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Black Box Warning
WARNING: RISK OF ANAPHYLAXIS:
See full prescribing information for complete Boxed Warning.
RISK OF ANAPHYLAXIS:
Life-threatening anaphylactic reactions have occurred in some patients during Vimizim infusions. Anaphylaxis, presenting as cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms (e.g., nausea, abdominal pain, retching, and vomiting) in conjunction with urticaria, have been reported to occur during Vimizim infusions, regardless of duration of the course of treatment. Closely observe patients during and after Vimizim administration and be prepared to manage anaphylaxis. Inform patients of the signs and symptoms of anaphylaxis and have them seek immediate medical care should symptoms occur. Patients with acute respiratory illness may be at risk of serious acute exacerbation of their respiratory compromise due to hypersensitivity reactions, and require additional monitoring
Overview
Elosulfase alfa is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme that is FDA approved for the treatment of Mucopolysaccharidosis type IVA. There is a Black Box Warning for this drug as shown here. Common adverse reactions include pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Vimizim (elosulfase alfa) is indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).
Dosage
Recommended Dose
The recommended dose is 2 mg per kg given intravenously over a minimum range of 3.5 to 4.5 hours, based on infusion volume, once every week. Pre-treatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion [see Warnings and Precautions (5.1)].
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
2.2 Preparation Instructions
Important Information: This product should be prepared and administered under the supervision of a healthcare professional with the ability to manage medical emergencies.
Determine the number of vials to be diluted based on the individual patient’s weight and the recommended dose of 2 mg/kg.
Dilute the calculated dose to a final volume of 100 mL or 250 mL using 0.9% Sodium Chloride Injection, USP.
The final volume is based on the patient’s weight as follows:
· For patients who weigh less than 25 kg, the final volume should be 100 mL;
· For patients who weigh 25 kg or more, the final volume should be 250 mL.
The solution should be clear to slightly opalescent and colorless to pale yellow when diluted. Do not use if the solution is discolored or if there is particulate matter in the solution. Note that a diluted solution with slight flocculation (e.g., thin translucent fibers) is acceptable for administration.
Avoid agitation during preparation. Gently rotate the bag to ensure proper distribution. Do not shake the solution.
2.3 Administration Instructions
Administer the diluted solution to patients using a low-protein binding infusion set equipped with a low-protein binding 0.2 micrometer (µm) in-line filter.
Note: The safety and effectiveness of Vimizim have not been established in pediatric patients less than 5 years of age [see Use in Specific Populations (8.4)].
For patients who weigh less than 25 kg: initial infusion rate should be 3 mL per hour for the first 15 minutes and, if tolerated, increased to 6 mL per hour for the next 15 minutes. If this rate is tolerated, then the rate may be increased every 15 minutes in 6 mL per hour increments, not to exceed 36 mL per hour. The total volume of the infusion should be delivered over a minimum of 3.5 hours.
For patients who weigh 25 kg or more: initial infusion rate should be 6 mL per hour for the first 15 minutes and, if tolerated, the infusion rate may be increased to 12 mL per hour for the next 15 minutes. If this rate is tolerated, then the rate may be increased every 15 minutes in 12 mL per hour increments, not to exceed 72 mL per hour. The total volume of the infusion should be delivered over a minimum of 4.5 hours.
The infusion rate may be slowed, temporarily stopped, or discontinued for that visit in the event of hypersensitivity reactions [see Warnings and Precautions (5.1)]. Do not infuse with other products in the infusion tubing. Compatibility with other products has not been evaluated.
2.4 Storage and Stability
Vimizim does not contain preservatives; therefore the product should be used immediately after dilution. If immediate use is not possible, the diluted product may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F) followed by up to 24 hours at 23°C to 27°C (73°F to 81°F). Administration of Vimizim should be completed within 48 hours from the time of dilution. Vials are for single-use only. Discard any unused product. Do not freeze or shake. Protect from light.
3 DOSAGE FORMS AND STRENGTHS
Injection: 5 mg/5 mL (1 mg/mL) in single-use vials.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Elosulfase alfa in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Elosulfase alfa in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Indications
Vimizim (elosulfase alfa) is indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).
Dosage
Recommended Dose
The recommended dose is 2 mg per kg given intravenously over a minimum range of 3.5 to 4.5 hours, based on infusion volume, once every week. Pre-treatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion [see Warnings and Precautions (5.1)].
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Administration Instructions
Administer the diluted solution to patients using a low-protein binding infusion set equipped with a low-protein binding 0.2 micrometer (µm) in-line filter.
Note: The safety and effectiveness of Vimizim have not been established in pediatric patients less than 5 years of age [see Use in Specific Populations (8.4)].
For patients who weigh less than 25 kg: initial infusion rate should be 3 mL per hour for the first 15 minutes and, if tolerated, increased to 6 mL per hour for the next 15 minutes. If this rate is tolerated, then the rate may be increased every 15 minutes in 6 mL per hour increments, not to exceed 36 mL per hour. The total volume of the infusion should be delivered over a minimum of 3.5 hours.
For patients who weigh 25 kg or more: initial infusion rate should be 6 mL per hour for the first 15 minutes and, if tolerated, the infusion rate may be increased to 12 mL per hour for the next 15 minutes. If this rate is tolerated, then the rate may be increased every 15 minutes in 12 mL per hour increments, not to exceed 72 mL per hour. The total volume of the infusion should be delivered over a minimum of 4.5 hours.
The infusion rate may be slowed, temporarily stopped, or discontinued for that visit in the event of hypersensitivity reactions [see Warnings and Precautions (5.1)]. Do not infuse with other products in the infusion tubing. Compatibility with other products has not been evaluated.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Elosulfase alfa in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Elosulfase alfa in pediatric patients.
Contraindications
None
Warnings
WARNING: RISK OF ANAPHYLAXIS:
See full prescribing information for complete Boxed Warning.
RISK OF ANAPHYLAXIS:
Life-threatening anaphylactic reactions have occurred in some patients during Vimizim infusions. Anaphylaxis, presenting as cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms (e.g., nausea, abdominal pain, retching, and vomiting) in conjunction with urticaria, have been reported to occur during Vimizim infusions, regardless of duration of the course of treatment. Closely observe patients during and after Vimizim administration and be prepared to manage anaphylaxis. Inform patients of the signs and symptoms of anaphylaxis and have them seek immediate medical care should symptoms occur. Patients with acute respiratory illness may be at risk of serious acute exacerbation of their respiratory compromise due to hypersensitivity reactions, and require additional monitoring
Anaphylaxis and Hypersensitivity Reactions
Anaphylaxis and hypersensitivity reactions have been reported in patients treated with Vimizim. In premarketing clinical trials, 18 of 235 (7.7%) patients treated with Vimizim experienced signs and symptoms consistent with anaphylaxis. These 18 patients experienced 26 anaphylactic reactions during infusion with signs and symptoms including cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms (e.g., nausea, abdominal pain, retching, and vomiting) in conjunction with urticaria. These cases of anaphylaxis occurred as early as 30 minutes from the start of infusion and up to three hours after infusion. Anaphylaxis occurred as late into treatment as the 47th infusion.
In clinical trials with Vimizim, 44 of 235 (18.7%) patients experienced hypersensitivity reactions, including anaphylaxis. Hypersensitivity reactions have occurred as early as 30 minutes from the start of infusion but as late as six days after infusion. Frequent symptoms of hypersensitivity reactions (occurring in more than 2 patients) included anaphylactic reactions, urticaria, peripheral edema, cough, dyspnea, and flushing.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when Vimizim is administered. Observe patients closely for an appropriate period of time after administration of Vimizim, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur.
Because of the potential for hypersensitivity reactions, administer antihistamines with or without antipyretics prior to infusion. Management of hypersensitivity reactions should be based on the severity of the reaction and include slowing or temporary interruption of the infusion and/or administration of additional antihistamines, antipyretics, and/or corticosteroids for mild reactions. However, if severe hypersensitivity reactions occur, immediately stop the infusion of Vimizim and initiate appropriate treatment.
Consider the risks and benefits of re-administering Vimizim following a severe reaction.
5.2 Risk of Acute Respiratory Complications
Patients with acute febrile or respiratory illness at the time of Vimizim infusion may be at higher risk of life-threatening complications from hypersensitivity reactions. Careful consideration should be given to the patient’s clinical status prior to administration of Vimizim and consider delaying the Vimizim infusion.
Sleep apnea is common in MPS IVA patients. Evaluation of airway patency should be considered prior to initiation of treatment with Vimizim. 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 acute reaction, or extreme drowsiness/sleep induced by antihistamine use.
5.3 Spinal or Cervical Cord Compression
Spinal or cervical cord compression (SCC) is a known and serious complication of MPS IVA and may occur as part of the natural history of the disease. In clinical trials, SCC was observed both in patients receiving Vimizim and patients receiving placebo. Patients with MPS IVA should be monitored for signs and symptoms of SCC (including back pain, paralysis of limbs below the level of compression, urinary and fecal incontinence) and given appropriate clinical care.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Elosulfase alfa in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Elosulfase alfa in the drug label.
