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Fam-trastuzumab deruxtecan: Drug information

Fam-trastuzumab deruxtecan: Drug information
(For additional information see "Fam-trastuzumab deruxtecan: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Interstitial lung disease:

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with fam-trastuzumab deruxtecan. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue fam-trastuzumab deruxtecan in all patients with ≥ grade 2 ILD/pneumonitis. Advise patients of the risk and the need to immediately report symptoms.

Embryo-fetal toxicity:

Exposure to fam-trastuzumab deruxtecan during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Brand Names: US
  • Enhertu
Brand Names: Canada
  • Enhertu
Pharmacologic Category
  • Antineoplastic Agent, Anti-HER2;
  • Antineoplastic Agent, Antibody Drug Conjugate;
  • Antineoplastic Agent, Monoclonal Antibody;
  • Antineoplastic Agent, Topoisomerase I Inhibitor
Dosing: Adult

Note: Do not substitute fam-trastuzumab deruxtecan for or with ado-trastuzumab emtansine, conventional trastuzumab (or trastuzumab biosimilars), pertuzumab/trastuzumab/hyaluronidase, or trastuzumab/hyaluronidase; products are different and are NOT interchangeable. Fam-trastuzumab deruxtecan is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]); delayed nausea and/or vomiting may occur.

Breast cancer, unresectable or metastatic, HER2-positive

Breast cancer, unresectable or metastatic, HER2-positive: IV: 5.4 mg/kg once every 3 weeks until disease progression or unacceptable toxicity (Modi 2020).

Colorectal cancer, metastatic, HER2-expressing

Colorectal cancer, metastatic, HER2-expressing (off-label use): IV: 6.4 mg/kg once every 3 weeks until disease progression or unacceptable toxicity (Siena 2021). Refer to protocol for dosage adjustment details.

Gastric cancer, locally advanced or metastatic, HER2-positive

Gastric cancer, locally advanced or metastatic, HER2-positive: IV: 6.4 mg/kg once every 3 weeks until disease progression or unacceptable toxicity (Shitara 2020). Select patients for therapy based on HER2 protein overexpression or HER2 gene amplification. If feasible to obtain a new tumor specimen, reassess HER2 status in between the prior trastuzumab therapy and fam-trastuzumab deruxtecan.

Non-small cell lung cancer, metastatic, relapsed/refractory, nonsquamous, HER2-mutant

Non-small cell lung cancer, metastatic, relapsed/refractory, nonsquamous, HER2-mutant (off-label use): IV: 6.4 mg/kg once every 3 weeks until disease progression or unacceptable toxicity (Li 2022). Refer to protocol for dosage adjustment details.

Missed dose: If a planned dose is delayed or missed, administer the dose as soon as possible (do not wait until the next planned cycle) and then adjust the administration schedule to maintain a 3-week interval between doses. Infuse the missed/delayed dose at the dose and rate the patient tolerated in the most recent infusion.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: No dosage adjustment necessary. Monitor for interstitial lung disease in patients with moderate impairment.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Monitor for interstitial lung disease in patients with severe impairment.

Dosing: Hepatic Impairment: Adult

Mild (total bilirubin ≤ ULN and any AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: No dosage adjustment necessary. Monitor closely for toxicities in patients with moderate impairment.

Severe impairment (total bilirubin >3 to 10 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Adverse reaction management may require treatment interruption, dosage reduction, and/or discontinuation. Do not re-escalate the fam-trastuzumab deruxtecan dose after a dosage reduction is made.

Recommended Fam-Trastuzumab Deruxtecan Dosage Reduction Levels

Dose reduction schedule

Breast cancer

Gastric cancer

Initial (usual) dose

5.4 mg/kg

6.4 mg/kg

First dose reduction level

4.4 mg/kg

5.4 mg/kg

Second dose reduction level

3.2 mg/kg

4.4 mg/kg

Further dosage adjustment required

Discontinue treatment

Discontinue treatment

Fam-Trastuzumab Deruxtecan Dosage Adjustment for Toxicities

Toxicity

Severity

Fam-Trastuzumab Deruxtecan Dose Modification

Neutropenia

Grade 3 (ANC 500 to 1,000/mm3)

Interrupt fam-trastuzumab deruxtecan until resolved to ≤ grade 2, then maintain dose.

Grade 4 (ANC <500/mm3)

Interrupt fam-trastuzumab deruxtecan until resolved to ≤ grade 2, then reduce dose by one dose level.

Neutropenic fever

ANC <1,000/mm3 and temperature >38.3°C or a sustained temperature of ≥38°C for >1 hour

Interrupt fam-trastuzumab deruxtecan until resolved, then reduce dose by one dose level.

Thrombocytopenia

Grade 3 (platelets 25,000 to <50,000/mm3)

Interrupt fam-trastuzumab deruxtecan until resolved to ≤ grade 1, then maintain dose.

Grade 4 (platelets <25,000/mm3)

Interrupt fam-trastuzumab deruxtecan until resolved to ≤ grade 1, then reduce dose by one dose level.

Cardiotoxicity: Left ventricular dysfunction

Left ventricular ejection fraction (LVEF) >45% and absolute decrease from baseline is 10% to 20%

Continue fam-trastuzumab deruxtecan treatment.

LVEF 40% to 45%

And absolute decrease from baseline is <10%

Continue fam-trastuzumab deruxtecan treatment and repeat LVEF assessment within 3 weeks.

And absolute decrease from baseline is 10% to 20%

Interrupt fam-trastuzumab deruxtecan treatment. Repeat LVEF assessment within 3 weeks.

If LVEF has not recovered to within 10% from baseline, permanently discontinue fam-trastuzumab deruxtecan.

If LVEF recovers to within 10% from baseline, resume fam-trastuzumab deruxtecan treatment at the same dose.

LVEF <40% or absolute decrease from baseline is >20%

Interrupt fam-trastuzumab deruxtecan treatment. Repeat LVEF assessment within 3 weeks.

If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue fam-trastuzumab deruxtecan.

Symptomatic heart failure

Permanently discontinue fam-trastuzumab deruxtecan.

Infusion reaction

Infusion-related symptoms

Interrupt infusion or slow infusion rate.

Severe infusion reaction

Permanently discontinue fam-trastuzumab deruxtecan.

Pulmonary toxicity: Interstitial lung disease (ILD)/pneumonitis

Asymptomatic ILD/pneumonitis (grade 1)

Interrupt fam-trastuzumab deruxtecan until resolved to grade 0, then:

• If resolved in ≤28 days from date of onset, maintain dose.

• If resolved in >28 days from date of onset, reduce dose by one dose level.

• Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (eg, ≥0.5 mg/kg/day prednisolone [or equivalent], followed by a gradual taper, if necessary).

• Consider consultation with a pulmonologist.

Symptomatic ILD/pneumonitis (≥ grade 2)

Permanently discontinue fam-trastuzumab deruxtecan.

Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (eg, ≥1 mg/kg/day prednisolone [or equivalent] for at least 14 days followed by a gradual taper over at least 4 weeks).

Consider consultation with a pulmonologist.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Enhertu: fam-trastuzumab deruxtecan-nxki 100 mg (1 ea) [contains polysorbate 80]

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Enhertu: 100 mg (1 ea) [contains polysorbate 80]

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s017s020lbl.pdf#page=21, must be dispensed with this medication.

Administration: Adult

IV: Administer the first infusion over 90 minutes. If initial infusion was tolerated well, administer subsequent infusions over 30 minutes. Do not administer as an IV push or bolus. Administer only with an infusion set made of polyolefin or polybutadiene and a 0.2- or 0.22-micron in-line polyethersulfone or polysulfone filter. If refrigerated, allow solution to reach room temperature prior to administration. Cover infusion bag during infusion to protect from light. Slow or interrupt the infusion rate if infusion-related symptoms develop; discontinue permanently for severe infusion reactions. Do not administer with other drugs through the same IV line.

Fam-trastuzumab deruxtecan is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; delayed nausea and/or vomiting may occur.

Check label to ensure appropriate product is being administered; fam-trastuzumab deruxtecan, trastuzumab/hyaluronidase, conventional trastuzumab products, ado-trastuzumab emtansine, and pertuzumab/trastuzumab/hyaluronidase are different products and are NOT interchangeable.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Breast cancer, unresectable or metastatic (HER2+ ): Treatment of unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer in adults who have received a prior anti–HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy.

Gastric cancer, locally advanced or metastatic (HER2+): Treatment of locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma in adults who have received a prior trastuzumab-based regimen.

Use: Off-Label: Adult

Colorectal cancer, metastatic, HER2-expressing; Non-small cell lung cancer, metastatic, relapsed/refractory, nonsquamous, HER2-mutant

Medication Safety Issues
Sound-alike/look-alike issues:

Fam-trastuzumab deruxtecan may be confused with ado-trastuzumab emtansine, brentuximab vedotin, pertuzumab, pertuzumab/trastuzumab/hyaluronidase, trastuzumab (conventional [or trastuzumab biosimilars]), trastuzumab/hyaluronidase.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Other safety concerns:

Fam-trastuzumab deruxtecan (Enhertu) may be confused with ado-trastuzumab emtansine (Kadcyla), conventional trastuzumab (Herceptin), pertuzumab/trastuzumab/hyaluronidase (Phesgo), trastuzumab biosimilars, and/or trastuzumab/hyaluronidase (Herceptin Hylecta); products are not interchangeable.

Adverse Reactions (Significant): Considerations
Bone marrow suppression

Neutropenia, including severe grades 3 and 4 toxicity, and febrile neutropenia, may occur. Therapy interruption and/or dose reduction may be warranted, depending on severity.

Mechanism: Dose-related

Onset: Varied; median time to first onset was 16 days (range: 4 to 187) for locally advanced or metastatic gastric cancer and 23 days (range: 6 to 547) for metastatic breast cancer.

Cardiotoxicity

Patients treated with fam-trastuzumab deruxtecan may be at an increased risk of developing left ventricular dysfunction. Decreased left ventricular ejection fraction (LVEF) has been observed with anti-human epidermal growth factor receptor 2 (HER2) therapies, including fam-trastuzumab deruxtecan. Therapy interruption and/or permanent discontinuation may be warranted, depending on degree of dysfunction. Patients with a history of clinically significant cardiac disease or LVEF <50% prior to treatment have not been studied.

GI effects

Nausea, vomiting, constipation, diarrhea, and stomatitis were commonly reported with fam-trastuzumab deruxtecan. Fam-trastuzumab deruxtecan is associated with a moderate emetic potential; antiemetics are recommended for prevention (Ref).

Pulmonary toxicity

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with fam-trastuzumab deruxtecan. Other similar HER2-directed therapies, such as trastuzumab, trastuzumab emtansine, and topoisomerase I inhibitors have also been associated with pulmonary toxicity (Ref). Interrupt therapy and immediately investigate any symptoms suggestive of ILD/pneumonitis during therapy; permanent discontinuation is recommended in any patient with grade 2 or higher ILD/pneumonitis.

Onset: Delayed; median time to first onset was 2.8 months (range: 1.2 to 21) for locally advanced or metastatic gastric cancer and 4.1 months (range: 1.2 to 8.3) for metastatic breast cancer.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Alopecia (22% to 46%)

Endocrine & metabolic: Hypokalemia (26% to 30%)

Gastrointestinal: Abdominal pain (14% to 19%), constipation (24% to 35%), decreased appetite (32% to 60%), diarrhea (29% to 32%), dyspepsia (12%), nausea (63% to 79%), stomatitis (11% to 14%; grades 3/4: ≤2%), vomiting (26% to 47%)

Hematologic & oncologic: Anemia (31% to 58%; grades 3/4: 7% to 38%), decreased neutrophils (62% to 72%; grades 3/4: 16% to 51%), decreased platelet count (37% to 68%; grades 3/4: 3% to 12%), decreased white blood cell count (70% to 74%; grades 3/4: 7% to 29%), lymphocytopenia (70%; grades 3/4: 28%)

Hepatic: Increased serum alanine aminotransferase (38% to 47%), increased serum alkaline phosphatase (54%), increased serum aspartate aminotransferase (41% to 58%), increased serum bilirubin (24%)

Nervous system: Fatigue (55% to 59%), headache (19%)

Ophthalmic: Dry eye syndrome (11%)

Respiratory: Cough (20%), dyspnea (13%), epistaxis (13%), upper respiratory tract infection (15%)

Miscellaneous: Fever (24%)

1% to 10%:

Cardiovascular: Decreased left ventricular ejection fraction (≤8%; asymptomatic grade 2), peripheral edema (10%)

Dermatologic: Cellulitis (can be severe), skin rash (10%)

Endocrine & metabolic: Dehydration (6%)

Gastrointestinal: Intestinal obstruction

Hematologic & oncologic: Febrile neutropenia (2% to 5%; grade 3/4: ≤5%), tumor hemorrhage (>2%)

Hepatic: Cholestatic jaundice (can be severe: >2%), hepatic insufficiency (8%)

Immunologic: Antibody development (2%; anti-drug)

Nervous system: Dizziness (10%)

Respiratory: Interstitial pulmonary disease (9% to 10%), pneumonia (6%)

Miscellaneous: Infusion related reaction (2% to 3%)

Frequency not defined: Respiratory: Pneumonitis

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to fam-trastuzumab deruxtecan or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Severe neutropenia may occur, including grades 3 and 4 toxicity and neutropenic fever. The median time to first onset was 16 to 22 days (range: 4 days to ~22 months).

• Cardiotoxicity: Patients treated with fam-trastuzumab deruxtecan may be at increased risk of developing left ventricular dysfunction. Decreased left ventricular ejection fraction (LVEF) has been observed with anti-human epidermal growth factor receptor 2 (HER2) therapies, including fam-trastuzumab deruxtecan. Cases of asymptomatic LVEF decrease have been reported. Fam-trastuzumab deruxtecan has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to treatment initiation.

• Pulmonary toxicity: Interstitial lung disease: Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with fam-trastuzumab deruxtecan. Promptly investigate signs/symptoms (eg, cough, dyspnea, fever, other new or worsening respiratory symptoms) for suspected ILD, including radiographic imaging. Advise patients of the risk and the need to immediately report symptoms. The median time to first onset was 2.8 to 5.5 months (range: 1.1 to ~21 months). A higher incidence of grade 1 or 2 ILD/pneumonitis has been observed in patients with moderate kidney impairment. ILD/pneumonitis may be severe or life-threatening.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Do not interchange: Fam-trastuzumab deruxtecan and ado-trastuzumab emtansine, conventional trastuzumab (or trastuzumab biosimilars), pertuzumab/trastuzumab/hyaluronidase, or trastuzumab/hyaluronidase products are different and are NOT interchangeable. Do not substitute. Dosing and treatment schedules among the various trastuzumab-based products differ; confusion between the products may potentially cause harm to the patient. Verify product label prior to reconstitution and administration to prevent medication errors.

• Human epidermal growth factor receptor 2 expression: For gastric cancer, select patients for therapy based on HER2 protein overexpression or HER2 gene amplification; reassess HER2 status in between the prior trastuzumab therapy and fam-trastuzumab deruxtecan if feasible to obtain a new tumor specimen. Information on approved tests for HER2 testing is available at http://www.fda.gov/CompanionDiagnostics.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Anthracyclines: Fam-Trastuzumab Deruxtecan may enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Reproductive Considerations

[US Boxed Warning]: Exposure to fam-trastuzumab deruxtecan during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for at least 7 months after the last fam-trastuzumab deruxtecan dose. Patients with partners who could become pregnant should use effective contraception during therapy and for at least 4 months after the last dose of fam-trastuzumab deruxtecan.

Pregnancy Considerations

[US Boxed Warning]: Exposure to fam-trastuzumab deruxtecan during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Oligohydramnios and oligohydramnios sequence (manifested as pulmonary hypoplasia, skeletal malformations, and neonatal death) were observed following trastuzumab exposure during pregnancy (trastuzumab is the antibody component of fam-trastuzumab deruxtecan). Monitor for oligohydramnios if trastuzumab exposure occurs during pregnancy or within 7 months prior to conception; conduct appropriate fetal testing if oligohydramnios occurs.

Breastfeeding Considerations

It is not known if fam-trastuzumab deruxtecan is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 7 months after the last fam-trastuzumab deruxtecan dose.

Monitoring Parameters

Human epidermal growth factor receptor 2 (HER2) status. CBC (prior to treatment initiation, prior to each dose, and as clinically indicated). Assess left ventricular ejection fraction prior to fam-trastuzumab deruxtecan initiation and at regular intervals during treatment as clinically indicated. Evaluate pregnancy status prior to therapy (in patients who could become pregnant). Monitor for signs/symptoms of interstitial lung disease/pneumonitis (eg, cough, dyspnea, fever, and/or any new or worsening respiratory symptoms [particularly in patients with moderate or severe kidney impairment]; obtain radiographic imaging for suspected ILD). Monitor for infusion reactions.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow up.

Mechanism of Action

Fam-trastuzumab deruxtecan is a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate composed of a humanized IgG1 monoclonal antibody, which has the same amino acid sequence as trastuzumab (and targets HER2), a cleavable tetrapeptide-based linker, and the cytotoxic component, a topoisomerase I inhibitor (Modi 2020). The deruxtecan component is a cleavable linker and the topoisomerase inhibitor, DXd (an exatecan derivative). Upon binding to HER2 on tumor cells, fam-trastuzumab deruxtecan undergoes internalization and intracellular linker cleavage by lysosomal enzymes, releasing DXd and resulting in DNA damage and cell death.

Pharmacokinetics

Distribution: Vd: Fam-trastuzumab deruxtecan: 2.71 L.

Protein binding: DXd: ~97% (to plasma proteins).

Metabolism: Fam-trastuzumab deruxtecan: Degradation via catabolic pathways into small peptides and amino acids; DXd: Primarily via CYP3A4.

Half-life elimination: Fam-trastuzumab deruxtecan: ~5.7 to 5.8 days; DXd: 5.5 to 5.8 days.

Excretion: Clearance: Fam-trastuzumab deruxtecan: 0.42 L/day; DXd: 19.4 L/hour.

Pricing: US

Solution (reconstituted) (Enhertu Intravenous)

100 mg (per each): $2,909.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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