trastuzumab/hyaluronidase (Rx)

Brand and Other Names:Herceptin Hylecta, trastuzumab-hyaluronidase-oysk
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

trastuzumab/hyaluronidase

injectable solution, single-dose vial

  • (120mg/2,000 units)/mL
  • Ready-to-use SC solution contains trastuzumab and hyaluronidase human

Adjuvant Breast Cancer

Indicated for adjuvant treatment of HER2-overexpressing breast cancer for the following:

In combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel OR

In combination with docetaxel and carboplatin OR

As a single agent following multimodality anthracycline-based therapy

600 mg trastuzumab/10,000 units hyaluronidase SC q3Weeks

Continue treatment for 52 weeks or until disease recurrence, whichever occurs first; extending treatment in adjuvant breast cancer >1 year is not recommended

Metastatic Breast Cancer

Indicated for HER2-overexpressing metastatic breast cancer in combination with paclitaxel for first-line treatment or as a single agent in patients who have received ≥1 chemotherapy regimens for metastatic disease

600 mg trastuzumab/10,000 units hyaluronidase SC q3Weeks

Continue until disease progression

Dosage Modifications

Cardiomyopathy

  • Withhold dose for ≥4 weeks
    • ≥16% absolute decrease in left ventricular ejection fraction (LVEF) from baseline
    • LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from baseline
    • Resume if, within 4−8 weeks, LVEF returns to normal limits and absolute decrease from baseline is ≤15%
  • Permanently discontinue
    • Persistent (>8 weeks) LVEF decline
    • Withheld dose on >3 occurrences for cardiomyopathy

Dosing Considerations

No loading dose is required

No dose adjustments for body weight or for different concomitant chemotherapy regimens are required

Do not substitute trastuzumab/hyaluronidase for or with ado-trastuzumab emtansine

Cardiac monitoring

  • Conduct thorough cardiac assessment (eg, history, physical examination, and determination of LVEF by echocardiogram, multigated acquisition scan)
  • Baseline LVEF measurement immediately prior to initiation
  • LVEF measurements q3Months during and upon completion of treatment
  • Repeat LVEF measurement at 4-week intervals if dose is withheld
  • LVEF measurements q6Months for ≥2 yr following completion of trastuzumab/hyaluronidase as a component of adjuvant therapy

Patient selection

  • Select patients based on an FDA-approved companion diagnostic for trastuzumab
  • Assess HER2 protein overexpression and HER2 gene amplification using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency
  • Information on FDA-approved tests for detecting HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics

Safety and efficacy not established

In patients receiving IV trastuzumab, risk of cardiac dysfunction was increased in geriatric patients as compared with younger patients, in both those receiving treatment for adjuvant therapy or metastatic disease

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Interactions

Interaction Checker

and trastuzumab/hyaluronidase

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              Serious - Use Alternative (2)

              • beclomethasone, inhaled

                beclomethasone, inhaled will decrease the level or effect of hyaluronidase by unspecified interaction mechanism. Avoid or Use Alternate Drug. Larger hyaluronidase doses may be required to achieve desired effect

              • daunorubicin

                trastuzumab, daunorubicin. Either increases toxicity of the other by unknown mechanism. Avoid or Use Alternate Drug. Trastuzumab may cause cardiomyopathy. Incidence and severity was highest when used with anthracycline-containing chemotherapy regimens. If possible, avoid anthracycline-based therapy for 7 months after last trastuzumab/hyaluronidase dose. If anthracyclines are used, carefully monitor cardiac function.

              Monitor Closely (181)

              • abatacept

                trastuzumab, abatacept. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • abemaciclib

                trastuzumab, abemaciclib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • acalabrutinib

                trastuzumab, acalabrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • ado-trastuzumab emtansine

                trastuzumab, ado-trastuzumab emtansine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • alemtuzumab

                trastuzumab, alemtuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • alprazolam

                hyaluronidase, alprazolam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • anakinra

                trastuzumab, anakinra. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • antithymocyte globulin equine

                trastuzumab, antithymocyte globulin equine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • antithymocyte globulin rabbit

                trastuzumab, antithymocyte globulin rabbit. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • articaine

                hyaluronidase, articaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • aspirin

                aspirin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • aspirin rectal

                aspirin rectal decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • azacitidine

                trastuzumab, azacitidine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • azathioprine

                trastuzumab, azathioprine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • azelastine

                azelastine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • baricitinib

                trastuzumab, baricitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • basiliximab

                trastuzumab, basiliximab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • bazedoxifene/conjugated estrogens

                bazedoxifene/conjugated estrogens decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • beclomethasone, inhaled

                trastuzumab, beclomethasone, inhaled. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • beclomethasone, intranasal

                trastuzumab, beclomethasone, intranasal. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • belatacept

                trastuzumab, belatacept. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • belimumab

                trastuzumab, belimumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • betamethasone

                trastuzumab, betamethasone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • bleomycin

                trastuzumab, bleomycin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • blinatumomab

                trastuzumab, blinatumomab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • brentuximab vedotin

                trastuzumab, brentuximab vedotin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • brodalumab

                trastuzumab, brodalumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • brompheniramine

                brompheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • budesonide

                trastuzumab, budesonide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • busulfan

                trastuzumab, busulfan. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • cabazitaxel

                trastuzumab, cabazitaxel. Either increases levels of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • canakinumab

                trastuzumab, canakinumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • capecitabine

                trastuzumab, capecitabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • carbinoxamine

                carbinoxamine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • carboplatin

                trastuzumab, carboplatin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • carmustine

                trastuzumab, carmustine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • certolizumab pegol

                trastuzumab, certolizumab pegol. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • cetirizine

                cetirizine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • chlorambucil

                trastuzumab, chlorambucil. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • chloroprocaine

                hyaluronidase, chloroprocaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • chlorpheniramine

                chlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • choline magnesium trisalicylate

                choline magnesium trisalicylate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • cisplatin

                trastuzumab, cisplatin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • cladribine

                trastuzumab, cladribine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • clemastine

                clemastine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • clofarabine

                trastuzumab, clofarabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • clonazepam

                hyaluronidase, clonazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • conjugated estrogens

                conjugated estrogens decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • conjugated estrogens, vaginal

                conjugated estrogens, vaginal decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • copanlisib

                trastuzumab, copanlisib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • corticotropin

                corticotropin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Corticotropin (ACTH), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

                trastuzumab, corticotropin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • cortisone

                cortisone decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Cortisone, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

                trastuzumab, cortisone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • cyclizine

                cyclizine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • cyclophosphamide

                trastuzumab, cyclophosphamide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • cyclosporine

                trastuzumab, cyclosporine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • cyproheptadine

                cyproheptadine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • cytarabine

                trastuzumab, cytarabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • dacarbazine

                trastuzumab, dacarbazine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • dactinomycin

                trastuzumab, dactinomycin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • dasatinib

                trastuzumab, dasatinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • daunorubicin

                trastuzumab, daunorubicin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • deflazacort

                trastuzumab, deflazacort. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • dengue vaccine

                trastuzumab decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

              • dexamethasone

                trastuzumab, dexamethasone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • dexbrompheniramine

                dexbrompheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • dexchlorpheniramine

                dexchlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • diazepam

                hyaluronidase, diazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • diflunisal

                diflunisal decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • dimenhydrinate

                dimenhydrinate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • dinutuximab

                trastuzumab, dinutuximab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • diphenhydramine

                diphenhydramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • docetaxel

                trastuzumab, docetaxel. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • doxorubicin

                trastuzumab, doxorubicin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • doxorubicin liposomal

                trastuzumab, doxorubicin liposomal. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • doxylamine

                doxylamine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • duvelisib

                trastuzumab, duvelisib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • eculizumab

                trastuzumab, eculizumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • elotuzumab

                trastuzumab, elotuzumab. Either increases levels of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • emapalumab

                trastuzumab, emapalumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • epirubicin

                trastuzumab, epirubicin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • estradiol

                estradiol decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • estramustine

                trastuzumab, estramustine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • estrogens conjugated synthetic

                estrogens conjugated synthetic decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • estrogens esterified

                estrogens esterified decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • estropipate

                estropipate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

              • etanercept

                trastuzumab, etanercept. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • ethinylestradiol

                ethinylestradiol decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • etoposide

                trastuzumab, etoposide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • everolimus

                trastuzumab, everolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • fludarabine

                trastuzumab, fludarabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • fludrocortisone

                trastuzumab, fludrocortisone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • fluorouracil

                trastuzumab, fluorouracil. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • fluticasone inhaled

                trastuzumab, fluticasone inhaled. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • furosemide

                hyaluronidase, furosemide. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • gemcitabine

                trastuzumab, gemcitabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • gemtuzumab

                trastuzumab, gemtuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • glatiramer

                trastuzumab, glatiramer. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • golimumab

                trastuzumab, golimumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • guselkumab

                trastuzumab, guselkumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • hydrocortisone

                trastuzumab, hydrocortisone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • hydroxyurea

                trastuzumab, hydroxyurea. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • hydroxyzine

                hydroxyzine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • ibritumomab tiuxetan

                trastuzumab, ibritumomab tiuxetan. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • ibrutinib

                trastuzumab, ibrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • idarubicin

                trastuzumab, idarubicin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • idelalisib

                trastuzumab, idelalisib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • ifosfamide

                trastuzumab, ifosfamide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • imatinib

                trastuzumab, imatinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • imiquimod

                trastuzumab, imiquimod. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • infliximab

                trastuzumab, infliximab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • inotuzumab

                trastuzumab, inotuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • irinotecan

                trastuzumab, irinotecan. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • irinotecan liposomal

                trastuzumab, irinotecan liposomal. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • ixekizumab

                trastuzumab, ixekizumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • leflunomide

                trastuzumab, leflunomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • lenalidomide

                trastuzumab, lenalidomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • levocetirizine

                levocetirizine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • lidocaine

                hyaluronidase, lidocaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • lomustine

                trastuzumab, lomustine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • lorazepam

                hyaluronidase, lorazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • mechlorethamine

                trastuzumab, mechlorethamine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • melphalan

                trastuzumab, melphalan. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • mercaptopurine

                trastuzumab, mercaptopurine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • methotrexate

                trastuzumab, methotrexate. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • methylprednisolone

                trastuzumab, methylprednisolone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • mitomycin

                trastuzumab, mitomycin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • mitoxantrone

                trastuzumab, mitoxantrone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • mogamulizumab

                trastuzumab, mogamulizumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • mometasone inhaled

                mometasone inhaled decreases effects of hyaluronidase by Other (see comment). Modify Therapy/Monitor Closely. Comment: Corticosteroids may decrease therapeutic effects of hyaluronidase.

              • mometasone topical

                mometasone topical decreases effects of hyaluronidase by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Patients receiving larger doses of corticosteriods may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required.

              • mycophenolate

                trastuzumab, mycophenolate. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • natalizumab

                trastuzumab, natalizumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • nelarabine

                trastuzumab, nelarabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • nilotinib

                trastuzumab, nilotinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • obinutuzumab

                trastuzumab, obinutuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • ocrelizumab

                trastuzumab, ocrelizumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • ofatumumab

                trastuzumab, ofatumumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • omacetaxine

                trastuzumab, omacetaxine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • osimertinib

                trastuzumab, osimertinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • oxaliplatin

                trastuzumab, oxaliplatin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • oxazepam

                hyaluronidase, oxazepam. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • paclitaxel

                trastuzumab, paclitaxel. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • paclitaxel protein bound

                trastuzumab, paclitaxel protein bound. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • palbociclib

                trastuzumab, palbociclib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • panobinostat

                trastuzumab, panobinostat. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • pazopanib

                trastuzumab, pazopanib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • pemetrexed

                trastuzumab, pemetrexed. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • pentostatin

                trastuzumab, pentostatin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • phenytoin

                hyaluronidase, phenytoin. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.

              • pomalidomide

                trastuzumab, pomalidomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • ponesimod

                ponesimod and trastuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • pralatrexate

                trastuzumab, pralatrexate. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • prednisolone

                trastuzumab, prednisolone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • prednisone

                trastuzumab, prednisone. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • procarbazine

                trastuzumab, procarbazine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • promethazine

                promethazine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

              • ravulizumab

                trastuzumab, ravulizumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • ribociclib

                trastuzumab, ribociclib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • rilonacept

                trastuzumab, rilonacept. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • rituximab

                trastuzumab, rituximab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • rituximab-hyaluronidase

                trastuzumab, rituximab-hyaluronidase. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • romidepsin

                trastuzumab, romidepsin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • ruxolitinib

                trastuzumab, ruxolitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • salicylates (non-asa)

                salicylates (non-asa) decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • salsalate

                salsalate decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

              • sarilumab

                trastuzumab, sarilumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • secukinumab

                trastuzumab, secukinumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • siltuximab

                trastuzumab, siltuximab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • siponimod

                siponimod and trastuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • sirolimus

                trastuzumab, sirolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • sorafenib

                trastuzumab, sorafenib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • streptozocin

                trastuzumab, streptozocin. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • sunitinib

                trastuzumab, sunitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • tacrolimus

                trastuzumab, tacrolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • temozolomide

                trastuzumab, temozolomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • temsirolimus

                trastuzumab, temsirolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • teniposide

                trastuzumab, teniposide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • teriflunomide

                trastuzumab, teriflunomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              • tetracaine

                hyaluronidase, tetracaine. Other (see comment). Use Caution/Monitor. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • thalidomide

                trastuzumab, thalidomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

              Minor (4)

              • bupivacaine

                hyaluronidase, bupivacaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • mepivacaine

                hyaluronidase, mepivacaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • prilocaine

                hyaluronidase, prilocaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

              • ropivacaine

                hyaluronidase, ropivacaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

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              Adverse Effects

              >10% (All Grades)

              Alopecia (63%)

              Nausea (49%)

              Fatigue (46%)

              Neutropenia (44%)

              Diarrhea (34%)

              Rash (26%)

              Upper respiratory tract infection (24%)

              Vomiting (23%)

              Stomatitis (21%)

              Myalgia (21%)

              Peripheral neuropathy (20%)

              Decreased appetite (20%)

              Arthralgia (18%)

              Headache (17%)

              Nail disorder (14%)

              Abdominal pain (14%)

              Flushing (14%)

              Edema (14%)

              Pyrexia (13%)

              Anemia (12%)

              Cough (12%)

              Dyspepsia (11%)

              Leukopenia (11%)

              Back pain (11%)

              Incision site complication (11%)

              >10% (Grade ≥3)

              Neutropenia (30%)

              1-10% (All Grades)

              Mucosal inflammation (10%)

              Injection site reactions (10%)

              Pain in extremity (10%)

              Dizziness (10%)

              Dysgeusia (10%)

              Pruritus (9%)

              Skin discoloration (9%)

              Pain (8%)

              Hypertension (8%)

              Erythema (7%)

              Dyspnea (7%)

              Hypersensitivity (7%)

              Febrile neutropenia (6%)

              Bone pain (6%)

              Epistaxis (6%)

              Abnormal liver function tests (6%)

              Pain (5%)

              Nasal inflammation/discomfort (5%)

              Arrhythmia (5%)

              Urinary tract infection (4%)

              1-10% (Grade ≥3)

              Febrile neutropenia (6%)

              Leukopenia (5%)

              Diarrhea (2.7%)

              Hypertension (2.4%)

              Alopecia (1.3%)

              Nausea (1.3%)

              Vomiting (1%)

              Upper respiratory tract infection (1%)

              Back pain (1%)

              Hypersensitivity (1%)

              Abnormal liver function tests (1%)

              <1% (Grade ≥3)

              Erythema

              Rash

              Stomatitis

              Fatigue

              Mucosal inflammation

              Anemia

              Bone pain

              Pain

              Headache

              Dizziness

              Cough

              Flushing

              Decreased appetite

              Postmarketing Reports

              Administration-related reaction

              Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death

              Glomerulopathy

              Immune thrombocytopenia

              Tumor lysis syndrome

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              Warnings

              Black Box Warnings

              Cardiomyopathy

              • Administration can result in subclinical and clinical cardiac failure
              • Highest incidence and severity occurred in patients receiving trastuzumab/hyaluronidase with anthracycline-containing chemotherapy regimens
              • Evaluate left ventricular function prior to and during treatment
              • Discontinue treatment in patients receiving adjuvant therapy and withhold dose in patients with metastatic disease for clinically significant decrease in left ventricular function

              Pulmonary toxicity

              • Serious and fatal pulmonary toxicity reported
              • Symptoms usually occur during or within 24 hr of administration
              • Discontinue treatment for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome)
              • Monitor until symptoms completely resolve

              Embryo-fetal toxicity

              • Exposure to trastuzumab/hyaluronidase during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
              • Inform patients of these risks and to use effective contraception

              Contraindications

              None

              Cautions

              Left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death may occur as well as asymptomatic decline in LVEF (see Black Box Warnings)

              Fetal harm may occur when administered to a pregnant woman (see Black Box Warnings and Pregnancy)

              Pulmonary toxicity (eg, dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, pulmonary fibrosis) reported; patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity (see Black Box Warnings)

              Chemotherapy-induced neutropenia may be exacerbated

              Severe administration-related reactions (ARRs), including hypersensitivity and anaphylaxis, reported; patients experiencing dyspnea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of a severe or fatal ARR

              Drug interaction overview

              • Since trastuzumab/hyaluronidase has a long washout period, patients who receive anthracycline after stopping trastuzumab/hyaluronidase may be at increased risk of cardiac dysfunction
              • If possible, avoid anthracycline-based therapy for at least 7 months after discontinuing trastuzumab/hyaluronidase
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              Pregnancy & Lactation

              Pregnancy

              Fetal harm when administered to a pregnant woman

              Verify pregnancy status of females of reproductive potential before initiation

              Female: Use effective contraception during treatment and for 7 months following the last dose

              Pregnancy pharmacovigilance program

              • If administered during pregnancy, or if a patient becomes pregnant while during treatment or within 7 months following the last dose, immediately report exposure to Genentech at 1-888-835-2555
              • In postmarketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
              • Advise patient of the potential risks to a fetus

              Clinical considerations

              • Monitor women who received treatment during pregnancy or within 7 months prior to conception for oligohydramnios
              • If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care

              Lactation

              There is no information regarding the presence of trastuzumab or hyaluronidase in human milk, the effects on the breastfed infant, or the effects on milk production

              Published data suggest human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts

              Present in the milk of lactating cynomolgus monkeys but not associated with neonatal toxicity

              Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for treatment and any potential adverse effects on the breastfed child or from the underlying maternal condition; also take into account the trastuzumab wash-out period of 7 months

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Trastuzumab

              • Monoclonal antibody; inhibits growth of tumor cells that overexpress HER2

              Hyaluronidase

              • Human hyaluronidase increases permeability of SC tissue by temporarily depolymerizing hyaluronan
              • Effects are reversible and permeability of SC tissue is restored within 24-48 hr

              Absorption

              Peak plasma concentration: 79.3 mcg/mL (Cycle 1); 149 mcg/mL (Cycle 7)

              Minimum plasma concentration: 28.2 mcg/mL (Cycle 1); 75 mcg/mL (Cycle 7)

              AUC: 1065 mcg/mL·day (Cycle 1); 2337 mcg/mL·day (Cycle 7)

              Absolute bioavailability: 0.77

              Peak plasma time: 3 days

              Steady-state reached after Cycle 7

              Distribution

              Vd: 2.9 L

              Elimination

              Linear elimination clearance: 0.11 L/day

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              Administration

              SC Administration

              SC administration only

              To prevent medication errors, check vial labels to ensure that the prepared drug to be administered is trastuzumab/hyaluronidase and not ado-trastuzumab emtansine or IV trastuzumab

              Compatible with polypropylene and polycarbonate syringe material and stainless steel transfer and injection needles

              Alternate injection site between the left and right thigh

              Administer new injections ≥2.5 cm from previous site on healthy skin; never inject into areas where the skin is red, bruised, tender, or hard, or areas where there are moles or scars

              During treatment course, inject other SC medicinal products at different sites

              Administer over ~2-5 min

              Missed dose

              • If 1 dose is missed, administer missed dose as soon as possible; interval between subsequent doses should not be <3 weeks

              Storage

              Protect from light; do not shake or freeze

              If syringe is not immediately used, refrigerate (2-8°C [36-46°F]) for up to 24 hr and subsequently at room temperature (20-25°C [68-77°F]) for up to 4 hr

              Vials

              • Refrigerate at 2-8°C (36-46°F) in original carton
              • Once removed from refrigerator, administer within 4 hr and keep <30°C (86°F)
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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.