Dosing and uses of Promacta (eltrombopag)
Adult dosage forms and strengths
tablet
- 12.5mg
- 25mg
- 50mg
- 75mg
- 100mg
Chronic Immune Thrombocytopenia (ITP)
Indicated for treatment of thrombocytopenia in adults and pediatric patients ≥6 yr with chronic immune (idiopathic) thrombocytopenia (ITP) with insufficient response to corticosteroids, immunoglobulins, or splenectomy
Initial: 50 mg PO qDay
Maintenance: Adjust dose to achieve and maintain platelet count (Plt) >50 x 10^9/L to reduce risk of bleeding; not to exceed 75 mg/day
Dosing considerations
- Should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding
- Use the lowest dose to achieve and maintain a platelet count >50 x 10^9/L as necessary to reduce the risk for bleeding
- Dose adjustment based upon the platelet count response; do not use to normalize platelet counts
- Monitor LFTs and CBC prior to initiation, and throughout therapy
Dosage modifications (ITP)
East Asian ancestry: Decrease initial dose to 25 mg PO qDay
Hepatic impairment
- Mild-to-severe (Child-Pugh A, B, or C): Decrease initial dose to 25 mg PO qDay
- East Asian ancestry with hepatic impairment: Decrease initial dose to 12.5 mg PO qDay
Adjust dose according to platelets
- Plt <50 x 10^9/L; after at least 2 weeks: Increase daily dose by 25 mg; not to exceed 75 mg/day
- Plt 200-400 x 10^9/L: Decrease daily dose by 25 mg; assess after 2 weeks
- Plt >400 x 10^9/L: Discontinue and monitor platelet 2x/week; once platelet <150 x 10^9/L; restart therapy with 25 mg reduction in daily dose
- Plt >400 x 10^9/L; after 2 weeks of therapy at lowest dose: Discontinue permanently
Discontinue if
- No improvement after 4 weeks at maximum dose, OR
- Abnormal LFTs or excessive Plt responses
Chronic Hepatitis C-Associated Thrombocytopenia
Indicated for treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy
Initial: 25 mg PO qDay
Adjust dose in 25 mg increments q2weeks PRN to achieve the target platelet count required to initiate antiviral therapy; not to exceed 100 mg/day
During antiviral therapy, adjust dose to avoid dose reductions of peginterferon
Dosage considerations
- Should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy
- Prior to starting antiviral therapy: Monitor platelet counts qWeek
- During antiviral therapy: Monitor CBCs with differentials (including platelet counts) qWeek until a stable platelet count achieved, then monitor platelet counts monthly thereafter
- Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection
Dosage modifications (CHC)
Hepatic impairment: No dosage adjustment required
Adjust dose according to platelets
- Plt <50 x 10^9/L after at least 2 weeks: Increase daily dose by 25 mg; not to exceed 100 mg/day
- Plt 200-400 x 10^9/L: Decrease daily dose by 25 mg; assess after 2 weeks
- Plt >400 x 10^9/L: Discontinue and monitor Plt 2x/week; once Plt <150 x 10^9/L, restart therapy with 25 mg reduction in daily dose
- Plt >400 x 10^9/L after 2 weeks of therapy at lowest dose: Discontinue permanently
Discontinue if
- Antiviral therapy is discontinued
- Abnormal LFTs or excessive Plt responses
Aplastic Anemia
Indicated for severe aplastic anemia (SAA) in patients who fail to respond adequately to at least 1 prior immunosuppressive therapy
Initial dose: 50 mg PO qDay
Adjust dose q2wk as needed to maintain platelet count ≥50 x 10^9/L; not to exceed 150 mg qDay
May take for up to 16 wk after initiating
Dosage modifications (SAA)
East Asian ancestry: Decrease initial dose to 25 mg/day
Hepatic impairment (Child-Pugh Class A, B, or C): Decrease initial dose to 25 mg/day
Adjust dose according to platelets
- <50 x 10^9/L following at least 2 wk after initiating: Increase by 50 mg/day to a maximum of 150 mg/day; if taking 25 mg/day, increase dose to 50 mg daily before increasing by 50 mg/day
- ≥200 x 10^9/L to ≤400 x 10^9/L at any time: Decrease by 50 mg/day, wait 2 wk to assess effects and the need for any subsequent dose adjustments
- >400 x 10^9/L: Stop for 1 wk, when platelet count <150 x 10^9/L, reinitiate at dose reduced by 50 mg/day
- >400 x 10^9/L after 2 wk of therapy at lowest dose: Discontinue
Tri-lineage response (including transfusion independence ≥8 wk)
- Reduce dose by 50%
- If counts remain stable after 8 weeks at the reduced dose, then discontinue eltrombopag and monitor blood counts
- If platelet counts drop to <30 x 10^9/L, hemoglobin <9 g/dL, or ANC <0.5 x 10^9/L: May reinitiated at the previous effective dose
Discontinue if
- No hematologic response after 16 wk
- New cytogenetic abnormalities observed, consider discontinuation
- Excessive platelet count responses (see Dosage modifications above) or important liver test abnormalities occur
Pediatric dosage forms and strengths
tablet
- 12.5mg
- 25mg
- 50mg
- 75mg
- 100mg
powder for oral suspension
- 25mg/unit dose (30-day supply kit)
Chronic Immune Thrombocytopenia (ITP)
Indicated for treatment of thrombocytopenia in adults and pediatric patients ≥1 yr with chronic immune (idiopathic) thrombocytopenia (ITP) with insufficient response to corticosteroids, immunoglobulins, or splenectomy
<1 year: Safety and efficacy not established
1-5 years (initial dose): 25 mg PO qDay (use oral suspension)
≥6 years (initial dose): 50 mg PO qDay
Maintenance: Adjust dose to achieve and maintain platelet count (Plt) >50 x 10^9/L to reduce risk of bleeding; not to exceed 75 mg/day
Dosing considerations
- Should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding
- Use the lowest dose to achieve and maintain a platelet count >50 x 10^9/L as necessary to reduce the risk for bleeding
- Dose adjustment based upon the platelet count response; do not use to normalize platelet counts
- Monitor LFTs and CBC prior to initiation, and throughout therapy
- When switching between the oral suspension and tablet, assess platelet counts weekly for 2 weeks, and then follow standard monthly monitoring
Dosage modifications (ITP)
East Asian ancestry: Decrease initial dose to 25 mg PO qDay
Hepatic impairment
- Mild-to-severe (Child-Pugh A, B, or C): Decrease initial dose to 25 mg PO qDay
- East Asian ancestry with hepatic impairment: Decrease initial dose to 12.5 mg PO qDay
Adjust dose according to platelets
- Plt <50 x 10^9/L; after at least 2 weeks: Increase daily dose by 25 mg; not to exceed 75 mg/day
- Plt 200-400 x 10^9/L: Decrease daily dose by 25 mg; assess after 2 weeks
- Plt >400 x 10^9/L: Discontinue and monitor platelet 2x/week; once platelet <150 x 10^9/L; restart therapy with 25 mg reduction in daily dose
- Plt >400 x 10^9/L; after 2 weeks of therapy at lowest dose: Discontinue permanently
Discontinue if
- No improvement after 4 weeks at maximum dose, OR
- Abnormal LFTs or excessive Plt responses
Promacta (eltrombopag) adverse (side) effects
>10%
Influenza-like symptoms (26-35%)
Headache (10-36%)
Rigor (6-32%)
Fatigue (3-29%)
Nausea (4-21%)
Arthralgia (3-21%)
Myalgia (3-21%)
Depression (5-17%)
Upper abdominal pain (11-14%)
Xerostomia (9-14%)
1-10%
Abnormal LFT's (10%)
Thrombocytopenia (2%)
Frequency not defined
Paresthesias
Vomiting
Dyspepsia
Thrombotic or thromboembolic complications
Hemorrhage
Conjunctival hemorrhage
Ecchymosis
Menorrhagia
Cataract
Postmarketing Reports
Thrombotic microangiopathy with acute renal failure
Warnings
Black box warnings
May cause hepatotoxicity; in combination with interferon and ribavirin in patients with chronic hepatitis C, may increase the risk of hepatic decompensation
Measure ALT, AST, and bilirubin level prior to initiation, q2 weeks during the dose adjustment phase, and monthly following establishment of a stable dose
If bilirubin level is elevated, perform fractionation
If serum liver test results are abnormal, repeat tests within 3-5 days; if the abnormalities are confirmed, obtain serum liver tests weekly until the abnormalities resolve, stabilize, or return to baseline
Discontinue if ALT levels increase to ≥3xULN in patients with normal liver function or ≥3x baseline in patients with pretreatment elevation in transaminases and are progressive, persistent for >4 wk, accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation
Contraindications
None reported
Cautions
Risk of hepatotoxicity (see Black box warnings); monitor liver function before and during therapy
Chronic hepatitis C with cirrhosis may increase risk of hepatic decompensation and death when treated with alfa interferons
Thrombotic/thromboembolic complications reported (rare)
Portal vein thrombosis reported in patients with chronic liver disease receiving therapy
Monitor platelet counts regularly
Risk of thrombocytopenia and hemorrhage after discontinuation
May develop or worsen cataracts; screen before administering and during treatment
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Promacta (eltrombopag)
Mechanism of action
Small-molecule thrombopoietin (TPO)-receptor agonist that interacts with human TPO receptor transmembrane domain of human TPO-receptor & initiates signaling cascades that induce proliferation & differentiation of megakaryocytes from bone marrow progenitor cells
Absorption
Bioavailability: 52%+
Peak Plasma Time: 2-6 hr
Peak plasma concentration: 8.-1-12.7 mcg/mL
AUC: 108-168 mcg·hr/mL
Distribution
Concentration in blood cells is ~50-79% of plasma concentrations
Metabolism
Extensively metabolized predominantly through pathways including cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine
In vitro studies suggest that CYP1A2 and CYP2C8 are responsible for the oxidative metabolism
UGT1A1 and UGT1A3 are responsible for the glucuronidation
Elimination
Half-life: 26-35 hr (in patients with ITP)
Excretion: Feces 59%; urine 31%
Administration
Instructions
Take on empty stomach 1 hr before or 2 hr after food
Allow 4-hr interval when taking foods/medication, calcium-rich foods, or supplements containing polyvalent cations (eg, calcium, iron, zinc, magnesium)
Do NOT administer more than 1 dose within a 24-hr period
Oral Suspension Preparation
Prior to use of the oral suspension, ensure patients or caregivers receive training on proper dosing, preparation, and administration of oral suspension
Prepare the suspension with cool or cold water only
NOTE: Do not use hot water to prepare the suspension
Measure 20 mL of drinking water in reusable oral syringe, empty water into mixing bottle provided in 30-day supply kit
Take only the prescribed number of packets for one dose out of the kit
Tap the top of each packet to make sure the contents fall to the bottom, and then cut off the top of the packet with scissors and empty the entire contents of the packet into the mixing bottle
Make sure not to spill the powder outside the mixing bottle
Screw the lid tightly onto the bottle and the cap is pushed onto the lid
Gently and slowly shake the bottle back and forth for a least 20 seconds to mix thoroughly without foaming (ie, do not shake the bottle hard)
The liquid will be dark brown in color
Pull cap off the mixing bottle lid and insert the syringe tip into the hole in the lid
Transfer the mixture into the oral syringe by turning the mixing bottle upside down along with the syringe
Measure prescribed dose into syringe (see full instructions within the Prescribing Information)
Oral Suspension Administration
Place the tip of the oral syringe into the inside of the child’s cheek
Slowly push the plunger all the way down to give the entire dose
Make sure the child has time to swallow the medicine
Storage
Powder for oral suspension or tablets: Store at room temperature between 68-77°F (20-25°C)
Reconstituted oral suspension
- After mixing, should be taken right away but may be stored for up to 30 minutes at room temperature between 68-77°F (20-25°C)
- Discard the mixture in trash if not used within 30 minutes; do not throw down the drain
