Version July 2025
Dosage guidance:
Safety: Perform ophthalmic examination (including visual acuity testing, slit lamp examination [with fluorescein staining], intraocular pressure, and fundoscopy) at baseline, annually while on treatment, at the end of treatment, and as clinically indicated. Patients should use preservative-free lubricant eye drops (or equivalent) at least 4 times a day, starting with the initial infusion and continuing until the end of therapy, and avoid contact lenses unless otherwise directed. To prevent (and treat) stomatitis, advise patients to use a steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL or equivalent) 4 times a day and as needed; patient should hold ice chips or ice water in the mouth throughout the datopotamab deruxtecan infusion. Premedicate with an antipyretic (acetaminophen 650 mg to 1 g [or equivalent] IV or oral) and an antihistamine (diphenhydramine 25 to 50 mg [or equivalent] IV or oral) with or without systemic corticosteroids 30 to 60 minutes prior to each datopotamab deruxtecan infusion. Administer in a setting with available resuscitation equipment/medications.
Clinical considerations: Datopotamab deruxtecan may be associated with a moderate emetic potential; antiemetics (5-HT3 serotonin receptor antagonist or appropriate alternative; IV or oral) are recommended prior to each infusion and thereafter as needed.
Breast cancer, unresectable or metastatic, hormone receptor positive, HER2 negative (as a single agent): IV: 6 mg/kg (maximum dose: 540 mg [in patients weighing ≥90 kg]) once every 3 weeks; continue until disease progression or unacceptable toxicity (Ref).
Missed doses: If a dose is delayed or missed, administer as soon as possible (do not wait until the next planned dose); adjust the administration schedule to maintain a 3-week interval between doses.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to treatment initiation:
CrCl 30 to <90 mL/minute: No dosage adjustment necessary. Monitor for increased adverse reactions, including respiratory reactions (interstitial lung disease/pneumonitis).
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effect on datopotamab deruxtecan or DXd pharmacokinetics is unknown).
Hepatic impairment prior to treatment initiation:
Mild (total bilirubin ≤ ULN and any AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) impairment: No dosage adjustment necessary.
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (limited data available). Monitor for increased adverse reactions.
Severe (total bilirubin >3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Note: Per the manufacturer's labeling, the maximum dose for patients weighing ≥90 kg is 540 mg.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref). Note: Per the manufacturer's labeling, do not re-escalate the datopotamab deruxtecan dose following a dose reduction.
|
Dosage reduction level |
Recommended datopotamab deruxtecan dosage and schedule |
|---|---|
|
a Do not re-escalate the datopotamab deruxtecan dose after a dosage reduction is made. | |
|
Usual (initial) dose |
6 mg/kg (maximum dose: 540 mg [in patients weighing ≥90 kg]) once every 3 weeks |
|
First dose reduction levela |
4 mg/kg (maximum dose: 360 mg [in patients weighing ≥90 kg]) once every 3 weeks |
|
Second dose reduction levela |
3 mg/kg (maximum dose: 270 mg [in patients weighing ≥90 kg]) once every 3 weeks |
|
Permanently discontinue datopotamab deruxtecan if unable to tolerate 3 mg/kg (maximum dose: 270 mg [in patients weighing ≥90 kg]) once every 3 weeks. | |
|
Adverse reaction |
Severity |
Datopotamab deruxtecan dosage modification |
|---|---|---|
|
a IRR = infusion-related reactions; ILD = interstitial lung disease. | ||
|
b Bardia 2025. | ||
|
IRRa |
Grade 1 |
If IRR suspected, reduce datopotamab deruxtecan infusion rate by 50%. Monitor patient closely. |
|
Grade 2 |
Interrupt datopotamab deruxtecan infusion and administer supportive care medications. Improvement or resolution to grade 1: Resume datopotamab deruxtecan infusion at 50% rate. Administer all subsequent infusions at the reduced rate. | |
|
Grade 3 or 4 |
Immediately interrupt datopotamab deruxtecan infusion and administer supportive care medications.b Permanently discontinue datopotamab deruxtecan. | |
|
Ocular toxicity: keratitis |
Any |
Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. |
|
Nonconfluent superficial keratitis |
Monitor. | |
|
Confluent superficial keratitis, corneal epithelial defect, or ≥3-line loss in best corrected visual acuity |
Withhold datopotamab deruxtecan until improved or resolved; resume at the current dose level or consider dose reduction. | |
|
Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse |
Withhold datopotamab deruxtecan until improved or resolved; resume with dose reduced by one dose level. | |
|
Corneal perforation |
Permanently discontinue datopotamab deruxtecan. | |
|
Pulmonary toxicity: ILDa/pneumonitis |
Asymptomatic; grade 1 |
Withhold datopotamab deruxtecan until ILD/pneumonitis is completely resolved. Consider corticosteroids (eg, ≥0.5 mg/kg/day prednisolone or equivalent) as soon as ILD/pneumonitis is suspected. Resolution in ≤28 days: Resume datopotamab deruxtecan at the current dose level. Resolution in >28 days: Resume datopotamab deruxtecan reduced by one dose level. |
|
Symptomatic or confirmed; grade ≥2 |
Permanently discontinue datopotamab deruxtecan. Promptly initiate corticosteroids (eg, ≥1 mg/kg/day prednisolone or equivalent for at least 14 days, followed by gradual taper for at least 4 weeks) as soon as ILD/pneumonitis is suspected. | |
|
Stomatitis |
Any |
If stomatitis occurs, increase the frequency of steroid-containing mouthwash and administer other topical treatments (eg, oral nystatinb) as clinically indicated. |
|
Grade 1 |
Optimize prophylactic and supportive care medications. | |
|
Grade 2 |
Withhold datopotamab deruxtecan until resolved to < grade 1. First occurrence: Resume datopotamab deruxtecan at the current dose level. Recurrent: Consider resuming datopotamab deruxtecan reduced by one dose level. | |
|
Grade 3 |
Withhold datopotamab deruxtecan until resolved to ≤ grade 1; resume with dose reduced by one dose level. | |
|
Grade 4 |
Permanently discontinue datopotamab deruxtecan. | |
|
Other nonhematologic adverse reactions |
Grade 3 |
Withhold datopotamab deruxtecan until resolved to ≤ grade 1 or baseline; resume with dose reduced by one dose level. |
|
Grade 4 |
Permanently discontinue datopotamab deruxtecan. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Alopecia (38%), skin rash (19%)
Endocrine & metabolic: Decreased serum calcium (39%)
Gastrointestinal: Abdominal pain (11%), constipation (34%), decreased appetite (16%), diarrhea (11%; grades 3/4: <1%), nausea (56%; grades 3/4: 1%), stomatitis (59%; grades 3/4: 7%), vomiting (24%; grades 3/4: 1%)
Hematologic & oncologic: Decreased hemoglobin (35%; grades 3/4: 3%), decreased neutrophils (30%; grades 3/4: 2%), leukopenia (41%; grades 3/4: 1%), lymphocytopenia (36%; grades 3/4: 9%)
Hepatic: Increased serum alanine aminotransferase (24%), increased serum alkaline phosphatase (23%), increased serum aspartate aminotransferase (23%)
Nervous system: Fatigue (44%)
Ophthalmic: Dry eye syndrome (27%), keratitis (24%)
Respiratory: Cough (15%)
1% to 10%:
Dermatologic: Madarosis of eyebrow, pruritus, skin hyperpigmentation, xeroderma
Gastrointestinal: Xerostomia
Hypersensitivity: Infusion-related reaction
Nervous system: Headache
Ophthalmic: Blepharitis (8%), blurred vision, conjunctivitis, increased lacrimation (8%), ophthalmic signs and symptoms (meibomian gland dysfunction: 7%), photophobia, visual impairment
Respiratory: Interstitial lung disease (≤4%), pneumonitis (≤4%)
Frequency not defined:
Cardiovascular: Pulmonary embolism
Endocrine & metabolic: Weight loss
Genitourinary: Urinary tract infection
Hematologic & oncologic: Anemia
Nervous system: Hemiparesis
Renal: Acute kidney injury
Respiratory: Pneumonia
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Ocular toxicity: Datopotamab deruxtecan may cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision. In the clinical trial, ocular adverse reactions occurred in approximately one-half of datopotamab deruxtecan-treated patients, including grade 3 events in a small percentage of patients. The most common ocular adverse reactions were dry eye, keratitis, blepharitis, increased lacrimation, and meibomian gland dysfunction. The median time to onset of ocular adverse reactions was 2.1 months (range: up to 23.2 months). In patients that experienced ocular adverse events, almost half had complete resolution with additional patients experiencing partial improvement (defined as a decrease in severity by ≥1 grades from the worst grade at last follow up); permanent discontinuation occurred rarely. Patients with clinically significant corneal disease were not included in the clinical study.
• Pulmonary toxicity: Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis has occurred with datopotamab deruxtecan. In the clinical trial, the median time to onset of ILD/pneumonitis was 3.5 months (range: 1.2 to 10.8 months). Patients with a history of ILD/pneumonitis requiring corticosteroid treatment or with ongoing ILD/pneumonitis were excluded from the clinical trial. A higher incidence of ILD/pneumonitis has been observed in patients with mild to moderate kidney impairment (CrCl 30 to <90 mL/minute).
• Stomatitis: Stomatitis, including mouth ulcers and oral mucositis, may occur with datopotamab deruxtecan. Over half of datopotamab deruxtecan–treated patients experienced stomatitis in the clinical trial, including patients experiencing grade 3 to 4 events; stomatitis led to dosage modification and permanent discontinuation in some patients. Median time to first onset of stomatitis was 0.7 months (range: up to 8.8 months). Corticosteroid-containing mouthwash for management or prophylaxis of stomatitis or oral mucositis was utilized in approximately one-third of patients at any time during treatment.
Special populations:
• Older adults: In patients treated with datopotamab deruxtecan, grade ≥3 and serious adverse reactions occurred more frequently in patients ≥65 years of age, when compared to patients <65 years of age.
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 (Ref). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Ref). See manufacturer's labeling.
Datroway: FDA approved January 2025; anticipated availability in January/February 2025.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Datroway: Datopotamab deruxtecan-dlnk 100 mg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Datroway Intravenous)
100 mg (per each): $5,869.28
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.
Datopotamab deruxtecan is available through specialty distributors, specialty pharmacy providers, and various specialty institutions/accounts. Examples from the manufacturer can be found at https://www.datroway4u.com/hcp-breast/distribution.html or at 1-855-328-7648.
IV: Administer the first infusion over 90 minutes and observe patient for at least 1 hour following the infusion for signs/symptoms of infusion-related reactions. If initial infusion was tolerated, administer second infusion over 30 minutes and observe patient for at least 1 hour following infusion. If prior infusions were well tolerated, administer all subsequent infusions over 30 minutes and observe patient for at least 30 minutes following infusion. Do not administer as an IV push or bolus. If refrigerated, allow diluted infusion solution to reach room temperature prior to administration. Administer only with an infusion set/line made of polyvinyl chloride, polybutadiene, or low-density polyethylene and a 0.2-micron in-line polytetrafluoroethylene, polyethersulfone, or nylon 66 filter. The maximum time from vial reconstitution through the completion of administration should not exceed 24 hours; discard the infusion bag if storage time exceeds the limit. Cover infusion bag during infusion to protect from light. Do not administer with other drugs through the same IV line. Instruct the patient to hold ice chips or ice water in the mouth throughout infusion. Administer in a setting where resuscitation medication and equipment are available. Slow or interrupt the infusion rate if infusion-related symptoms develop; discontinue permanently for severe infusion reactions.
Premedicate with an antipyretic (acetaminophen 650 mg to 1 g [or equivalent] IV or oral) and an antihistamine (diphenhydramine 25 to 50 mg [or equivalent] IV or oral) with or without systemic corticosteroids 30 to 60 minutes prior to each datopotamab deruxtecan infusion.
Datopotamab deruxtecan may be associated with a moderate emetic potential; antiemetics (5-HT3 serotonin receptor antagonist or appropriate alternative; IV or oral) are recommended prior to each infusion and as needed.
This medication is not on the NIOSH (2024) list; however, it meets the criteria for a hazardous drug. Datopotamab deruxtecan contains manufacturer's special handling information and is a hazardous drug (per the product labeling). 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 (Ref).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication.
Datroway: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761394s000lbl.pdf#page=16
Breast cancer, unresectable or metastatic, hormone receptor positive, HER2 negative: Treatment of unresectable or metastatic, hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer in adults who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
Datopotamab deruxtecan may be confused with daratumumab, dinutuximab, fam-trastuzumab deruxtecan.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP, CYP3A4 (Minor), MATE1/2-K, OATP1B1/1B3, P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 7 months after the last dose of datopotamab deruxtecan. Patients with partners who could become pregnant should use effective contraception during therapy and for 4 months after the last datopotamab deruxtecan dose.
Irreversible adverse impairment to fertility were observed in animal toxicology studies; data are lacking on possible fertility effects in humans.
Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to datopotamab deruxtecan may cause fetal harm due to its effects on dividing cells.
It is not known if datopotamab 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 1 month after the last dose of datopotamab deruxtecan.
HER2-negative status (IHC 0, IHC 1+, or IHC 2+/ISH-). Monitor liver and kidney function. Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Perform ophthalmic examinations (visual acuity, slit lamp [with fluorescein staining], IOP, and fundoscopy) at baseline, annually while on treatment, at end of treatment, and as clinically indicated; promptly refer for any new or worsening ocular adverse reactions.
Monitor patients for signs/symptoms of interstitial lung disease/pneumonitis (eg, dyspnea, cough, fever, and/or any new or worsening respiratory symptoms [particularly in patients with kidney impairment]), ocular toxicity, and/or stomatitis. Monitor patients for infusion-related reactions for at least 1 hour for the first 2 cycles of datopotamab deruxtecan. If there are no infusion-related reactions observed, monitor patients for at least 30 minutes for all subsequent cycles. Monitor patients with moderate hepatic impairment for increased risk of adverse reactions.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) 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.
Datopotamab deruxtecan, is a Trop2-directed antibody-drug conjugate composed of a humanized IgG1 monoclonal antibody targeting Trop2, a cleavable tetrapeptide-based linker, and the cytotoxic component, a topoisomerase I inhibitor. The deruxtecan component is composed of a cleavable linker and the topoisomerase I inhibitor, DXd (an exatecan derivative). Upon binding to Trop2 on tumor cells, datopotamab deruxtecan undergoes internalization and intracellular linker cleavage by lysosomal enzymes, releasing DXd and resulting in DNA damage and apoptotic cell death. Datopotamab deruxtecan demonstrated anti-tumor activity in a mouse model of breast cancer.
Distribution: Vdss: Datopotamab deruxtecan: 3.5 L.
Protein binding: Dxd: ~98%.
Metabolism: Datopotamab deruxtecan: Intracellular cleavage by lysosomal enzymes to release DXd; Humanized Trop-2 IgG1 monoclonal antibody: Degradation via catabolic pathways into small peptides and amino acids via catabolic pathways; DXd: Primarily via CYP3A4.
Half-life elimination (median): Datopotamab deruxtecan: 4.8 days (range 1 to 8.2 days); Dxd: ~5.5 days (range: 3.2 to 8.8 days).
Excretion: Datopotamab deruxtecan: Clearance: 0.6 L/day.
Liver function impairment: The steady state average Dxd AUC was 2.4-fold higher in patents with moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment when compared to patients with normal hepatic function.
Body weight: The mean volume of distribution and clearance of datopotamab deruxtecan and DXd increase with increasing body weight (36 kg to 156 kg).
