Infuse NAGLAZYME® (galsulfase)

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View video: Administering the NAGLAZYME® (galsulfase) infusion

Equipment setup

Following are the steps for setting up the equipment for infusing NAGLAZYME. If you are using plain saline as a primary line, connect the NAGLAZYME tubing at the port closest to the patient.

  1. Prime the IV tubing with NAGLAZYME solution
  2. Attach a 0.2-um in‐line filter to the end of the tubing and slowly prime the filter
  3. Prime tubing and filter SLOWLY to prevent foaming
  4. Be sure the drug administration tubing and filter are primed with drug solution (not plain saline). This will ensure that the correct volume is delivered in the first hour of infusion

Infusion rate

Use an infusion pump for NAGLAZYME administration.

Infuse the total volume of NAGLAZYME solution over no less than 4 hours as follows:

  • 2.5% of the total NAGLAZYME solution volume in the first hour
  • 97.5% of the total volume over the next 3 hours

Infusion rate examples

For 250-mL volume:

6 mL/hour for the first hour. If the infusion is well tolerated, the infusion rate can be increased to 80 mL/hour for approximately 3 hours.

For 120-mL volume:

3 mL/hour for the first hour. If the infusion is well tolerated, the infusion rate can be increased to 39 mL/hour for approximately 3 hours.

Note: Patients and families often ask if the infusion can be administered in a shorter amount of time. For maximum safety and efficacy, do not administer NAGLAZYME at a faster rate than recommended.

Patient monitoring during NAGLAZYME infusion

What to monitor

Monitor vital signs:

  • Prior to infusion
  • Every hour during the infusion especially after increases in infusion rate
  • At infusion completion
  • Prior to discharge

What to look for

When monitoring vital signs, look for signs of infusion‐associated reactions (IARs), such as:

  • Increase or decrease in heart rate
  • Increase or decrease in respiratory rate
  • Decrease in oxygen saturation (pulse oximetry)
  • Increase or decrease in temperature

 

Other mild reactions (including shivering, rashes, or swelling of the lips) may progress rapidly if not treated.

Be prepared for infusion‐associated reactions (IARs)

The first IARs occurred as late as 146 weeks in the clinical studies. Therefore it is important that:

  • A physician be available or accessible by phone or pager
  • The patient be monitored closely for IAR signs and symptoms
  • Emergency procedures be in place in the event a severe IAR occurs
  • Patients and/or parents be educated and encouraged to report IAR symptoms
    • This is especially important for parents of younger patients who may not be able to self‐report IAR symptoms

 

NAGLAZYME IARs1,2

  • IARs occurred in 33 of 59 patients treated with NAGLAZYME
    • Initial reactions occurred as early as week 1 and as late as week 146
  • The most frequent serious adverse events related to the use of NAGLAZYME occurred during infusions and included:
    • Laryngeal edema, apnea, pyrexia, urticaria, respiratory distress, angioedema, and anaphylactoid reaction
  • Severe symptoms included:
  • Urticaria, chest pain, rash, dyspnea, apnea, laryngeal edema, and conjunctivitis
  • The most common symptoms of infusion‐associated reactions included:
    • Pyrexia, chills, rash, urticaria, dyspnea, nausea, vomiting, pruritus, erythema, abdominal pain, hypertension, and headache
    • Respiratory distress, chest pain, hypotension, angioedema, conjunctivitis, tremor, and cough were also reported
  • Because of the potential for IARs, patients should receive antihistamines with or without antipyretics prior to infusion
  • For 23 of 33 patients who experienced IARs, they were recurrent despite these measures
  • Symptoms typically abated with slowing or interruption of infusion and additional antihistamines, antipyretics, and occasionally steroids

 

Special safety considerations for patients with airway obstruction

  • Patients with highly compromised upper airway disease warrant close monitoring during infusions
  • Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apneic episodes
  • Caution should be exercised when administering prophylactic antihistamines as patients may have airway difficulty during deep sleep
  • Use of continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) during infusion should be considered in patients with sleep apnea who are using positive airway pressure machines
  • Evaluation of airway patency should be considered prior to initiation of treatment due to the increased risk of sleep apnea

Manage IARs

If an IAR occurs, stop the infusion promptly. Then:

  • Assess and appropriately manage the patient’s symptoms
  • Consider administration of additional antihistamines, antipyretics, and possibly corticosteroids

If symptoms subside, consider restarting the infusion at a slower rate, eg, half the rate at which the IAR occurred.

Subsequent infusions may be managed with:

  • A slower rate of infusion
  • Additional prophylactic antihistamines
  • Antipyretics
  • Possibly prophylactic corticosteroids

The physician should evaluate the risks and benefits of readministering NAGLAZYME following a severe hypersensitivity or anaphylactic reaction.

Note: Caution should be exercised if epinephrine use is being considered in patients with MPS VI, due to increased prevalence of coronary artery disease.

Please see Important Safety Information below and full Prescribing Information for more information.

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View video: Managing infusion reactions

Postinfusion procedures

After the infusion is complete:

  • Run normal saline to clear NAGLAZYME solution from tubing
  • Obtain postinfusion vital signs
  • Observe the patient for a postinfusion period specified by the treating physician
  • Discard and dispose of infusion‐related materials in accordance with your institutional policies

Downloadable infusion resources for you and your patients »

References: 1. NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2013. 2. Data on file. BioMarin Pharmaceutical Inc.

Important Safety Information

Indication

NAGLAZYME® (galsulfase) is indicated for patients with Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity.

Important Safety Information

Life-threatening anaphylactic reactions and severe allergic reactions have been observed in some patients during NAGLAZYME (galsulfase) infusions and up to 24 hours after infusion. If these reactions occur, immediate discontinuation of NAGLAZYME is recommended and appropriate medical treatment should be initiated, which may include resuscitation, epinephrine, administering additional antihistamines, antipyretics or corticosteroids. In patients who have experienced anaphylaxis or other severe allergic reactions during infusion with NAGLAZYME, caution should be exercised upon rechallenge; appropriately trained personnel and equipment for emergency resuscitation (including epinephrine) should be available during infusions.

As with other enzyme replacement therapies, immune-mediated reactions, including membranous glomerulonephritis have been observed. In clinical trials, nearly all patients developed antibodies as a result of treatment with NAGLAZYME; however, the analysis revealed no consistent predictive relationship between total antibody titer, neutralizing or IgE antibodies, and infusion-associated reactions, urinary glycosaminoglycan (GAG) levels, or endurance measures.

Caution should be exercised when administering NAGLAZYME to patients susceptible to fluid volume overload because congestive heart failure may result. Consider a decreased total infusion volume and infusion rate when administering NAGLAZYME to these patients.

Consideration to delay NAGLAZYME infusion should be given when treating patients who present with an acute febrile or respiratory illness. Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apneic episodes. Evaluation of airway patency should be considered prior to the initiation of treatment. 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.

Pretreatment with antihistamines with or without antipyretics is recommended prior to the start of infusion to reduce the risk of infusion reactions. If infusion reactions occur, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antihistamines and/or antipyretics is recommended.

During infusion, serious adverse reactions included laryngeal edema, apnea, pyrexia, urticaria, respiratory distress, angioedema, and anaphylactoid reaction; severe adverse reactions included urticaria, chest pain, rash, abdominal pain, dyspnea, apnea, laryngeal edema, and conjunctivitis. The most common adverse events (=10%) observed in clinical trials in patients treated with NAGLAZYME were rash, pain, urticaria, pyrexia, pruritus, chills, headache, nausea, vomiting, abdominal pain and dyspnea. The most common adverse reactions requiring interventions are infusion-related reactions.

Spinal/cervical cord compression is a known and serious complication that is expected to occur during the natural course of MPS VI. Signs and symptoms of spinal/cervical cord compression include back pain, paralysis of limbs below the level of compression, and urinary or fecal incontinence. Patients should be evaluated for spinal/cervical cord compression prior to initiation of NAGLAZYME to establish a baseline and risk profile. Patients treated with NAGLAZYME should be regularly monitored for the development or progression of spinal/cervical cord compression and be given appropriate clinical care.

To report SUSPECTED ADVERSE REACTIONS contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088 or go to www.fda.gov/medwatch.

Please see full Prescribing Information.