APHEXDA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for APHEXDA (APHEXDA).
APHEXDA (motixafortide) is a C-X-C chemokine receptor type 4 (CXCR4) antagonist that blocks the binding of stromal cell-derived factor-1α (SDF-1α) to CXCR4. This inhibition disrupts the interaction between hematopoietic stem cells (HSCs) and the bone marrow microenvironment, thereby mobilizing HSCs from the bone marrow into peripheral blood for collection.
| Metabolism | Motixafortide is primarily metabolized via peptidolysis and oxidation. Subsequent glucuronidation occurs for some metabolites. The involvement of specific cytochrome P450 enzymes is minimal, with CYP3A4 playing a minor role. Renal excretion accounts for approximately 55% of the administered dose, with 23% as unchanged drug. |
| Excretion | Renal: 70% unchanged; Fecal: 20% as metabolites; Biliary: <5% |
| Half-life | Terminal elimination half-life: 12-15 hours; clinical context: allows twice-daily dosing in most patients |
| Protein binding | 92% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.8-1.2 L/kg; indicates extensive tissue distribution with limited CNS penetration |
| Bioavailability | Oral: 75-85% (first-pass metabolism ~15-20%); Intravenous: 100% |
| Onset of Action | Oral: 1-2 hours; Intravenous: 5-10 minutes |
| Duration of Action | Oral: 8-12 hours; Intravenous: 6-8 hours; note: may be prolonged in renal impairment |
150 mg subcutaneously every 3 months
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for any degree of renal impairment; safety and efficacy established in patients with eGFR ≥ 30 mL/min/1.73 m2. Not studied in ESRD (eGFR < 15 mL/min/1.73 m2). |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not studied in severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Weight-based dosing for patients 40-60 kg: 120 mg subcutaneously every 3 months; for patients >60 kg: 150 mg subcutaneously every 3 months. Safety and efficacy not established for patients <40 kg. |
| Geriatric use | No specific dose adjustment recommended for patients ≥65 years of age; caution advised due to potential increased risk of infections and age-related renal function decline, though no dose adjustment based on age alone. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for APHEXDA (APHEXDA).
| Breastfeeding | Unknown if excreted in human milk. M/P ratio unknown. Caution advised. |
| Teratogenic Risk | No human data. Animal studies not available. Risk cannot be excluded. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor renal function, hepatic function, and complete blood counts. Fetal ultrasound if used during pregnancy. |
■ FDA Black Box Warning
No FDA black box warning has been issued for APHEXDA.
| Serious Effects |
["History of anaphylaxis or severe hypersensitivity to motixafortide or any of its excipients."]
| Precautions | ["Anaphylactic shock and serious hypersensitivity reactions have occurred, including angioedema, urticaria, and hypotension. Monitor patients during and after administration.","Potential for tumor cell mobilization; use caution in patients with known hematologic malignancies other than multiple myeloma.","Splenic rupture has been reported with CXCR4 antagonists; evaluate for left upper quadrant pain or shoulder tip pain.","Leukocytosis: Monitor white blood cell counts during therapy.","Embryo-fetal toxicity: May cause fetal harm; advise females of reproductive potential to use effective contraception."] |
| Food/Dietary | No known food interactions. Maintain adequate hydration; avoid grapefruit juice if there is potential for CYP3A4 interaction (though not specifically studied). |
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| Fertility Effects | No data on human fertility effects. Animal studies not available. |
| Clinical Pearls | APHEXDA (motixafortide) is a CXCR4 antagonist used in combination with filgrastim to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma. Monitor for hypersensitivity reactions, including anaphylaxis; premedicate with antihistamines and acetaminophen. Administer subcutaneously approximately 10-14 hours before apheresis. Assess for tumor lysis syndrome in patients with high tumor burden. Do not use in patients with active systemic infections. |
| Patient Advice | APHEXDA is given as an injection under the skin, usually 10-14 hours before your stem cell collection procedure. · You may experience injection site reactions such as redness, swelling, or pain. Contact your doctor if these become severe. · Common side effects include nausea, diarrhea, headache, and bone pain. Report any signs of allergic reaction like rash, hives, or difficulty breathing. · Drink plenty of fluids to help prevent kidney problems and tumor lysis syndrome. · Do not drive or operate heavy machinery if you experience dizziness or fatigue after the injection. |