Datroway (datopotamab deruxtecan-dlnk)

If adverse events occur during therapy, temporary interruption, dosage reduction, and/or discontinuance of datopotamab deruxtecan-dlnk may be necessary. If dosage reduction is necessary, an initial reduction to 4 mg/kg (up to a maximum of 360 mg for patients >=90 kg) is recommended. If further dosage reduction is necessary, the dosage should be reduced to 3 mg/kg (up to a maximum of 270 mg for patients >=90 kg). If a dosage of 3 mg/kg is not tolerated, datopotamab deruxtecan-dlnk should be permanently discontinued. Once the dosage has been reduced for adverse reactions, do not subsequently increase the dose of datopotamab deruxtecan-dlnk.

Administer datopotamab deruxtecan-dlnk via IV infusion in a dedicated line with a low protein-binding 0.2-micron in-line filter. Do not administer via rapid IV bolus injection.

Instruct patients to hold ice chips or ice water in their mouth throughout the infusion.

Datopotamab deruxtecan-dlnk is available as a 100 mg single-dose vial of preservative-free lyophilized powder that must be reconstituted and diluted prior to IV infusion.

Do not administer in the same IV line with other medications.

Cover the infusion bag to protect from light during administration.

Store vials of datopotamab deruxtecan-dlnk refrigerated at 2-8degreesC in the original carton. Do not freeze.

Datopotamab deruxtecan-dlnk is compatible with 5% dextrose injection.

No dosing information is available for this tab.

No formal drug interaction studies have been performed with datopotamab deruxtecan-dlnk; however, pharmacokinetic interactions with DXd, the topoisomerase I inhibitor component of the antibody-drug conjugate, have been studied with a DXd-containing antibody-drug conjugate similar in structure to datopotamab deruxtecan-dlnk. No clinically significant differences in DXd pharmacokinetics were predicted when used concomitantly with a strong cytochrome P-450 (CYP) isoenzyme 3A (itraconazole) or a dual organic anion transporting polypeptide (OATP) 1B and CYP3A inhibitor (ritonavir).

In vitro studies indicate that DXd does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A, and does not induce CYP1A2, CYP2B6, or CYP3A.

In vitro studies indicate that DXd is not a substrate of UDP-glucuronosyltransferase (UGT).

In vitro studies indicate that DXd is a substrate of OATP1B1, OATP1B3, multidrug and toxin extrusion (MATE)2-k, P-glycoprotein (P-gp), multidrug resistance associated protein (MRP)1, and breast cancer resistance protein (BCRP). DXd does not inhibit organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, OATP1B3, MATE1, MATE2-K, P-gp, BCRP, or bile salt export pump (BSEP) transporters.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Igg Antibodies And Derivatives/Efgartigimod-Alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

Igg Antibodies And Derivatives/Nipocalimab-Aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Igg Antibodies And Derivatives/Rozanolixizumab-Noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

*None.

• Lactation

• Pregnancy

• Child-pugh class B hepatic impairment
• Disease of liver
• Interstitial lung disease

The most common adverse reactions (incidence >=20%), including laboratory abnormalities, reported with datopotamab deruxtecan-dlnk in patients with EGFR-mutated NSCLC were stomatitis, nausea, alopecia, fatigue, decreased hemoglobin, decreased lymphocytes, constipation, increased calcium, increased AST, decreased white blood cell count, increased lactate dehydrogenase, musculoskeletal pain, decreased appetite, increased ALT, and rash.

The most common adverse reactions (incidence >=20%), including laboratory abnormalities, reported with datopotamab deruxtecan-dlnk in patients with triple-negative breast cancer were stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium, decreased lymphocytes, fatigue, decreased neutrophils, increased ALT, increased AST, dry eye, keratitis, decreased albumin, vomiting, musculoskeletal pain, decreased sodium, and increased blood alkaline phosphatase.

The most common adverse reactions (incidence >=20%), including laboratory abnormalities, reported with datopotamab deruxtecan-dlnk in patients with HR-positive, HER2-negative breast cancer were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase.

More Frequent

• COVId-19
• Elevated serum amylase
• Skin rash

Rare or Very Rare

• Epithelial keratopathy
• Interstitial lung disease
• Pneumonia
• Pulmonary thromboembolism
• Urinary tract infection

More Frequent

• Abnormal hepatic function tests
• Alopecia
• Anemia
• Anorexia
• Constipation
• Dry eye
• Fatigue
• Hypoalbuminemia
• Hypocalcemia
• Hyponatremia
• Increased alanine transaminase
• Increased alkaline phosphatase
• Increased aspartate transaminase
• Keratitis
• Leukopenia
• Lymphopenia
• Musculoskeletal pain
• Nausea
• Neutropenic disorder
• Stomatitis
• Vomiting

Less Frequent

• Blepharitis
• Blurred vision
• Conjunctivitis
• Dry skin
• Dyschromia
• Eye tearing
• Headache disorder
• Injection site sequelae
• Madarosis of eyelid
• Meibomianitis
• Photophobia
• Pruritus of skin
• Upper respiratory infection
• Vision impairment
• Xerostomia

No enhanced messaging available.

Safety and efficacy of datopotamab deruxtecan-dlnk have not been established in pediatric patients <18 years of age.

There are no human or animal data on datopotamab deruxtecan-dlnk use in pregnant women. However, based on its mechanism of action, datopotamab deruxtecan-dlnk can cause fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component, deruxtecan-dlnk, is genotoxic and affects actively dividing cells.

Verify the pregnancy status of females of reproductive potential prior to the initiation of datopotamab deruxtecan-dlnk. Advise pregnant women and females of reproductive potential that exposure to datopotamab deruxtecan-dlnk during pregnancy can result in fetal harm.

It is not known whether datopotamab deruxtecan-dlnk is distributed into human milk. Effects of the drug on breastfed infants or milk production are also not known. However, because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with datopotamab deruxtecan-dlnk and for 1 month after the last dose.

The manufacturer makes no specific dosing recommendations for geriatric patients.

In clinical studies of patients with EGFR-mutated NSCLC, 44% of 125 patients were >=65 years of age; 10% were >=75 years of age. No overall differences in safety or efficacy were observed between geriatric patients (>=65 years of age) and younger adults (<65 years of age).

In clinical studies of patients with breast cancer, 23% of 841 patients were >=65 years of age; 4.5% were >=75 years of age. Grade >=3 and serious adverse reactions were more common in patients >=65 years of age (45% and 22%, respectively) compared to younger adults <65 years of age (38% and 16%, respectively). No other differences in safety or efficacy were observed between geriatric patients (>=65 years of age) and younger adults (<65 years of age).