lusutrombopag (Rx)

1-10%

Headache (5%)

Portal vein thrombosis (1%)

Contraindications

None

Cautions

Thrombotic or thromboembolic complications

• Thrombopoietin (TPO) receptor agonists, such as lusutrombopag, have been associated with thrombotic and thromboembolic complications (eg, portal vein thrombosis) in patients with chronic liver disease
• Consider the potential increased thrombotic risk when administering drug to patients with known risk factors for thromboembolism (eg, genetic prothrombotic conditions [factor V Leiden, prothrombin 20210A, antithrombin deficiency, or protein C or S deficiency])
• In patients with ongoing or prior thrombosis or absence of hepatopetal blood flow, use lusutrombopag if the potential benefit justifies the potential risk
• Should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts

Pregnancy

There are no available data on use in pregnant women to inform a drug-associated risk

Animal data

• In animal reproduction studies, oral administration of lusutrombopag to pregnant rats during organogenesis and the lactation period resulted in adverse developmental outcomes
• These finding were observed at exposures based on AUC that were substantially higher than the AUC observed in patients (~89 times) at the recommended clinical dose of 3 mg qDay; advise pregnant women of the potential risk to a fetus

Lactation

There is no information on the presence of lusutrombopag in human milk, the effects on the breastfed child, and the effects on milk production

Drug was present in the milk of lactating rats

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Clinical considerations

• Lactating women should interrupt breastfeeding and pump and discard breast milk during treatment and for 28 days after the last dose in order to minimize exposure to a breastfed child

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.

Mechanism of Action

Thrombopoietin (TPO) receptor agonist

Orally bioavailable, small molecule that interacts with the transmembrane domain of human TPO receptors expressed on megakaryocytes to induce the proliferation and differentiation of megakaryocytic progenitor cells from hematopoietic stem cells and megakaryocyte maturation

Absorption

Peak plasma concentration: 111 ng/mL

Peak plasma time: 6-8 hr

AUC: 2931 ng·hr/mL

Food effect

• AUC and peak plasma concentration were not affected when coadministered with a high–fat meal (~900 calories [total calories], with 500, 250, and 150 calories from fat, carbohydrate, and protein, respectively)

Distribution

Vd: 39.5 L

Protein binding: >99.9%

Metabolism

Metabolized by CYP4 enzymes, including CYP4A11

Elimination

Half-life: 27 hr

Clearance: 1.1 L/hr

Excretion: Feces (83%, 16% [unchanged]); Urine (~1%)

Oral Administration

Administer orally once a day with or without food for 7 days

Missed dose: Take the missed dose as soon as possible on the same day and return to the normal schedule the following day

Storage

Store tablets in original package at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)