liver disease, and stomach/intestinal bleeding (see also Side Effects section). Kidney disease may be more likely to occur in people with kidney problems and in people with serious blood diseases. Liver disease may be more likely to occur in people with liver problems (such as cirrhosis) and in older adults.
Stomach/intestinal bleeding may be more likely to occur in older adults with serious blood diseases (including blood cancers). Consult your doctor for more details. Your doctor will monitor you closely while you are taking this medication. Keep all regular medical and lab appointments.
The following icd codes are available for EXJADE (deferasirox)'s list of indications:
| Chronic iron overload due to repeated blood transfusions | |
| E83.111 | Hemochromatosis due to repeated red blood cell transfusions |
| Chronic iron overload in NTD thalassemia | |
| E83.118 | Other hemochromatosis |
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