"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
Mononine® is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. Because Mononine® is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. 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 viral infections and by inactivating and/or removing certain viruses during manufacture (see DESCRIPTION section for virus reduction measures). The manufacturing procedure for Mononine® (coagulation factor ix (human)) includes processing steps designed to reduce further the risk of virus transmission. Stringent procedures, utilized at plasma collection centers, plasma testing laboratories, and fractionation facilities are designed to reduce the risk of virus transmission. The primary virus reduction step of the Mononine® (coagulation factor ix (human)) manufacturing process is the use of two sequential virus retentive ultrafilter membranes designed to separate viruses from Factor IX. In addition, the purification procedure (several chromatography steps) used in the manufacture of Mononine® (coagulation factor ix (human)) also provides virus reduction capacity. Despite these measures, such products may still potentially contain human pathogenic agents, including those not yet known or identified. Thus the risk of transmission of infectious agents cannot be totally eliminated. Any infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to ZLBBehring at 800-504-5434 (in the U. S. and Canada). The physician should discuss the risks and benefits of this product with the patient.
Since the use of Factor IX Complex concentrates has historically been associated with the development of thromboembolic complications, the use of Factor IX-containing products may be potentially hazardous in patients with signs of fibrinolysis and in patients with disseminated intravascular coagulation (DIC).
Hypersensitivity and allergic type hypersensitivity reactions, including anaphylaxis, have been reported for all factor IX products. Frequently, these events have occurred in close temporal association with the development of factor IX inhibitors. Patients should be informed of the early symptoms and signs of hypersensitivity reactions, including hives, generalized urticaria, angioedema, chest tightness, dyspnea, wheezing, faint-ness, hypotension, tachycardia, and anaphylaxis. Patients should be advised to discontinue use of product and contact their physician and/or seek immediate emergency care, depending on the severity of the reac-tion, if any of these symptoms occur.
Preliminary information suggests a relationship may exist between the presence of major deletion mutations in the factor IX gene and an increased risk of inhibitor formation and of acute hypersensitivity reactions. Patients known to have major deletion mutations of the factor IX gene should be observed closely for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of initial exposure to product.
Nephrotic syndrome has been reported following attempted immune tolerance induction with factor IX products in Hemophilia B patients with factor IX inhibitors and a history of severe allergic reactions to factor IX. The safety and efficacy of using Mononine® (coagulation factor ix (human)) in attempted immune tolerance induction has not been established.
Extensive clinical experience suggests that there is a lower risk of thromboembolic complications with the use of Mononine® (coagulation factor ix (human)) than with prothrombin complex concentrates. However, as with all products containing Factor IX, caution should be exercised when administering Mononine® (coagulation factor ix (human)) to patients with liver disease, to patients post-operatively, to neonates, or to patients at risk of thromboembolic phenomena or DIC. 8, 9 In each of these situations, the potential benefit of treatment with Mononine® (coagulation factor ix (human)) should be weighed against the potential risk of these complications.
Coagulation Factor IX (Human), Mononine® (coagulation factor ix (human)) , should be administered intravenously at a rate that will permit observation of the patient for any immediate reaction. Rates of infusion of up to 225 IU per minute have been regularly tolerated with no adverse reactions. If any reaction takes place that is thought to be related to the administration of Mononine® (coagulation factor ix (human)) , the rate of infusion should be decreased or the infusion stopped, as dictated by the response of the patient. The infusion should be stopped promptly and appropriate countermeasures and supportive therapy should be administered should evidence of an acute hypersensitivity reaction be observed. Patients known to have major deletion mutations of the factor IXgene may be at increased risk for inhibitor formation and acute hypersensitivity reactions. (See WARNINGS.)
During the course of treatment, determination of daily Factor IX levels is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to Mononine® (coagulation factor ix (human)) , achieving different levels of in vivo recovery and demonstrating different half-lives.
The use of high doses of Factor IX Complex concentrates has been reported to be associated with instances of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism. Generally a Factor IX level of 25-50% [IU/dL] is considered adequate for hemostasis, including major hemorrhages and surgery. Attempting to maintain Factor IX levels of > 75-100% [IU/dL] during treatment is not routinely recommended nor required. To achieve Factor IX levels that will remain above 25% [IU/dL] between once a day administrations, each daily dose should attempt to raise the 30-minute post-infusion Factor IX level to 50-60% [IU/dL] (see DOSAGE AND ADMINISTRATION).
No controlled studies have been available regarding the use of ε-amino caproic acid or other antifibrinolyt-ic agents following an initial infusion of Mononine® (coagulation factor ix (human)) for the prevention or treatment of oral bleeding following trauma or dental procedures such as extractions.
Pregnancy Category C
Animal reproduction studies have not been conducted with Mononine® (coagulation factor ix (human)) . It is also not known whether Mononine® (coagulation factor ix (human)) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Mononine® (coagulation factor ix (human)) should be given to a pregnant woman only if clearly needed.
Evaluation of the safety and effectiveness of Mononine® (coagulation factor ix (human)) treatment in 51 pediatric patients between the ages of 1 day and 20 years, as a part of virus safety trials and trials for surgery, trauma or spontaneous bleeding, showed that excellent hemostasis was achieved with no thrombotic complications. 10 Included in the experience with patients aged birth to 20 years are two long-term virus safety studies demonstrating lack of virus transmission. Dosing in children is based on body weight and is generally based on the same guidelines as for adults (see DOSAGE AND ADMINISTRATION).
Clinical studies of Mononine® (coagulation factor ix (human)) did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. As for all patients, dosing for geriatric patients should be appropriate to their overall situation.
8. Aledort LM: Factor IX and Thrombosis. Scand J Haematology Suppl. 30:40, 1977.
9. Cederbaum AI, Blatt PM, Roberts HR. Intravascular coagulation with useof human prothrombin complex concentrates. Ann Intern Med 84:683-687, 1976.
10. Kurczynski E, Lusher JM, Pitel P, Shapiro AD, Bergman GE, the Mononine® (coagulation factor ix (human)) StudyGroup. Safetyand efficacyofmonoclonal antibody-purified factor IX concentrate for management of bleeding and surgical prophylaxis in previously treated children with hemophilia B. Int J Ped Hemat/Oncol 2:211-216, 1995.
Last reviewed on RxList: 3/6/2009
This monograph has been modified to include the generic and brand name in many instances.
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