This is the Header Notice module. It can be used for Cookie Law messages or any other text. Multiple modules with different styles can be added on any page.
Herceptin 150 Mg 1 Vial

Unlimited Blocks

There's no limit to how many blocks you can create. You can position custom product page blocks in different positions and can also display custom blocks on out of stock products only.

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY

1 INDICATIONS AND USAGE

1.1 Adjuvant Breast Cancer

1.2 Metastatic Breast Cancer

1.3 Metastatic Gastric Cancer

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Doses and Schedules

2.2 Dose Modifications

2.3 Preparation for Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Cardiomyopathy

5.2 Infusion Reactions

5.3 Embryo-Fetal Toxicity

5.4 Pulmonary Toxicity

5.5 Exacerbation of Chemotherapy-Induced Neutropenia

5.6 HER2 Testing

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Immunogenicity

6.3 Post-Marketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Adjuvant Breast Cancer

14.2 Metastatic Breast Cancer

14.3 Metastatic Gastric Cancer

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Stability and Storage

17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY

Cardiomyopathy

Herceptin administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens.

Evaluate left ventricular function in all patients prior to and during treatment with Herceptin. Discontinue Herceptin treatment in patients receiving adjuvant therapy and withhold Herceptin in patients with metastatic disease for clinically significant decrease in left ventricular function. [see Warnings and Precautions (5.1) and Dosage and Administration (2.2)]

Infusion Reactions; Pulmonary Toxicity

Herceptin administration can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of Herceptin administration. Interrupt Herceptin infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. [see Warnings and Precautions (5.2, 5.4)]

Embryo Fetal Toxicity

Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. [see Warnings and Precautions (5.3), Use in Specific Populations (8.1)]

1 INDICATIONS AND USAGE

1.1 Adjuvant Breast Cancer

Herceptin is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies (14.1)]) breast cancer

  • as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
  • with docetaxel and carboplatin
  • as a single agent following multi-modality anthracycline based therapy.

1.2 Metastatic Breast Cancer

Herceptin is indicated:

  • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer
  • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.

1.3 Metastatic Gastric Cancer

Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Doses and Schedules

  • Do not administer as an intravenous push or bolus. Do not mix Herceptin with other drugs.
  • Do not substitute Herceptin (trastuzumab) for or with ado-trastuzumab emtansine.

Adjuvant Treatment, Breast Cancer:

Administer according to one of the following doses and schedules for a total of 52 weeks of Herceptin therapy:

During and following paclitaxel, docetaxel, or docetaxel/carboplatin:

  • Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin).
  • One week following the last weekly dose of Herceptin, administer Herceptin at 6 mg/kg as an intravenous infusion over 30–90 minutes every three weeks.

As a single agent within three weeks following completion of multi-modality, anthracycline-based chemotherapy regimens:

  • Initial dose at 8 mg/kg as an intravenous infusion over 90 minutes
  • Subsequent doses at 6 mg/kg as an intravenous infusion over 30–90 minutes every three weeks.

[see Dosage and Administration (2.2)]

  • Extending adjuvant treatment beyond one year is not recommended [see Adverse Reactions (6.1)].

Metastatic Treatment, Breast Cancer:

  • Administer Herceptin, alone or in combination with paclitaxel, at an initial dose of 4 mg/kg as a 90 minute intravenous infusion followed by subsequent once weekly doses of 2 mg/kg as 30 minute intravenous infusions until disease progression.

Metastatic Gastric Cancer:

  • Administer Herceptin at an initial dose of 8 mg/kg as a 90 minute intravenous infusion followed by subsequent doses of 6 mg/kg as an intravenous infusion over 30-90 minutes every three weeks until disease progression [see Dosage and Administration (2.2)].

2.2 Dose Modifications

Infusion Reactions

[see Boxed Warning, Warnings and Precautions (5.2)]

  • Decrease the rate of infusion for mild or moderate infusion reactions
  • Interrupt the infusion in patients with dyspnea or clinically significant hypotension
  • Discontinue Herceptin for severe or life-threatening infusion reactions.

Cardiomyopathy

[see Boxed Warning, Warnings and Precautions (5.1)]

Assess left ventricular ejection fraction (LVEF) prior to initiation of Herceptin and at regular intervals during treatment. Withhold Herceptin dosing for at least 4 weeks for either of the following:

  • ≥ 16% absolute decrease in LVEF from pre-treatment values
  • LVEF below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values.

Herceptin may be resumed if, within 4–8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is ≤ 15%.

Permanently discontinue Herceptin for a persistent (> 8 weeks) LVEF decline or for suspension of Herceptin dosing on more than 3 occasions for cardiomyopathy.

2.3 Preparation for Administration

To prevent medication errors, it is important to check the vial labels to ensure that the drug being prepared and administered is Herceptin (trastuzumab) and not ado-trastuzumab emtansine.

Reconstitution

Reconstitute each 440 mg vial of Herceptin with 20 mL of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multi-dose solution containing 21 mg/mL trastuzumab. In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20 mL of Sterile Water for Injection (SWFI) without preservative to yield a single use solution.

Use appropriate aseptic technique when performing the following reconstitution steps:

  • Using a sterile syringe, slowly inject the 20 mL of diluent into the vial containing the lyophilized cake of Herceptin. The stream of diluent should be directed into the lyophilized cake.
  • Swirl the vial gently to aid reconstitution. DO NOT SHAKE.
  • Slight foaming of the product may be present upon reconstitution. Allow the vial to stand undisturbed for approximately 5 minutes.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Inspect visually for particulates and discoloration. The solution should be free of visible particulates, clear to slightly opalescent and colorless to pale yellow.
  • Store reconstituted Herceptin at 2–8° C; discard unused Herceptin after 28 days. If Herceptin is reconstituted with SWFI without preservative, use immediately and discard any unused portion.

Dilution

  • Determine the dose (mg) of Herceptin [see Dosage and Administration (2.1)]. Calculate the volume of the 21 mg/mL reconstituted Herceptin solution needed, withdraw this amount from the vial and add it to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection, USP.
    DO NOT USE DEXTROSE (5%) SOLUTION.
  • Gently invert the bag to mix the solution.

3 DOSAGE FORMS AND STRENGTHS

440 mg lyophilized powder per multi-use vial.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Cardiomyopathy

Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy]. Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF).

There is a 4–6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not receiving Herceptin. The highest absolute incidence occurs when Herceptin is administered with an anthracycline.

Withhold Herceptin for ≥ 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values [see Dosage and Administration (2.2)]. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied.

Cardiac Monitoring

Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended:

  • Baseline LVEF measurement immediately prior to initiation of Herceptin
  • LVEF measurements every 3 months during and upon completion of Herceptin
  • Repeat LVEF measurement at 4 week intervals if Herceptin is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration (2.2)]
  • LVEF measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy.

In Study 1, 15% (158/1031) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF after a median follow-up duration of 8.7 years in the AC-TH arm. In Study 3 (one-year Herceptin treatment), the number of patients who discontinued Herceptin due to cardiac toxicity at 12.6 months median duration of follow-up was 2.6% (44/1678). In Study 4, a total of 2.9% (31/1056) patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) patients in the AC-TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity.

Among 64 patients receiving adjuvant chemotherapy (Studies 1 and 2) who developed congestive heart failure, one patient died of cardiomyopathy, one patient died suddenly without documented etiology and 33 patients were receiving cardiac medication at last follow-up. Approximately 24% of the surviving patients had recovery to a normal LVEF (defined as ≥50%) and no symptoms on continuing medical management at the time of last follow-up. Incidence of congestive heart failure is presented in Table 1. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied.

Table 1: Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies

   

Incidence of CHF

Study

Regimen

Herceptin

Control

*Median follow-up duration for studies 1 and 2 combined was 8.3 years in the AC→TH arm.

†Anthracycline (doxorubicin) and cyclophosphamide.

Includes 1 patient with fatal cardiomyopathy and 1 patient with sudden death without documented etiology.

§Includes NYHA II-IV and cardiac death at 12.6 months median duration of follow-up in the one-year Herceptin arm.

1 & 2*

AC† → Paclitaxel+Herceptin

3.2% (64/2000)‡

1.3% (21/1655)

Chemo → Herceptin

2% (30/1678)

0.3% (5/1708)

4

AC† → Docetaxel+Herceptin

2% (20/1068)

0.3% (3/1050)

4

Docetaxel+Carbo+Herceptin

0.4% (4/1056)

0.3% (3/1050)

In Study 3 (one-year Herceptin treatment), at a median follow-up duration of 8 years, the incidence of severe CHF (NYHA III & IV) was 0.8%, and the rate of mild symptomatic and asymptomatic left ventricular dysfunction was 4.6%.

Table 2: Incidence of Cardiac Dysfunction* in Metastatic Breast Cancer Studies

 

 

Incidence

 

 

NYHA I-IV

NYHA III-IV

Study

Event

Herceptin

Control

Herceptin

Control

*Congestive heart failure or significant asymptomatic decrease in LVEF.

†Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.

‡Includes 1 patient with fatal cardiomyopathy.

5 (AC)†

Cardiac Dysfunction

28%

7%

19%

3%

5 (paclitaxel)

Cardiac Dysfunction

11%

1%

4%

1%

6

Cardiac Dysfunction‡

7%

N/A

5%

N/A

In Study 4, the incidence of NCI-CTC Grade 3/4 cardiac ischemia/infarction was higher in the Herceptin containing regimens: (AC-TH: 0.3% (3/1068) and TCH 0.2% (2/1056)) as compared to none in AC-T.

5.2 Infusion Reactions

Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia. [see Adverse Reactions (6.1)]

In postmarketing reports, serious and fatal infusion reactions have been reported. Severe reactions which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable including progressive worsening, initial improvement followed by clinical deterioration, or delayed post-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction.

Interrupt Herceptin infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered, which may include: epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen. Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions.

There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Herceptin after experiencing a severe infusion reaction. Prior to resumption of Herceptin infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Herceptin infusions, others had recurrent severe infusion reactions despite pre-medications.

5.3 Embryo-Fetal Toxicity

Herceptin can cause fetal harm when administered to a pregnant woman. In post marketing reports, use of Herceptin during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy and provide contraception counseling to women of childbearing potential. [see Use in Specific Populations (8.1), Patient Counseling Information (17)].

5.4 Pulmonary Toxicity

Herceptin use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions [see Warnings and Precautions (5.2)]. 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.

5.5 Exacerbation of Chemotherapy-Induced Neutropenia

In randomized, controlled clinical trials the per-patient incidences of NCI CTC Grade 3–4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received Herceptin and those who did not. [see Adverse Reactions (6.1)]

5.6 HER2 Testing

Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown. Due to differences in tumor histopathology, use FDA-approved tests for the specific tumor type (breast or gastric/gastroesophageal adenocarcinoma) to assess HER2 protein overexpression and HER2 gene amplification. Tests should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.

Several FDA-approved commercial assays are available to aid in the selection of breast cancer and metastatic gastric cancer patients for Herceptin therapy. Users should refer to the package inserts of specific assay kits for information on the Intended Use, and the validation and performance of each assay.

Limitations in assay precision make it inadvisable to rely on a single method to rule out potential Herceptin benefit.

Treatment outcomes for adjuvant breast cancer (Studies 2 and 3) and for metastatic breast cancer (Study 5) as a function of IHC and FISH testing are provided in Tables 8 and 10.

Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-approved tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers. Study 7 demonstrated that gene amplification and protein overexpression were not as well correlated as with breast cancer. Treatment outcomes for metastatic gastric cancer (Study 7), based on HER2 gene amplification (FISH) and HER2 protein overexpression (IHC) test results are provided in Table 12.

6 ADVERSE REACTIONS

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

  • Cardiomyopathy [see Warnings and Precautions (5.1)]
  • Infusion reactions [see Warnings and Precautions (5.2)]
  • Embryo-fetal Toxicity [see Warnings and Precautions (5.3)]
  • Pulmonary toxicity [see Warnings and Precautions (5.4)]
  • Exacerbation of chemotherapy-induced neutropenia [see Warnings and Precautions (5.5)]

The most common adverse reactions in patients receiving Herceptin in the adjuvant and metastatic breast cancer setting are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity [see Dosage and Administration (2.2)].

In the metastatic gastric cancer setting, the most common adverse reactions (≥ 10%) that were increased (≥ 5% difference) in the Herceptin arm as compared to the chemotherapy alone arm were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common adverse reactions which resulted in discontinuation of treatment on the Herceptin-containing arm in the absence of disease progression were infection, diarrhea, and febrile neutropenia.

6.1 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.

Adjuvant Breast Cancer Studies

The data below reflect exposure to one-year Herceptin therapy across three randomized, open-label studies, Studies 1, 2, and 3, with (n=3678) or without (n= 3363) trastuzumab in the adjuvant treatment of breast cancer.

The data summarized in Table 3 below, from Study 3, reflect exposure to Herceptin in 1678 patients; the median treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patients enrolled in the observation and one-year Herceptin arms of Study 3 at a median duration of follow-up of 12.6 months in the Herceptin arm, the median age was 49 years (range: 21 to 80 years), 83% of patients were Caucasian, and 13% were Asian.

Table 3: Adverse Reactions for Study 3*, All Grades†:

 

One Year Herceptin

Observation

Adverse Reaction

(n=1678)

(n=1708)

*Median follow-up duration of 12.6 months in the one-year Herceptin treatment arm.

†The incidence of Grade 3 or higher adverse reactions was <1% in both arms for each listed term.

‡Higher level grouping term.


Cardiac

   

Hypertension

64 (4%)

35 (2%)

Dizziness

60 (4%)

29 (2%)

Ejection Fraction Decreased

58 (3.5%)

11 (0.6%)

Palpitations

48 (3%)

12 (0.7%)

Cardiac Arrhythmias‡

40 (3%)

17 (1%)

Cardiac Failure Congestive

30 (2%)

5 (0.3%)

Cardiac Failure

9 (0.5%)

4 (0.2%)

Cardiac Disorder

5 (0.3%)

0 (0%)

Ventricular Dysfunction

4 (0.2%)

0 (0%)


Respiratory Thoracic Mediastinal Disorders

Cough

81 (5%)

34 (2%)

Influenza

70 (4%)

9 (0.5%)

Dyspnea

57 (3%)

26 (2%)

URI

46 (3%)

20 (1%)

Rhinitis

36 (2%)

6 (0.4%)

Pharyngolaryngeal Pain

32 (2%)

8 (0.5%)

Sinusitis

26 (2%)

5 (0.3%)

Epistaxis

25 (2%)

1 (0.06%)

Pulmonary Hypertension

4 (0.2%)

0 (0%)

Interstitial Pneumonitis

4 (0.2%)

0 (0%)


Gastrointestinal Disorders

Diarrhea

123 (7%)

16 (1%)

Nausea

108 (6%)

19 (1%)

Vomiting

58 (3.5%)

10 (0.6%)

Constipation

33 (2%)

17 (1%)

Dyspepsia

30 (2%)

9 (0.5%)

Upper Abdominal Pain

29 (2%)

15 (1%)


Musculoskeletal & Connective Tissue Disorders

Arthralgia

137 (8%)

98 (6%)

Back Pain

91 (5%)

58 (3%)

Myalgia

63 (4%)

17 (1%)

Bone Pain

49 (3%)

26 (2%)

Muscle Spasm

46 (3%)

3 (0.2%)


Nervous System Disorders

Headache

162 (10%)

4

Write a review

Note: HTML is not translated!
    Bad           Good

Herceptin 150 Mg 1 Vial

  • Brand: Roche
  • Product Code: 8699548152719
  • Availability: In Stock
  • $1thousand_point730.00

Tags: Herceptin 150 Mg 1 Vial, Roche, All Products, Anticancer