1) ADVERSE EFFECTS: SERIOUS: Potentially serious events reported with therapy have included: abnormal increase in liver enzymes and bilirubin, thrombotic/thromboembolic complications, and the development of hemorrhage following the discontinuation of therapy. OTHER: Nausea, vomiting, menorrhagia, myalgia, paresthesia, cataract, dyspepsia, ecchymosis, thrombocytopenia and conjunctival hemorrhage have been observed with therapy.

1) MILD TO MODERATE POISONING: It is anticipated that toxicity is likely an extension of pharmacologic events which may include the development of thrombocytosis, hepatotoxicity, bone marrow reticulin formation and bone marrow fibrosis. Rash, bradycardia, elevated aminotransferase concentrations, and thrombocytosis have been reported after overdose. Hemorrhage may also be observed as a result of rebound thrombocytopenia following the discontinuation of therapy.
2) SEVERE POISONING: An excessive increase in platelet count may increase the risk of developing a thrombotic and/or thromboembolic events.

1) Fever may develop with therapeutic use of eltrombopag.

1) Treatment is symptomatic and supportive.

1) An excessive exposure may increase the platelet count leading to the development of thrombotic/thromboembolic events. Monitor serial CBC and platelet counts. Evidence of an acute thrombotic/thromboembolic event (e.g., sudden onset of swelling/tenderness in a limb and/or shortness of breath) requires prompt diagnostic evaluation (e.g., ultrasound, CT scan, venogram, etc) and intervention as indicated. Cytapheresis may be useful in patients who develop severe thrombocytosis. Monitor for rebound thrombocytopenia and potential bleeding following the discontinuation of eltrombopag therapy. Transfuse patient as indicated for severe thrombocytopenia, bleeding. Hepatotoxicity has been observed with therapy; monitor liver function (i.e., ALT, AST, and bilirubin) following overdose.

1) PREHOSPITAL: Consider activated charcoal in a patient who is awake and alert and able to protect their airway. Based on limited experience, oral administration of a metal cation-containing preparation (e.g., calcium, aluminum, or magnesium) may be used to chelate eltrombopag and limit absorption.
2) HOSPITAL: Consider activated charcoal, if the patient is able to maintain airway or if airway is protected. Based on limited experience, oral administration of a metal cation-containing preparation (e.g., calcium, aluminum, or magnesium) may be used to chelate eltrombopag and limit absorption.

1) Assess airway patency. Oxygen therapy may be required in patients who develop a thromboembolic event, but this is rare with therapeutic use.

1) None.

1) Rebound thrombocytopenia has been observed with the discontinuation of eltrombopag therapy. Monitor CBC and platelet counts. Blood transfusions may be indicated for severe thrombocytopenia, bleeding.

1) Hemodialysis is unlikely to be beneficial because eltrombopag is highly bound to plasma proteins.

1) HOME CRITERIA: Asymptomatic patients with a minor inadvertent ingestion can be monitored at home.
2) ADMISSION CRITERIA: Patients with deliberate ingestions that are demonstrating severe hepatotoxicity, an increased platelet count that may produce a thrombolic/thromboembolic event, or evidence of bleeding (rebound effect) should be admitted.
3) OBSERVATION CRITERIA: All patients with a deliberate ingestion should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with an unintentional ingestion who are symptomatic should be observed in a healthcare facility.
4) CONSULT CRITERIA: Call a Poison Center for assistance in managing a patient with severe toxicity or in whom the diagnosis is unclear.

1) When managing a suspected eltrombopag overdose, the possibility of multi-drug involvement should be considered.

1) Patients with a history of Factor V Leiden, ATIII deficiency, antiphospholipid syndrome may be at greater risk to develop a thromboembolism. Monitor patients with a history of hepatic insufficiency closely for hepatotoxicity following acute exposure.

1) Eltrombopag is absorbed with a peak concentration at 2 to 6 hours after oral administration and has an estimated plasma protein binding of greater than 99%. Approximately 31% of an eltrombopag dose is excreted via the kidney; primary excretion is via the feces (59%). The elimination half-life of eltrombopag is approximately 21 to 32 hours in healthy individuals and approximately 26 to 35 hours in patients with idiopathic thrombocytopenic purpura.

1) Includes other agents that may cause or potentiate the elevation of liver enzymes (e.g., alcohol, acetaminophen) or thrombocytopenia (e.g., antineoplastic agents).

1) Fever may develop with therapeutic use of eltrombopag.

1) Fever was reported in 7%, 16% and 9% of patients receiving eltrombopag 30 mg, 50 mg and 75 mg, respectively as compared to 0% in the placebo group in the 8-week antiviral treatment phase of an international, multicenter, randomized, double-blind, phase 2 trial for thrombocytopenia associated with hepatitis C virus-related cirrhosis. This phase consisted of concomitant use of eltrombopag or placebo with peginterferon alfa plus ribavirin (McHutchison et al, 2007).

1) Cataracts were observed in 3% of patients with chronic ITP receiving eltrombopag 50 mg/day (n=106) as compared with 1% in the placebo group (n=67) in two randomized, placebo-controlled trials with a maximum treatment duration of 6 weeks (Prod Info PROMACTA(R) oral tablets, 2008).
2) Conjunctival hemorrhage was reported in 2% of patients with chronic ITP received eltrombopag (n=106) as compared with 1% in the placebo group (n=67) in two randomized, placebo-controlled trials with a maximum treatment duration of 6 weeks (Prod Info PROMACTA(R) oral tablets, 2008).

1) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) In an embryofetal development study of pregnant rabbits, there was no evidence of teratogenicity when administered eltrombopag orally at doses of 30, 80 and 150 mg/kg/day (0.1, 0.3, and 0.6 times the human exposure, respectively) (Prod Info PROMACTA(R) oral tablets, 2012).

1) Eltrombopag has been classified as FDA pregnancy category C (Prod Info PROMACTA(R) oral tablets, 2012).

1) There are no adequate and well-controlled studies of eltrombopag use in pregnancy. Embryolethality and reduced fetal weight were observed at maternally toxic doses in animal reproductive studies. The manufacturer maintains a pregnancy registry to collect information about the effects of eltrombopag use during pregnancy. Health care providers are encouraged to register pregnant patients by calling the registry at 1-888-825-5249 (Prod Info PROMACTA(R) oral tablets, 2012).

1) RATS: During an early embryonic development study, administration of oral eltrombopag 10 , 20, or 60 mg/kg/day resulted in increased pre- and postimplantation loss and reduced fetal weight at the highest dose. Maternal toxicity was also observed at the highest dose (Prod Info PROMACTA(R) oral tablets, 2012).
2) RATS: In an embryofetal development study of pregnant rats administered doses of 10, 20 and 60 mg/kg/day (up to 0.8, 2 and 7 times the human exposure, respectively), there was a decrease in fetal weights and a slight increase in the presence of cervical ribs, as well as maternal toxicity at the highest dose. However, there was no evidence of major structural malformations. No adverse effects were noted at doses of 10 and 20 mg/kg/day (up to 0.8 and 2 times the human exposure) (Prod Info PROMACTA(R) oral tablets, 2012).
3) RATS: In a toxicity study in pregnant rats prenatally and postnatally, there was no evidence of adverse effects on maternal reproduction or offspring development at doses up to 2 times the human clinical exposure. Eltrombopag was detected in the plasma of offspring and increased with maternal doses that were up to 0.8 and 2 times the human exposure (Prod Info PROMACTA(R) oral tablets, 2012).
4) RABBITS: In an embryofetal development study of pregnant rabbits, there was no evidence of fetotoxicity or embryolethality, when administered eltrombopag orally at doses of 30, 80, or 150 mg/kg/day (up to 0.1, 0.3, and 0.6 times the human exposure, respectively) (Prod Info PROMACTA(R) oral tablets, 2012).

1) It is not known whether eltrombopag is excreted into human breast milk, and the potential for adverse effects in the nursing infant from exposure to the drug are unknown (Prod Info PROMACTA(R) oral tablets, 2012).

1) Eltrombopag did not affect male or female fertility in rats given doses up to 40 mg/kg/day (5 times the human clinical exposure based on AUC) or 20 mg/kg/day (2 times the human clinical exposure based on AUC), respectively (Prod Info PROMACTA(R) oral tablets, 2008).

A) Patients with deliberate ingestions that are demonstrating severe hepatotoxicity, an increased platelet count that may produce a thrombolic/thromboembolic event or evidence of bleeding (rebound effect) should be admitted.

A) Asymptomatic patients with a minor inadvertent ingestion can be monitored at home.

A) Call a Poison Center for assistance in managing a patient with severe toxicity or in whom the diagnosis is unclear.

A) All patients with a deliberate ingestion should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with an unintentional ingestion who are symptomatic should be observed in a healthcare facility.

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

1) Based on limited experience, oral administration of a metal cation-containing preparation (e.g., calcium, aluminum, or magnesium) may be used to chelate eltrombopag and limit absorption.

1) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

1) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
2) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Treatment is symptomatic and supportive. There is no known antidote.

1) Obtain serial CBC with differential and platelet counts. Monitor vital signs and liver enzyme ; repeat as indicated. Monitor electrolytes concentrations after significant overdose, monitor electrolytes and fluid status in patients with significant vomiting.

1) Monitor liver enzymes (i.e., ALT, AST, and bilirubin) following exposure. Hepatotoxicity has been reported with therapeutic use.

1) Obtain serial platelet counts until platelet count has clearly peaked and begun to decline. Monitor for thrombotic/thromboembolic events.

1) Rebound thrombocytopenia has been observed with the discontinuation of eltrombopag therapy. Monitor CBC and platelet counts. Blood transfusions may be indicated for severe thrombocytopenia, bleeding.

1) Initial dose, 50 mg orally once daily, and increasing the daily dose by 25 mg to achieve and maintain a platelet count of 50 x 10(9)/L or greater, with a MAX dose of 75 mg/day (Prod Info PROMACTA(R) oral tablets, suspension, 2015).

1) Initial dose of 25 mg orally once daily, and adjusting by 25 mg increments every 2 weeks to achieve a target platelet count of 50 x 10(9)/L or greater, up to a MAX dose of 100 mg/day (Prod Info PROMACTA(R) oral tablets, suspension, 2015).

1) Initial dose of 50 mg orally once daily, and adjust by 50 mg increment every 2 weeks to achieve a target platelet count of 50 x 10(9)/L or greater, up to a MAX dose of 150 mg/day (Prod Info PROMACTA(R) oral tablets, suspension, 2015).

1) PATIENTS 1 TO 5 YEARS OLD: Initial dose, 25 mg orally once daily and increasing the daily dose by 25 mg to achieve and maintain a platelet count of 50 x 10(9)/L or greater, with a MAX dose of 75 mg/day (Prod Info PROMACTA(R) oral tablets, suspension, 2015).
2) PATIENTS 6 YEARS AND OLDER: Initial dose, 50 mg orally once daily, and increasing the daily dose by 25 mg to achieve and maintain a platelet count of 50 x 10(9)/L or greater, with a MAX dose of 75 mg/day (Prod Info PROMACTA(R) oral tablets, suspension, 2015).