"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
Anaphylaxis and Allergic Reactions
[see BOXED WARNING]
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 medical 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 [see ADVERSE REACTIONS].
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.
Acute Respiratory Complications Associated with Administration
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. One patient with acute bronchitis and hypoxia experienced increased tachypnea during the first ALDURAZYME infusion that resolved without intervention. The patient's respiratory symptoms returned within 30 minutes of completing the infusion and responded to bronchodilator therapy. Approximately 6 hours after the infusion, the patient experienced coughing, then respiratory arrest, and died.
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.
Risk of Acute Cardiorespiratory Failure
Caution should be exercised when administering ALDURAZYME to patients susceptible to fluid overload, or patients with 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 [see ADVERSE REACTIONS].
Because of the potential for infusion reactions, patients should receive antipyretics and/or antihistamines prior to infusion. If an infusion reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antipyretics and/or antihistamines may ameliorate the symptoms [see ADVERSE REACTIONS].
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies to assess the mutagenic and carcinogenic potential of laronidase have not been conducted.
Laronidase at IV doses up to 3.6 mg/kg (6.2 times the human dose) was found to have no effect on the fertility and reproductive performance of male and female rats.
Use In Specific Populations
Pregnancy Category B
A developmental toxicity study has been performed in rats at doses up to 6.2 times the human dose and has revealed no evidence of impaired fertility or harm to the fetus due to ALDURAZYME. However, there are no adequate and well-controlled studies of ALDURAZYME in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnant women with MPS I should be encouraged to enroll in the MPS I Registry. For more information, visit www.MPSIregistry.com or call (800) 745-4447 [see PATIENT INFORMATION].
It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ALDURAZYME is administered to a nursing woman.
Nursing mothers with MPS I should be encouraged to enroll in the MPS I Registry [see PATIENT INFORMATION].
The safety and effectiveness of ALDURAZYME was assessed in a 52-week, open-label, uncontrolled clinical study in 20 patients with MPS I, ages 6 months to 5 years old, and was found to be similar to the safety and effectiveness of ALDURAZYME in pediatric patients 6 to 18 years, and adults [see ADVERSE REACTIONS and Clinical Studies].
Clinical studies of ALDURAZYME did not include patients aged 65 and over. It is not known whether they respond differently from younger patients.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/18/2013
Additional Aldurazyme Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.