OCTAPLAS Solution for infusion Ref.[27452] Active ingredients: Human plasma protein fraction

5.1 Transfusion reactions

Transfusion reactions can occur with ABO blood group mismatches. Administration of Octaplas must be based on ABO-blood group compatibility.

5.2 Hypervolemia

High infusion rates can induce hypervolemia with consequent pulmonary edema or heart failure. Monitor patients for signs and symptoms of pulmonary edema or heart failure and institute appropriate management.

5.3 Hyperfibrinolysis

Excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha 2-antiplasmin. Monitor for signs of excessive bleeding in patients undergoing liver transplantation.

5.4 Thrombosis

Thrombosis can occur due to low levels of Protein S. Monitor for signs and symptoms of thrombosis in patients at risk.

5.5 Citrate Toxicity

Citrate toxicity can occur with volumes exceeding one milliliter of Octaplas per kg per minute. The infusion rate should not exceed 0.020-0.025 mmol citrate per kilogram per minute (i.e., less than one milliliter Octaplas per kg per minute). Symptoms attributable to citrate toxicity (hypocalcemia) include fatigue, paresthesia and muscle spasms, especially in patients with liver function disorders. Administer calcium gluconate intravenously into another vein in order to minimize citrate toxicity.

5.6 Infection Risk from Human Plasma

Because Octaplas is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. ALL infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Octapharma [1-866-766-4860] or FDA at 1-800-FDA-1088 or www.fea.gov/medwatch. See Description (11)

Serious adverse reactions seen in clinical trials were anaphylactic shock, citrate toxicity and severe hypotension.

The most common adverse reactions observed in ≥1% of subjects included pruritis, urticaria, nausea, headache and paresthesia.

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

Adverse reactions observed in clinical trials derive from 9 clinical trials. The mean dose administered ranged from 6 to 15 milliliters/kg body weight; when used in plasma exchange the dose was between 15 to 75 milliliters/kg. Two of the studies were conducted in healthy volunteers (n=90).

In total, 359 subjects received about 600 transfusion episodes in these trials.

The following table shows the adverse reactions observed in ≥1% of subjects in order of severity:

Nervous system disorders: Headache, paresthesia

Gastrointestinal disorders: Nausea

Skin and subcutaneous tissue disorders: Pruritis, urticaria

Because post-marketing 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.

Blood system disorders: Hyperfibrinolysis

Immune system disorders: Hypersensitivity reactions including anaphylactoid and allergic type of reactions

Metabolic and nutritional disorders: Alkalosis

Cardiovascular disorders: Cardiac arrest, circulatory overload, thromboembolism, tachycardia

Respiratory, thoracic and mediastinal disorders: Respiratory arrest or failure, bronchospasm, pulmonary edema, dyspnea, tachypnea

Gastrointestinal disorders: Abdominal pain, vomiting

Skin and subcutaneous tissue disorders: Rash, erythema

General disorders and administration site conditions: Fever and/or chills, chest discomfort or pain

Investigations: Seroconversions (passive transfer of antibodies); passive transmission of analytes, e.g. β-human chorionic gonadotropin³

Injury, poisoning and procedural complications: Citrate toxicity

Do not inject drugs containing calcium in the same intravenous line with Octaplas because precipitants may block the line.

Passive transmission of analytes (e.g., β-human chorionic gonadotropin) may result in misleading positive results³.

Risk Summary

Animal reproduction studies have not been conducted with Octaplas. It is not known whether Octaplas can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Octaplas should be given to a pregnant woman only if clearly needed.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively⁴.

Risk Summary

Efficacy and safety of Octaplas in lactating women is unknown.

Octaplas was evaluated in 91 pediatric patients (age range 0-20 years) in two post-marketing requirement studies. Patients were dosed based on body weight and doses were adjusted as needed. There were no hyperfibrinolytic or treatment-related thromboembolic events reported by investigators. Please refer to Section 14 for information on clinical studies in the pediatric population.

Clinical studies of Octaplas did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.