Aphexda Drug Information
Generic name: MOTIXAFORTIDE
Uses of Aphexda
is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. APHEXDA, a hematopoietic stem cell mobilizer, is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.
Dosage & Administration of Aphexda
Important Dosing Information Premedicate all patients before each dose of
APHEXDA to reduce the risk of hypersensitivity and injection site reactions: Administer diphenhydramine (12.5 mg intravenously or 25 mg to 50 mg orally, or another H1-antihistamine), an H2 blocker (e.g., famotidine), and a leukotriene inhibitor (e.g., montelukast) approximately 30 to 60 minutes before injection of APHEXDA. The addition of an analgesic medication (e.g., acetaminophen) to the premedication regimen is recommended. Administer filgrastim 10 mcg/kg subcutaneously once daily for 4 days prior to the first dose of APHEXDA and on each day prior to each apheresis.
Recommended Dosage
The recommended dosage of APHEXDA is 1.25 mg/kg administered via slow (approximately 2 minutes) subcutaneous injection 10 to 14 hours prior to the initiation of the first apheresis. Dosing is based on actual body weight. A second dose of APHEXDA can be administered 10 to 14 hours before a third apheresis, if necessary.
Preparation and
Administration Use aseptic technique to prepare and administer APHEXDA: More than one vial may be needed for a full dose. Calculate the dose, the total volume of reconstituted APHEXDA solution required, and number of APHEXDA vials required based on patient’s actual body weight. Remove the APHEXDA vial(s) from the refrigerator and allow to reach room temperature at 20°C to 25°C (68°F to 77°F) for at least 30 minutes.
Reconstitute each vial with 2 mL of 0.45% Sodium Chloride Injection, USP at room temperature (20°C to 25°C (68°F to 77°F)) resulting in a concentration of 36.5 mg/mL of APHEXDA and permitting withdrawal of up to 1.7 mL (62 mg). Alternatively, you can reconstitute each vial with 1 mL of Sterile Water for Injection, USP and 1 mL of 0.9% Sodium Chloride Injection, USP. Gently swirl and invert for up to 3 minutes slowly until completely dissolved. Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted solution should appear clear and colorless.
Do not use if the reconstituted solution is discolored, is cloudy, or contains visible particulates. If needed, store the reconstituted APHEXDA solution refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 24 hours protected from light. Withdraw the required injection volume of APHEXDA from the vial(s) into an appropriately sized syringe.
Each injection volume should not exceed 2 mL. Divide doses requiring greater than 2 mL into multiple syringes to allow different injection sites. Administration Administer injection into the abdomen, the back or side of the upper arms, or the thighs. Rotate injection sites.
An injection should never be given into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid a 5 cm diameter circle around the navel. If more than one injection is needed for a single dose of APHEXDA, the injection sites should be at least 2 cm apart from previous injection locations.
Discard unused portion of the drug. Monitor patients for one hour after administration.
Side Effects of Aphexda
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of APHEXDA was evaluated in the GENESIS study based on data from 92 patients with multiple myeloma who received at least one dose of APHEXDA 1.25 mg/kg subcutaneously and filgrastim and 42 patients who received placebo and filgrastim for mobilization of hematopoietic stem cells for collection and apheresis. The premedication regimen changed during the conduct of the trial as evidence of hypersensitivity reactions was noted.
Of the 92 patients who received at least one dose of APHEXDA, 14 patients received the triple-drug premedication regimen and 78 did not receive the triple-drug premedication regimen (either received no premedication or another premedication regimen). Serious adverse reactions occurred in 5.4% of patients receiving APHEXDA in combination with filgrastim. Serious adverse reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia and hypoxia. One patient did not receive the 5th dose of filgrastim due to an elevated white blood cell count following administration of APHEXDA. The most common adverse reactions occurring in GENESIS (>20% and at least 2% higher than the filgrastim + placebo arm) were injection site reactions (pain, erythema and pruritus), pruritus, flushing, and back pain.
Table 1 summarizes the common adverse reactions in GENESIS. Table 1: Common Adverse Reactions in Patients with Multiple Myeloma During Hematopoietic Stem Cell Mobilization and Apheresis in GENESIS a APHEXDA and Filgrastim n=92 % Placebo and Filgrastim n=42 % Injection site reactions c All Grades a Grade > 3 b All Grades a Grade > 3 b Injection site reactions 73 8 5 0 Injection site pain 53 7 5 0 Injection site erythema 27 0 0 0 Injection site pruritus 24 0 0 0 Pruritus 38 11 0 0 Flushing d 33 7 0 0 Rash e 16 0 5 0 Urticaria 14 1.1 0 0 Erythema 12 0 0 0 Back pain f 21 0 17 0 Paresthesia g 19 0 17 0 Hypokalemia 15 4.3 12 0 Nausea 14 0 12 0 (a) Adverse reactions that occurred in ≥10% in APHEXDA-treated patients and ≥2% more than placebo-treated patients. (b) All reactions were grade 3. (c) Injection site reactions includes: injection site bruising, injection site discomfort, injection site erythema, injection site induration, injection site mass, injection site nodule, injection site pain, injection site pruritus, injection site rash, injection site swelling, injection site urticaria, injection site cellulitis and injection related reaction. (d) Flushing includes hot flush. (e) Rash includes: rash erythematous, rash maculo-papular, rash papular and rash pruritic. (f) Back pain includes spinal pain and sacral pain. (g) Paresthesia includes: paresthesia oral, hypoesthesia, hypoesthesia oral and burning sensation. Clinically relevant adverse reactions that occurred in the APHEXDA arm only in <10% of patients include dermatitis exfoliative generalized, ear swelling, pyrexia, chills, dizziness, tremor and hypertension.
Warnings & Cautions for Aphexda
Anaphylactic Shock and Hypersensitivity Reactions Anaphylactic shock occurred in 0.7% of
APHEXDA-treated patients in clinical studies (n=407). The time to anaphylactic shock was between 5 minutes and 30 minutes after drug administration. Hypersensitivity reactions occurred in 7.6% of APHEXDA-treated patients in the GENESIS study. In addition, pruritus, flushing, urticaria, rash, erythema, vomiting, nausea and chills have been reported.
Premedicate all patients prior to each dose of APHEXDA 30-60 minutes prior to administration with a triple-drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor. Patients receiving concomitant negative chronotropic drugs (e.g., beta blockers) may be more at risk for hypotension in case of hypersensitivity reaction. When appropriate, beta blockers should be replaced with non-chronotropic drugs.
Administer APHEXDA only in a setting where personnel and therapies are immediately available for the treatment of anaphylaxis and other systemic reactions. Monitor patients for signs or symptoms of hypersensitivity reactions for one hour following administration of APHEXDA and manage reactions promptly.
Injection Site Reactions Injection site reactions were reported in 73% of patients
receiving APHEXDA in the GENESIS trial. Symptoms of injection site reactions included pain, erythema, pruritus, bruising, discomfort, induration, mass, nodule, rash, swelling, and urticaria. Among 92 patients treated with APHEXDA, the highest severity of the reactions was severe in 9%. Premedicate with an analgesic medication (e.g., acetaminophen) prior to each APHEXDA dose.
Use analgesic medication and local treatments postdose, as needed.
Tumor Cell Mobilization in Patients with Leukemia For the purpose of hematopoietic
stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia.
Leukocytosis
Administration of APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use.
Potential for Tumor Cell Mobilization
When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
Embryo-fetal Toxicity
Based on its mechanism of action, APHEXDA can cause fetal harm when administered to a pregnant woman. Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to normal placental development. Advise pregnant women of the potential risk to the fetus.
Advise females of reproductive potential to use effective contraception during treatment with APHEXDA and for 8 days after the final dose.
Contraindications for Aphexda
is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide . History of serious hypersensitivity to APHEXDA.
Clinical Studies of Aphexda
The efficacy of APHEXDA in combination with filgrastim was evaluated in the GENESIS study (NCT 03246529). In this randomized, double-blind, placebo-controlled study, 122 patients with multiple myeloma were randomized in a 2:1 ratio to receive APHEXDA 1.25 mg/kg subcutaneously (N=80) or placebo (N=42). Prior to receiving APHEXDA or placebo, patients received daily morning doses of filgrastim 10-15 mcg/kg for 4 days. On the evening of Day 4, patients received APHEXDA or placebo. On Day 5, patients received a fifth morning dose of filgrastim within 1 hour prior to their first apheresis (12 hours ± 2 hours from the APHEXDA/placebo administration). The apheresis cell collection goal for the study was ≥ 6 × 10 6 CD34+ cells/kg.
The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions.
In the event that the cell collection goal was not achieved with the first apheresis on Day 5, patients received another morning dose of filgrastim on Day 6 within 1 hour prior to their second apheresis. In the event that the cell collection goal was still not achieved, patients received a second administration of APHEXDA or placebo on the evening of Day 6 and a seventh dose of filgrastim in the morning of Day 7 within 1 hour prior to a third apheresis. If the collection goal was not achieved, patients received an eighth dose of filgrastim in the morning of Day 8 within 1 hour prior to a fourth apheresis.
The median age of the study population was 63 years (range 34-75); 65% were males, 86% Caucasian, 8% African American, 2% Asian and 10% were of Hispanic or Latino ethnicity. Seventy percent of patients were previously treated with lenalidomide. The efficacy of APHEXDA was based upon the proportion of patients who achieved a cell collection goal of ≥ 6 × 10 6 CD34+ cells/kg in up to 2 aphereses after administration of filgrastim and a single administration of APHEXDA or placebo.
Efficacy results showed that 67.5% of patients in the APHEXDA treatment arm versus 9.5% in the placebo arm achieved the cell collection goal of ≥ 6 × 10 6 CD34+ cells/kg in up to 2 aphereses after a single administration of APHEXDA or placebo, resulting in an adjusted difference between treatment arms of 56.8% (p < 0.0001) (Table 3). Table 3: Proportion of Patients Who Achieved CD34+ Cell Collection Goal Following Single Administration of APHEXDA or Placebo (GENESIS) Cell Collection Goal APHEXDA and Filgrastim (N = 80) Placebo and Filgrastim (N = 42) p-value* Proportion of patients with ≥ 6 × 10 6 CD34+ cells/kg in up to 2 aphereses – Central laboratory 67.5% 9.5% <0.0001 Proportion of patients with ≥ 6 × 10 6 CD34+ cells/kg in 1 apheresis – Central laboratory 63.8% 2.4% <0.0001 Proportion of patients with ≥ 2 × 10 6 CD34+ cells/kg in 1 apheresis – Central laboratory 87.5% 38.1% <0.0001 *The reported p values are two sided based on the Cochran-Mantel-Haenszel common proportion difference method stratifying for response status (CR or PR) at baseline and to baseline platelet count (<200 × 10 9 /L or ≥ 200 × 10 9 /L). Multiple factors can influence time to engraftment and graft durability following stem cell transplantation. In the GENESIS study, time to neutrophil and platelet engraftment and graft durability following transplantation were similar across treatment groups.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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