Product Information

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New product candidates and exciting advances in technology are featured in our product pipeline, which highlights our key research from early stage programs to phase 3 clinical trials.

For more than 30 years, Genzyme has leveraged our expertise in multiple therapeutic areas and technology platforms to develop innovative, targeted answers to unmet medical needs worldwide. The result: a specialized product portfolio that makes a major positive impact on the lives of patients with serious medical conditions.

The list below includes Genzyme's products marketed in the United States. Many of these, as well as other Genzyme products, are also approved and marketed in other parts of the world.

If you are outside the U.S. and want to learn about products available in your area:

 



INDICATIONS AND USAGE

ALDURAZYME (laronidase) is indicated for patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected patients with the Scheie form have not been established.
 

ALDURAZYME has been shown to improve pulmonary function and walking capacity.  ALDURAZYME has not been evaluated for effects on the central nervous system manifestations of the disorder.

Important Safety Information

WARNING: Risk of anaphylaxis.

Life-threatening anaphylactic reactions have been observed in some patients during ALDURAZYME infusions. Therefore, appropriate medical support should be readily available when ALDURAZYME is administered. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions, and require additional monitoring.

Anaphylaxis and severe allergic reactions have been observed in patients during or up to 3 hours after ALDURAZYME infusions. Some of these reactions were life-threatening and included respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, obstructive airways disorder, hypoxia, hypotension, bradycardia, and urticaria. If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion of ALDURAZYME and initiate appropriate treatment. Caution should be exercised if epinephrine is being considered for use in patients with MPS I due to the increased prevalence of coronary artery disease in these patients. Interventions have included resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.
 
In clinical studies and postmarketing safety experience with ALDURAZYME, approximately 1% of patients experienced severe or serious allergic reactions. In patients with MPS I, pre-existing upper airway obstruction may have contributed to the severity of some reactions. Due to the potential for severe allergic reactions, appropriate medical support should be readily available when ALDURAZYME is administered. Because of the potential for recurrent reactions, some patients who experience initial severe reactions may require prolonged observation.
 
The risks and benefits of re-administering ALDURAZYME following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
 
Patients with an acute febrile or respiratory illness at the time of ALDURAZYME infusion may be at greater risk for infusion reactions. Careful consideration should be given to the patient’s clinical status prior to administration of ALDURAZYME and consider delaying ALDURAZYME infusion.
 
Sleep apnea is common in MPS I patients. Evaluation of airway patency should be considered prior to initiation of treatment with ALDURAZYME. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction or extreme drowsiness/sleep induced by antihistamine use.
 
Caution should be exercised when administering ALDURAZYME to patients susceptible to fluid overload or patients with an acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid restriction is indicated. These patients may be at risk of serious exacerbation of their cardiac or respiratory status during infusions. Appropriate medical support and monitoring measures should be readily available during ALDURAZYME infusion, and some patients may require prolonged observation times that should be based on the individual needs of the patient.
 
Because of the potential for infusion reactions, patients should receive antipyretics and/or antihistamines prior to infusion. If an infusion-related reaction occurs, regardless of pre-treatment, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antipyretics and/or antihistamines may ameliorate the symptoms.
 
The most serious adverse reactions reported with ALDURAZYME treatment during clinical trials were anaphylactic and allergic reactions.
 
In a 26-week, placebo-controlled clinical trial in patients 6 years and older, the most commonly reported infusion reactions regardless of treatment group were flushing, pyrexia, headache, and rash. Flushing occurred in 5 patients (23%) receiving ALDURAZYME; the other reactions were less frequent. Less common infusion reactions included angioedema (including face edema), hypotension, paresthesia, feeling hot, hyperhidrosis, tachycardia, vomiting, back pain, and cough. Other reported adverse reactions included bronchospasm, dyspnea, urticaria, and pruritus. In the open-label, uncontrolled extension phase of this clinical trial, the infusion reactions were similar, but also included abdominal pain or discomfort and injection site reaction. Less commonly reported infusion reactions included nausea, diarrhea, feeling hot or cold, vomiting, pruritus, arthralgia and urticaria. Additional common adverse reactions included, back pain and musculoskeletal pain.
 
In an open-label, uncontrolled clinical trial in patients 6 years and younger who received ALDURAZYME treatment for up to 52 weeks, the most commonly reported serious adverse events (regardless of relationship) in patients 6 years and younger, were otitis media (20%), and central venous catherization required for ALDURAZYME infusion (15%). The most commonly reported adverse reactions in patients 6 years and younger were infusion reactions reported in 35% (7 of 20) of patients and included pyrexia (30%), chills (20%), blood pressure increased (10%), tachycardia (10%), and oxygen saturation decreased (10%). Other commonly reported infusion reactions occurring in ≥5% of patients were pallor, tremor, respiratory distress, wheezing, crepitations (pulmonary), pruritus, and rash.
 
In postmarketing experience with ALDURAZYME, severe and serious infusion reactions have been reported, some of which were life-threatening, including anaphylactic shock. Adverse reactions resulting in death reported in the postmarketing setting with ALDURAZYME treatment included cardio-respiratory arrest, respiratory failure, cardiac failure, and pneumonia. These events have been reported in MPS I patients with significant underlying disease. Additional common adverse reactions included erythema and cyanosis. There have been a small number of reports of extravasation in patients treated with ALDURAZYME. There have been no reports of tissue necrosis associated with extravasation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
 
In clinical trials, 99 of 102 patients (97%) treated with ALDURAZYME were positive for IgG antibodies to ALDURAZYME. In the 2 trials of patients 6 years and older, 9 patients who experienced severe infusion reactions were tested for ALDURAZYME-specific IgE antibodies and complement activation. One of the nine patients had an anaphylactic reaction consisting of urticaria and airway obstruction and tested positive for both ALDURAZYME-specific IgE binding antibodies and complement activation. In the postmarketing setting, approximately 1% of patients experienced severe or serious infusion-allergic reactions and tested positive for IgE. Of these IgE-positive patients, some have discontinued treatment, but some have been successfully re-challenged. The clinical significance of antibodies to ALDURAZYME, including the potential for product neutralization, is not known.
 
Adverse events should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
 
ALDURAZYME is available by prescription only. To learn more, please see the Full Prescribing Information including Boxed Warning, visit www.ALDURAZYME.com or contact Genzyme at 1-800-745-4447, option 2.


Indication and Usage

AUBAGIO® (teriflunomide) is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS). AUBAGIO can decrease the number of MS flare-ups (relapses). AUBAGIO does not cure MS, but it can help slow down the physical problems that MS causes.

    Important Safety Information

    WARNING: HEPATOTOXICITY and RISK OF TERATOGENICITY

    Hepatotoxicity

    Severe liver injury fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO and monitor ALT levels at least monthly for six months (5.1). If drug induced liver injury is suspected, discontinue AUBAGIO and start accelerated elimination procedure (5.3).

    Risk of Teratogenicity

    Based on animal data, AUBAGIO may cause birth defects if used during pregnancy. AUBAGIO is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during AUBAGIO treatment.

    Who should not take AUBAGIO?

    AUBAGIO may cause serious liver problems, which can be life-threatening. If you are taking AUBAGIO, tell your doctor right away if you develop any of these symptoms of liver problems: nausea; vomiting; stomach pain; loss of appetite; unusual tiredness; yellowing of your skin or whites of your eyes; unusual darkening of your urine.

    AUBAGIO should not be used if you are pregnant or plan to become pregnant. Use effective birth control while taking AUBAGIO. If you become pregnant while on AUBAGIO or within 2 years after you stop taking it, tell your doctor right away.

    If you are a man taking AUBAGIO whose female partner plans to become pregnant, talk to your doctor immediately. If your female partner does not plan to become pregnant, use effective birth control while taking AUBAGIO.

    AUBAGIO may stay in your blood for up to 2 years after you stop taking it. Your doctor can prescribe a medicine that can help remove AUBAGIO from your body more quickly.

    What should I talk to my doctor about?

    Before you start AUBAGIO, tell your doctor if you have: liver or kidney problems; a fever or infection; numbness or tingling in your hands or feet; diabetes, serious skin problems when taking other medications; breathing problems; high blood pressure; or if you are breast feeding or plan to breast feed.

    Tell your doctor about all the medications, vitamins, and herbal supplements you take. This can help you avoid serious drug interactions. Do not start taking any new medications or receive vaccinations without talking to your doctor.

    Call your doctor right away if you have any of these symptoms of an infection while on AUBAGIO: fever; tiredness; body aches; chills; nausea; vomiting. AUBAGIO may decrease your white blood cell count, which may mean you could have more frequent infections.

    What are some of the possible side effects of AUBAGIO?

    Other possible side effects of AUBAGIO include numbness or tingling in your hands or feet that is different from your MS; kidney problems; high potassium levels in your blood; serious skin problems; breathing problems (new or worsening); high blood pressure.

    The most common side effects of AUBAGIO include:

    • abnormal liver tests
    • hair thinning
    • diarrhea
    • flu
    • nausea
    • a burning or prickling feeling in your skin

    Tell your doctor right about any side effect that bothers you or that does not go away. These are not all the side effects of AUBAGIO. Call your doctor or pharmacist for medical advice about side effects. You may report side effects to FDA at 1-800-332-1088.

    Please see full prescribing information including boxed WARNING, with Medication Guide.

    Cerdelga<sup>&trade;</sup> (eliglustat) capsules
    Cerdelga (eliglustat) capsules U.S. Product Website
    U.S. Prescribing Information (PDF)

    Indications and Usage

    CERDELGATM (eliglustat) capsules are indicated for the long-term treatment of adults with Gaucher disease type 1 (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test. Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect.  A specific dose cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).

    Important Safety Information

    CERDELGA is contraindicated in the following patients due to the risk of significantly increased CERDELGA plasma concentrations which may result in prolongation of the PR, QTc, and/or QRS cardiac intervals that could result in cardiac arrhythmias: EMs or IMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor and IMs or PMs taking a strong CYP3A inhibitor.

    Drugs that inhibit CYP2D6 and CYP3A may significantly increase the exposure to CERDELGA; Cerdelga dose adjustment may be needed, depending on metabolizer status. See section 7 of the full Prescribing Information for more details and other potentially significant drug interactions.

    Because CERDELGA is predicted to cause increases in ECG intervals at substantially elevated plasma concentrations, use is not recommended in patients with pre-existing cardiac disease, long QT syndrome, or in combination with Class IA and Class III antiarrhythmic medications.

    The most common adverse reactions (≥10%) for CERDELGA are: fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain. 

    Only administer CERDELGA during pregnancy if the potential benefit justifies the potential risk; based on animal data, CERDELGA may cause fetal harm. Discontinue drug or nursing based on importance of drug to mother. CERDELGA is not recommended in patients with moderate to severe renal impairment or in patients with hepatic impairment.

    To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at (1-800-745-4447) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see full Prescribing Information, including patient Medication Guide, for additional important safety information.

    Cerezyme<sup>®</sup>
    Cerezyme® (imiglucerase for injection) U.S. Product Website
    U.S. Prescribing Information (PDF)
    Indication and Usage

    Cerezyme® (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions:

         a. anemia (low red blood cell count)
         b. thrombocytopenia (low blood platelet count)
         c. bone disease
         d. hepatomegaly or splenomegaly (enlarged liver or spleen)

      Important Safety Information

      Approximately 15% of patients have developed immune responses (antibodies). These patients have a higher risk of an allergic reaction (hypersensitivity). Use Cerezyme® (imiglucerase for injection) carefully if you have had an allergic reaction to the product in the past. Symptoms suggestive of allergic reaction happened in 6.6% of patients, and include anaphylactoid reaction (a serious allergic reaction), itching, flushing, hives, an accumulation of fluid under the skin, chest discomfort, shortness of breath, coughing, cyanosis (a bluish discoloration of the skin due to diminished oxygen), and low blood pressure.

      Side effects related to Cerezyme administration have been reported in less than 15% of patients. Each of the following events occurred in less than 2% of the total patient population. Reported side effects include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and rapid heart rate. Because Cerezyme therapy is administered by intravenous infusion, reactions at the site of injection may occur: discomfort, itching, burning, swelling or uninfected abscess. Cerezyme is available by prescription only. For more information, consult your physician.

      Please see full prescribing information.


      Indication and Usage

      Fabrazyme® (agalsidase beta) is used to treat patients with Fabry disease. Fabrazyme lowers the amount of a substance called globotriaosylceramide (GL-3), which builds up in cells lining the blood vessels of the kidney and certain other cells.

      The lowering of GL-3 suggests that Fabrazyme may improve how Fabry disease affects your body; however a relationship of lower GL-3 to specific signs and symptoms of Fabry disease has not been proven.

      Important Safety Information

      Life-threatening severe allergic (anaphylactic) reactions have been seen in patients during Fabrazyme infusions. Approximately 1% of patients who have received Fabrazyme either during a clinical study or after Fabrazyme was approved have experienced anaphylactic or severe allergic reactions during their infusion. These reactions have included: localized swelling of the face, mouth and throat, narrowing of breathing airways, low blood pressure, hives, difficulty swallowing, rash, trouble breathing, flushing, chest discomfort, itching and nasal congestion. People who have experienced these reactions have required treatment including heart/lung resuscitation, oxygen, fluids given through the vein, hospitalization, and have needed treatment with inhaled drugs called beta-adrenergic agonists to help open the breathing airways, antihistamines, epinephrine (also known as adrenalin), and a medication given through the vein called a corticosteroid (or steroid) which helps to decrease the body’s allergic reaction by decreasing inflammation. If you experience a severe allergic or anaphylactic reaction, your healthcare professional will immediately stop the infusion of Fabrazyme and provide you the necessary emergency medical treatment. Because of the possibility that severe allergic reactions may occur, appropriate medical support should be available during your Fabrazyme infusion.

      For patients who have had reactions to their infusions, it is recommended that they be given anti-fever and antihistamine medications right before their next infusions. Infusion reactions have happened in some patients even after taking these medications and steroids by mouth before their infusions. If an infusion reaction occurs, slowing the infusion rate, stopping the infusion for a short time and/or giving more anti-fever and antihistamine medications and or steroids may improve the symptoms. If severe infusion reactions happen, your healthcare professional should consider stopping the Fabrazyme infusion right away and should provide medical care for your condition. Severe reactions are generally managed by giving antihistamine medications, corticosteroids, fluids through the vein, and/or oxygen when needed. Because severe infusions reactions may happen, medical treatment should be readily available during your Fabrazyme infusion.

      Providing Fabrazyme to patients who have experienced severe or serious allergic reactions to Fabrazyme should only be done after carefully considering the risks and benefits of continuing the treatment, and only under the direct supervision of a qualified healthcare professional and with appropriate medical support readily available.

      The most common side effects reported with Fabrazyme are infusion reactions, some of which were severe. When Fabrazyme was tested in clinical studies, infusion reactions occurred in approximately 50-55% of patients. Serious and/or frequently occurring side effects (occurring in 5% or more of the patients) thought to be related to Fabrazyme have included one or more of the following: chills, fever, feeling hot or cold, trouble breathing, nausea, flushing of the skin, headache, vomiting, burning and/or tingling sensation, fatigue, itching, pain in the hands and feet, high blood pressure, chest pain, throat tightness, abdominal pain, dizziness, rapid heart rate, nasal congestion, diarrhea, swelling in the legs, muscle pain, back pain, paleness of the skin, slow heart rate, hives, low blood pressure, face swelling, rash and sleepiness.

      People with advanced Fabry disease may have heart problems, which may put them at a higher risk for severe complications from infusion reactions, and these patients should be watched closely during their infusion if the decision is made to give them Fabrazyme.

      Other serious side effects that were seen in the clinical studies included stroke, pain, lack of muscle coordination, slow or irregular heartbeat, stopping of the heartbeat , decreased blood pumped by the heart, dizziness, hearing loss, and kidney problems resulting in too much protein leaving the body in the urine (nephrotic syndrome). These side effects also occur as part of Fabry disease.

      Severe and serious infusion reactions have been reported since Fabrazyme has been approved, some of which were life threatening including anaphylactic shock (a severe allergic reaction). In addition to the above side effects, the following have been reported since Fabrazyme has been approved: joint pain, lack of strength or energy, redness of the skin, increased sweating, reactions at the place where the catheter to give the infusion is placed, increased tearing from the eyes, allergic inflammation of blood vessels, enlarged lymph nodes, decreased sensitivity to touch or pressure, decreased sensitivity of the mouth, sensations of an abnormal heartbeat, runny nose, low oxygen (in general), and low oxygen levels reaching different parts of the body.

      Since Fabrazyme has been approved, there have been side effects that resulted in death that may or may not be related to the use of Fabrazyme. These included: the heart and/or lungs stop working (known as cardiorespiratory arrest, respiratory failure, and/or cardiac failure), life-threatening infection in the blood stream (known as sepsis), stroke, heart attack, kidney failure, and pneumonia. Some of these side effects were reported in Fabry disease patients with significant underlying disease.

      The safety and effectiveness of Fabrazyme in patients younger than 8 years of age have not been studied.

      Most patients taking Fabrazyme who develop IgG antibodies, which are commonly produced by your immune system in response to things it does not recognize as naturally being part of your body, do so within the first three months of taking the medication. In children, the development of these IgG antibodies was associated with Fabrazyme staying in the body for a longer time (prolonged half-life), which was rarely seen in adult patients.

      In the clinical studies, a few patients developed IgE antibodies or a reaction to an allergy skin test specific to Fabrazyme. IgE antibodies are usually produced by the body’s immune system during an allergic reaction. Your doctor should consider testing for IgE antibodies if you experience suspected allergic reactions and consider the risks and benefits of continued treatment with Fabrazyme if you have IgE antibodies against Fabrazyme.

      Fabrazyme is available by prescription only. Side effects should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. To learn more, please see the full prescribing information (PDF) or contact Genzyme at 1-800-745-4447.


      Indication

      KYNAMROTM (mipomersen sodium) is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

      Limitations of Use

      The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH

      The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.

      Important Safety Information

      WARNING: RISK OF HEPATOTOXICITY

      KYNAMRO can cause elevations in transaminases. In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT).

      KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis.

      Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of KYNAMRO if the ALT or AST are ≥3 x ULN. Discontinue KYNAMRO for clinically significant liver toxicity.

      Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS.

      Other Warnings and Precautions

      Patients are advised to read the KYNAMRO medication guide before starting treatment with KYNAMRO, and each time they receive a refill. There may be new information. This information does not take the place of talking to a doctor about a medical condition or treatment.

      KYNAMRO may cause serious side effects, including liver problems. A doctor should be informed of any liver problems, including liver problems while taking other medicines, or if a patient has any of these symptoms of liver problems while taking KYNAMRO: nausea, vomiting, fever, loss of appetite, being (or feeling) more tired than usual, yellowing of eyes or skin, dark urine, itching, or stomach pain.

      Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking KYNAMRO should consume no more than one alcoholic drink per day.

      Caution should be exercised when KYNAMRO is used with other medications known to have potential for hepatotoxicity.

      KYNAMRO should be used during pregnancy only if clearly needed. Females who become pregnant during KYNAMRO therapy should notify their healthcare provider.

      Safety and effectiveness have not been established in pediatric patients.

      KYNAMRO is not recommended in patients with severe renal impairment, clinically significant proteinuria, or on renal dialysis.

      The safety and effectiveness of KYNAMRO as an adjunct to LDL apheresis have not been established; therefore, the use of KYNAMRO as an adjunct to LDL apheresis is not recommended.

      Contraindications

      KYNAMRO is contraindicated in the following conditions:

      • Moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease, including unexplained persistent elevations of serum transaminases.

         

      • Patients with a known hypersensitivity to any component of this product.

      Common Side Effects

      In clinical trials the most commonly-reported adverse reactions were injection site reactions occurring in 84% of patients receiving KYNAMRO versus 33% of placebo treated patients. The most common injection site reactions were erythema (59%), pain (56%), hematoma (32%), pruritus (29%), swelling (18%) and discoloration (17%). Injection site reactions did not occur with every injection but resulted in discontinuation of therapy in 5% of patients in pooled phase 3 trials.

      Flu-like symptoms, defined as any one of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue and occurring within 2 days of injection, have been reported more frequently in patients receiving KYNAMRO (30%) versus placebo (16%) in the pooled Phase 3 trials. Flu-like symptoms did not occur with all injections but resulted in discontinuation of therapy in 3% of patients in pooled phase 3 trials.

      See full prescribing information for more details about Warnings & Precautions, complete list of Adverse Reactions and Boxed Warning.

      INDICATION

      LUMIZYME® (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of LUMIZYME have not been evaluated in controlled clinical trials in infantile-onset patients, or in late (non-infantile) onset patients less than 8 years of age.

      IMPORTANT SAFETY INFORMATION

      WARNING - ANAPHYLAXIS and RESTRICTED DISTRIBUTION PROGRAM

      Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered.

      Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME is available only through a restricted distribution program called the LUMIZYME ACE Program. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense, or administer LUMIZYME. LUMIZYME may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME ACE Program. To enroll in the LUMIZYME ACE Program call 1-800-745-4447.

      Anaphylaxis and Allergic Reactions: Anaphylaxis and severe allergic reactions have been observed in patients during and up to 3 hours after LUMIZYME infusion. Some of the reactions were life-threatening and included anaphylactic shock, respiratory arrest, apnea, dyspnea, bradycardia, tachycardia, and hypotension. Other accompanying reactions included chest discomfort/pain, throat tightness, bronchospasm, wheezing, tachypnea, cyanosis, decreased oxygen saturation/hypoxia, convulsions, angioedema (including tongue or lip swelling, periorbital edema, and face edema), pruritus, rash, urticaria, hyperhidrosis, nausea, dizziness, hypertension, flushing/erythema, fever, pallor, peripheral coldness, feeling hot, restlessness, nervousness, headache, back pain, and paraesthesia. Some of these reactions were IgE-mediated.

      If anaphylaxis or other severe allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylaxis, epinephrine has been administered. Because of the potential for severe allergic reactions, appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when LUMIZYME is administered. The risk and benefits of re-administering LUMIZYME following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.

      Immune Mediated Reactions: Severe cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions. Systemic immune mediated reactions, including possible type III immune mediated reactions have been observed with alglucosidase alfa. These reactions occurred several weeks to 3 years after initiation of alglucosidase alfa infusions. Skin biopsy in one patient demonstrated deposition of anti-rhGAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with fever and elevated erythrocyte sedimentation rate. Nephrotic syndrome secondary to membranous glomerulonephritis was observed in a few Pompe disease patients treated with alglucosidase alfa who had persistently positive anti-rhGAA IgG antibody titers. In these patients renal biopsy was consistent with immune complex deposition. Patients improved following treatment interruption. It is therefore recommended to perform periodic urinalysis.

      Patients should be monitored for the development of systemic immune mediated reactions involving skin and other organs while receiving LUMIZYME. If immune mediated reactions occur, discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune mediated reaction should be considered. Some patients have successfully been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.

      LUMIZYME ACE Program®: LUMIZYME is available only under a restricted distribution program called the LUMIZYME ACE (Alglucosidase Alfa Control and Education) Program. The purpose of the program is to ensure that the known risks of anaphylaxis and severe allergic reactions and the potential risks of severe cutaneous and systemic immune mediated reactions associated with the use of LUMIZYME are communicated to patients and prescribers. In addition, the program is designed to mitigate the potential risk of rapid disease progression in infantile-onset Pompe disease patients and late (non-infantile) onset Pompe disease patients less than 8 years of age for whom the safety and effectiveness of LUMIZYME have not been evaluated. For information about the ACE Program call 1-800-745-4447.

      Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during infusions and some patients may require prolonged observation times that should be based on the individual needs of the patient. Acute cardiorespiratory failure has been observed in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa.

      Precautions for General/Regional Anesthesia: Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness, therefore, caution should be used when administering general anesthesia in Pompe disease patients.

      Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.

      Adverse Reactions:

      Serious adverse reactions reported with LUMIZYME in the randomized, double-blind, placebo-controlled study included anaphylaxis. Anaphylactic reactions included: angioedema, throat tightness and chest pain/discomfort. One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia. Other serious adverse events that occurred in a higher incidence in LUMIZYME treated patients compared to placebo included coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis, and dehydration.

      The most common adverse reactions observed in clinical studies were infusion reactions. Infusion reactions, defined as an adverse reaction occurring during the infusion or within 2 hours after completion of the infusion, that occurred in LUMIZYME treated patients at an incidence of ≥ 5% compared to placebo included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort. Additional infusion reactions observed in other clinical trials and expanded access programs with LUMIZYME included respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor and increased lacrimation.

      Delayed onset infusion reactions defined as adverse reactions that occurred within 48 hours after completion of LUMIZYME infusion, occurred in LUMIZYME treated patients at an incidence of ≥ 3% compared to placebo treated patients in a controlled clinical trial. Symptoms included urticaria, dizziness, procedural pain, pharyngolaryngeal pain, malaise, muscle spasms, musculoskeletal pain, musculoskeletal weakness, musculoskeletal stiffness, neck pain, insomnia, and epistaxis. Patients should be counseled about the possibility of delayed onset infusion reactions and given proper follow up instructions.

      If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion or allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Patients who have experienced infusion reactions should be treated with caution when they are re-administered LUMIZYME.

      In postmarketing experience with LUMIZYME, deaths, and serious adverse reactions have been reported, including anaphylaxis. Adverse events resulting in death reported in the postmarketing setting with LUMIZYME treatment included cardiorespiratory arrest, respiratory failure, hemothorax, pneumothorax, cardiac failure, sepsis, aortic dissection, cerebrovascular accident, and skin necrosis. The most frequently reported serious adverse reactions were infusion reactions. In addition to the infusion reactions reported in clinical trials, the following serious adverse events have been reported in at least 2 patients: dyspnea, respiratory failure, bronchospasm, stridor, decreased oxygen saturation/hypoxia, pharyngeal edema, chest discomfort, chest pain, hypotension, hypertension, erythema, flushing, lung infection, tachycardia, cyanosis, hypersensitivity and abdominal pain. One case of hyperparathyroidism has been reported. Additional adverse drug reactions included proteinuria and nephrotic syndrome.

      Immunogenicity: In the randomized, double-blind, placebo-controlled study, all patients with available samples treated with LUMIZYME (N=59, 100%) developed IgG antibodies to alglucosidase alfa. All patients who developed IgG antibodies did so within the first 3 months of exposure (median time to seroconversion was 4 weeks). There was no apparent association between mean or peak IgG antibody titers and the occurrence of adverse reactions. A small number of LUMIZYME treated patients in the postmarketing setting who were evaluated tested positive for presence of alglucosidase alfa-specific IgE antibodies. Some of these patients experienced anaphylaxis. Some patients who tested positive for alglucosidase alfa-specific IgE antibodies were successfully rechallenged with LUMIZYME using a slower infusion rate at lower initial doses and have continued to receive treatment under close clinical supervision. Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions. Therefore, these patients should be monitored more closely during administration of LUMIZYME.

      To report suspected adverse reactions, contact Genzyme Medical Information at 800-745-4447, option 2.

      Please see the full prescribing information for complete details, including boxed warning.

       


      Indication

      MYOZYME® (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for use in patients with Pompe disease (GAA deficiency). MYOZYME has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of MYOZYME in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.

      Important Safety Information

      WARNING

      Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during MYOZYME infusions. Therefore, appropriate medical support should be readily available when MYOZYME is administered.

      Risk of Cardiorespiratory Failure:
      Patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to infusion reactions, and require additional monitoring.

      Anaphylaxis and Allergic Reactions: Anaphylaxis and severe allergic reactions have been reported in some patients during and up to three hours after MYOZYME infusion, some of which were IgE-mediated. Some of the reactions were life-threatening and included: anaphylactic shock, cardiac arrest, respiratory distress, hypotension, bradycardia, hypoxia, bronchospasm, throat tightness, dyspnea, angioedema, and urticaria. Interventions have included: cardiopulmonary resuscitation, mechanical ventilatory support, oxygen supplementation, intravenous (IV) fluids, hospitalization, treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.

      In clinical trials and postmarketing safety experience with MYOZYME, approximately 1% of patients developed anaphylactic shock and/or cardiac arrest during MYOZYME infusion that required life-support measures. In clinical trials and expanded access programs with MYOZYME, approximately 14% of patients treated with MYOZYME have developed allergic reactions that involved at least 2 of 3 body systems, cutaneous, respiratory or cardiovascular systems. These events included: Cardiovascular: hypotension, cyanosis, hypertension, tachycardia, ventricular extrasystoles, bradycardia, pallor, flushing, nodal rhythm, peripheral coldness; Respiratory: tachypnea, wheezing/bronchospasm, rales, throat tightness, hypoxia, dyspnea, cough, respiratory tract irritation, decreased oxygen saturation; Cutaneous: angioedema, urticaria, rash, erythema, periorbital edema, pruritus, hyperhidrosis, cold sweat, livedo reticularis.

      If anaphylactic or other severe allergic reactions occur, immediate discontinuation of the administration of MYOZYME should be considered, and appropriate medical treatment should be initiated. Because of the potential for severe allergic reactions, appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when MYOZYME is administered.

      Risk of Acute Cardiorespiratory Failure:
      Acute cardiorespiratory failure requiring intubation and inotropic support has been observed up to 72 hours after infusion with MYOZYME in infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of MYOZYME. Patients with acute underlying respiratory illness, compromised cardiac function and/or sepsis may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during MYOZYME infusion, and infants with cardiac dysfunction may require prolonged observation times that should be individualized based on the needs of the patient.

      Risk of Cardiac Arrhythmia and Sudden Cardiac Death During General Anesthesia for Central Venous Catheter Placement:
      Cardiac arrhythmia, including ventricular fibrillation, ventricular tachycardia and bradycardia, resulting in cardiac arrest or death, or requiring cardiac resuscitation or defibrillation have been observed in infantile-onset Pompe disease patients with cardiac hypertrophy, associated with the use of general anesthesia for the placement of a central venous catheter intended for MYOZYME infusion. Caution should be used when administering general anesthesia for the placement of a central venous catheter in infantile-onset Pompe disease patients with cardiac hypertrophy.

      Infusion Reactions: Infusion reactions occurred in 20 of 39 (51%) of patients treated with MYOZYME in clinical studies. Severe infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included: fever, decreased oxygen saturation, tachycardia, cyanosis and hypotension. Other infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included: rash, flushing, urticaria, fever, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure/hypertension, cyanosis, irritability, pallor, pruritus, retching, rigors, tremor, hypotension, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, increased lacrimation, livedo reticularis, nausea, periorbital edema, restlessness and wheezing. Some patients were pre-treated with antihistamines, antipyretics and/or steroids. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines, or steroids. Infusion reactions may occur at any time during, or up to 2 hours after, the infusion of MYOZYME, and are more likely with higher infusion rates.

      Immune Mediated Reactions:
      Severe cutaneous and systemic immune mediated reactions have been reported in postmarketing experience with MYOZYME in at least 2 patients, including ulcerative and necrotizing skin lesions, and possible type III immune complex-mediated reactions. Patients should be monitored for the development of systemic immune complex-mediated reactions involving skin and other organs while receiving MYOZYME.

      Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.

      Adverse Reactions: The most serious adverse reactions reported with MYOZYME were anaphylactic reactions, acute cardiorespiratory failure, and cardiac arrest. Anaphylactic reactions have been reported during and within 3 hours after MYOZYME infusion. Acute cardiorespiratory failure has been observed in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa.

      The most common serious treatment-emergent adverse reactions occurring in >10% of patients observed in clinical studies with MYOZYME were pneumonia, respiratory failure, respiratory distress, catheter-related infection, respiratory syncytial virus infection, gastroenteritis and fever. The most common treatment-emergent adverse reactions occurring in ≥ 20% of patients were fever, diarrhea, rash, vomiting, cough, pneumonia, otitis media, upper respiratory tract infection, gastroenteritis and decreased oxygen saturation.

      The most common adverse reactions requiring intervention were infusion reactions. Twenty of 39 patients (51%) treated with MYOZYME in clinical studies developed infusion reactions.

      Immunogenicity: The majority of patients (34 of 38; 89%) in the two clinical trials tested positive for IgG antibodies to alglucosidase alfa. Most patients who develop antibodies do so within the first 3 months of exposure. There is evidence to suggest that patients developing sustained titers ≥12,800 of anti-alglucosidase alfa antibodies may have a poorer clinical response to treatment, or may lose motor function as antibody titers increase. Five patients with antibody titers ≥ 12,800 at Week 12 had an average increase in clearance of 50% from Week 1 to Week 12. The effect of antibody development on the long-term efficacy of MYOZYME is not fully understood. However, CRIM-negative infants have shown poorer clinical response in the presence of high sustained IgG antibody titers and inhibitory and positive inhibitory antibodies. Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions. Therefore, these patients should be monitored more closely during administration of MYOZYME.

      To report suspected adverse reactions, contact Genzyme at 800-745-4447, option 2 or FDA at 800-FDA-1088 or http://www.fda.gov/Safety/MedWatch

      Please see full prescribing information for complete details, including boxed warning.

       

      Thyrogen<sup>®</sup>
      Thyrogen® (thyrotropin alfa for injection) U.S. Product Website
      U.S. Prescribing Information (PDF)
      Indication

      Thyrogen® (thyrotropin alfa for injection) is indicated for use as an additional tool to identify thyroid disease (by testing the blood for a hormone called thyroglobulin), with or without a radiology test using a form of iodine, in the follow-up of patients with a certain type of thyroid cancer (known as well-differentiated thyroid cancer).

      Thyrogen (thyrotropin alfa for injection) is also indicated for use as a preparation for treatment with a form of iodine to remove left over thyroid tissue in patients who have had surgery to take out the entire thyroid gland for a certain type of thyroid cancer (known as well-differentiated thyroid cancer) and who do not have signs of thyroid cancer which has spread to other parts of the body.

       

      Important Safety Information

      • When Thyrogen is used to help detect thyroid cancer, there is still a chance all—or parts of—your cancer could be missed.
      • In a study of people being prepared for treatment with a form of iodine after thyroid surgery, results were similar between those who received Thyrogen and those who stopped taking their thyroid hormone. Researchers do not know if results would be similar over a longer period of time.
      • Your doctor may take extra steps to care for you during Thyrogen treatment if you have heart disease and large amounts of remaining thyroid tissue after surgery.
      • If you are over 65 years old and did not have your entire thyroid removed during treatment of your cancer, you may be at risk for abnormal heartbeat while receiving Thyrogen. Because of this, you and your doctor will need to carefully consider the risks and benefits of Thyrogen before starting it.
      • In clinical studies, the most common side effects reported were upset stomach, headache, tiredness, throwing up, dizziness, prickling and tingling sensation, weakness, difficulty sleeping, and diarrhea.

      Please see accompanying full Product Information.


      Product Information

      INDICATIONS AND USAGE

      ALDURAZYME (laronidase) is indicated for patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected patients with the Scheie form have not been established.
       

      ALDURAZYME has been shown to improve pulmonary function and walking capacity.  ALDURAZYME has not been evaluated for effects on the central nervous system manifestations of the disorder.

      Important Safety Information

      WARNING: Risk of anaphylaxis.

      Life-threatening anaphylactic reactions have been observed in some patients during ALDURAZYME infusions. Therefore, appropriate medical support should be readily available when ALDURAZYME is administered. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions, and require additional monitoring.

      Anaphylaxis and severe allergic reactions have been observed in patients during or up to 3 hours after ALDURAZYME infusions. Some of these reactions were life-threatening and included respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, obstructive airways disorder, hypoxia, hypotension, bradycardia, and urticaria. If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion of ALDURAZYME and initiate appropriate treatment. Caution should be exercised if epinephrine is being considered for use in patients with MPS I due to the increased prevalence of coronary artery disease in these patients. Interventions have included resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.
       
      In clinical studies and postmarketing safety experience with ALDURAZYME, approximately 1% of patients experienced severe or serious allergic reactions. In patients with MPS I, pre-existing upper airway obstruction may have contributed to the severity of some reactions. Due to the potential for severe allergic reactions, appropriate medical support should be readily available when ALDURAZYME is administered. Because of the potential for recurrent reactions, some patients who experience initial severe reactions may require prolonged observation.
       
      The risks and benefits of re-administering ALDURAZYME following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
       
      Patients with an acute febrile or respiratory illness at the time of ALDURAZYME infusion may be at greater risk for infusion reactions. Careful consideration should be given to the patient’s clinical status prior to administration of ALDURAZYME and consider delaying ALDURAZYME infusion.
       
      Sleep apnea is common in MPS I patients. Evaluation of airway patency should be considered prior to initiation of treatment with ALDURAZYME. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction or extreme drowsiness/sleep induced by antihistamine use.
       
      Caution should be exercised when administering ALDURAZYME to patients susceptible to fluid overload or patients with an acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid restriction is indicated. These patients may be at risk of serious exacerbation of their cardiac or respiratory status during infusions. Appropriate medical support and monitoring measures should be readily available during ALDURAZYME infusion, and some patients may require prolonged observation times that should be based on the individual needs of the patient.
       
      Because of the potential for infusion reactions, patients should receive antipyretics and/or antihistamines prior to infusion. If an infusion-related reaction occurs, regardless of pre-treatment, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antipyretics and/or antihistamines may ameliorate the symptoms.
       
      The most serious adverse reactions reported with ALDURAZYME treatment during clinical trials were anaphylactic and allergic reactions.
       
      In a 26-week, placebo-controlled clinical trial in patients 6 years and older, the most commonly reported infusion reactions regardless of treatment group were flushing, pyrexia, headache, and rash. Flushing occurred in 5 patients (23%) receiving ALDURAZYME; the other reactions were less frequent. Less common infusion reactions included angioedema (including face edema), hypotension, paresthesia, feeling hot, hyperhidrosis, tachycardia, vomiting, back pain, and cough. Other reported adverse reactions included bronchospasm, dyspnea, urticaria, and pruritus. In the open-label, uncontrolled extension phase of this clinical trial, the infusion reactions were similar, but also included abdominal pain or discomfort and injection site reaction. Less commonly reported infusion reactions included nausea, diarrhea, feeling hot or cold, vomiting, pruritus, arthralgia and urticaria. Additional common adverse reactions included, back pain and musculoskeletal pain.
       
      In an open-label, uncontrolled clinical trial in patients 6 years and younger who received ALDURAZYME treatment for up to 52 weeks, the most commonly reported serious adverse events (regardless of relationship) in patients 6 years and younger, were otitis media (20%), and central venous catherization required for ALDURAZYME infusion (15%). The most commonly reported adverse reactions in patients 6 years and younger were infusion reactions reported in 35% (7 of 20) of patients and included pyrexia (30%), chills (20%), blood pressure increased (10%), tachycardia (10%), and oxygen saturation decreased (10%). Other commonly reported infusion reactions occurring in ≥5% of patients were pallor, tremor, respiratory distress, wheezing, crepitations (pulmonary), pruritus, and rash.
       
      In postmarketing experience with ALDURAZYME, severe and serious infusion reactions have been reported, some of which were life-threatening, including anaphylactic shock. Adverse reactions resulting in death reported in the postmarketing setting with ALDURAZYME treatment included cardio-respiratory arrest, respiratory failure, cardiac failure, and pneumonia. These events have been reported in MPS I patients with significant underlying disease. Additional common adverse reactions included erythema and cyanosis. There have been a small number of reports of extravasation in patients treated with ALDURAZYME. There have been no reports of tissue necrosis associated with extravasation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
       
      In clinical trials, 99 of 102 patients (97%) treated with ALDURAZYME were positive for IgG antibodies to ALDURAZYME. In the 2 trials of patients 6 years and older, 9 patients who experienced severe infusion reactions were tested for ALDURAZYME-specific IgE antibodies and complement activation. One of the nine patients had an anaphylactic reaction consisting of urticaria and airway obstruction and tested positive for both ALDURAZYME-specific IgE binding antibodies and complement activation. In the postmarketing setting, approximately 1% of patients experienced severe or serious infusion-allergic reactions and tested positive for IgE. Of these IgE-positive patients, some have discontinued treatment, but some have been successfully re-challenged. The clinical significance of antibodies to ALDURAZYME, including the potential for product neutralization, is not known.
       
      Adverse events should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
       
      ALDURAZYME is available by prescription only. To learn more, please see the Full Prescribing Information including Boxed Warning, visit www.ALDURAZYME.com or contact Genzyme at 1-800-745-4447, option 2.


      Indication and Usage

      AUBAGIO® (teriflunomide) is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS). AUBAGIO can decrease the number of MS flare-ups (relapses). AUBAGIO does not cure MS, but it can help slow down the physical problems that MS causes.

        Important Safety Information

        WARNING: HEPATOTOXICITY and RISK OF TERATOGENICITY

        Hepatotoxicity

        Severe liver injury fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO and monitor ALT levels at least monthly for six months (5.1). If drug induced liver injury is suspected, discontinue AUBAGIO and start accelerated elimination procedure (5.3).

        Risk of Teratogenicity

        Based on animal data, AUBAGIO may cause birth defects if used during pregnancy. AUBAGIO is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during AUBAGIO treatment.

        Who should not take AUBAGIO?

        AUBAGIO may cause serious liver problems, which can be life-threatening. If you are taking AUBAGIO, tell your doctor right away if you develop any of these symptoms of liver problems: nausea; vomiting; stomach pain; loss of appetite; unusual tiredness; yellowing of your skin or whites of your eyes; unusual darkening of your urine.

        AUBAGIO should not be used if you are pregnant or plan to become pregnant. Use effective birth control while taking AUBAGIO. If you become pregnant while on AUBAGIO or within 2 years after you stop taking it, tell your doctor right away.

        If you are a man taking AUBAGIO whose female partner plans to become pregnant, talk to your doctor immediately. If your female partner does not plan to become pregnant, use effective birth control while taking AUBAGIO.

        AUBAGIO may stay in your blood for up to 2 years after you stop taking it. Your doctor can prescribe a medicine that can help remove AUBAGIO from your body more quickly.

        What should I talk to my doctor about?

        Before you start AUBAGIO, tell your doctor if you have: liver or kidney problems; a fever or infection; numbness or tingling in your hands or feet; diabetes, serious skin problems when taking other medications; breathing problems; high blood pressure; or if you are breast feeding or plan to breast feed.

        Tell your doctor about all the medications, vitamins, and herbal supplements you take. This can help you avoid serious drug interactions. Do not start taking any new medications or receive vaccinations without talking to your doctor.

        Call your doctor right away if you have any of these symptoms of an infection while on AUBAGIO: fever; tiredness; body aches; chills; nausea; vomiting. AUBAGIO may decrease your white blood cell count, which may mean you could have more frequent infections.

        What are some of the possible side effects of AUBAGIO?

        Other possible side effects of AUBAGIO include numbness or tingling in your hands or feet that is different from your MS; kidney problems; high potassium levels in your blood; serious skin problems; breathing problems (new or worsening); high blood pressure.

        The most common side effects of AUBAGIO include:

        • abnormal liver tests
        • hair thinning
        • diarrhea
        • flu
        • nausea
        • a burning or prickling feeling in your skin

        Tell your doctor right about any side effect that bothers you or that does not go away. These are not all the side effects of AUBAGIO. Call your doctor or pharmacist for medical advice about side effects. You may report side effects to FDA at 1-800-332-1088.

        Please see full prescribing information including boxed WARNING, with Medication Guide.

        Indications and Usage

        CERDELGATM (eliglustat) capsules are indicated for the long-term treatment of adults with Gaucher disease type 1 (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test. Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect.  A specific dose cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).

        Important Safety Information

        CERDELGA is contraindicated in the following patients due to the risk of significantly increased CERDELGA plasma concentrations which may result in prolongation of the PR, QTc, and/or QRS cardiac intervals that could result in cardiac arrhythmias: EMs or IMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor and IMs or PMs taking a strong CYP3A inhibitor.

        Drugs that inhibit CYP2D6 and CYP3A may significantly increase the exposure to CERDELGA; Cerdelga dose adjustment may be needed, depending on metabolizer status. See section 7 of the full Prescribing Information for more details and other potentially significant drug interactions.

        Because CERDELGA is predicted to cause increases in ECG intervals at substantially elevated plasma concentrations, use is not recommended in patients with pre-existing cardiac disease, long QT syndrome, or in combination with Class IA and Class III antiarrhythmic medications.

        The most common adverse reactions (≥10%) for CERDELGA are: fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain. 

        Only administer CERDELGA during pregnancy if the potential benefit justifies the potential risk; based on animal data, CERDELGA may cause fetal harm. Discontinue drug or nursing based on importance of drug to mother. CERDELGA is not recommended in patients with moderate to severe renal impairment or in patients with hepatic impairment.

        To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at (1-800-745-4447) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

        Please see full Prescribing Information, including patient Medication Guide, for additional important safety information.

        Indication and Usage

        Cerezyme® (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions:

             a. anemia (low red blood cell count)
             b. thrombocytopenia (low blood platelet count)
             c. bone disease
             d. hepatomegaly or splenomegaly (enlarged liver or spleen)

          Important Safety Information

          Approximately 15% of patients have developed immune responses (antibodies). These patients have a higher risk of an allergic reaction (hypersensitivity). Use Cerezyme® (imiglucerase for injection) carefully if you have had an allergic reaction to the product in the past. Symptoms suggestive of allergic reaction happened in 6.6% of patients, and include anaphylactoid reaction (a serious allergic reaction), itching, flushing, hives, an accumulation of fluid under the skin, chest discomfort, shortness of breath, coughing, cyanosis (a bluish discoloration of the skin due to diminished oxygen), and low blood pressure.

          Side effects related to Cerezyme administration have been reported in less than 15% of patients. Each of the following events occurred in less than 2% of the total patient population. Reported side effects include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and rapid heart rate. Because Cerezyme therapy is administered by intravenous infusion, reactions at the site of injection may occur: discomfort, itching, burning, swelling or uninfected abscess. Cerezyme is available by prescription only. For more information, consult your physician.

          Please see full prescribing information.


          Indication and Usage

          Fabrazyme® (agalsidase beta) is used to treat patients with Fabry disease. Fabrazyme lowers the amount of a substance called globotriaosylceramide (GL-3), which builds up in cells lining the blood vessels of the kidney and certain other cells.

          The lowering of GL-3 suggests that Fabrazyme may improve how Fabry disease affects your body; however a relationship of lower GL-3 to specific signs and symptoms of Fabry disease has not been proven.

          Important Safety Information

          Life-threatening severe allergic (anaphylactic) reactions have been seen in patients during Fabrazyme infusions. Approximately 1% of patients who have received Fabrazyme either during a clinical study or after Fabrazyme was approved have experienced anaphylactic or severe allergic reactions during their infusion. These reactions have included: localized swelling of the face, mouth and throat, narrowing of breathing airways, low blood pressure, hives, difficulty swallowing, rash, trouble breathing, flushing, chest discomfort, itching and nasal congestion. People who have experienced these reactions have required treatment including heart/lung resuscitation, oxygen, fluids given through the vein, hospitalization, and have needed treatment with inhaled drugs called beta-adrenergic agonists to help open the breathing airways, antihistamines, epinephrine (also known as adrenalin), and a medication given through the vein called a corticosteroid (or steroid) which helps to decrease the body’s allergic reaction by decreasing inflammation. If you experience a severe allergic or anaphylactic reaction, your healthcare professional will immediately stop the infusion of Fabrazyme and provide you the necessary emergency medical treatment. Because of the possibility that severe allergic reactions may occur, appropriate medical support should be available during your Fabrazyme infusion.

          For patients who have had reactions to their infusions, it is recommended that they be given anti-fever and antihistamine medications right before their next infusions. Infusion reactions have happened in some patients even after taking these medications and steroids by mouth before their infusions. If an infusion reaction occurs, slowing the infusion rate, stopping the infusion for a short time and/or giving more anti-fever and antihistamine medications and or steroids may improve the symptoms. If severe infusion reactions happen, your healthcare professional should consider stopping the Fabrazyme infusion right away and should provide medical care for your condition. Severe reactions are generally managed by giving antihistamine medications, corticosteroids, fluids through the vein, and/or oxygen when needed. Because severe infusions reactions may happen, medical treatment should be readily available during your Fabrazyme infusion.

          Providing Fabrazyme to patients who have experienced severe or serious allergic reactions to Fabrazyme should only be done after carefully considering the risks and benefits of continuing the treatment, and only under the direct supervision of a qualified healthcare professional and with appropriate medical support readily available.

          The most common side effects reported with Fabrazyme are infusion reactions, some of which were severe. When Fabrazyme was tested in clinical studies, infusion reactions occurred in approximately 50-55% of patients. Serious and/or frequently occurring side effects (occurring in 5% or more of the patients) thought to be related to Fabrazyme have included one or more of the following: chills, fever, feeling hot or cold, trouble breathing, nausea, flushing of the skin, headache, vomiting, burning and/or tingling sensation, fatigue, itching, pain in the hands and feet, high blood pressure, chest pain, throat tightness, abdominal pain, dizziness, rapid heart rate, nasal congestion, diarrhea, swelling in the legs, muscle pain, back pain, paleness of the skin, slow heart rate, hives, low blood pressure, face swelling, rash and sleepiness.

          People with advanced Fabry disease may have heart problems, which may put them at a higher risk for severe complications from infusion reactions, and these patients should be watched closely during their infusion if the decision is made to give them Fabrazyme.

          Other serious side effects that were seen in the clinical studies included stroke, pain, lack of muscle coordination, slow or irregular heartbeat, stopping of the heartbeat , decreased blood pumped by the heart, dizziness, hearing loss, and kidney problems resulting in too much protein leaving the body in the urine (nephrotic syndrome). These side effects also occur as part of Fabry disease.

          Severe and serious infusion reactions have been reported since Fabrazyme has been approved, some of which were life threatening including anaphylactic shock (a severe allergic reaction). In addition to the above side effects, the following have been reported since Fabrazyme has been approved: joint pain, lack of strength or energy, redness of the skin, increased sweating, reactions at the place where the catheter to give the infusion is placed, increased tearing from the eyes, allergic inflammation of blood vessels, enlarged lymph nodes, decreased sensitivity to touch or pressure, decreased sensitivity of the mouth, sensations of an abnormal heartbeat, runny nose, low oxygen (in general), and low oxygen levels reaching different parts of the body.

          Since Fabrazyme has been approved, there have been side effects that resulted in death that may or may not be related to the use of Fabrazyme. These included: the heart and/or lungs stop working (known as cardiorespiratory arrest, respiratory failure, and/or cardiac failure), life-threatening infection in the blood stream (known as sepsis), stroke, heart attack, kidney failure, and pneumonia. Some of these side effects were reported in Fabry disease patients with significant underlying disease.

          The safety and effectiveness of Fabrazyme in patients younger than 8 years of age have not been studied.

          Most patients taking Fabrazyme who develop IgG antibodies, which are commonly produced by your immune system in response to things it does not recognize as naturally being part of your body, do so within the first three months of taking the medication. In children, the development of these IgG antibodies was associated with Fabrazyme staying in the body for a longer time (prolonged half-life), which was rarely seen in adult patients.

          In the clinical studies, a few patients developed IgE antibodies or a reaction to an allergy skin test specific to Fabrazyme. IgE antibodies are usually produced by the body’s immune system during an allergic reaction. Your doctor should consider testing for IgE antibodies if you experience suspected allergic reactions and consider the risks and benefits of continued treatment with Fabrazyme if you have IgE antibodies against Fabrazyme.

          Fabrazyme is available by prescription only. Side effects should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. To learn more, please see the full prescribing information (PDF) or contact Genzyme at 1-800-745-4447.


          Indication

          KYNAMROTM (mipomersen sodium) is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

          Limitations of Use

          The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH

          The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.

          Important Safety Information

          WARNING: RISK OF HEPATOTOXICITY

          KYNAMRO can cause elevations in transaminases. In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT).

          KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis.

          Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of KYNAMRO if the ALT or AST are ≥3 x ULN. Discontinue KYNAMRO for clinically significant liver toxicity.

          Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS.

          Other Warnings and Precautions

          Patients are advised to read the KYNAMRO medication guide before starting treatment with KYNAMRO, and each time they receive a refill. There may be new information. This information does not take the place of talking to a doctor about a medical condition or treatment.

          KYNAMRO may cause serious side effects, including liver problems. A doctor should be informed of any liver problems, including liver problems while taking other medicines, or if a patient has any of these symptoms of liver problems while taking KYNAMRO: nausea, vomiting, fever, loss of appetite, being (or feeling) more tired than usual, yellowing of eyes or skin, dark urine, itching, or stomach pain.

          Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking KYNAMRO should consume no more than one alcoholic drink per day.

          Caution should be exercised when KYNAMRO is used with other medications known to have potential for hepatotoxicity.

          KYNAMRO should be used during pregnancy only if clearly needed. Females who become pregnant during KYNAMRO therapy should notify their healthcare provider.

          Safety and effectiveness have not been established in pediatric patients.

          KYNAMRO is not recommended in patients with severe renal impairment, clinically significant proteinuria, or on renal dialysis.

          The safety and effectiveness of KYNAMRO as an adjunct to LDL apheresis have not been established; therefore, the use of KYNAMRO as an adjunct to LDL apheresis is not recommended.

          Contraindications

          KYNAMRO is contraindicated in the following conditions:

          • Moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease, including unexplained persistent elevations of serum transaminases.

             

          • Patients with a known hypersensitivity to any component of this product.

          Common Side Effects

          In clinical trials the most commonly-reported adverse reactions were injection site reactions occurring in 84% of patients receiving KYNAMRO versus 33% of placebo treated patients. The most common injection site reactions were erythema (59%), pain (56%), hematoma (32%), pruritus (29%), swelling (18%) and discoloration (17%). Injection site reactions did not occur with every injection but resulted in discontinuation of therapy in 5% of patients in pooled phase 3 trials.

          Flu-like symptoms, defined as any one of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue and occurring within 2 days of injection, have been reported more frequently in patients receiving KYNAMRO (30%) versus placebo (16%) in the pooled Phase 3 trials. Flu-like symptoms did not occur with all injections but resulted in discontinuation of therapy in 3% of patients in pooled phase 3 trials.

          See full prescribing information for more details about Warnings & Precautions, complete list of Adverse Reactions and Boxed Warning.

          INDICATION

          LUMIZYME® (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of LUMIZYME have not been evaluated in controlled clinical trials in infantile-onset patients, or in late (non-infantile) onset patients less than 8 years of age.

          IMPORTANT SAFETY INFORMATION

          WARNING - ANAPHYLAXIS and RESTRICTED DISTRIBUTION PROGRAM

          Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered.

          Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME is available only through a restricted distribution program called the LUMIZYME ACE Program. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense, or administer LUMIZYME. LUMIZYME may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME ACE Program. To enroll in the LUMIZYME ACE Program call 1-800-745-4447.

          Anaphylaxis and Allergic Reactions: Anaphylaxis and severe allergic reactions have been observed in patients during and up to 3 hours after LUMIZYME infusion. Some of the reactions were life-threatening and included anaphylactic shock, respiratory arrest, apnea, dyspnea, bradycardia, tachycardia, and hypotension. Other accompanying reactions included chest discomfort/pain, throat tightness, bronchospasm, wheezing, tachypnea, cyanosis, decreased oxygen saturation/hypoxia, convulsions, angioedema (including tongue or lip swelling, periorbital edema, and face edema), pruritus, rash, urticaria, hyperhidrosis, nausea, dizziness, hypertension, flushing/erythema, fever, pallor, peripheral coldness, feeling hot, restlessness, nervousness, headache, back pain, and paraesthesia. Some of these reactions were IgE-mediated.

          If anaphylaxis or other severe allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylaxis, epinephrine has been administered. Because of the potential for severe allergic reactions, appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when LUMIZYME is administered. The risk and benefits of re-administering LUMIZYME following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.

          Immune Mediated Reactions: Severe cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions. Systemic immune mediated reactions, including possible type III immune mediated reactions have been observed with alglucosidase alfa. These reactions occurred several weeks to 3 years after initiation of alglucosidase alfa infusions. Skin biopsy in one patient demonstrated deposition of anti-rhGAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with fever and elevated erythrocyte sedimentation rate. Nephrotic syndrome secondary to membranous glomerulonephritis was observed in a few Pompe disease patients treated with alglucosidase alfa who had persistently positive anti-rhGAA IgG antibody titers. In these patients renal biopsy was consistent with immune complex deposition. Patients improved following treatment interruption. It is therefore recommended to perform periodic urinalysis.

          Patients should be monitored for the development of systemic immune mediated reactions involving skin and other organs while receiving LUMIZYME. If immune mediated reactions occur, discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune mediated reaction should be considered. Some patients have successfully been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.

          LUMIZYME ACE Program®: LUMIZYME is available only under a restricted distribution program called the LUMIZYME ACE (Alglucosidase Alfa Control and Education) Program. The purpose of the program is to ensure that the known risks of anaphylaxis and severe allergic reactions and the potential risks of severe cutaneous and systemic immune mediated reactions associated with the use of LUMIZYME are communicated to patients and prescribers. In addition, the program is designed to mitigate the potential risk of rapid disease progression in infantile-onset Pompe disease patients and late (non-infantile) onset Pompe disease patients less than 8 years of age for whom the safety and effectiveness of LUMIZYME have not been evaluated. For information about the ACE Program call 1-800-745-4447.

          Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during infusions and some patients may require prolonged observation times that should be based on the individual needs of the patient. Acute cardiorespiratory failure has been observed in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa.

          Precautions for General/Regional Anesthesia: Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness, therefore, caution should be used when administering general anesthesia in Pompe disease patients.

          Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.

          Adverse Reactions:

          Serious adverse reactions reported with LUMIZYME in the randomized, double-blind, placebo-controlled study included anaphylaxis. Anaphylactic reactions included: angioedema, throat tightness and chest pain/discomfort. One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia. Other serious adverse events that occurred in a higher incidence in LUMIZYME treated patients compared to placebo included coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis, and dehydration.

          The most common adverse reactions observed in clinical studies were infusion reactions. Infusion reactions, defined as an adverse reaction occurring during the infusion or within 2 hours after completion of the infusion, that occurred in LUMIZYME treated patients at an incidence of ≥ 5% compared to placebo included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort. Additional infusion reactions observed in other clinical trials and expanded access programs with LUMIZYME included respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor and increased lacrimation.

          Delayed onset infusion reactions defined as adverse reactions that occurred within 48 hours after completion of LUMIZYME infusion, occurred in LUMIZYME treated patients at an incidence of ≥ 3% compared to placebo treated patients in a controlled clinical trial. Symptoms included urticaria, dizziness, procedural pain, pharyngolaryngeal pain, malaise, muscle spasms, musculoskeletal pain, musculoskeletal weakness, musculoskeletal stiffness, neck pain, insomnia, and epistaxis. Patients should be counseled about the possibility of delayed onset infusion reactions and given proper follow up instructions.

          If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion or allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Patients who have experienced infusion reactions should be treated with caution when they are re-administered LUMIZYME.

          In postmarketing experience with LUMIZYME, deaths, and serious adverse reactions have been reported, including anaphylaxis. Adverse events resulting in death reported in the postmarketing setting with LUMIZYME treatment included cardiorespiratory arrest, respiratory failure, hemothorax, pneumothorax, cardiac failure, sepsis, aortic dissection, cerebrovascular accident, and skin necrosis. The most frequently reported serious adverse reactions were infusion reactions. In addition to the infusion reactions reported in clinical trials, the following serious adverse events have been reported in at least 2 patients: dyspnea, respiratory failure, bronchospasm, stridor, decreased oxygen saturation/hypoxia, pharyngeal edema, chest discomfort, chest pain, hypotension, hypertension, erythema, flushing, lung infection, tachycardia, cyanosis, hypersensitivity and abdominal pain. One case of hyperparathyroidism has been reported. Additional adverse drug reactions included proteinuria and nephrotic syndrome.

          Immunogenicity: In the randomized, double-blind, placebo-controlled study, all patients with available samples treated with LUMIZYME (N=59, 100%) developed IgG antibodies to alglucosidase alfa. All patients who developed IgG antibodies did so within the first 3 months of exposure (median time to seroconversion was 4 weeks). There was no apparent association between mean or peak IgG antibody titers and the occurrence of adverse reactions. A small number of LUMIZYME treated patients in the postmarketing setting who were evaluated tested positive for presence of alglucosidase alfa-specific IgE antibodies. Some of these patients experienced anaphylaxis. Some patients who tested positive for alglucosidase alfa-specific IgE antibodies were successfully rechallenged with LUMIZYME using a slower infusion rate at lower initial doses and have continued to receive treatment under close clinical supervision. Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions. Therefore, these patients should be monitored more closely during administration of LUMIZYME.

          To report suspected adverse reactions, contact Genzyme Medical Information at 800-745-4447, option 2.

          Please see the full prescribing information for complete details, including boxed warning.

           


          Indication

          MYOZYME® (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for use in patients with Pompe disease (GAA deficiency). MYOZYME has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of MYOZYME in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.

          Important Safety Information

          WARNING

          Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during MYOZYME infusions. Therefore, appropriate medical support should be readily available when MYOZYME is administered.

          Risk of Cardiorespiratory Failure:
          Patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to infusion reactions, and require additional monitoring.

          Anaphylaxis and Allergic Reactions: Anaphylaxis and severe allergic reactions have been reported in some patients during and up to three hours after MYOZYME infusion, some of which were IgE-mediated. Some of the reactions were life-threatening and included: anaphylactic shock, cardiac arrest, respiratory distress, hypotension, bradycardia, hypoxia, bronchospasm, throat tightness, dyspnea, angioedema, and urticaria. Interventions have included: cardiopulmonary resuscitation, mechanical ventilatory support, oxygen supplementation, intravenous (IV) fluids, hospitalization, treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.

          In clinical trials and postmarketing safety experience with MYOZYME, approximately 1% of patients developed anaphylactic shock and/or cardiac arrest during MYOZYME infusion that required life-support measures. In clinical trials and expanded access programs with MYOZYME, approximately 14% of patients treated with MYOZYME have developed allergic reactions that involved at least 2 of 3 body systems, cutaneous, respiratory or cardiovascular systems. These events included: Cardiovascular: hypotension, cyanosis, hypertension, tachycardia, ventricular extrasystoles, bradycardia, pallor, flushing, nodal rhythm, peripheral coldness; Respiratory: tachypnea, wheezing/bronchospasm, rales, throat tightness, hypoxia, dyspnea, cough, respiratory tract irritation, decreased oxygen saturation; Cutaneous: angioedema, urticaria, rash, erythema, periorbital edema, pruritus, hyperhidrosis, cold sweat, livedo reticularis.

          If anaphylactic or other severe allergic reactions occur, immediate discontinuation of the administration of MYOZYME should be considered, and appropriate medical treatment should be initiated. Because of the potential for severe allergic reactions, appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when MYOZYME is administered.

          Risk of Acute Cardiorespiratory Failure:
          Acute cardiorespiratory failure requiring intubation and inotropic support has been observed up to 72 hours after infusion with MYOZYME in infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of MYOZYME. Patients with acute underlying respiratory illness, compromised cardiac function and/or sepsis may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during MYOZYME infusion, and infants with cardiac dysfunction may require prolonged observation times that should be individualized based on the needs of the patient.

          Risk of Cardiac Arrhythmia and Sudden Cardiac Death During General Anesthesia for Central Venous Catheter Placement:
          Cardiac arrhythmia, including ventricular fibrillation, ventricular tachycardia and bradycardia, resulting in cardiac arrest or death, or requiring cardiac resuscitation or defibrillation have been observed in infantile-onset Pompe disease patients with cardiac hypertrophy, associated with the use of general anesthesia for the placement of a central venous catheter intended for MYOZYME infusion. Caution should be used when administering general anesthesia for the placement of a central venous catheter in infantile-onset Pompe disease patients with cardiac hypertrophy.

          Infusion Reactions: Infusion reactions occurred in 20 of 39 (51%) of patients treated with MYOZYME in clinical studies. Severe infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included: fever, decreased oxygen saturation, tachycardia, cyanosis and hypotension. Other infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included: rash, flushing, urticaria, fever, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure/hypertension, cyanosis, irritability, pallor, pruritus, retching, rigors, tremor, hypotension, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, increased lacrimation, livedo reticularis, nausea, periorbital edema, restlessness and wheezing. Some patients were pre-treated with antihistamines, antipyretics and/or steroids. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines, or steroids. Infusion reactions may occur at any time during, or up to 2 hours after, the infusion of MYOZYME, and are more likely with higher infusion rates.

          Immune Mediated Reactions:
          Severe cutaneous and systemic immune mediated reactions have been reported in postmarketing experience with MYOZYME in at least 2 patients, including ulcerative and necrotizing skin lesions, and possible type III immune complex-mediated reactions. Patients should be monitored for the development of systemic immune complex-mediated reactions involving skin and other organs while receiving MYOZYME.

          Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.

          Adverse Reactions: The most serious adverse reactions reported with MYOZYME were anaphylactic reactions, acute cardiorespiratory failure, and cardiac arrest. Anaphylactic reactions have been reported during and within 3 hours after MYOZYME infusion. Acute cardiorespiratory failure has been observed in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa.

          The most common serious treatment-emergent adverse reactions occurring in >10% of patients observed in clinical studies with MYOZYME were pneumonia, respiratory failure, respiratory distress, catheter-related infection, respiratory syncytial virus infection, gastroenteritis and fever. The most common treatment-emergent adverse reactions occurring in ≥ 20% of patients were fever, diarrhea, rash, vomiting, cough, pneumonia, otitis media, upper respiratory tract infection, gastroenteritis and decreased oxygen saturation.

          The most common adverse reactions requiring intervention were infusion reactions. Twenty of 39 patients (51%) treated with MYOZYME in clinical studies developed infusion reactions.

          Immunogenicity: The majority of patients (34 of 38; 89%) in the two clinical trials tested positive for IgG antibodies to alglucosidase alfa. Most patients who develop antibodies do so within the first 3 months of exposure. There is evidence to suggest that patients developing sustained titers ≥12,800 of anti-alglucosidase alfa antibodies may have a poorer clinical response to treatment, or may lose motor function as antibody titers increase. Five patients with antibody titers ≥ 12,800 at Week 12 had an average increase in clearance of 50% from Week 1 to Week 12. The effect of antibody development on the long-term efficacy of MYOZYME is not fully understood. However, CRIM-negative infants have shown poorer clinical response in the presence of high sustained IgG antibody titers and inhibitory and positive inhibitory antibodies. Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions. Therefore, these patients should be monitored more closely during administration of MYOZYME.

          To report suspected adverse reactions, contact Genzyme at 800-745-4447, option 2 or FDA at 800-FDA-1088 or http://www.fda.gov/Safety/MedWatch

          Please see full prescribing information for complete details, including boxed warning.

           

          Indication

          Thyrogen® (thyrotropin alfa for injection) is indicated for use as an additional tool to identify thyroid disease (by testing the blood for a hormone called thyroglobulin), with or without a radiology test using a form of iodine, in the follow-up of patients with a certain type of thyroid cancer (known as well-differentiated thyroid cancer).

          Thyrogen (thyrotropin alfa for injection) is also indicated for use as a preparation for treatment with a form of iodine to remove left over thyroid tissue in patients who have had surgery to take out the entire thyroid gland for a certain type of thyroid cancer (known as well-differentiated thyroid cancer) and who do not have signs of thyroid cancer which has spread to other parts of the body.

           

          Important Safety Information

          • When Thyrogen is used to help detect thyroid cancer, there is still a chance all—or parts of—your cancer could be missed.
          • In a study of people being prepared for treatment with a form of iodine after thyroid surgery, results were similar between those who received Thyrogen and those who stopped taking their thyroid hormone. Researchers do not know if results would be similar over a longer period of time.
          • Your doctor may take extra steps to care for you during Thyrogen treatment if you have heart disease and large amounts of remaining thyroid tissue after surgery.
          • If you are over 65 years old and did not have your entire thyroid removed during treatment of your cancer, you may be at risk for abnormal heartbeat while receiving Thyrogen. Because of this, you and your doctor will need to carefully consider the risks and benefits of Thyrogen before starting it.
          • In clinical studies, the most common side effects reported were upset stomach, headache, tiredness, throwing up, dizziness, prickling and tingling sensation, weakness, difficulty sleeping, and diarrhea.

          Please see accompanying full Product Information.


          Last Updated: 9/4/2014
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