Portrazza

Last updated on RxList: 11/15/2018
Portrazza Side Effects Center

Last reviewed on RxList 11/15/2018

Portrazza (necitumumab) injection is an epidermal growth factor receptor (EGFR) antagonist indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. Common side effects of Portrazza include:

The recommended dose of Portrazza is 800 mg as an intravenous infusion over 60 minutes on Days 1 and 8 of each 3-week cycle. Portrazza may interact with other drugs. Tell your doctor all medications and supplements you use. Portrazza is not recommended for use during pregnancy; it may harm a fetus. Breastfeeding during treatment with Portrazza is not recommended.

Our Portrazza (necitumumab) injection 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.

SLIDESHOW

Lung Cancer: Early Signs, Symptoms, Stages See Slideshow
Portrazza 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 chilled or feverish, or if you have trouble breathing.

Call your doctor at once if you have:

  • acne-like skin rash;
  • thickened skin or a hard lump where the medicine was injected;
  • slow heart rate, weak pulse, fainting, slow breathing (breathing may stop);
  • chest pain or pressure, pain spreading to your jaw or shoulder;
  • signs of a blood clot--sudden numbness or weakness, problems with vision or speech, sudden cough, wheezing, coughing up blood, pain or swelling in an arm or leg; or
  • symptoms of an electrolyte imbalance--numbness or tingling, irregular heartbeats, muscle tightness, tremors, muscle weakness or limp feeling, leg cramps, increased thirst or urination, behavior changes, seizure (convulsions).

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • vomiting, diarrhea;
  • skin rash; or
  • low levels of magnesium in your blood.

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 Portrazza (Necitumumab Intravenous Injection)

QUESTION

Lung cancer is a disease in which lung cells grow abnormally in an uncontrolled way. See Answer
Portrazza Professional Information

SIDE EFFECTS

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

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 PORTRAZZA was evaluated in two randomized, open-label trials comparing PORTRAZZA plus gemcitabine and cisplatin to gemcitabine and cisplatin alone in patients with squamous NSCLC (Study 1), and PORTRAZZA plus pemetrexed and cisplatin to pemetrexed and cisplatin alone in patients with non-squamous NSCLC (Study 2). Since the data in Study 2 demonstrated similar incidence of adverse reactions over control as observed in Study 1, the safety data from Study 1 alone is described below.

For patients who received at least 1 dose of treatment in Study 1, the median age was 62 years (range 32 to 84), 83% were male; 84% were Caucasian; and 92% were smokers. Baseline ECOG performance status was 0 or 1 for 91%, and 2 for 9% of patients; 90% had metastatic disease in 2 or more sites. Patients received PORTRAZZA 800 mg intravenously on days 1 and 8 of each 21 day cycle in combination with up to six cycles of gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin (75 mg/m2 on day 1). Patients received PORTRAZZA until progressive disease or unacceptable toxicity.

Patients in the gemcitabine and cisplatin alone arm received a maximum of 6 cycles, while patients in the PORTRAZZA plus gemcitabine and cisplatin arm demonstrating at least stable disease were permitted to continue to receive additional cycles of PORTRAZZA until disease progression or unacceptable toxicity. The median duration of exposure to PORTRAZZA in 538 patients who received at least 1 dose of treatment in Study 1 was 4.6 months (range 0.5 months to 34 months), including 182 patients exposed for at least 6 months and 41 patients exposed for greater than 1 year. Patients were monitored for safety until 30 days after treatment discontinuation and resolution of treatment-emergent adverse events.

The most common adverse reactions (all grades) observed in PORTRAZZA-treated patients at a rate of ≥ 15% and ≥ 2% higher than gemcitabine and cisplatin alone were rash (44%), vomiting (29%), diarrhea (16%), and dermatitis acneiform (15%). The most common severe (Grade 3 or higher) adverse events that occurred at a ≥ 2% higher rate in PORTRAZZA-treated patients compared to patients treated with gemcitabine and cisplatin alone were venous thromboembolic events (5%; including pulmonary embolism), rash (4%), and vomiting (3%).

Table 1 contains selected adverse drug reactions observed in Study 1 at an incidence of ≥ 5% in the PORTRAZZA arm and at ≥ 2% higher incidence than the control arm.

Table 1: Adverse Reactions Occurring at Incidence Rate ≥ 5% All Grades or a ≥ 2% Grade 3-4 Difference Between Arms in Patients Receiving PORTRAZZA in Study 1

Adverse Reactions (MedDRA) System Organ Class PORTRAZZA PLUS GEMCITABINE AND CISPLATIN N=538 (%) GEMCITABINE AND CISPLATIN N=541(%)
All Grades (Frequency %) Grade 3-4 (Frequency %) All Grades (Frequency %) Grade 3-4 (Frequency %)
Skin and Subcutaneous Tissue Disorders
  Rash 44 4 6 0.2
  Dermatitis Acneiform 15 1 0.6 0
  Acne 9 0.4 0.6 0
  Pruritus 7 0.2 0.9 0.2
  Dry Skin 7 0 1 0
  Skin fissures 5 0.4 0 0
Gastrointestinal Disorders
Vomiting 29 3 25 0.9
Diarrhea 16 2 11 1
  Stomatitis 11 1 6 0.6
Investigations
  Weight decreased 13 0.7 6 0.6
Respiratory, Thoracic and Mediastinal Disorders
  Hemoptysis 10 1 5 0.9
  Pulmonary embolisma 5 4 2 2
Nervous System Disorders
  Headache 11 0 6 0.4
Vascular Disorders
  Venous Thromboembolic Events (VTE)b 9 5 5 3
Infections and Infestations
  Paronychia 7 0.4 0.2 0
Eye Disorders
  ConjunctivitisC 7 0.4 2 0
a Pulmonary embolism is also included in the composite term venous thromboembolic events under system organ class vascular disorders.
b VTE is a composite term which includes: pulmonary embolism, deep vein thrombosis, thrombosis, mesenteric veins thrombosis, pulmonary artery thrombosis, pulmonary venous thrombosis, venous thrombosis limb, axillary vein thrombosis, thrombophlebitis, thrombosis in device, vena cava thrombosis, venous thrombosis, subclavian vein thrombosis, superior vena cava syndrome, and thrombophlebitis superficial.
c Conjunctivitis is a composite term that includes conjunctivitis, eye irritation, vision blurred, conjunctivitis bacterial, dry eye, visual acuity reduced, blepharitis, allergic blepharitis, conjunctiva hemorrhage, eye infection, eye pain, lacrimation increased, ocular hyperemia, Sjogren's syndrome, visual impairment, and eye pruritus.

Clinically relevant adverse reactions (all grades) reported in ≥ 1% and <5% of patients treated with PORTRAZZA were: dysphagia (3%), oropharyngeal pain (1%), muscle spasms (2%), phlebitis (2%), and hypersensitivity/IRR (1.5%).

In Study 1, 12% of the patients on the PORTRAZZA arm discontinued study treatment due to an adverse reaction. The most common PORTRAZZA related toxicity leading to PORTRAZZA discontinuation was skin rash (1%).

Table 2 contains selected electrolyte abnormalities observed in Study 1 according to laboratory assessment at an incidence of >10% in the PORTRAZZA arm and at >2% higher incidence than the control arm.

The median time to onset of hypomagnesemia was 6 weeks (25th percentile 4 weeks; 75th percentile 9 weeks). Hypomagnesemia was reported as resolved in 43% of the patients who received PORTRAZZA. In Study 1, 32% of the patients in the PORTRAZZA arm and 16% of the patients who received gemcitabine and cisplatin alone received magnesium replacement.

Table 2: Electrolyte Abnormalities according to Laboratory Assessment at Incidence Rate >10% and a >2% Difference between Arms in Patients Receiving PORTRAZZA in Study 1a

LABORATORY PARAMETER PORTRAZZA PLUS GEMCITABINE AND CISPLATIN GEMCITABINE AND CISPLATIN
N=538 N=541
Na All Grades Grade 3 or 4 Na All Grades Grade 3 or 4
(Frequency %) (Frequency %) (Frequency %) (Frequency %)
Hypomagnesemia 461 83 20 457 70 7
Hypokalemia 505 28 5 505 18 3
Hypocalcemia 502 45 6 499 30 2
Hypocalcemia (albumin corrected) 477 36 4 480 23 2
Hypophosphatemia 462 31 8 454 23 6
a Only patients with baseline and at least one post-baseline result are included.

Immunogenicity

As with all therapeutic proteins, there is the potential for immunogenicity. In clinical trials, treatment-emergent anti-necitumumab antibodies (ADA) were detected in 4.1% (33/814) of patients using an enzyme-linked immunosorbent assay (ELISA). Neutralizing antibodies were detected in 1.4% (11/814) of patients post exposure to PORTRAZZA. No relationship was found between the presence of ADA and incidence of infusion-related reactions. The impact of ADA on efficacy (overall survival) could not be assessed due to the limited number of patients with treatment-emergent ADA. In Study 1, the exposure to necitumumab was lower in patients with ADA post-treatment than in patients without detectable ADA [see CLINICAL PHARMACOLOGY].

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 incidence of antibodies to PORTRAZZA with the incidences of antibodies to other products may be misleading.

Read the entire FDA prescribing information for Portrazza (Necitumumab Intravenous Injection)

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

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