Herceptin Hylecta

Last updated on RxList: 3/7/2019
Herceptin Hylecta Side Effects Center

Last reviewed on RxList 3/7/2019

Herceptin Hylecta (trastuzumab and hyaluronidase-oysk) is a combination of a HER2/neu receptor antagonist, and an endoglycosidase, indicated in adults for the treatment of HER2-overexpressing breast cancer. Common side effects of Herceptin Hylecta include:

  • fatigue,
  • joint pain,
  • diarrhea,
  • injection site reactions,
  • upper respiratory tract infection,
  • rash,
  • muscle pain
  • ,
  • nausea,
  • headache,
  • fluid retention,
  • flushing,
  • fever,
  • cough,
  • pain in extremities,
  • chills,
  • infection,
  • congestive heart failure, and
  • insomnia

The recommended dose of HERCEPTIN HYLECTA Is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously over approximately 2-5 minutes once every three weeks. Herceptin Hylecta may interact with anthracycline-based therapy. Tell your doctor all medications and supplements you use. Herceptin Hylecta is not recommended for use during pregnancy; it may harm a fetus. Tell your doctor if you become pregnant while using Herceptin Hylecta. There is a pregnancy pharmacovigilance program for Herceptin Hylecta. It is unknown if Herceptin Hylecta passes into breast milk. Consult your doctor before breastfeeding.

Our Herceptin Hylecta (trastuzumab and hyaluronidase-oysk) Injection, for Subcutaneous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

A lump in the breast is almost always cancer. See Answer
Herceptin Hylecta Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, nauseated, feverish, chilled, short of breath, or if you have diarrhea, a rash, chest pain, swelling in your face, or trouble breathing.

Call your doctor at once if you have:

  • new or worsening cough, wheezing, shortness of breath or rapid breathing;
  • swelling in your face or lower legs, rapid weight gain;
  • fast or pounding heartbeats, fluttering in your chest;
  • a light-headed feeling, like you might pass out;
  • blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
  • fluid build-up in the lungs--pain when you breathe, feeling short of breath while lying down, gasping for breath, cough with foamy mucus; or
  • low blood cell counts--fever, sore throat, tiredness, skin sores, pale skin, cold hands and feet, feeling light-headed.

Common side effects may include:

  • nausea, vomiting, diarrhea;
  • fever, chills, tiredness;
  • cough, breathing problems;
  • swelling;
  • hair loss;
  • flushing (sudden warmth, redness, or tingly feeling);
  • headache, muscle or joint pain;
  • cold symptoms such as stuffy nose, sneezing, sore throat;
  • sleep problems (insomnia);
  • rash; or
  • pain, burning, itching, swelling, warmth redness, bruising, bleeding, skin changes, or a hard lump where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Herceptin Hylecta (Trastuzumab and Hyaluronidase-oysk Injection, for Subcutaneous Use)

SLIDESHOW

Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See Slideshow
Herceptin Hylecta Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

  • Cardiomyopathy [see WARNINGS AND PRECAUTIONS]
  • Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]
  • Pulmonary Toxicity [see WARNINGS AND PRECAUTIONS]
  • Exacerbation of Chemotherapy-Induced Neutropenia [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity and Administration-Related Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of HERCEPTIN HYLECTA administered subcutaneously has been established in the HannaH and SafeHER studies conducted in patients with HER2 overexpressing breast cancer. The safety of intravenous trastuzumab has been established in studies H0648g and H0649g conducted in patients with HER2 overexpressing metastatic breast cancer.

Adjuvant Breast Cancer

HannaH

HannaH was a randomized, open-label study to compare the pharmacokinetics, efficacy, and safety of HERCEPTIN HYLECTA compared to intravenous trastuzumab in women with HER2-positive breast cancer. Patients randomized to the HERCEPTIN HYLECTA arm received a dose of 600 mg HERCEPTIN HYLECTA every 3 weeks throughout the treatment phase. Patients were treated for 8 cycles in combination with chemotherapy (docetaxel followed by 5FU, epirubicin and cyclophosphamide), then underwent surgery, and continued HERCEPTIN HYLECTA to complete 18 cycles of therapy. The median age of patients was 50 (range: 25-81 years), all patients were female, and a majority of patients were white (67%). The median number of HERCEPTIN HYLECTA cycles received was 18 (range 1-18).

The most common adverse reactions of any grade (occurring in ≥10% of patients) with HERCEPTIN HYLECTA were alopecia (63%), nausea (49%), ARRs (48%), neutropenia (44%), diarrhea (34%), asthenia (25%), fatigue (24%), vomiting (23%), myalgia (21%), decreased appetite (20%), stomatitis (19%), arthralgia (18%), headache (17%), rash (16%), constipation (14%), radiation skin injury (14%), pyrexia (12%), cough (12%), anemia (11%), dyspnea (11%), incision site pain (11%), peripheral sensory neuropathy (11%), leukopenia (10%), mucosal inflammation (10%), hot flush (10%), upper respiratory tract infection (10%).

The most common Grade ≥3 adverse reactions (occurring in >1% of patients) in the HERCEPTIN HYLECTA arm were neutropenia (30%), febrile neutropenia (6%), leukopenia (4%), diarrhea (3%), hypertension (2%), irregular menstruation (2%), alopecia (1%), nausea (1%), granulocytopenia (1%), vomiting (1%), amenorrhea (1%), and cellulitis (1%). Adverse reactions leading to interruption of any study drug in the HERCEPTIN HYLECTA arm occurred in 34% of patients; 31% of patients had these events during the neoadjuvant phase of the study with concurrent chemotherapy and 9% of patients had these events during the adjuvant phase. Overall, the most common (> 1%) were neutropenia (21%), leukopenia (2.4%), ALT increase (1.7%), pyrexia (1.7%), anemia (1%), bronchitis (1%), and left ventricular dysfunction (1%). Adverse reactions that led to discontinuation of any study drug in the HERCEPTIN HYLECTA arm (>1 patient) were left ventricular dysfunction (2%).

The incidence of ARRs in the HERCEPTIN HYLECTA arm was 48% and was 37% in the intravenous trastuzumab arm. Five (2%) patients in the HERCEPTIN HYLECTA arm experienced a Grade 3 ARR. Three of the events in the HERCEPTIN HYLECTA arm occurred on the day of study drug administration when docetaxel treatment was administered concurrently. The most commonly reported ARRs in the HERCEPTIN HYLECTA arm (≥5% of patients) were rash, pruritus, erythema, cough and dyspnea. Grade 1 and 2 injection-site reactions (ISRs) occurred in 10% of patients in the HERCEPTIN HYLECTA arm. The most common ISRs were injection-site pain and injection-site erythema.

The data in Table 3 were obtained from the HannaH trial for adverse reactions that occurred in ≥ 5% of the patients treated with HERCEPTIN HYLECTA.

Table 3 : Adverse Reactions* (≥ 5% Incidence) Reported in HannaH

Adverse Reactions HERCEPTIN HYLECTA 600 mg
n=297
Intravenous Trastuzumab (loading dose: 8 mg/kg; maintenance dose: 6 mg/kg)
n=298
All Grades % Grades 3 to 5 % All Grades % Grades 3 to 5 %
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Alopecia*,† 63 1.3 63 1.7
Rash*,† 26 < 1 26 -
Nail Disorder*,† 14 - 14 < 1
Pruritus*,† 9 - 9 -
Skin Discoloration* 9 - 8 -
Erythema* 7 < 1 3 -
GASTROINTESTINAL DISORDERS
Nausea 49 1.3 49 1.3
Diarrhea*,† 34 2.7 37 2.7
Vomiting† 23 1 23 1.7
Stomatitis* 21 < 1 18 < 1
Abdominal Pain*,† 14 - 14 < 1
Dyspepsia 11 - 10 -
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Fatigue*,† 46 < 1 49 2
Edema*,† 14 - 15 -
Pyrexia* 13 1 12 < 1
Mucosal Inflammation† 10 < 1 13 -
Pain*,† 5 - 8 < 1
Injection Site Reaction*,‡ 10 - < 1 -
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Neutropenia† 44 30 47 34
Leukopenia*,† 11 5 16 8
Anemia*,† 12 < 1 14 1
Febrile Neutropenia* 6 6 4 4
INFECTIONS AND INFESTATIONS
Upper Respiratory Tract Infection*,† 24 1 27 < 1
Urinary Tract Infection*,† 4 - 8 < 1
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Myalgia* 21 - 19 < 1
Arthralgia*,† 18 - 21 < 1
Back Pain* 11 1 9 1
Pain in Extremity 10 - 9 < 1
Pain*,† 8 < 1 9 -
Bone Pain 6 < 1 3.4 -
NERVOUS SYSTEM DISORDERS
Neuropathy Peripheral* 20 - 15 -
Headache* 17 < 1 15 < 1
Dizziness* 10 < 1 9 < 1
Dysgeusia* 10 - 8 -
INJURY, POISONING AND PROCEDURAL COMPLICATIONS
Incision Site Complication* 11 - 8 < 1
Pain* 6 - 5 < 1
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Cough* 12 < 1 8 -
Dyspnea*,† 7 - 8 -
Epistaxis 6 - 6 -
Nasal Inflammation / Discomfort*,† 5 - 7 -
VASCULAR DISORDERS
Flushing* 14 < 1 13 < 1
Hypertension* 8 2.4 5 < 1
METABOLISM AND NUTRITION DISORDERS
Decreased Appetite 20 < 1 20 < 1
INVESTIGATIONS
Liver Function Analysis Abnormal*,† 6 1 9 1.7
CARDIAC DISORDERS
Arrhythmia*,† 5 - 5 < 1
IMMUNE SYSTEM DISORDERS
Hypersensitivity *,† 7 1 7 1.3
* Contains grouped terms
† The HannaH trial was not designed to demonstrate a statistically significant difference in adverse reaction rates between HERCEPTIN HYLECTA and intravenous trastuzumab.
‡ Injection Site Reaction includes terms for injection related reaction and injection site joint pain, bruising, dermatitis, discoloration, discomfort, erythema, extravasation, fibrosis, hematoma, hemorrhage, hypersensitivity, induration, inflammation, irritation, macule, mass, nodule, edema, pallor, paraesthesia, pruritus, rash, reaction, swelling, ulcer, vesicles and warmth.

SafeHER

SafeHER was a prospective, two-cohort, non-randomized, multi-center, multinational, open-label study to assess the safety of HERCEPTIN HYLECTA in patients with operable HER2-positive breast cancer. In SafeHER, 1864 patients were enrolled and treated with 600 mg of HERCEPTIN HYLECTA administered subcutaneously once every three weeks for 18 cycles.

The median age of patients was 54 (range: 20-88 years), 99.8% were female, and a majority were white (76%). A majority of the patients received HERCEPTIN HYLECTA concurrently with a chemotherapy regimen (58%). The median number of HERCEPTIN HYLECTA cycles administered was 18 and the median duration of HERCEPTIN HYLECTA exposure was 11.8 months. The median duration of follow-up was 23.7 months.

During the treatment period, the most common adverse reactions of any grade (occurring in ≥10% of patients) were ARRs (39%), diarrhea (21%), fatigue (21%), arthralgia (21%), nausea (15%), myalgia (14%), headache (13%), asthenia (12%), pain in extremity (11%), cough (11%), pyrexia (11%), hot flush (10%), and rash (10%). The most common Grade ≥3 adverse reactions (occurring in >1% of patients) were neutropenia (4%), febrile neutropenia (2%), hypertension (2%), leukopenia (1%), and diarrhea (1%). Adverse reactions that led to study drug discontinuation (≥0.5% of patients) were ejection fraction decreased (2%) and left ventricular dysfunction (1%).

The incidence of ARRs was 39%, with Grade ≥3 ARRs reported in 1% of patients treated with HERCEPTIN HYLECTA. The most frequently reported Grade ≥3 ARRs were dyspnea (<1%), cough (<1%), erythema (<1%), rash (<1%), and drug hypersensitivity (<1%). ISRs were reported in 20% of patients treated with HERCEPTIN HYLECTA. The most common ISRs were injection-site erythema (7%) and injection-site pain (6%). All ISRs were Grade 1 or 2, except for one (<1%) Grade 3 injection site discomfort.

The data in Table 4 were obtained from the SafeHER trial for adverse reactions that occurred in ≥5% of the patients treated with HERCEPTIN HYLECTA.

Table 4 : Adverse Reactions* (≥ 5% Incidence) Reported in SafeHER

Adverse Reactions*,† HERCEPTIN HYLECTA 600 mg (once every 3 weeks)
n=1864
All Grades % Grades 3 to 5 %
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Fatigue* 33 < 1
Injection Site Reaction*,‡ 20 < 1
Edema* 12 < 1
Pyrexia* 11 < 1
Pain* 8 < 1
Mucosal Inflammation 6 < 1
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Arthralgia* 21 < 1
Myalgia* 17 < 1
Pain in Extremity 11 < 1
Back Pain* 8 < 1
Pain* 7 < 1
GASTROINTESTINAL DISORDERS
Diarrhea* 21 1
Nausea 15 < 1
Abdominal Pain* 10 < 1
Constipation 9 < 1
Stomatitis* 8 < 1
Vomiting 7 < 1
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Rash* 17 < 1
Nail Disorder* 10 < 1
Alopecia* 9 < 1
Erythema* 9 < 1
Pruritus* 6 -
INFECTIONS AND INFESTATIONS
Upper Respiratory Tract Infection* 19 < 1
Urinary Tract Infection* 6 < 1
Viral Infection* 5 -
NERVOUS SYSTEM DISORDERS
Neuropathy Peripheral* 14 < 1
Headache* 13 < 1
Dizziness* 6 < 1
Paresthesia 6 < 1
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Cough* 11 < 1
Dyspnea* 8 < 1
Epistaxis 6 -
Nasal Inflammation/Discomfort* 6 -
VASCULAR DISORDERS
Flushing* 12 < 1
Hypertension* 8 2
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Anemia* 8 < 1
Neutropenia 6 4
PSYCHIATRIC DISORDERS
Insomnia* 7 < 1
* Contains grouped terms
† Includes adverse reactions reported throughout study treatment and follow-up.
‡ ISR includes injection related reaction and injection site joint pain, bruising, dermatitis, discoloration, discomfort, erythema, extravasation, fibrosis, hematoma, hemorrhage, hypersensitivity, induration, inflammation, irritation, macule, mass, nodule, edema, pallor, paresthesia, pruritus, rash, reaction, swelling, ulcer, vesicles and warmth.

Metastatic Breast Cancer (Based On Intravenous Trastuzumab)

The data below reflect exposure to intravenous trastuzumab in one randomized, open-label study, H0648g, of chemotherapy with (n=235) or without (n=234) intravenous trastuzumab in patients with metastatic breast cancer, and one single-arm study (H0649g; n=222) in patients with metastatic breast cancer. Data in Table 5 are based on H0648g and H0649g.

Among the 464 patients treated in H0648g, the median age was 52 years (range: 25-77 years). Eighty-nine percent were white, 5% black, 1% Asian, and 5% other racial/ethnic groups. All patients received 4 mg/kg initial dose of intravenous trastuzumab followed by 2 mg/kg weekly. The percentages of patients who received intravenous trastuzumab treatment for ≥ 6 months and ≥ 12 months were 58% and 9%, respectively. Among the 352 patients treated in single agent studies (213 patients from H0649g), the median age was 50 years (range 28-86 years), 86% were white, 3% were black, 3% were Asian, and 8% in other racial/ethnic groups. Most of the patients received 4 mg/kg initial dose of intravenous trastuzumab followed by 2 mg/kg weekly. The percentages of patients who received intravenous trastuzumab treatment for ≥ 6 months and ≥ 12 months were 31% and 16%, respectively.

Table 5 : Per-Patient Incidence of Adverse Reactions Occurring in ≥ 5% of Patients in Uncontrolled Studies or at Increased Incidence in the Intravenous Trastuzumab Arm (H0648g and H0649g)

  Single agent*
n=352
Intravenous trastuzumab + paclitaxel
n=91
Paclitaxel alone
n=95
Intravenous trastuzumab + AC†
n=143
AC† alone
n=135
Body as a Whole
Pain 47% 61% 62% 57% 42%
Asthenia 42% 62% 57% 54% 55%
Fever 36% 49% 23% 56% 34%
Chills 32% 41% 4% 35% 11%
Headache 26% 36% 28% 44% 31%
Abdominal pain 22% 34% 22% 23% 18%
Back pain 22% 34% 30% 27% 15%
Infection 20% 47% 27% 47% 31%
Flu syndrome 10% 12% 5% 12% 6%
Accidental injury 6% 13% 3% 9% 4%
Allergic reaction 3% 8% 2% 4% 2%
Cardiovascular
Tachycardia 5% 12% 4% 10% 5%
Congestive heart failure 7% 11% 1% 28% 7%
Digestive
Nausea 33% 51% 9% 76% 77%
Diarrhea 25% 45% 29% 45% 26%
Vomiting 23% 37% 28% 53% 49%
Nausea and vomiting 8% 14% 11% 18% 9%
Anorexia 14% 24% 16% 31% 26%
Heme & Lymphatic
Anemia 4% 14% 9% 36% 26%
Leukopenia 3% 24% 17% 52% 34%
Metabolic
Peripheral edema 10% 22% 20% 20% 17%
Edema 8% 10% 8% 11% 5%
Musculoskeletal
Bone pain 7% 24% 18% 7% 7%
Arthralgia 6% 37% 21% 8% 9%
Nervous
Insomnia 14% 25% 13% 29% 15%
Dizziness 13% 22% 24% 24% 18%
Paresthesia 9% 48% 39% 17% 11%
Depression 6% 12% 13% 20% 12%
Peripheral neuritis 2% 23% 16% 2% 2%
Neuropathy 1% 13% 5% 4% 4%
Respiratory
Cough increased 26% 41% 22% 43% 29%
Dyspnea 22% 27% 26% 42% 25%
Rhinitis 14% 22% 5% 22% 16%
Pharyngitis 12% 22% 14% 30% 18%
Sinusitis 9% 21% 7% 13% 6%
Skin
Rash 18% 38% 18% 27% 17%
Herpes simplex 2% 12% 3% 7% 9%
Acne 2% 11% 3% 3% < 1%
Urogenital
Urinary tract infection 5% 18% 14% 13% 7%
* Data for intravenous trastuzumab single agent were from 4 studies, including 213 patients from H0649g.
† Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to HERCEPTIN HYLECTA and intravenous trastuzumab in the study described below with the incidence of antibodies in other studies or to other products may be misleading.

In the HannaH study, at a median follow-up exceeding 60 months, the incidence of treatment-induced/enhanced anti-trastuzumab antibodies was 10% (30/296) in patients treated with intravenous trastuzumab and 16% (47/295) in patients receiving HERCEPTIN HYLECTA. Neutralizing anti-trastuzumab antibodies were detected in post-baseline samples in 2/30 patients in the intravenous trastuzumab arm and 3/47 patients in the HERCEPTIN HYLECTA arm. The incidence of treatment-induced/enhanced anti-recombinant human hyaluronidase antibodies was 21% (62/295) in the HERCEPTIN HYLECTA arm. None of the patients who tested positive for anti-recombinant human hyaluronidase antibodies tested positive for neutralizing antibodies.

The clinical relevance of the development of anti-trastuzumab or anti-recombinant human hyaluronidase antibodies after treatment with HERCEPTIN HYLECTA is not known.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of trastuzumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Administration-related reaction [see WARNINGS AND PRECAUTIONS]
  • Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death [see WARNINGS AND PRECAUTIONS]
  • Glomerulopathy [see Clinical Trials Experience]
  • Immune thrombocytopenia
  • Tumor lysis syndrome (TLS): Cases of possible TLS have been reported in patients treated with trastuzumab. Patients with significant tumor burden (e.g. bulky metastases) may be at a higher risk. Patients could present with hyperuricemia, hyperphosphatemia, and acute renal failure which may represent possible TLS. Providers should consider additional monitoring and/or treatment as clinically indicated.

Read the entire FDA prescribing information for Herceptin Hylecta (Trastuzumab and Hyaluronidase-oysk Injection, for Subcutaneous Use)

© Herceptin Hylecta Patient Information is supplied by Cerner Multum, Inc. and Herceptin Hylecta Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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