ATryn

Biosynthetic (recombinant DNA origin) preparation of human antithrombin III, a naturally occurring anticoagulant.1 3 4 5 9

Contraindications

• Known hypersensitivity to goat and goat milk proteins.1

Warnings/Precautions

Warnings

Potential for enhanced anticoagulant effects if used concomitantly with unfractionated heparin, low molecular weight heparin, or other drugs that use antithrombin III to exert their anticoagulant effects.1 (See Interactions.)

Perform coagulation tests (e.g., aPTT, anti-factor Xa activity) at regular and frequent intervals in patients receiving concomitant anticoagulant therapy, especially in the first few hours following initiation or withdrawal of antithrombin alfa (antithrombin [recombinant]) therapy.1 Closely monitor for bleeding or thrombosis.1

Sensitivity Reactions

Potential for allergic-type hypersensitivity reactions, including anaphylaxis.1 Closely monitor for manifestations of hypersensitivity (e.g., hives, generalized urticaria, chest tightness, wheezing, hypotension, anaphylaxis).1 Immediately discontinue drug and administer appropriate emergency treatment if hypersensitivity occurs.1

Potential for antibody development to antithrombin alfa, goat antithrombin, or goat-milk proteins.1 6 11 Confirmed immunologic reactions not reported to date.1 3 4 5 6 10 11

A patient registry has been established to further evaluate immunogenic potential of antithrombin alfa.1 Clinicians encouraged to participate by calling Lundbeck Inc. at 800-455-1141.1

Specific Populations

Category C.1

Does not appear to be associated with an increased risk of fetal abnormalities when administered during the third trimester.1 5 However, use during pregnancy only if clearly indicated.1

Distributed into milk in low concentrations.1 Use with caution and only if clearly indicated.1

Safety and efficacy not established in pediatric patients <18 years of age.1 10

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger patients.1 Select dosage with caution, initiating at low end of dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.1

Common Adverse Effects

Hemorrhage,1 infusion site reactions.1

Distribution

Special Populations

Higher volume of distribution in pregnant versus nonpregnant patients.1 5

Elimination

Elimination Route

Irreversible complexes formed between antithrombin III and its target protease are rapidly removed by the liver.1 4 7 11

Half-life

Mean half-life following a single IV dose of 50 or 100 units/kg in patients with congenital antithrombin III deficiency is 11.6 or 17.7 hours, respectively.1

Shorter elimination half-life and more rapid clearance compared with plasma-derived antithrombin III.1 5 6 11

Special Populations

Increased clearance in pregnant women compared with nonpregnant patients.1 5

• If you have an allergy to antithrombin or any other part of ATryn (antithrombin).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about ATryn, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about ATryn. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using ATryn.

Review Date: October 4, 2017

ATryn is contraindicated in patients with known hypersensitivity to goat and goat milk proteins.

ATryn is the first recombinant antithrombin product approved in the world and the first antithrombin product that has been approved through the centralized procedure in the European Union. It is now also the first recombinant antithrombin product approved by the FDA.

Most common adverse reactions reported in clinical trials at a frequency of = 5% were hemorrhage and infusion site reaction.

To report suspected adverse reactions, contact Ovation Pharmaceuticals at 1-800-455-1141 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

• ATryn enhances anticoagulant effect of heparin and low molecular weight heparin.
• The half-life of ATryn may be altered by concomitant treatment with anticoagulants that use antithrombin to exert their anticoagulant effect.

Use in Specific Populations

• Pregnancy Category C. Studies in pregnant women have not shown that ATryn increases the risk of fetal abnormalities if administered during the third trimester of pregnancy. No data is available for use of ATryn in earlier stages of pregnancy.
• Labor and Delivery: ATryn is used in the treatment of peri-partum women with hereditary antithrombin deficiency.
• Nursing Mothers: ATryn administered by infusion will be present in breast milk at estimated concentrations 1/50 to 1/100 that of concentration in blood. Use only if clearly needed.

Inform patients that allergic-type hypersensitivity reactions are possible and instruct them to inform their physicians about any past or present known hypersensitivity to goats or goat milk proteins prior to treatment with ATryn. Inform patients of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis and to notify their health care provider immediately if these events develop.

Inform patients about the risk of bleeding when ATryn is administered with other anticoagulants and instruct them to notify their physicians of any bleeding events while on treatment with ATryn.