Promacta

Drug overview for PROMACTA (eltrombopag olamine):

Generic name: eltrombopag olamine (el-TROM-boe-pag)
Drug class: Thrombopoietic Growth Factors
Therapeutic class: Hematological Agents

Eltrombopag olamine is a small-molecule thrombopoietin receptor agonist (TPO-RA).

No enhanced Uses information available for this drug.

DRUG IMAGES

PROMACTA 50 MG TABLET
PROMACTA 75 MG TABLET
PROMACTA 12.5 MG TABLET
PROMACTA 25 MG TABLET

The following indications for PROMACTA (eltrombopag olamine) have been approved by the FDA:

Indications:
Aplastic anemia
Severe thrombocytopenia in refractory chronic immune thrombocytopenia purpura
Thrombocytopenia associated with chronic hepatitis C

Professional Synonyms:
Anemia gravis
Ehrlich's anemia
Severe thrombocytopenia in refractory chronic idiopathic thrombocytopenia purpura

The following dosing information is available for PROMACTA (eltrombopag olamine):

Dosing
Administration
PROMACTA
Generic

Dosage of eltrombopag olamine is expressed in terms of eltrombopag.

The usual initial dosage of eltrombopag for the treatment of persistent or chronic ITP in adults and pediatric patients >=6 years of age is 50 mg once daily. In patients with Asian ancestry (e.g., Chinese, Japanese, Taiwanese, Korean, or Thai) or hepatic impairment (Child-Pugh class A, B, or C), the usual initial dosage is 25 mg once daily. In patients with both Asian ancestry and hepatic impairment, consider initiating eltrombopag at a reduced dosage of 12.5

mg once daily.

The usual initial dosage of eltrombopag for the treatment of persistent or chronic ITP in pediatric patients 1-5 years of age is 25 mg once daily.

Periodically monitor clinical hematology tests and adjust the dosage of eltrombopag based on platelet counts (see Table 1); the manufacturer recommends that a platelet count >=50,000/mm3 be achieved and maintained as necessary to reduce the risk of bleeding. Do not exceed a maximum dosage of 75 mg daily.

Table 1. Dosage Adjustment of Eltrombopag in Patients with Persistent or Chronic Immune Thrombocytopenia

Platelet Count Dosage Adjustment <50,000/mm3 following at least 2 Increase daily dosage by 25 mg to a weeks of treatment maximum of 75 mg daily For patients taking 12.5 mg once daily, increase the dosage to 25 mg daily before increasing the dose amount by 25 mg >=200,000/mm3 to <=400,000/mm3 at Decrease the daily dosage by 25 mg; any time wait 2 weeks to assess the effects of this and any subsequent dosage adjustments For patients taking a dosage of 25 mg once daily, decrease to 12.5 mg once daily >400,000/mm3 Discontinue eltrombopag and increase the frequency of platelet monitoring to twice weekly Once the platelet count <150,000/mm3, reinitiate therapy at a daily dosage reduced by 25 mg For patients taking a dosage of 25 mg once daily, reinitiate therapy at 12 .5

mg daily >400,000/mm3 after 2 weeks of Discontinue therapy therapy at lowest dose of eltrombopag

In patients with ITP and hepatic impairment (Child-Pugh class A, B, or C), dosage should not be increased any sooner than 3 weeks after initiation of eltrombopag or after any subsequent dosage increase.

Discontinue therapy if the platelet count has not reached a level sufficient to avoid clinically relevant bleeding after 4 weeks of treatment at the maximum recommended dosage. Monitor CBCs with differentials, including platelet counts, weekly for at least 4 weeks following discontinuance of therapy.

Administer eltrombopag orally as tablets or an oral suspension. Do not administer the drug more often than once within any 24-hour period. Administer at the lowest dosage to achieve and maintain a platelet count >=50,000/mm3 as necessary to reduce the risk of bleeding or maintain a hematologic response.

Administer eltrombopag without a meal or with a meal containing a low amount of calcium (<=50 mg). Calcium-containing foods and medications may decrease the rate and extent of eltrombopag absorption; therefore, administer eltrombopag at least 2 hours before or 4 hours after other medications (e.g., antacids), calcium-rich foods (e.g., dairy products, certain fruits and vegetables), or supplements that contain polyvalent cations (e.g., iron, calcium, aluminum, magnesium, selenium, zinc). Because calcium-containing foods are more frequently consumed at breakfast, it has been suggested that eltrombopag be taken in the evening, if possible, unless patients are also taking an antacid preparation containing polyvalent cations at that time.

Dosing information for PROMACTA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
PROMACTA 12.5 MG TABLET	Maintenance	Adults take 1 tablet (12.5 mg) by oral route once daily on an empty stomach, 1 hour before or 2 hours after a meal
PROMACTA 25 MG TABLET	Maintenance	Adults take 2 tablets (50 mg) by oral route once daily on an empty stomach, 1 hour before or 2 hours after a meal
PROMACTA 50 MG TABLET	Maintenance	Adults take 1 tablet (50 mg) by oral route once daily on an empty stomach, 1 hour before or 2 hours after a meal
PROMACTA 75 MG TABLET	Maintenance	Adults take 1 tablet (75 mg) by oral route once daily on an empty stomach, 1 hour before or 2 hours after a meal
PROMACTA 25 MG SUSPENSION PCKT	Maintenance	Adults take 2 packets (50 mg) mixed with 20 mL cool/cold water by oral route once daily on an empty stomach, 1 hour before or 2 hours after a meal
PROMACTA 12.5 MG SUSPEN PACKET	Maintenance	Adults take 1 packet (12.5 mg) mixed with 20 mL cool/cold water by oral route once daily on an empty stomach, 1 hour before or 2 hours after a meal

No generic dosing information available.

The following drug interaction information is available for PROMACTA (eltrombopag olamine):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 5 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
Eluxadoline/OATP1B1 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: OATP1B1 inhibitors may decrease the hepatic uptake of eluxadoline.(1) CLINICAL EFFECTS: Concurrent use of OATP1B1 inhibitors may result in elevated levels of and side effects from eluxadoline, including constipation, nausea, abdominal pain, and impaired mental and physical abilities.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent OATP1B1 inhibitors should receive a dose of eluxadoline of 75 mg twice daily. Monitor patients for impaired mental or physical abilities, abdominal pain, nausea, and constipation.(1) DISCUSSION: Concurrent administration of a single dose (600 mg) of cyclosporine, an OATP1B1 inhibitor, increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of eluxadoline (100 mg) by 4.4-fold and 6.2-fold, respectively.(1) OATP1B1 inhibitors include asciminib, atazanavir, belumosudil, boceprevir, cyclosporine, darunavir, encorafenib, eltrombopag, erythromycin, gemfibrozil, leflunomide, letermovir, lopinavir, paritaprevir, resmetirom, rifampin, ritonavir, roxadustat, saquinavir, simeprevir, telaprevir, teriflunomide, tipranavir, vadadustat, and voclosporin.(1,2)	VIBERZI
Pazopanib/Selected Inhibitors of P-gp or BCRP SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of pazopanib.(1) CLINICAL EFFECTS: The concurrent administration of pazopanib with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of pazopanib and signs of toxicity.(1) PREDISPOSING FACTORS: The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The US manufacturer of pazopanib states concurrent use of P-gp inhibitors or BCRP inhibitors should be avoided.(1) Monitor patients for increased side effects from pazopanib. If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: Pazopanib is a substrate of P-gp and BCRP. Inhibitors of these transporters are expected to increase pazopanib levels.(1) BCRP inhibitors linked to this monograph include: asciminib, belumosudil, clopidogrel, cyclosporine, darolutamide, eltrombopag, gefitinib, grazoprevir, lazertinib, leflunomide, momelotinib, oteseconazole, rolapitant, roxadustat, tafamidis, teriflunomide, and vadadustat.(1,3-5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, capmatinib, carvedilol, cyclosporine, danicopan, daridorexant, diltiazem, flibanserin, fostamatinib, ginseng, glecaprevir/pibrentasvir, isavuconazonium, ivacaftor, ledipasvir, neratinib, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, tezacaftor, ticagrelor, valbenazine, verapamil, vimseltinib, and voclosporin.(3,4)	PAZOPANIB HCL, VOTRIENT
Cladribine/Selected Inhibitors of BCRP SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of BCRP may increase the absorption of cladribine.(1-2) CLINICAL EFFECTS: The concurrent administration of cladribine with an inhibitor of BCRP may result in elevated levels of cladribine and signs of toxicity.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of cladribine states concurrent use of BCRP inhibitors should be avoided during the 4- to 5-day cladribine treatment.(1-2) Selection of an alternative concurrent medication with no or minimal transporter inhibiting proprieties should be considered. If this is not possible, dose reduction to the minimum mandatory dose of the BCRP inhibitor, separation in timing of administration, and careful patient monitoring is recommended.(1-2) Monitor for signs of hematologic toxicity. Lymphocyte counts should be monitored. DISCUSSION: Cladribine is a substrate of BCRP. Inhibitors of this transporter are expected to increase cladribine levels.(1-2) BCRP inhibitors linked to this monograph include: capmatinib, clopidogrel, cobicistat, curcumin, danicopan, darolutamide, eltrombopag, elvitegravir, grazoprevir, lazertinib, oteseconazole, pacritinib, ritonavir, roxadustat, tafamidis, ticagrelor, turmeric, and vadadustat.(1-4)	CLADRIBINE, MAVENCLAD
Brincidofovir/OATP1B1-3 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: OATP1B1 and 1B3 inhibitors may increase the absorption and/or decrease the hepatic uptake of brincidofovir.(1) CLINICAL EFFECTS: Concurrent use of OATP1B1 or 1B3 inhibitors may result in elevated levels of and side effects from brincidofovir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of brincidofovir states that alternative medications that are not OATP1B1 or 1B3 inhibitors should be considered. If concurrent use is necessary, instruct the patient to take the OATP1B1 or 1B3 inhibitor at least 3 hours after brincidofovir and increase monitoring for side effects, including transaminase and bilirubin elevations and GI side effects like diarrhea.(1) DISCUSSION: In a clinical trial, single-dose oral cyclosporine (600 mg, an OATP1B1 and 1B3 inhibitor) increased the mean brincidofovir area-under-curve (AUC) and maximum concentration (Cmax) by 374% and 269%, respectively.(1) OATP1B1 and 1B3 inhibitors include asciminib, atazanavir, belumosudil, boceprevir, clarithromycin, cyclosporine, darunavir, eltrombopag, encorafenib, erythromycin, gemfibrozil, glecaprevir-pibrentasvir, ledipasvir, leflunomide, letermovir, lopinavir, ombitasvir-paritaprevir, paritaprevir, resmetirom, rifampin, ritonavir, roxadustat, saquinavir, simeprevir, sofosbuvir, telaprevir, teriflunomide, tipranavir, vadadustat, velpatasvir, and voclosporin.(1,2)	TEMBEXA
Atrasentan/OATP1B1-3 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: OATP1B1 and 1B3 inhibitors may increase the absorption and/or decrease the hepatic uptake of atrasentan.(1) CLINICAL EFFECTS: Concurrent use of OATP1B1 or 1B3 inhibitors may result in elevated levels of and side effects from atrasentan, including fluid retention and hepatotoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of atrasentan states that concurrent use of OATP1B1 or 1B3 inhibitors should be avoided.(1) DISCUSSION: In a clinical study, atrasentan maximum concentration (Cmax) was 4.3 times higher and area-under-curve (AUC) was 3.8 times higher following coadministration of a single dose of 0.75 mg atrasentan with cyclosporine (OATP1B1 and 1B3 inhibitor) compared to atrasentan alone. OATP1B1 and 1B3 inhibitors include asciminib, atazanavir, belumosudil, boceprevir, clarithromycin, cobicistat, cyclosporine, eltrombopag, erythromycin, fostemsavir, gemfibrozil, glecaprevir-pibrentasvir, leflunomide, letermovir, lopinavir, nirmatrelvir, ombitasvir-paritaprevir, resmetirom, ritonavir, roxadustat, saquinavir, simeprevir, telaprevir, teriflunomide, tipranavir, vadadustat, velpatasvir, voclosporin, and voxilaprevir.(1,2)	VANRAFIA

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
Eltrombopag/Polyvalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Eltrombopag chelates polyvalent cations such as aluminum, calcium, iron, magnesium, selenium, and zinc.(1) CLINICAL EFFECTS: Simultaneous administration of eltrombopag and polyvalent cations may decrease the absorption and clinical effects of eltrombopag. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of eltrombopag states that it should be administered at least 2 hours before or 4 hours after any medications or products containing polyvalent cations such as antacids or mineral supplements.(1) DISCUSSION: In a crossover study in 25 healthy subjects, administration of eltrombopag with an antacid (1524 mg aluminum hydroxide/1425 mg magnesium carbonate/sodium alginate) decreased eltrombopag levels by 70%.(1,2)	ACCRUFER, ALUMINUM HYDROXIDE, ATTAPULGITE, AUROVELA 24 FE, AUROVELA FE, AURYXIA, AVIDOXY DK, BALCOLTRA, BISMUTH CITRATE, BISMUTH SUBSALICYLATE, BLISOVI 24 FE, BLISOVI FE, CALCIUM ACETATE, CALCIUM CHLORIDE, CALCIUM GLUCONATE, CALCIUM GLUCONATE MONOHYDRATE, CARAFATE, CHARLOTTE 24 FE, CLENPIQ, FEIRZA, FERRIC CITRATE, FINZALA, FOSRENOL, GALZIN, GEMMILY, HAILEY 24 FE, HAILEY FE, JOYEAUX, JUNEL FE, JUNEL FE 24, KAITLIB FE, KAOLIN, LANTHANUM CARBONATE, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEVONORG-ETH ESTRAD-FE BISGLYC, LO LOESTRIN FE, LOESTRIN FE, MAGNESIUM CHLORIDE, MAGNESIUM CITRATE, MAGNESIUM OXIDE, MAGNESIUM SULFATE, MERZEE, MIBELAS 24 FE, MICROGESTIN FE, MINZOYA, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRONE-E.ESTRADIOL-IRON, SOD SULF-POTASS SULF-MAG SULF, SUCRALFATE, SUFLAVE, SUPREP, SUTAB, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-LEGEST FE, VELPHORO, WILZIN, WYMZYA FE, XARAH FE, XELRIA FE, ZINC ACETATE, ZINC CHLORIDE, ZINC OXIDE, ZINC SULFATE, ZINC UNDECYLENATE
Eltrombopag/Rosuvastatin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Eltrombopag has been shown to inhibit OATP1B1. Rosuvastatin is a substrate of this transporter.(1,2) CLINICAL EFFECTS: Simultaneous use of eltrombopag may result in increased levels and side effects from rosuvastatin, including rhabdomyolysis.(1,2) PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. Patients on rosuvastatin with ABCG2 polymorphisms leading to decreased or poor BCRP transporter function may have increased rosuvastatin concentrations and risk of myopathy. PATIENT MANAGEMENT: In clinical trials, a 50% rosuvastatin dosage reduction was recommended during concurrent eltrombopag.(1) DISCUSSION: In a clinical trial in 39 healthy subjects, administration of eltrombopag (75 mg daily) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of rosuvastatin (10 mg) by 55% and 103%, respectively.(1-3)	CRESTOR, EZALLOR SPRINKLE, ROSUVASTATIN CALCIUM, ROSUVASTATIN-EZETIMIBE, ROSZET
Ubrogepant/P-gp or BCRP Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of ubrogepant.(1) CLINICAL EFFECTS: The concurrent administration of ubrogepant with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of ubrogepant.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with P-gp or BCRP inhibitors. The dose of ubrogepant should not exceed 50 mg for initial dose. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(1) The manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to ubrogepant.(3) DISCUSSION: Ubrogepant is a substrate of P-gp and BCRP transporters. Use of P-gp or BCRP inhibitors may increase the exposure of ubrogepant. Clinical drug interaction studies with inhibitors of these transporters were not conducted. The US manufacturer of ubrogepant recommends dose adjustment if ubrogepant is coadministered with P-gp or BCRP inhibitors.(1) BCRP inhibitors linked to this monograph include: belumosudil, clopidogrel, curcumin, eltrombopag, gefitinib, grazoprevir, momelotinib, oteseconazole, rolapitant, roxadustat, safinamide, tafamidis, oral tedizolid, and vadadustat.(2-5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, carvedilol, danicopan, daridorexant, neratinib, osimertinib, propafenone, quinidine, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, tezacaftor, valbenazine, vimseltinib, and voclosporin.(2-5)	UBRELVY
BCRP or OATP1B1 Substrates/Eltrombopag SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Eltrombopag has been shown to inhibit BCRP and OATP1B1.(1-3) Inhibition of BCRP may increase absorption and/or decrease biliary excretion of substrates, while inhibition of OATP1B1 may decrease hepatic uptake of substrates. CLINICAL EFFECTS: Simultaneous use of eltrombopag with BCRP or OATP1B1 substrates may result in increased levels and side effects from the substrates.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of eltrombopag states that concomitant BCRP or OATP1B1 substrates should be used cautiously. Patients on concurrent therapy should be closely monitored for adverse effects, and dose reduction of the substrate should be considered.(1) DISCUSSION: In a clinical trial in 39 healthy subjects, administration of eltrombopag (75 mg daily) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of rosuvastatin (10 mg, a BCRP and OATP1B1 substrate) by 55% and 103%, respectively.(1,4) In a physiologically-based pharmacokinetic (PBPK) model, eltrombopag 75 mg was predicted to increase the AUC and Cmax of pitavastatin 1 mg by approximately 2-fold.(5) BCRP substrates linked to this monograph include: ciprofloxacin, imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, and topotecan.(1) OATP1B1 substrates linked to this monograph include: atorvastatin, bosentan, fluvastatin, glyburide, irinotecan, letermovir, pitavastatin, pravastatin, repaglinide, and simvastatin.(1)	AMLODIPINE-ATORVASTATIN, ATORVALIQ, ATORVASTATIN CALCIUM, BOSENTAN, CADUET, CAMPTOSAR, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, CIPROFLOXACIN-D5W, EZETIMIBE-SIMVASTATIN, FLOLIPID, FLUVASTATIN ER, FLUVASTATIN SODIUM, GLEEVEC, GLYBURIDE, GLYBURIDE MICRONIZED, GLYBURIDE-METFORMIN HCL, HYCAMTIN, IMATINIB MESYLATE, IMKELDI, IRINOTECAN HCL, JYLAMVO, LAPATINIB, LESCOL XL, LIPITOR, LIVALO, METHOTREXATE, METHOTREXATE SODIUM, MITOXANTRONE HCL, ONIVYDE, OTREXUP, PITAVASTATIN CALCIUM, PRAVASTATIN SODIUM, PREVYMIS, RASUVO, REPAGLINIDE, SIMVASTATIN, TOPOTECAN HCL, TRACLEER, TREXALL, TYKERB, VYTORIN, XATMEP, ZOCOR, ZYPITAMAG
Atogepant/OATP1B1-3 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Atogepant is a substrate of OATP1B1 and 1B3. Inhibitors of these transporters may increase the GI absorption and/or decrease the hepatic uptake of atogepant.(1) CLINICAL EFFECTS: Concurrent use of OATP1B1 or 1B3 inhibitors may result in elevated levels of and side effects from atogepant, including nausea, constipation and fatigue.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of atogepant states that, when used concurrently with an OATP inhibitor for prevention of episodic migraine, the atogepant dose should be limited to 10 mg or 30 mg once daily. When used concurrently with an OATP inhibitor for prevention of chronic migraines, the atogepant dose should be limited to 30 mg once daily.(1) DISCUSSION: In a clinical trial of healthy subjects, single-dose rifampin, an OATP inhibitor, increased the atogepant area-under-curve (AUC) and maximum concentration (Cmax) by 2.85-fold and 2.23-fold, respectively.(1) OATP1B1 and 1B3 inhibitors include asciminib, atazanavir, belumosudil, cyclosporine, darunavir, eltrombopag, erythromycin, gemfibrozil, glecaprevir-pibrentasvir, ledipasvir, leflunomide, letermovir, paritaprevir, resmetirom, ritonavir, roxadustat, simeprevir, sofosbuvir, teriflunomide, vadadustat, velpatasvir, and voclosporin.(1,2)	QULIPTA
Momelotinib/OATP1B1-3 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: OATP1B1 and 1B3 inhibitors may decrease the hepatic uptake of momelotinib.(1) CLINICAL EFFECTS: Concurrent use of OATP1B1 and 1B3 inhibitors may result in elevated levels of and side effects from momelotinib, including myelosuppression and hepatotoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of momelotinib with OATP1B1 and 1B3 inhibitors should be approached with caution. Monitor patients closely for adverse reactions and consider dose modifications per momelotinib prescribing recommendations.(1) DISCUSSION: Concurrent administration of a single dose rifampin, an OATP1B1/1B3 inhibitor, increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of momelotinib by 40% and 57%, respectively. The M21 metabolite Cmax increased 6% and AUC increased 12%.(1) OATP1B1 inhibitors include asciminib, atazanavir, belumosudil, boceprevir, cobicistat, cyclosporine, darolutamide, darunavir, eltrombopag, enasidenib, encorafenib, erythromycin, fostemsavir, gemfibrozil, glecaprevir-pibrentasvir, ledipasvir, letermovir, lopinavir, nirmatrelvir, paritaprevir, resmetirom, rifampin, roxadustat, saquinavir, simeprevir, telaprevir, tipranavir, vadadustat, velpatasvir, and voclosporin.(1,2)	OJJAARA

The following contraindication information is available for PROMACTA (eltrombopag olamine):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*None.

There are 4 contraindications. Absolute contraindication.

Contraindication List
Acute hepatic failure
Drug-induced hepatitis
Lactation
Portal vein thrombosis

There are 7 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Child-pugh class A hepatic impairment
Child-pugh class B hepatic impairment
Child-pugh class C hepatic impairment
Disease of liver
Hyperbilirubinemia
Predisposition to thrombosis
Thromboembolic disorder

There are 5 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Antiphospholipid syndrome
Antithrombin III deficiency due to SERPINc1 mutation
Cataracts
Factor V leiden mutation
Kidney disease with reduction in glomerular filtration rate (GFr)

The following adverse reaction information is available for PROMACTA (eltrombopag olamine):

Overview
Severe
Less Severe

Adverse reaction overview.

Across all indications, the most common adverse reactions (>=20%) associated with eltrombopag were anemia, nausea, pyrexia, increased ALT concentrations, cough, fatigue, headache, and diarrhea.

There are 12 severe adverse reactions.

More Frequent	Less Frequent
Anemia Increased alanine transaminase Increased aspartate transaminase	Abnormal hepatic function tests Cataracts

Rare/Very Rare
Acute myeloid leukemia Acute renal failure Hepatic failure Hepatic vein thrombosis Thromboembolic disorder Thrombotic disorder Thrombotic thrombocytopenic purpura

There are 33 less severe adverse reactions.

More Frequent	Less Frequent
Alopecia Anorexia Chills Cough Diarrhea Fatigue Fever Flu-like symptoms General weakness Headache disorder Hyperbilirubinemia Insomnia Myalgia Nausea Pharyngitis Pruritus of skin Upper respiratory infection Vomiting	Acute abdominal pain Arthralgia Back pain Dizziness Influenza Muscle spasm Pain in oropharynx Paresthesia Peripheral edema Rhinorrhea Skin rash Sleep disorder Sore throat Urinary tract infection

Rare/Very Rare
Dyschromia

The following precautions are available for PROMACTA (eltrombopag olamine):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of eltrombopag have been established in pediatric patients >=1 year of age with persistent or chronic ITP and in pediatric patients >=2 years of age with immunosuppressant therapy-naive severe aplastic anemia (in combination with h-ATG and cyclosporine). Safety and efficacy of eltrombopag have not been established for the treatment of ITP in pediatric patients < 1 year of age, for the treatment thrombocytopenia associated with chronic hepatitis C in pediatric patients, and for the treatment of refractory severe aplastic anemia in pediatric patients.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Available data on use of eltrombopag in pregnant women are insufficient to assess drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. May cause fetal harm; embryolethality and reduced fetal weights reported in rats at maternally toxic dosages (6 times the human clinical exposure based on AUC). (See Females and Males of Reproductive Potential under Cautions.)

It is not known whether eltrombopag is distributed into human milk. Because of the potential for serious adverse effects in a breast-fed infant, breast-feeding is not recommended during treatment.

No substantial differences in safety and efficacy have been observed in geriatric patients >=65 years of age relative to younger adults, but increased sensitivity cannot be ruled out.

Aplastic anemia
D61	Other aplastic anemias and other bone marrow failure syndromes
D61.0	Constitutional aplastic anemia
D61.09	Other constitutional aplastic anemia
D61.1	Drug-induced aplastic anemia
D61.2	Aplastic anemia due to other external agents
D61.3	Idiopathic aplastic anemia
D61.9	Aplastic anemia, unspecified
Severe thrombocytopenia in refractory chronic ITP
D69.3	Immune thrombocytopenic purpura
Thrombocytopenia associated with chronic hepatitis C
D69.59	Other secondary thrombocytopenia