Gammaked

Last updated on RxList: 3/16/2018
Gammaked Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 3/16/2018

Gammaked [immune globulin injection (human), 10% caprylate/chromatography purified] is an immune globulin injection (human) liquid indicated for treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older, idiopathic thrombocytopenic purpura (ITP) in adults and children, and chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. Common side effects of Gammaked include:

dose and infusion rate of Gammaked depends on the condition being treated. Gammaked may interact with live virus vaccines and simultaneous administration heparin. Tell your doctor all medications and supplements you use and all vaccine you recently received. Tell your doctor if you are pregnant or plan to become pregnant before using Gammaked; it is unknown how it would affect a fetus. It is unknown if Gammaked passes into breast milk. Consult your doctor before breastfeeding.

Our Gammaked [immune globulin injection (human), 10% caprylate/chromatography purified] 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.

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Gammaked Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; wheezing, difficulty breathing; dizziness, feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver if you feel light-headed, itchy, chilled, sweaty, or have chest discomfort, fast heartbeats, severe headache, or pounding in your neck or ears.

Call your doctor at once if you have:

  • a blood cell disorder--pale or yellowed skin, dark colored urine, fever, confusion or weakness;
  • dehydration symptoms--feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;
  • kidney problems--little or no urination, swelling, rapid weight gain, feeling short of breath;
  • lung problems--chest pain, wheezing, trouble breathing, blue colored lips, fingers, or toes;
  • signs of a new infection--fever with a severe headache, neck stiffness, eye pain, and increased sensitivity to light; or
  • signs of a blood clot--shortness of breath, chest pain with deep breathing, rapid heart rate, numbness or weakness on one side of the body, swelling and warmth or discoloration in an arm or leg.

Common side effects may include:

  • runny or stuffy nose, sinus pain, cough, sore throat;
  • fever, chills, weakness;
  • headache, back pain, muscle or joint pain;
  • dizziness, tiredness, depressed mood;
  • swelling in your hands or feet;
  • skin rash, redness, or bruising;
  • blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
  • nausea, diarrhea, stomach pain, upset stomach;
  • increased blood pressure; or
  • redness, swelling, or itching where an injection was given.

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 Gammaked (Immune Globulin (Human), 10% Caprylate/Chromatography Purified Injection)

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Gammaked Professional Information

SIDE EFFECTS

PI

Intravenous

The most common adverse reactions observed at a rate ≥ 5% in subjects with intravenous treatment in the clinical trials were cough increased, rhinitis, pharyngitis, headache, asthma, nausea, fever, diarrhea, and sinusitis.

PI

Subcutaneous

The most common adverse reactions observed at a rate ≥ 5% of subjects with subcutaneous treatment in the clinical trials were local infusion site reactions, fatigue, headache, upper respiratory tract infection, arthralgia, diarrhea, nausea, sinusitis, bronchitis, depression, allergic dermatitis, migraine, myalgia, viral infection, and pyrexia.

ITP

The most common adverse reactions observed at a rate ≥ 5% in subjects in the clinical trials were headache, ecchymosis, vomiting, fever, nausea, rash, abdominal pain, back pain and dyspepsia.

CIDP

The most common adverse reactions observed at a rate ≥ 5% in subjects in the clinical trial were headache, pyrexia, hypertension, chills, rash, nausea, arthralgia, and asthenia.

Clinical Trials Experience

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

PI

Intravenous Administration

The most serious adverse event observed in clinical study subjects receiving GAMMAKED IV for PI was an exacerbation of autoimmune pure red cell aplasia in one subject.

In four different clinical trials to study PI, out of 157 subjects treated with GAMMAKED, 4 subjects discontinued due to the following adverse events: Coombs negative hypochromic anemia, autoimmune pure red cell aplasia, arthralgia/hyperhidrosis/fatigue/myalgia/nausea and migraine.

In a study of 87 subjects, 9 subjects in each treatment group were pretreated with non-steroidal medication prior to infusion, such as diphenhydramine and acetaminophen.

Table 2 lists the adverse reactions reported by at least 5% of subjects during the 9-month treatment.

Table 2: Adverse Reactions Occurring in ≥ 5% of Subjects

Adverse Reactions GAMMAKED™
No. of subjects: 87
No. of subjects with adverse reaction
(percentage of all subjects)
GAMIMUNE® N, 10%
No. of subjects: 85
No. of subjects with adverse reaction
(percentage of all subjects)
Cough increased 27 (31.0%) 25 (29.4%)
Rhinitis 21 (24.1% 24 (28.2%)
Headache 13 (14.9%) 17 (20.0%)
Pharyngitis 14 (16.1%) 16 (18.8%)
Asthma 13 (14.9%) 10 (11.8%)
Fever 6 (6.9%) 10 (11.8%)
Nausea 10 (11.5%) 9 (10.6%)
Diarrhea 6 (6.9%) 9 (10.6%)
Sinusitis 5 (5.7%) 6 (7.1%)
* An adverse reaction is an adverse event that meets any of the following 3 criteria: (a) that began during or within 72 hours of the end of product infusion, (b) that was considered at least possibly related by either the investigator or the applicant, and/or (c) whose causality assessment by the investigator was missing or indeterminate.

Table 3 lists the frequency of adverse reactions (as defined for Table 2), which were reported by at least 5% of subjects.

Table 3: Adverse Reactions Frequency

Adverse Reactions GAMMAKED™
No. of infusions: 825
Number (percentage of all infusions)
GAMIMUNE® N, 10%
No. of infusions: 865
Number (percentage of all infusions)
Cough increased 40 (4.8%) 47 (5.4%)
Rhinitis 34 (4.1%) 44 (5.1%)
Headache 17 (2.1%) 24 (2.8%)
Pharyngitis 20 (2.4%) 24 (2.8%)
Asthma 13 (14.9%) 10 (11.8%)
Fever 8 (1.0%) 20 (2.3%)
Asthma 17 (2.1%) 12 (1.4%)
Diarrhea 10 (1.2%) 10 (1.2%)
Nausea 10 (1.2%) 10 (1.2%)
Sinusitis 6 (0.7%) 7 (0.8%)

The mean number of adverse reactions per infusion that occurred during or within 72 hours of the end of product infusion was 0.33 for the GAMMAKED® and 0.39 for the GAMIMUNE N, 10% [Immune Globulin Intravenous (Human), 10%] treatment group.

In all three trials in primary humoral immunodeficiencies, the maximum infusion rate was 0.08 mL/kg/min (8 mg/kg/min). The infusion rate was reduced for 11 of 222 exposed subjects (7 GAMMAKED, 4 GAMIMUNE N, 10%) at 17 occasions. In most instances, mild to moderate hives/urticaria, itching, pain or reaction at infusion site, anxiety or headache was the main reason. There was one case of severe chills. There were no anaphylactic or anaphylactoid reactions to GAMMAKED or GAMIMUNE N, 10% in clinical trials.

In the IV efficacy and safety study, serum samples were drawn to monitor the virus safety at baseline and one week after the first infusion of IGIV (for parvovirus B19), eight weeks after first and fifth infusion of IGIV (for hepatitis C, hepatitis B, and HIV-1), 16 weeks after the first and fifth infusion of IGIV (for hepatitis C) and at any time of premature discontinuation of the study (for hepatitis C, hepatitis B, HIV-1, and parvovirus B19). Viral markers of hepatitis C, hepatitis B, HIV-1, and parvovirus B19 were monitored by nucleic acid testing (NAT, Polymerase Chain Reaction [PCR]) and serological testing. There were no treatment related emergent findings of virus transmission for either GAMMAKED or GAMIMUNE N, 10%.

PI

Subcutaneous Administration (PK and Safety Studies )

Adverse reactions were divided into 2 types: 1) Local infusion site reactions, and 2) Non-infusion site adverse reactions. Table 4 lists those adverse reactions (as defined for Table 2) occurring in ≥ 2% of infusions during the SC phase of two pharmacokinetic (PK) crossover and safety trials, one in adults and adolescents and the other in children and adolescents. [see CLINICAL PHARMACOLOGY]

Table 4: Most Frequent Adverse Reactions (≥ 2% of infusions ) by Infusion in the SC Phase

Adverse Reactions Number (Rate* )
Adult, Adolescent
(Study 060001)
Child, Adolescent
(Study T5004-401)
Non-infusion Site Adverse Reactions
  Headache 25 (0.03) 1 (0.01)
  Abdominal Pain 1 (<0.01) 2 (0.02)
Local Infusion Site Reactions,
  Mild 389 (0.54) 56 (0.46)
  Moderate 29 (0.04) 4 (0.03)
  Severe 9 (0.01) 1 (0.01)
*For each trial, rate is calculated by the total number of events divided by the number of infusions received (725 for the adult and adolescent trial and 121 for the children / adolescent trial).
All local infusion site reactions were a priori considered drug-related.
At each level of summation (Preferred Term), local infusion site reactions are counted only once if they occur at the same infusion visit.
  Mild - usually transient in nature and generally not interfering with normal activities
  Moderate - sufficiently discomforting to interfere with normal activities
  Severe - prevents normal activities

Table 5 lists the adverse reactions occurring in ≥ 5% of subjects and the frequency of adverse reactions (as defined for Table 2) per infusion.

Table 5: Most Frequent Adverse Reactions (≥ 5% of subjects ) by Subject and Infusion in the SC Phase

Adverse Reaction Adult, Adolescent
(Study 060001)
Child, Adolescent
(Study T5004-401)
No. of
Subjects
n=32
(%)
No. of
Adverse Reactions
(Rate*)
No. of
Subjects
n=11
(%)
No. of
Adverse Reactions
(Rate* )
Local Infusion Site Reaction, 24 (75.0%) 427 (0.59) 11 (100%) 61 (0.50)
Fatigue 5 (15.6%) 6 (0.01) 0 0
Headache 4 (12.5%) 25 (0.03) 1 (9.1%) 1 (0.01)
Upper respiratory tract infection 4 (12.5%) 5 (0.01) 1 (9.1%) 1 (0.01)
Arthralgia 3 (9.4%) 6 (0.01) 0 0
Diarrhea 3 (9.4%) 6 (0.01) 0 0
Nausea 3 (9.4%) 4 (0.01) 0 0
Sinusitis 3 (9.4%) 4 (0.01) 0 0
Abdominal pain 1 (3.1%) 1 (<0.01) 1 (9.1%) 2 (0.02)
Abdominal pain upper 0 0 1 (9.1%) 1 (0.01)
Autoimmune thyroiditis 0 0 1 (9.1%) 1 (0.01)
Drug hypersensitivity 0 0 1 (9.1%) 1 (0.01)
Influenza 0 0 1 (9.1%) 1 (0.01)
Oropharyngeal pain 0 0 1 (9.1%) 1 (0.01)
Skin chapped 0 0 1 (9.1%) 1 (0.01)
Viral upper respiratory tract infection 0 0 1 (9.1%) 1 (0.01)
Wheezing 1 (3.1%) 1 (<0.01) 1 (9.1%) 1 (0.01)
Bronchitis 2 (6.3%) 2 (<0.01) 0 0
Depression 2 (6.3%) 2 (<0.01) 0 0
Dermatitis allergic 2 (6.3%) 2 (<0.01) 0 0
Erythema 2 (6.3%) 2 (<0.01) 0 0
Migraine 2 (6.3%) 2 (<0.01) 0 0
Myalgia 2 (6.3%) 2 (<0.01) 0 0
Pyrexia 2 (6.3%) 2 (<0.01) 0 0
Viral infection 2 (6.3%) 2 (<0.01) 0 0
* For each trial, rate is calculated by the total number of events divided by the number of infusions received (725 for the adult and adolescent trial and 121 for the children / adolescent trial).
All local infusion site reactions were a priori considered drug-related
At each level of summation (Preferred Term), infusion site reactions are counted only once if they occur at the same infusion visit.

There were no serious bacterial infections in the SC phase of the PK and safety trials.

Local Infusion Site Reactions

Local infusion site reactions with SC GAMMAKED consisted of erythema, pain and swelling. One child discontinued due to infusion site pain. The majority of local infusion site reactions resolved within 3 days. The number of subjects experiencing an infusion site reaction and the number of infusion site reactions decreased over time as subjects received continued weekly SC infusions. At the beginning of the SC phase (week 1) in the adult and adolescent trial, a rate of approximately 1 infusion site reaction per infusion was reported, whereas at the end of the study (week 24) this rate was reduced to 0.5 infusion site reactions per infusion, a reduction of 50%. In the children and adolescent trial, the rate of local infusion site reactions decreased from week 1 for all age groups by the end of the study.

ITP

In two different clinical trials to study ITP, out of 76 subjects treated with GAMMAKED, 2 subjects discontinued due to the following adverse reactions: Hives and Headache/Fever/Vomiting.

One subject, a 10-year-old boy, died suddenly from myocarditis 50 days after his second infusion of GAMMAKED. The death was judged to be unrelated to GAMMAKED.

No pre-medication with corticosteroids was permitted by the protocol. Twelve ITP subjects treated in each treatment group were pretreated with medication prior to infusion. Generally, diphenhydramine and/or acetaminophen were used. More than 90% of the observed drug related adverse events were of mild to moderate severity and of transient nature.

The infusion rate was reduced for 4 of the 97 exposed subjects (1 GAMMAKED™, 3 GAMIMUNE N, 10%) on 4 occasions. Mild to moderate headache, nausea, and fever were the reported reasons.

Table 6 lists the adverse reactions (as defined for Table 2) reported by at least 5% of subjects during the 3-month efficacy and safety study.

Table 6: Adverse Reactions Occurring in ≥ 5% of Subjects

Adverse Reactions GAMMAKED™
No. of subjects: 48
Number
(percentage of all subjects)
GAMIMUNE® N, 10%
No. of subjects: 49
Number
(percentage of all subjects)
Headache 25 (52.1%) 26 (53.1%)
Vomiting 6 (12.5%) 8 (16.3%)
Ecchymosis 7 (14.6%) 2 (4.1%)
Fever 6 (12.5%) 6 (12.2%)
Nausea 6 (12.5%) 5 (10.2%)
Rash 4 (8.3%) 0
Abdominal pain 3 (6.3%) 3 (6.1%)
Back pain 3 (6.3%) 2 (4.1%)
Dyspepsia 3 (6.3%) 0
Asthenia 2 (4.2%) 3 (6.1%)
Dizziness 2 (4.2%) 3 (6.1%)

Serum samples were drawn to monitor the virus safety of the ITP subjects at baseline, nine days after the first infusion (for parvovirus B19), and 3 months after the first infusion of IGIV and at any time of premature discontinuation of the study. Viral markers of hepatitis C, hepatitis B, HIV-1, and parvovirus B19 were monitored by nucleic acid testing (NAT, PCR), and serological testing. There were no treatment related emergent findings of virus transmission for either GAMMAKED or GAMIMUNE N, 10%.

CIDP

In the CIDP efficacy and safety study, 113 subjects were exposed to GAMMAKED and 95 were exposed to Placebo. [see Clinical Studies] As a result of the study design, the drug exposure with GAMMAKED was almost twice that of Placebo, with 1096 GAMMAKED infusions versus 575 Placebo infusions. Therefore, adverse reactions are reported per infusion (represented as frequency) to correct for differences in drug exposure between the 2 groups. The majority of loading-doses were administered over 2 days. The majority of maintenance-doses were administered over 1 day. Infusions were administered in the mean over 2.7 hours.

Table 7 shows the numbers of subjects per treatment group in the CIDP clinical trial, and the reason for discontinuation due to adverse events.

Table 7: Reasons for Discontinuation Due to Adverse Events

Number of Subjects Number of Subjects Discontinued due to Adverse Events Adverse Event
GAMMAKED™ 113 3 (2.7%) Urticaria, Dyspnea, Bronchopneumonia
Placebo 95 2 (2.1%) Cerebrovascular Accident, Deep Vein Thrombosis

The most common adverse reactions with GAMMAKED were headache and pyrexia. Table 8 lists adverse reactions (as defined for Table 2) reported by at least 5% of subjects in any treatment group.

Table 8: Adverse Reactions Occurring in ≥ 5% of Subjects

MedDRA Preferred Term* GAMMAKED™
No. of subjects: 113
Placebo
No. of subjects: 95
No. of
Subjects
(%)
No. of
Adverse Reactions
Incidence density No. of
Subjects
(%)
No. of
Adverse Reactions
Incidence density
Headache 35 (31.0%) 50 0.046 7 (7.4%) 9 0.016
Pyrexia 15 (13.3%) 27 0.025 0 0  
Hypertension 10 (8.8%) 19 0.017 3 (3.2%) 3 0.005
Chills 9 (8.0%) 10 0.009 0 0  
Nausea 7 (6.2%) 9 0.008 3 (3.2%) 3 0.005
Rash 7 (6.2%) 10 0.009 1 (1.1%) 1 0.002
Arthralgia 6 (5.3%) 7 0.006 0 0  
Asthenia 6 (5.3%) 6 0.005 1 (1.1%) 2 0.003
*Reported in ≥ 5% of subjects in any treatment group.
Calculated by the total number of adverse reactions divided by the number of infusions received (1096 for GAMMAKED and 575 for Placebo).

The most serious adverse reaction observed in clinical study subjects receiving GAMMAKED for CIDP was pulmonary embolism (PE) in one subject with a history of PE.

Laboratory Abnormalities

During the course of the clinical program, ALT and AST elevations were identified in some subjects.

  • For ALT, in the IV PI study treatment emergent elevations above the upper limit of normal were transient and observed among 14/80 (18%) of subjects in the GAMMAKED group versus 5/88 (6%) of subjects in the GAMIMUNE N, 10% group (p = 0.026).
  • In the SC PI study treatment emergent laboratory abnormalities during the SC phase occurred in several subjects. Four subjects (4/32, 13%) had elevated Alkaline Phosphatase. One subject (1/32, 3%) had an elevated ALT and three subjects (3/32, 9%) had an elevated AST. No elevations were > 1.6 times the upper limit of normal.
  • In the ITP study which employed a higher dose per infusion, but a maximum of only two infusions, the reverse finding for elevation of ALT was observed among 3/44 (7%) of subjects in the GAMMAKED group versus 8/43 (19%) of subjects in the GAMIMUNE N, 10% group (p = 0.118).
  • In the CIDP study, 15/113 (13%) of subjects in the GAMMAKED group and 7/95 (7%) in the Placebo group (p=0.168) had a treatment emergent transient elevation of ALT.

Elevations of ALT and AST were generally mild (< 3 times upper limit of normal), transient, and were not associated with obvious symptoms of liver dysfunction.

GAMMAKED may contain low levels of anti-Blood Group A and B antibodies primarily of the IgG4 class. Direct antiglobulin tests (DAT or direct Coombs tests), which are carried out in some centers as a safety check prior to red blood cell transfusions, may become positive temporarily. There were 2 cases of hemolytic anemia across these clinical trials. One hemolytic event not associated with positive DAT findings was observed in the IV PI study in a woman with common variable immune deficiency and B12 deficiency (pernicious anemia) at a dose of (450 mg/kg). The other hemolytic event occurred in the CIDP study in a subject with positive DAT at a dose of 1g/kg.

Postmarketing Experience

Because adverse reactions are voluntarily reported post-approval from a population of uncertain size, it is not always possible to reliably estimate their frequencies or establish a causal relationship to product exposure.

The following adverse reactions have been identified during post-approval use of IGIV products,(8,20) including GAMMAKED:

  • Infusion Reactions:
Hypersensitivity (e.g., anaphylaxis), tachycardia, malaise, flushing, or other skin reactions, chest discomfort, rigors, and changes in blood pressure
  • Renal:
Acute renal dysfunction/failure, osmotic nephropathy
  • Respiratory:
Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, bronchospasm
  • Cardiovascular:
Cardiac arrest, thromboembolism, vascular collapse, hypotension
  • Neurological:
Coma, loss of consciousness, seizures/convulsions, tremor, aseptic meningitis
  • Integumentary:
Stevens-Johnson syndrome, epidermolysis, erythema multiforme, dermatitis (e.g., bullous dermatitis)
  • Hematologic:
Pancytopenia, leukopenia, hemolysis, hemolytic anemia, positive direct antiglobulin (Coombs test)
  • General/Body as a Whole:
Rigors
  • Gastrointestinal:
Hepatic dysfunction

Read the entire FDA prescribing information for Gammaked (Immune Globulin (Human), 10% Caprylate/Chromatography Purified Injection)

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

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