Galsulfase (Naglazyme)
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Galsulfase (Naglazyme)

NAGLAZYME
(galsulfase)

DRUG DESCRIPTION

NAGLAZYME is a formulation of galsulfase, which is a purified human enzyme that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase (glycosaminoglycan Nacetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal enzyme that catalyzes the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG), chondroitm 4-sulfate and dermatan sulfate.

Galsulfase is a glycoprotein with a molecular weight of approximately 56 kDa. The recombinant protein consists of 495 amino acids and possesses six asparagine-linked glycosylation sites, four of which carry a bis-mannose-6-phosphate residue for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue, Ca-formylglycine, which is required for enzyme activity. NAGLAZYME has a specific activity of approximately 70 units per mg of protein content. One activity unit is defined as the amount of enzyme required to convert 1 micromole of 4-methylumbelliferyl sulfate to 4- methylumbelliferone and free sulfate per minute at 37°C.

NAGLAZYME is intended for intravenous infusion and is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration. NAGLAZYME is supplied in clear Type I glass 5 mL vials. Each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80 in a 5 mL extractable solution with pH of approximately 5.8. NAGLAZYME does not contain preservatives. Each vial is for single use only.

What are the possible side effects of galsulfase (Naglazyme)?

Some people receiving a galsulfase injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you have a headache, fever or chills, skin rash, itching, nausea, vomiting, stomach pain, pain in your chest, trouble breathing, or if you feel like you might pass out when galsulfase is injected.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Less serious side effects may...

Read All Potential Side Effects and See Pictures of Naglazyme »

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

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.

DOSAGE AND ADMINISTRATION

Recommended Dose

The recommended dosage regimen of NAGLAZYME is 1 mg per kg of body weight administered once weekly as an intravenous infusion.

Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion [see WARNINGS AND PRECAUTIONS].

The total volume of the infusion should be delivered over a period of time of no less than 4 hours. NAGLAZYME should be diluted with 0.9% Sodium Chloride Injection, USP, to a final volume of 250 mL and delivered by controlled intravenous infusion using an infusion pump. The initial infusion rate should be 6 mL per hour for the first hour. If the infusion is well tolerated, the rate of infusion may be increased to 80 mL per hour for the remaining 3 hours. The infusion time can be extended up to 20 hours if infusion reactions occur.

For patients 20 kg and under or those who are susceptible to fluid volume overload, physicians may consider diluting NAGLAZYME in a volume of 100 mL [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. The infusion rate (mL per min) should be decreased so that the total infusion duration remains no less than 4 hours.

Each vial of NAGLAZYME provides 5 mg of galsulfase (expressed as protein content) in 5 mL of solution and is intended for single use only. Do not use the vial more than one time. The concentrated solution for infusion must be diluted with 0.9% Sodium Chloride Injection, USP, using aseptic techniques. NAGLAZYME should be prepared using low-protein-binding containers and administered with a low-protein-binding infusion set equipped with an in-line, low-protein-binding 0.2 micrometer filter. There is no information on the compatibility of diluted NAGLAZYME with glass containers.

Instructions for Use

Prepare and use NAGLAZYME according to the following steps. Use aseptic techniques.

  1. Determine the number of vials to be used based on the patient's weight and the recommended dose of 1 mg per kg:
    Patient's weight (kg) x 1 mL/kg of NAGLAZYME = Total number of mL of NAGLAZYME
    Total number of mL of NAGLAZYME/ 5 mL per vial = Total number of vials
    Round up to the next whole vial. Remove the required number of vials from the refrigerator to allow them to reach room temperature. Do not allow vials to remain at room temperature longer than 24 hours prior to dilution. Do not heat or microwave vials.
  2. Before withdrawing the NAGLAZYME solution from the vial, visually inspect each vial for particulate matter and discoloration. The NAGLAZYME solution should be clear to slightly opalescent and colorless to pale yellow. Some translucency may be present in the solution. Do not use if the solution is discolored or if there is particulate matter in the solution.
  3. From a 250 mL infusion bag of 0.9% Sodium Chloride Injection, USP, withdraw and discard a volume equal to the volume of NAGLAZYME solution to be added. If using a 100 mL infusion bag, this step is not necessary.
  4. Slowly withdraw the calculated volume of NAGLAZYME from the appropriate number of vials using caution to avoid excessive agitation. Do not use a filter needle, as this may cause agitation. Agitation may denature NAGLAZYME, rendering it biologically inactive.
  5. Slowly add the NAGLAZYME solution to the 0.9% Sodium Chloride Injection, USP, using care to avoid agitation of the solutions. Do not use a filter needle.
  6. Gently rotate the infusion bag to ensure proper distribution of NAGLAZYME. Do not shake the solution.

NAGLAZYME does not contain preservatives; therefore, after dilution with saline, the infusion bags should be used immediately. If immediate use is not possible, the diluted solution must be stored refrigerated at 2°C to 8°C (36°F to 46°F) and administered within 48 hours from the time of dilution to completion of administration. Other than during infusion, do not store the diluted NAGLAZYME solution at room temperature. Any unused product or waste material must be discarded and disposed of in accordance with local requirements.

NAGLAZYME must not be infused with other products in the infusion tubing. The compatibility of NAGLAZYME in solution with other products has not been evaluated.

HOW SUPPLIED

Dosage Forms And Strengths

Injection; 5 mL vials (5 mg per 5 mL).

Storage And Handling

NAGLAZYME is supplied as a sterile injection in clear Type I glass 5 mL vials, containing 5 mg galsulfase (expressed as protein content) per 5 mL solution. The closure consists of a siliconized chlorobutyl rubber stopper and an aluminum seal with a plastic flip-off cap.

NDC 68135-020-01, 5 mL vial

Store NAGLAZYME under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. Do not use NAGLAZYME after the expiration date on the vial. This product contains no preservatives.

NAGLAZYME is manufactured and distributed by: BioMarin Pharmaceutical Inc. 105 Digital Drive, Novato, CA 94949. Revised: 04/2011

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates observed in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

NAGLAZYME was studied in a randomized, double-blind, placebo-controlled trial in which 19 patients received weekly infusions of 1 mg/kg NAGLAZYME and 20 patients received placebo; of the 39 patients 66% were female, and 62% were White, non-Hispanic. Patients were aged 5 years to 29 years. NAGLAZYME-treated patients were approximately 3 years older than placebo-treated patients (mean age 13.7 years versus 10.7 years, respectively).

Serious adverse reactions experienced in this trial include, apnea, pyrexia, and, respiratory distress. Severe adverse reactions include chest pain, dyspnea, laryngeal edema, and conjunctivitis. The most common adverse reactions requiring interventions were infusion reactions.

Table 1 summarizes the adverse reactions that occurred in the placebo-controlled trial in at least 2 patients more in the NAGLAZYME-treated group than in the placebo-treated group.

Table 1: Adverse Reactions that Occurred in the Placebo-Controlled Trial in at least 2 Patients More in the NAGLAZYME Group than in the Placebo Group

MedDRA Preferred Term NAGLAZYME
(n = 19)
No. Patients (%)
Placebo
(n = 20*)
No. Patients (%)
All 19(100) 20 (100)
Abdominal Pain 9(47) 7(35)
Ear Pain 8(42) 4(20)
Arthralgia 8(42) 5(25)
Pain 6(32) 1(5)
Conjunctivitis 4(21) 0
Dyspnea 4(21) 2(10)
Rash 4(21) 2(10)
Chills 4(21) 0
Chest Pain 3(16) 1(5)
Pharyngitis 2(11) 0
Areflexia 2(11) 0
Corneal Opacity 2(11) 0
Gastroenteritis 2(11) 0
Hypertension 2(11) 0
Malaise 2(11) 0
Nasal Congestion 2(11) 0
Umbilical Hernia 2(11) 0
Hearing Impairment 2(11) 0
*One of the 20 patients in the placebo group dropped out after Week 4 infusion

Four open-label clinical trials were conducted in MPS VI patients aged 3 months to 29 years with NAGLAZYME administered at doses of 0.2 mg/kg (n = 2), 1 mg/kg (n = 55), and 2 mg/kg (n = 2). The mean exposure to the recommended dose of NAGLAZYME (1 mg/kg) was 138 weeks (range = 54 to 261 weeks). Two infants (12.1 months and 12.7 months) were exposed to 2 mg/kg of NAGLAZYME for 105 and 81 weeks, respectively.

In addition to those listed in Table 1, common adverse reactions observed in the open-label trials include pruritus, urticaria, pyrexia, headache, nausea, and vomiting. The most common adverse reactions requiring interventions were infusion reactions. Serious adverse reactions included laryngeal edema, urticaria, angioedema, and other allergic reactions. Severe adverse reactions included urticaria, rash, and abdominal pain.

Observed adverse events in four open-label studies (up to 261 weeks treatment) were not different in nature or severity to those observed in the placebo-controlled study. No patients discontinued during open-label treatment with NAGLAZYME due to adverse events.

Immunogenicity

Ninety-eight percent (53/54) of patients treated with NAGLAZYME and evaluable for the presence of antibodies to galsulfase developed anti-galsulfase IgG antibodies within 4 to 8 weeks of treatment (in four clinical studies). In 19 patients treated with NAGLAZYME from the placebo-controlled study, serum samples were evaluated for a potential relationship of anti-galsulfase antibody development to clinical outcome measures. All 19 patients treated with NAGLAZYME developed antibodies specific to galsulfase; 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. Antibodies were assessed for the ability to inhibit enzymatic activity but not cellular uptake.

The data reflect the percentage of patients whose test results were considered positive for antibodies to galsulfase using specific assays and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibodies in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to galsulfase with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of NAGLAZYME. 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 addition to infusion reactions reported in clinical trials, serious reactions which occurred during NAGLAZYME infusion in the worldwide marketing experience include anaphylaxis, shock, hypotension, bronchospasm, and respiratory failure.

Additional infusion reactions included pyrexia, erythema, pallor, bradycardia, tachycardia, hypoxia, cyanosis, tachypnea, and paresthesia.

During postmarketing surveillance, there has been a single case of membranous nephropathy and rare cases of thrombocytopenia reported. In the case of membranous nephropathy, renal biopsy revealed galsulfase-immunoglobulin complexes in the glomeruli. With both membranous nephropathy and thrombocytopenia, patients have been successfully rechallenged and have continued to receive NAGLAZYME.

Read the Naglazyme (galsulfase) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

No information provided.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Infusion Reactions

Because of the potential for infusion reactions, patients should receive antihistamines with or without antipyretics prior to infusion. Despite routine pretreatment with antihistamines, infusion reactions, some severe, occurred in 30 of 55 patients treated with NAGLAZYME (galsulfase) . Severe symptoms included angioneurotic edema, hypotension, dyspnea, bronchospasm, respiratory distress, apnea, and urticaria. The most common symptoms of infusion reactions included fever, chills/rigors, headache, rash, and mild to moderate urticaria. Nausea, vomiting, elevated blood pressure, retrosternal pain, abdominal pain, malaise, and joint pain were also reported. Initial reactions were observed as late as Week 55 of treatment.

Symptoms typically abated with slowing or temporary interruption of the infusion and administration of additional antihistamines, antipyretics, and occasionally corticosteroids. Most patients were able to complete their infusions. Subsequent infusions were managed with a slower rate of NAGLAZYME (galsulfase) administration, treatment with additional prophylactic antihistamines, and, in the event of a more severe reaction, treatment with prophylactic corticosteroids. Despite these measures, 13 of 30 patients had additional infusion reactions.

If severe infusion reactions occur, immediately discontinue the infusion of NAGLAZYME (galsulfase) and initiate appropriate treatment. The risks and benefits of re-administering NAGLAZYME (galsulfase) following a severe reaction should be considered.

No factors were identified that predisposed patients to infusion reactions. There was no association between severity of infusion reactions and titer of anti-galsulfase antibodies.

PRECAUTIONS

General

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 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.

Consider delaying NAGLAZYME (galsulfase) infusions in patients who present with an acute febrile or respiratory illness.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to assess the mutagenic and carcinogenic potential of NAGLAZYME (galsulfase) have not been conducted.

Reproductive studies in rats have not demonstrated impairment of fertility (see PRECAUTIONS: Pregnancy).

Pregnancy: Category B

Reproduction studies have been performed in rats at doses up to 3 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to NAGLAZYME (galsulfase) . There are, however, no adequate and well-controlled studies 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.

Nursing Mothers

It is not known whether NAGLAZYME (galsulfase) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NAGLAZYME (galsulfase) is administered to a nursing woman. (See PRECAUTIONS: Information for Patients regarding the Clinical Surveillance Program. Nursing women are encouraged to participate in this program.)

Pediatric Use

The majority of individuals in the clinical studies were pediatric patients; however, patients younger than 5 years of age were not included in the clinical studies. Safety and efficacy in patients younger than 5 years of age have not been evaluated.

Geriatric Use

Clinical studies of NAGLAZYME (galsulfase) did not include patients older than 29 years of age. It is not known whether older patients respond differently from younger patients.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

No information provided.

CONTRAINDICATIONS

None.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of GAG. MPS VI is characterized by the absence or marked reduction in N-acetylgalactosamine 4-sulfatase. The sulfatase activity deficiency results in the accumulation of the GAG substrate, dermatan sulfate, throughout the body. This accumulation leads to widespread cellular, tissue, and organ dysfunction. NAGLAZYME is intended to provide an exogenous enzyme that will be taken up into lysosomes and increase the catabolism of GAG. Galsulfase uptake by cells into lysosomes is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors.

Pharmacodynamics

The responsiveness of urinary GAG to dosage alterations of NAGLAZYME is unknown, and the relationship of urinary GAG to other measures of clinical response has not been established. No association was observed between antibody development and urinary GAG levels [see ADVERSE REACTIONS].

Pharmacokinetics

The pharmacokinetic parameters of galsulfase were evaluated in 13 patients with MPS VI who received 1 mg /kg of NAGLAZYME as a weekly 4-hour infusion for 24 weeks. The pharmacokinetic parameters at Week 1 and Week 24 are shown in Table 2.

Table 2: Pharmacokinetic Parameters (Median, Range)

Pharmacokinetic Parameter Week 1 Week 24
Cmax (mcg/mL) 0.8 (0.4 to 1.3) 1.5 (0.2 to 5.5)
AUCo-t (hr•mcg/mL)* 2.3 (1.0 to 3.5) 4.3 (0.3 to 14.2)
Vz (mL/kg) 103 (56 to 323) 69 (59 to 2,799)
CL (mL/kg/min) 7.2 (4.7 to 10.5) 3.7 (1.1 to 55.9)
Half-life (min) 9 (6 to 21) 26 (8 to 40)
*Area under the plasma galsulfase concentration-time curve from start of infusion to 60 minutes post infusion.

Galsulfase pharmacokinetic parameters listed in Table 2 require cautious interpretation because of large assay variability. Development of anti-galsulfase antibodies appears to affect galsulfase pharmacokinetics, however, the data are limited.

Clinical Studies

A total of 56 patients with MPS VI, ages 5 years to 29 years, were enrolled in four clinical studies. The majority of patients had severe manifestations of the disease as evidenced by poor performance on a test of physical endurance.

In the randomized, double-blind, multicenter, placebo-controlled clinical trial, 38 patients with MPS VI received 1 mg/kg NAGLAZYME or placebo, once-weekly for 24 weeks. The patients' ages ranged from 5 to 29 years. Enrollment was restricted to patients with a 12-minute walk distance of 5 to 400 meters. All patients were treated with antihistamines prior to each infusion.

The NAGLAZYME-treated group showed greater mean increases in the distance walked in 12 minutes (12-minute walk test, 12-MWT) and in the rate of stair climbing in a 3-minute stair climb test, compared with the placebo group (Table 3).

Table 3: Results from Placebo-Controlled Clinical Study

  NAGLAZYME Placebo NAGLAZYME vs. Placebo Difference in
Baseline Week 24 Change Baseline Week 24 Change Changes
N 19 19 19 20 19* 19  
Results from the 12-Minute Walk Test (Meter s)
  Mean ± SD 227±170 336 ± 227 109 ±154 381 ±202 399 ± 217 26 ± 122 83+45&†
92 ± 40‡
(p = 0.025)‡,§
  Median Percentiles 210 316 48 365 373 34  
  (25th, 75*) 90, 330 125,483 7,183 256, 560 204, 573 -3,89  
Results from 3-Minute Stair Climb Test( Stairs/Minute)
  Mean ± SD 19.4 ± 2.9 26.9±16.8 7.4 ± 9.9 31.0 ± 18.1 32.6±19.6 2.7± 6.9 4.7±2.8†
5.7+2.9‡*
(p = 0.053)‡,§
  Median 16.7 22.8 5.2 24.7 29.0 4.3  
  Percentiles (25th, 75th) 10.0, 26.3 14.8,33.0 2.2, 9.9 18.1,51.5 14.2, 57.9 1.0,6.2  
* One patient in the placebo group dropped out after 4 weeks of infusion
† Observed mean of NAGLAZYME - Placebo ± SE
‡ Model-based mean of NAGLAZYME - Placebo ± SE, adjusted for baseline
§ p-value based on the model-based mean difference

Following the 24-week placebo-controlled study period, 38 patients received open-label NAGLAZYME for 72 weeks. Among the 19 patients who were initially randomized to NAGLAZYME and who continued to receive treatment for 72 weeks (total of 96 weeks), increases in the 12-MWT distance and in the rate of stair climbing were observed compared to the start of the open-label period (mean [ ± SD] change): 72 ± 116 meters and 5.6 ± 10.6 stairs/minute, respectively). Among the 19 patients who were randomized initially to placebo for 24 weeks, and then crossed over to treatment with NAGLAZYME, the increases after 72 weeks of NAGLAZYME treatment compared to the start of the open-label period, (mean [ ± SD] change): were 118 ± 127 meters and 11.1 ± 10.0 stairs/minute, for the 12-MWT and the rate of stair climbing, respectively.

Bioactivity was evaluated with urinary GAG concentration. Overall, 95% of patients showed at least a 50% reduction in urinary GAG levels after 72 weeks of treatment with NAGLAZYME. No patient receiving NAGLAZYME reached the normal range for urinary GAG levels.

In an additional open-label extension study, patients receiving NAGLAZYME showed maintenance of initial improvement in endurance for approximately 240 weeks.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Infusion Reactions

Patients and caregivers should be counseled that reactions related to administration and infusion may occur during NAGLAZYME treatment, including life-threatening anaphylaxis. Premedication and reduction of infusion rate may alleviate those reactions associated with the infusion. [see WARNINGS AND PRECAUTIONS].

Patients should be advised to report any adverse reactions experienced while on NAGLAZYME treatment.

Clinical Surveillance Program

Patients should be informed that a Clinical Surveillance Program has been established in order to better understand the variability and progression of the disease in the population as a whole, and to monitor and evaluate long-term treatment effects of NAGLAZYME. The Clinical Surveillance Program will also monitor the effect of NAGLAZYME on pregnant women, nursing mothers and their offspring, and determine if NAGLAZYME is excreted in breast milk. Patients should be encouraged to participate and advised that their participation is voluntary and may involve long-term follow-up. For more information call 800-983-4587.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Infusion Reactions

Patients and caregivers should be counseled that reactions related to administration and infusion may occur during NAGLAZYME treatment, including life-threatening anaphylaxis. Premedication and reduction of infusion rate may alleviate those reactions associated with the infusion. [see WARNINGS AND PRECAUTIONS].

Patients should be advised to report any adverse reactions experienced while on NAGLAZYME treatment.

Clinical Surveillance Program

Patients should be informed that a Clinical Surveillance Program has been established in order to better understand the variability and progression of the disease in the population as a whole, and to monitor and evaluate long-term treatment effects of NAGLAZYME. The Clinical Surveillance Program will also monitor the effect of NAGLAZYME on pregnant women, nursing mothers and their offspring, and determine if NAGLAZYME is excreted in breast milk. Patients should be encouraged to participate and advised that their participation is voluntary and may involve long-term follow-up. For more information call 800-983-4587.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

NAGLAZYME
(galsulfase)

DRUG DESCRIPTION

NAGLAZYME is a formulation of galsulfase, which is a purified human enzyme that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase (glycosaminoglycan Nacetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal enzyme that catalyzes the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG), chondroitm 4-sulfate and dermatan sulfate.

Galsulfase is a glycoprotein with a molecular weight of approximately 56 kDa. The recombinant protein consists of 495 amino acids and possesses six asparagine-linked glycosylation sites, four of which carry a bis-mannose-6-phosphate residue for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue, Ca-formylglycine, which is required for enzyme activity. NAGLAZYME has a specific activity of approximately 70 units per mg of protein content. One activity unit is defined as the amount of enzyme required to convert 1 micromole of 4-methylumbelliferyl sulfate to 4- methylumbelliferone and free sulfate per minute at 37°C.

NAGLAZYME is intended for intravenous infusion and is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration. NAGLAZYME is supplied in clear Type I glass 5 mL vials. Each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80 in a 5 mL extractable solution with pH of approximately 5.8. NAGLAZYME does not contain preservatives. Each vial is for single use only.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

NAGLAZYME
(galsulfase)

DRUG DESCRIPTION

NAGLAZYME is a formulation of galsulfase, which is a purified human enzyme that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase (glycosaminoglycan Nacetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal enzyme that catalyzes the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG), chondroitm 4-sulfate and dermatan sulfate.

Galsulfase is a glycoprotein with a molecular weight of approximately 56 kDa. The recombinant protein consists of 495 amino acids and possesses six asparagine-linked glycosylation sites, four of which carry a bis-mannose-6-phosphate residue for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue, Ca-formylglycine, which is required for enzyme activity. NAGLAZYME has a specific activity of approximately 70 units per mg of protein content. One activity unit is defined as the amount of enzyme required to convert 1 micromole of 4-methylumbelliferyl sulfate to 4- methylumbelliferone and free sulfate per minute at 37°C.

NAGLAZYME is intended for intravenous infusion and is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration. NAGLAZYME is supplied in clear Type I glass 5 mL vials. Each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80 in a 5 mL extractable solution with pH of approximately 5.8. NAGLAZYME does not contain preservatives. Each vial is for single use only.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

NAGLAZYME
(galsulfase)

DRUG DESCRIPTION

NAGLAZYME is a formulation of galsulfase, which is a purified human enzyme that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase (glycosaminoglycan Nacetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal enzyme that catalyzes the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG), chondroitm 4-sulfate and dermatan sulfate.

Galsulfase is a glycoprotein with a molecular weight of approximately 56 kDa. The recombinant protein consists of 495 amino acids and possesses six asparagine-linked glycosylation sites, four of which carry a bis-mannose-6-phosphate residue for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue, Ca-formylglycine, which is required for enzyme activity. NAGLAZYME has a specific activity of approximately 70 units per mg of protein content. One activity unit is defined as the amount of enzyme required to convert 1 micromole of 4-methylumbelliferyl sulfate to 4- methylumbelliferone and free sulfate per minute at 37°C.

NAGLAZYME is intended for intravenous infusion and is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration. NAGLAZYME is supplied in clear Type I glass 5 mL vials. Each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80 in a 5 mL extractable solution with pH of approximately 5.8. NAGLAZYME does not contain preservatives. Each vial is for single use only.

Last reviewed on RxList: 6/23/2011
This monograph has been modified to include the generic and brand name in many instances.

Naglazyme Patient Information Including Side Effects

Brand Names: Naglazyme

Generic Name: galsulfase (Pronunciation: gal SUL fase)

What is galsulfase (Naglazyme)?

Galsulfase is used to treat some of the symptoms of a genetic condition called Maroteaux-Lamy syndrome. Maroteaux-Lamy syndrome is also called mucopolysaccharidosis (MYOO-koe-pol-ee-SAK-a-rye-DOE-sis).

Maroteaux-Lamy syndrome is a metabolic disorder in which the body lacks the enzyme needed to break down certain sugars and proteins. These substances can build up in the body, causing enlarged organs, abnormal bone structure, changes in facial features, breathing problems, heart problems, vision or hearing loss, and changes in mental or physical abilities.

Galsulfase may improve walking and stair-climbing ability in people with this condition. However, this medication is not a cure for Maroteaux-Lamy syndrome.

Galsulfase may also be used for other purposes not listed in this medication guide.

What are the possible side effects of galsulfase (Naglazyme)?

Some people receiving a galsulfase injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you have a headache, fever or chills, skin rash, itching, nausea, vomiting, stomach pain, pain in your chest, trouble breathing, or if you feel like you might pass out when galsulfase is injected.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Less serious side effects may include:

  • headache;
  • joint pain;
  • eye redness;
  • nausea, vomiting, stomach pain, diarrhea;
  • runny or stuffy nose, sore throat, cough, ear pain; or
  • pain, redness, swelling, or other irritation where the medicine was injected.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Naglazyme (galsulfase) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about galsulfase (Naglazyme)?

Galsulfase may improve walking and stair-climbing ability in people with Maroteaux-Lamy syndrome. However, galsulfase is not a cure for this condition.

Some people receiving a galsulfase injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you have a headache, fever or chills, skin rash, itching, nausea, vomiting, stomach pain, pain in your chest, trouble breathing, or if you feel like you might pass out when galsulfase is injected.

Your name may need to be listed on a patient registry while you are using this medication. The purpose of this registry is to track the progression of this disorder and the effects that galsulfase has on long-term treatment of Maroteaux-Lamy syndrome.

Side Effects Centers

Naglazyme Patient Information including How Should I Take

What should I discuss with my health care provider before receiving galsulfase (Naglazyme)?

You should not use this medication if you are allergic to galsulfase or mouse proteins.

Before receiving galsulfase, tell your doctor if you are allergic to any drugs, or if you have:

  • sleep apnea (breathing stops during sleep);
  • a fever; or
  • flu symptoms, or a common cold.

If you have any of these conditions, you may need a dose adjustment or special tests to safely use galsulfase.

Your name may need to be listed on a patient registry while you are using this medication. The purpose of this registry is to track the progression of this disorder and the effects that galsulfase has on long-term treatment of Maroteaux-Lamy syndrome.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether galsulfase passes into breast milk or if it could harm a nursing baby. Do not receive this medication without telling your doctor if you are breast-feeding a baby.

How is galsulfase given (Naglazyme)?

Galsulfase is given as an injection through a needle placed into a vein. You will most likely receive this injection in a clinic or hospital setting. Galsulfase is usually given once per week.

The medicine must be given slowly through an IV infusion, and can take up to 4 hours to complete.

Your doctor may also prescribe other medications to help prevent an allergic reaction to galsulfase. Take all of your medications as directed.

To be sure this medication is helping your condition and not causing harmful effects, your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

Side Effects Centers

Naglazyme Patient Information including If I Miss a Dose

What happens if I miss a dose (Naglazyme)?

Contact your doctor if you miss an appointment for your galsulfase injection.

What happens if I overdose (Naglazyme)?

Seek emergency medical attention if you think you have received too much of this medicine.

Symptoms of a galsulfase overdose are not known.

What should I avoid while receiving galsulfase (Naglazyme)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are receiving galsulfase.

What other drugs will affect galsulfase (Naglazyme)?

There may be other drugs that can interact with galsulfase. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about galsulfase.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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