Octagam Side Effects

Please note - some side effects for Octagam may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Octagam Side Effects - for the Professional

Octagam

Adverse Drug Reaction Overview

The most serious adverse reactions observed with Octagam 5% Liquid treatment have been immediate anaphylactic reactions, aseptic meningitis, and hemolytic anemia.

The most common adverse reactions observed with Octagam 5% Liquid treatment during clinical trial (> 5%) were headache and nausea.

Clinical Trials Experience

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

The clinical trial database includes a multi-center, open-label, single arm study in 46 children and adults with PI. Subjects participated in the study for a mean of 346 days and received 300 to 450 mg/kg every 21 days or 400 to 600 mg/kg every 28 days. Infusions were initiated at a rate of 30 mg/kg/hour for the first 30 minutes, and, if tolerated, could be advanced to a maximum tolerated rate not exceeding 200 mg/kg/hour. Over half of the subjects were male (n=28; 61%), and more than half were on the 28-day infusion schedule (n=27; 59%). The mean age of subjects was 31.5 years.

Six subjects experienced a total of 12 SAEs (abdominal pain (2 occurrences), cardiac arrest, pneumonia, cellulitis, coxsackie viral infection, renal calculus (2 occurrences), blood culture positive, ketonuria, gastroenteritis, and colitis pseudomembranosus). Eleven of the 12 SAEs were not suspected to be related to study drug; the other SAE was noted before the subject began receiving the next scheduled infusion, and it was not temporally related to the previous infusion.

Pre-medications were used in 165 (25.2%) out of 654 infusions and in 14 (30.4%) out of 46 patients. Infusions were slowed or interrupted in 9 out of 489 infusions (1.84%) without pre-medication and in 10 out of 165 infusions (6.06%) with pre-medication. Five out of 32 (15.63%) patients who never received any pre-medication had at least one slowed or interrupted infusion, whereas 9 out of 14 (64.29%) patients who received pre-medication at least once also had a slowed or interrupted infusion.

Six of the 46 subjects in the trial (13%) were withdrawn from the study: 2 on the subjects' request; 1 because of investigator's decision (non-compliance); 1 because of loss to follow-up; 1 death (cardiac arrest, not suspected to be related to study drug); and 1 by error of the study coordinator.

All adverse events in trial OCTA-06, irrespective of the causality assessment, reported by at least 5% of subjects during the 12-months treatment are given in the table below.

Table 2: Subjects and Infusions with at least one Adverse Event Irrespective of Causality (Study OCTA-06)

	Octagam	5% liquid
	No. of subjects (%)	No. of infusions (%)
Total	46 (100%)	654 (100%)
Nasal congestion	24 (52%)	39 (6%)
Sinusitis NOS	23 (50%)	45 (7%)
Headache NOS	22 (48%)	62 (9%)
Cough	20 (43%)	46 (7%)
Sore throat NOS	16 (35%)	25 (4%)
Fever	15 (33%)	19 (3%)
Vomiting NOS	12 (26%)	15 (2%)
Diarrhoea NOS	11 (24%)	22 (3%)
Bronchitis NOS	10 (22%)	14 (2%)
Abdominal pain upper	9 (20%)	11 (2%)
Arthralgia	9 (20%)	15 (2%)
Nasopharyngitis	8 (17%)	14 (2%)
Rhinorrhoea	8 (17%)	9 (1%)
Upper respiratory tract infection NOS	8 (17%)	13 (2%)
Fatigue	7 (15%)	9 (1%)
Nausea	7 (15%)	8 (1%)
Pain in limb	7 (15%)	10 (2%)
Sinus congestion	7 (15%)	9 (1%)
Back pain	5 (11%)	10 (2%)
Injection site reaction NOS	5 (11%)	11 (2%)
Wheezing	5 (11%)	8 (1%)
Asthma NOS	4 (9%)	5 (0.8%)
Asthma aggravated	4 (9%)	10 (2%)
Chest pain NEC	4 (9%)	4 (0.6%)
Conjunctivitis NEC	4 (9%)	4 (0.6%)
Dyspepsia	4 (9%)	5 (0.8%)
Earache	4 (9%)	6 (0.9%)
Ecchymosis	4 (9%)	7 (1%)
Fungal infection NOS	4 (9%)	4 (0.6%)
Injection site pain	4 (9%)	4 (0.6%)
Insomnia NEC	4 (9%)	4 (0.6%)
Sinusitis acute NOS	4 (9%)	8 (1%)
Urinary tract infection NOS	4 (9%)	8 (1%)
Vaginal candidiasis	4 (9%)	7 (1%)
Abdominal pain NOS	3 (7%)	3 (0.5%)
Dizziness (exc vertigo)	3 (7%)	4 (0.6%)
Dyspnoea NOS	3 (7%)	3 (0.5%)
Epistaxis	3 (7%)	5 (0.8%)
Eye discharge	3 (7%)	3 (0.5%)
Eye irritation	3 (7%)	3 (0.5%)
Hypertension NOS	3 (7%)	5 (0.8%)
Otitis media NOS	3 (7%)	4 (0.6%)
Pain NOS	3 (7%)	4 (0.6%)
Postnasal drip	3 (7%)	3 (0.5%)
Productive cough	3 (7%)	3 (0.5%)
Rigors	3 (7%)	4 (0.6%)
Throat irritation	3 (7%)	3 (0.5%)
Urticaria NOS	3 (7%)	8 (1%)

The adverse reactions in trial OCTA-06 reported by at least 5% of subjects during the 12-month treatment are given in the table below.

Table 3: Subjects and Infusions with At Least One Adverse Reaction (Study OCTA-06)

	Octagam	5% liquid
	No. of subjects (%)	No. of infusions (%)
Total	46 (100%)	654 (100%)
Headache NOS	7 (15%)	18 (3%)
Nausea	3 (7%)	4 (0.6%)

The following table provides an overview on the temporally associated adverse events (TAAEs) during and within different time-points after the end of Octagam infusion.

Table 4: Overview on TAAEs Occurring During and Over a Specified Number of Hours after the End of Infusion, Irrespective of Causality (Study OCTA-06)

Total # of infusions (N=654)	Time-Points
	24 hrs	48hrs	72hrs
Total # of TAAEs	172	183	189
Proportion of infusions with TAAEs	26.3%	28.0%	28.9%
Upper bound 1 sided 97.5% CI for proportion of TAAEs	29.7%	31.4%	32.4%

All temporally associated adverse events (TAAEs) in trial OCTA-06, irrespective of the causality assessment, reported by at least 5% of subjects within 72 hours after the end of the infusion are given in the table below.

Table 5: TAAEs During and Over 72 Hours After End of Infusion, Irrespective of Causality (Study OCTA-06)

TAAE	Subjects (%)n=46	Infusion (%)N=654
Headache NOS	15 (32.6%)	28 (4.3%)
Sinusitis NOS	12 (26.1%)	13 (2.0%)
Nasal congestion	10 (21.7%)	11 (1.7%)
Arthralgia	7 (15.2%)	10 (1.5%)
Cough	7 (15.2%)	7 (1.1%)
Injection site reaction NOS	5 (10.9%)	11 (1.7%)
Sore throat NOS	5 (10.9%)	5 (0.8%)
Vomiting NOS	5 (10.9%)	5 (0.8%)
Back pain	4 (8.7%)	6 (0.9%)
Diarrhoea NOS	4 (8.7%)	5 (0.8%)
Ecchymosis	4 (8.7%)	5 (0.8%)
Injection site pain	4 (8.7%)	4 (0.6%)
Nausea	4 (8.7%)	5 (0.8%)
Upper respiratory tract infection NOS	4 (8.7%)	5 (0.8%)
Wheezing	4 (8.7%)	6 (0.9%)
Asthma aggravated	3 (6.5%)	4 (0.6%)
Eye irritation	3 (6.5%)	3 (0.5%)
Fungal infection NOS	3 (6.5%)	3 (0.5%)
Pain in limb	3 (6.5%)	5 (0.8%)
Rhinorrhoea	3 (6.5%)	3 (0.5%)
Urinary tract infection NOS	3 (6.5%)	3 (0.5%)

The subset of drug related temporally associated adverse events (TAAEs) in trial OCTA-06 reported by at least 5% of subjects within 72 hours after the end of the infusion is given in the table below.

Table 6: Drug-Related TAAEs During and Over 72 Hours After End of Infusion (Study OCTA-06)

TAAE	Subjects (%)n=46	Infusion (%)N=654
Headache NOS	6 (13.0%)	15 (2.3%)
Nausea	3 (6.5%)	4 (0.6%)

Laboratory Abnormalities

Standard clinical laboratory evaluations were performed Study OCTA-06. Three subjects (7%) had incidences of AST (>2.5 x ULN) which were all assessed as clinically non-significant. Four subjects (9%) had incidences of serum creatinine increases being stable throughout the course of the study. Therefore, these observations were not regarded as indicative of acute renal dysfunction.

Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

Octagam 5% liquid Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Octagam 5% liquid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to Octagam 5% liquid.

Blood and lymphatic system disordersLeukopenia, haemolytic anaemia
Immune system disorders Hypersensitivity, anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, angioneurotic oedema, face oedema
Metabolic and nutritional disorders Fluid overload
Psychiatric disorders Agitation
Nervous system disorders Headache, cerebrovascular accident, meningitis aseptic, migraine, dizziness, paraesthesia
Cardiac disorders Myocardial infarction, tachycardia, palpitations, cyanosis
Vascular disorders Hypotension, thrombosis, peripheral circulatory failure, hypertension
Respiratory, thoracic and mediastinal disorders Respiratory failure, pulmonary embolism, pulmonary oedema, bronchospasm, dyspnoea, cough
Gastrointestinal disorders Nausea, vomiting, diarrhoea, abdominal pain
Skin and subcutaneous tissue disorders Eczema, urticaria, rash, rash erythematous, dermatitis, pruritus, alopecia
Musculoskeletal and connective tissue disorders Back pain, arthralgia, myalgia, pain in extremity
Renal and urinary disorders Renal failure acute
General disorders and administration site conditions Fatigue, injection site reaction, pyrexia, chills, chest pain, hot flush, flushing, hyperhidrosis, malaise
Investigations Hepatic enzymes increased, blood glucose false positive

General

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

RespiratoryApnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion Related Acute Lung Injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
Cardiovascular Cardiac arrest, thromboembolism, vascular collapse, hypotension
Neurological Coma, loss of consciousness, seizures, tremor
Integumentary Steven-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis
Hematologic Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs) test
General / Body as a Whole Pyrexia, rigors
Musculoskeletal Back pain
Gastrointestinal Hepatic dysfunction, abdominal pain

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Side Effects by Body System - for Healthcare Professionals

General

In general, immune globulin intravenous human (IGIV) has been well tolerated. Mild infusion related symptoms of headache, myalgia, backache, fever, pruritus, hypotension/hypertension, tachycardia, chest tightness, chills, flushing, and nausea have been reported. Slowing or temporarily discontinuing the infusion has usually resulted in resolution of symptoms.

Renal

Renal side effects have included acute renal failure, acute tubular necrosis, proximal tubular nephropathy, and osmotic nephrosis, primarily in patients with baseline renal impairment. Some patients have required dialysis. Elevations in creatinine and BUN have been noted within 1 to 2 days following infusion. The incidence of adverse reactions may be greater in products containing sucrose as a stabilizer. Maltose containing products may cause mild diuresis. At least one case of reversible oliguria requiring only supportive care and renal failure requiring transplantation in a patient with baseline renal dysfunction has also been reported.

Twenty cases of IGIV related renal impairment have been reported.

Renal impairment, including renal failure, usually occurred in the first 5 days of therapy and more frequently in patients receiving high IGIV dosages for immune thrombocytopenia purpura.

Spontaneous reports to one manufacturer suggest that diabetic patients over the age of 70 years and patients with lupus nephritis receiving dosages greater than 400 mg/kg/day may be at increased risk of renal impairment. The mechanism has not been fully established, but may be related to renal tubular sucrose-induced osmotic injury or an immune mechanism.

Hypersensitivity

Hypersensitivity side effects have included responses in the form of an inflammatory reaction (fever, chills, nausea, vomiting, hypotension) in 10% of patients with agammaglobulinemia or severe hypogammaglobulinemia who have not received IGIV within 8 weeks or who have never received IGIV. True anaphylaxis, rarely resulting in death, has been reported.

Anaphylaxis has occurred more frequently in patients with previous severe hypersensitivity reactions to IGIV, but has been reported in patients without a history of IGIV allergy. Patients previously sensitized to antibodies, such as IgA, may be at increased risk for immediate hypersensitivity reactions. Epinephrine, oxygen, IV antihistamines, and IV corticosteroids should be immediately available as such reactions can occur seconds to hours after the initiation of the infusion.

Nervous system

Limited data suggest that a history of migraine headaches may be associated with an increased risk of aseptic meningitis syndrome.

Nervous system side effects have been reported rarely. Mild, post infusion headache has been reported in 2% of patients with Immune Thrombocytopenic Purpura (ITP) who received dosages equal to or greater than 0.4 g/kg/day. An Aseptic Meningitis Syndrome (AMS), primarily associated with dosages greater than 2 g/kg, has occasionally been reported. Discontinuation of IGIV has resulted in AMS resolution without sequelae. Rarely, seizures have been reported.

Metabolic

Metabolic side effects have been reported rarely. Hyponatremia has been reported in products containing 10% maltose.

Hematologic

Hematologic side effects have been reported rarely. These have included reports of mild hemolysis due to transfer of blood group antibodies, and thrombotic complications. At least 6 cases of disseminated intravascular coagulation (DIC) associated with acute hemoglinemia or hemoglobinuria following immune globulin intravenous administration have been reported.

A recent report of two women who received high dose IVIg and subsequently developed thromboembolic complications suggests that high-dose IVIg increases blood viscosity that may last for several weeks, which may increase susceptibility to thromboembolism in predisposed patients.

Out of the 6 patients who developed DIC, 1 child recovered without sequelae and 5 adults all died. The attending or consulting physicians assessed that acute hemolysis or DIC caused or contributed to each death.

Cardiovascular

Cardiovascular side effects have included rare reports of cardiovascular and cerebrovascular thrombosis.

Local

IGIV products with a more acidic pH have been reported to cause greater vein irritation.

Local side effects have included injection site reactions. These have included erythema, pain, infection, venous thrombosis, thrombophlebitis, and eczema.

Immunologic

Immunologic side effects have been reported rarely. All U.S. immune globulin products undergo viral inactivation and/or removal. However, no method has been totally effective in removing all risk and the potential exists for the presence of unknown infectious agents.

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