Prescription Drugs

GamaSTAN® S/D Immune Globulin (Human) for Injection Solvent/Detergent Treated DESCRIPTION Table 1 : Product Information Summary Route of Administration Dosage Form, Strength Clinically Relevant Nonmedicinal Ingredients intramuscular injection injectable solution, 15-18% protein For a complete listing see Dosage Forms, Composition And Packaging section. GamaSTAN® S/D treated with solvent/detergent is a sterile solution of immune globulin for intramuscular administration; it contains no preservative. GamaSTAN® S/D is prepared by cold ethanol fractionation from human plasma. The immune globulin is isolated from solubilized Cohn fraction II. The fraction II solution is adjusted to a final concentration of 0.3% tri-n-butyl phosphate (TNBP) and 0.2% sodium cholate. After the addition of solvent (TNBP) and detergent (sodium cholate), the solution is heated to 30°C and maintained at that temperature for not less than 6 hours. After the viral inactivation step, the reactants are removed by precipitation, filtration and finally ultrafiltration and diafiltration. GamaSTAN® S/D is formulated as a 15-18% protein solution at a pH of 6.4-7.2 in 0.21-0.32 M glycine. The pH is adjusted with sodium carbonate. GamaSTAN® S/D is then incubated in the final container for 21-28 days at 20-27°C.

INDICATIONS Clinical Use Passive immunization should be considered when vaccines for active immunization are not available, or in situations when vaccine has not been used prior to exposure to the infective agent or is contraindicated (1). GamaSTAN® S/D is indicated in the following situations. Hepatitis A The prophylactic value of GamaSTAN® S/D is greatest when given before or soon after exposure to hepatitis A. GamaSTAN® S/D is not indicated in persons with clinical manifestations of hepatitis A or in those exposed more than 2 weeks previously. Measles (Rubeola) GamaSTAN® S/D should be given to prevent or modify measles in susceptible person exposed fewer than 6 days previously (2). A susceptible person is one who has not been vaccinated and has not had measles previously. GamaSTAN® S/D may be especially indicated for susceptible household contacts of measles patients, particularly contacts under 1 year of age, for whom the risk of complications is highest (2). GamaSTAN® S/D and measles vaccine should not be given at the same time (2). If a child is older than 12 months and has received GamaSTAN® S/D, he should be given measles vaccine about 5 months later when the measles antibody titer will have disappeared, provided there are no contraindications to the vaccine (1). If a susceptible child exposed to measles is immunocompromised, GamaSTAN® S/D should be given immediately (3). GamaSTAN® S/D may also be considered for severely immunocompromised individuals exposed to measles regardless of immunization status. Children who are immunocompromised should not receive measles vaccine or any other live viral vaccine (4). Varicella Passive immunization against varicella in immunosuppressed patients is best accomplished by use of Varicella-Zoster Immune Globulin (Human) [VZIG]. If VZIG is unavailable, GamaSTAN® S/D, promptly given, may also modify varicella (5). Rubella The routine use of GamaSTAN® S/D for prophylaxis of rubella in early pregnancy is of dubious value and cannot be justified. Some studies suggest that the use of GamaSTAN® S/D in exposed, susceptible women can lessen the likelihood of infection and fetal damage; therefore, GamaSTAN® S/D may benefit those women who will not consider a therapeutic abortion (3). DOSAGE AND ADMINISTRATION Dosing Considerations For intramuscular injection only. Do not give intravenously or subcutaneously. Recommended Dose And Dosage Adjustment Hepatitis A GamaSTAN® S/D in a dose of 0.02 mL/kg is recommended for household and institutional hepatitis A case contacts. The following doses of GamaSTAN® S/D are recommended for persons who plan to travel in areas where hepatitis A is common (8). Length of Stay Dose Volume Less than 3 months 0.02 mL/kg 3 months or longer 0.06 mL/kg (repeat every 4-6 months) Measles (Rubeola) GamaSTAN® S/D should be given in a dose of 0.25 mL/kg to prevent or modify measles in a susceptible person exposed fewer than 6 days previously (1,2). A susceptible child who is exposed to measles and who is immunocompromised should receive a dose of 0.5 mL/kg (maximum dose, 15 mL) of GamaSTAN® S/D immediately (3). The dosage of Immune Globulin (Human) for exposed individuals who have underlying malignant disease should be 0.5 mL/kg or 15 mL maximum (1). Varicella If Varicella-Zoster Immune Globulin (Human) is unavailable, GamaSTAN® S/D at a dose of 0.6 to 1.2 mL/kg, promptly given, may also modify varicella (5). Rubella Some studies suggest that the use of GamaSTAN® S/D in exposed, susceptible women can lessen the likelihood of infection and fetal damage; therefore, GamaSTAN® S/D at a dose of 0.55 mL/kg may benefit those women who will not consider a therapeutic abortion (3). Administration GamaSTAN® S/D is administered intramuscularly (see WARNINGS AND PRECAUTIONS: General), preferably in the anterolateral aspects of the upper thigh and the deltoid muscle of the upper arm. The gluteal region should not be used routinely as an injection site because of the risk of injury to the sciatic nerve. Doses over 10 mL should be divided and injected into several muscle sites to reduce local pain and discomfort. An individual decision as to which muscle is injected must be made for each patient based on the volume of material to be administered. If the gluteal region is used when very large volumes are to be injected or multiple doses are necessary, the central region MUST be avoided; only the upper, outer quadrant should be used (9). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use Reconstitution Not required. HOW SUPPLIED Storage And Stability Store at 2-8°C. Do not freeze. Do not use after expiration date. The vials are single use. Once entered, discard any unused contents. Dosage Forms, Composition And Packaging GamaSTAN® S/D contains 15-18% immune globulin (human) as active ingredient. It also contains 0.21-0.32 M glycine, USP. GamaSTAN® S/D is supplied in 2 mL, 5 mL and 10 mL single use vials. REFERENCES 1. NACI. Canadian Immunization Guide, 6th ed. Ottawa: National Advisory Committee on Immunization. 2002. 2. CDC. Measles, mumps, and rubella - vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1998;47(RR-8):1-58. 3. AAP. Passive immunization. In: Pickering LK, editor. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003. pp. 53-66. 4. Bruton OC. Agammaglobulinemia. Pediatrics 1952;9(6):722-8. 5. Gershon AA, Piomelli S, Karpatkin M, Smithwick E, Steinberg S. Antibody to varicella-zoster virus after passive immunization against chickenpox. J Clin Microbiol 1978;8(6):733-5. 9. CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physician (AAFP). MMWR 2002;51(RR-2):1-36. Grifols Therapeutics Inc. (Manufacturer) 8368 US 70 Bus. Hwy West Clayton, NC 27520. Grifols Canada Ltd. (Importer and Distributor), 5060 Spectrum Way, Suite 405, Mississauga, Ontario, L4W 5N5. Revised: Jul 2014

PATIENT INFORMATION GamaSTAN® S/D Immune Globulin (Human) Solvent/Detergent Treated This leaflet is Part 3 of a three-part “Product Monograph” published when GamaSTAN® S/D was approved for sale in Canada and is designed specifically for Consumers. This leaflet is a summary and will not tell you everything about GamaSTAN® S/D. Contact your doctor or pharmacist if you have any questions about the drug. About This Medication What the medication is used for: GamaSTAN® S/D may be used if you have not had a vaccine for hepatitis A, measles, chickenpox, rubella, or other infections and have been around people who have been sick with these illnesses. What it does: GamaSTAN® S/D provides antibodies to help prevent or lessen the severity of hepatitis A, measles, chickenpox, rubella, or other infections. When it should not be used: You should not use this medicine if your body does not make enough immunoglobulin A (IgA), which could cause you to have an allergic reaction to blood products that contain IgA. You should not be given GamaSTAN® S/D if you have any bleeding disorder that would make it unsafe for you to be given an injection into the muscles. What the medicinal ingredient is: The medicinal ingredient of GamaSTAN® S/D is 15-18% human immune globulin protein. What the nonmedicinal ingredients are: GamaSTAN® S/D also contains the amino acid glycine (at a concentration of 0.21-0.32 M), which acts as a stabilizer. What dosage forms it comes in: GamaSTAN® S/D comes in 2 mL, 5 mL and 10 mL vials. WARNINGS AND PRECAUTIONS Serious Warnings and Precautions GamaSTAN® S/D must be injected into muscles only. It should not be injected directly into blood vessels (intravenously) or under the skin (subcutaneously). Products made from human plasma may contain infectious agents such as viruses. However, the manufacturing process of GamaSTAN® S/D is designed to inactivate and eliminate possible infectious agents. You should discuss the risks and benefits of this product with your healthcare provider. Immune Globulin (Human) products have been reported to be associated with heart and blood circulation problems such as heart attack, stroke and blood clots (thrombosis). You should talk to your doctor if you have risk factors for these kinds of conditions. Some of these risk factors include obesity, old age, high blood pressure, diabetes, or a history of heart disease. Thrombosis may occur even in the absence of known risk factor. BEFORE you use GamaSTAN® S/D talk to your doctor or pharmacist if: you are pregnant or breastfeeding you have had an allergic reaction to immune globulin or any of the other ingredients in the medicine Interactions With This Medication GamaSTAN® S/D may interfere with some vaccines. Talk with your healthcare professional if you will receive any type of vaccine within 6 months of GamaSTAN® S/D treatment. See also ABOUT THIS MEDICATION: When it should not be used, and SIDE EFFECTS AND WHAT TO DO ABOUT THEM. Proper Use Of This Medication Usual dose Your doctor will determine the amount of GamaSTAN® S/D that is right for you and when your shots should be given. An intramuscular or IM injection is a shot given into a muscle, usually in the buttocks. A doctor, nurse or other caregiver trained to give injections will give your treatment. Overdose Although there is no information on the effects of GamaSTAN® S/D overdose, experience with similar medicines suggests that the only effect would be pain and tenderness at the needle injection site. Missed Dose It is important that you receive GamaSTAN® S/D as instructed by your healthcare professional. If your doctor tells you that more than one treatment is required, you should consult him/her if a treatment appointment is missed. Side Effects And What To Do About Them Pain may occur where the injection is given. Talk with your doctor if the pain is severe. You should talk with your healthcare professional if you experience rash or hives (swelling, redness, intense itching, and burning). or if you develop swelling of the lips, other parts of the parts of the mouth and throat, eyelids, genitals, hands or feet Allergic reactions, although rare, have been reported following the injection of human immune globulin. Talk with your doctor immediately if you experience any of these side effects: wheezing or trouble breathing chest tightness severe abdominal cramps severe vomiting severe diarrhea This is not a complete list of side effects. For any unexpected effects while taking GamaSTAN® S/D, contact your doctor or pharmacist. HOW TO STORE IT GamaSTAN® S/D should be stored at 2-8°C. It should not be frozen or used past the expiration date. Reporting Suspected Side Effects To monitor drug safety, Health Canada collects information on serious and unexpected effects of drugs. If you suspect you have had a serious or unexpected reaction to this drug you may notify Health Canada by: toll-free telephone: 866-234-2345 toll-free fax: 866-678-6789 By email: cadrmp@hc-sc.gc.ca By regular mail: National AR Centre Marketed Health Products Safety and Effectiveness Information Division Marketed Health Products DirectorateTunney's Pasture, AL 0701C Ottawa ON K1A 0K9 NOTE: Before contacting Health Canada, you should contact your physician or pharmacist.

OVERDOSE Although no data are available, clinical experience with other immunoglobulin preparations suggests that the only manifestations would be pain and tenderness at the injection site. CONTRAINDICATIONS GamaSTAN® S/D should not be given to patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition And Packaging section. GamaSTAN® S/D should not be given to persons with isolated immunoglobulin A (IgA) deficiency. Such persons have the potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products that contain IgA (7). GamaSTAN® S/D should not be administered to patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections. REFERENCES 7. Fudenberg HH. Sensitization to immunoglobulins and hazards of gamma globulin therapy. In: Merler E, editor. Immunoglobulins: biological aspects and clinical uses. Washington, DC: Nat Acad Sci; 1970. pp. 211-20.

SIDE EFFECTS Adverse Drug Reaction Overview Local pain and tenderness at the injection site, urticaria, and angioedema may occur. Anaphylactic reactions, although rare, have been reported following the injection of human immune globulin preparations. Anaphylaxis is more likely to occur if GamaSTAN® S/D is given intravenously; therefore, GamaSTAN® S/D must be administered only intramuscularly. Table 2 :Adverse Drug Reactions Associated with Immune Globulin (Human) General disorders and administration site conditions Local pain and injection site tenderness Immune system disorders Angioedema Anaphylaxis Urticaria DRUG INTERACTIONS Drug-Drug Interactions Table 3 : Established or Potential Drug-drug Interactions Proper Name Ref Effect Clinical Comment Live viral vaccines T Antibodies in the globulin preparation may interfere with the response to live viral vaccines such as measles, mumps, polio and rubella (1). Use of such vaccines should be deferred until approximately 5 months after GamaSTAN® S/D administration (1). Legend: C=Case Study; CT=Clinical Trial; T=Theoretical Drug-Food Interactions No interactions are known. Drug-Herb Interactions No interactions are known. Drug-Laboratory Interactions No interactions are known. REFERENCES 1. NACI. Canadian Immunization Guide, 6th ed. Ottawa: National Advisory Committee on Immunization. 2002.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Serious WARNINGS AND PRECAUTIONS For intramuscular injection only. Do not give intravenously or subcutaneously (see WARNINGS AND PRECAUTIONS: General). Products made from human plasma may contain infectious agents such as viruses (see WARNINGS AND PRECAUTIONS: General). There is clinical evidence of an association between the administration of all immunoglobulins and thromboembolic events such as myocardial infarction, stroke, pulmonary embolism and deep vein thrombosis. Therefore, caution should be exercised when prescribing and administering immunogloblins. Thrombosis may occur even in the absence of known risk factors. Risk factors for thromboembolic events include: obesity, advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged periods of immobilization, severely hypovolemic patients, diseases which increase blood viscosity, hypercoagulable conditions, use of estrogens, indwelling central venous catheters, and cardiovascular risk factors (see Thromboembolic Events subsection). General GamaSTAN® S/D should not be administered intravenously or subcutaneously because of the potential for serious reactions. Injections should be made intramuscularly, and care should be taken to draw back on the plunger of the syringe before injection in order to be certain that the needle is not in a blood vessel. Skin tests should not be done. In most human beings the intradermal injection of concentrated gamma globulin solution with its buffers causes a localized area of inflammation which can be misinterpreted as a positive allergic reaction. In actuality, this does not represent an allergy; rather, it is localized tissue irritation of a chemical nature. Misinterpretation of the results of such tests can lead the physician to withhold badly needed human immunoglobulin from a patient who is not actually allergic to this material. True allergic responses to human gamma globulin given in the prescribed intramuscular manner are rare. Although systemic reactions to intramuscularly administered immunoglobulin preparations are rare, epinephrine should be available for treatment of acute allergic symptoms. GamaSTAN® S/D is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Canada Ltd. [1-866-482-5226]. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering to the patient. Thromboembolic Events There is clinical evidence of an association between the administration of all immunoglobulins and thromboembolic events such as myocardial infarction, stroke, pulmonary embolism and deep vein thrombosis. Since thrombosis may occur in the absence of known risk factors, caution should be exercised in prescribing and administering immunoglobulins. The drug product should be administered at the minimum concentration available and at the minimum rate of infusion practicable. Patients should be adequately hydrated before administration. Baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia / markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. Patients at risk of hyperviscosity should be monitored for signs and symptoms of thrombosis and blood viscosity assessed. Risk factors for thromboembolic adverse events include: obesity, advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged periods of immobilisation, severely hypovolemic patients, diseases which increase blood viscosity, hypercoagulable conditions, use of estrogens, indwelling central vascular catheters, and cardiovascular risk factors. Special Populations Pregnant Women There is no experience of exposure in pregnancy during clinical trials. Animal reproduction studies have not been conducted with GamaSTAN® S/D. It is also not known whether GamaSTAN® S/D can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. GamaSTAN® S/D should be given to a pregnant woman only if clearly needed. Nursing Women Because of the potential for unknown effects from GamaSTAN® S/D in infants being nursed by mothers taking GamaSTAN® S/D, a decision should be made to either discontinue nursing or discontinue the administration of GamaSTAN® S/D, taking into account the importance of GamaSTAN® S/D therapy to the mother and the possible risk to the infant. Pediatrics ( < 18 years of age) The safety and effectiveness of GamaSTAN® S/D in the pediatric population have not been established. Monitoring And Laboratory Tests None required.