Velmanase Alfa-tycv (Monograph)

Brand name: Lamzede
Drug class: Enzymes

Medically reviewed by Drugs.com on Feb 10, 2025. Written by ASHP.

Warning

Hypersensitivity reactions, including anaphylaxis, reported.
Appropriate medical support measures should be readily available during administration.
If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue drug immediately and initiate appropriate treatment.
In patients with severe hypersensitivity reactions, may consider a desensitization procedure.

Introduction

Recombinant preparation of human lysosomal alpha-mannosidase.

Uses for Velmanase Alfa-tycv

Alpha-Mannosidosis

Treatment of non-CNS manifestations of alpha-mannosidosis in adults and pediatric patients; designated an orphan drug by FDA for treatment of this condition.

Limited treatment options available for alpha-mannosidosis; current standard of care includes supportive and symptomatic treatment.

Velmanase Alfa-tycv Dosage and Administration

General

Pretreatment Screening

In females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment.

Patient Monitoring

Monitor patients for symptoms of infusion-associated reactions and hypersensitivity reactions during administration.

Premedication and Prophylaxis

Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids prior to administration.

Dispensing and Administration Precautions

Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during administration.

Administration

IV Administration

Administer by IV infusion after reconstitution.

Use an infusion set equipped with a pump and a low protein binding, 0.2 micron in-line filter to administer the drug; do not shake the syringe.

Reconstitution

Determine number of vials needed based on patient's weight (in kg) and recommended dose; round to nearest whole number of vials.

Remove vials from refrigerator and set aside for approximately 30 minutes.

Reconstitute lyophilized powder by slowly injecting 5 mL of sterile water for injection down the inside wall of each vial.

Avoid adding the sterile water forcefully or directly onto powder to minimize foaming. Allow vial to stand for 5–15 minutes and then gently tilt and roll for 15–20 seconds. Do not invert, swirl, or shake vials.

Slowly withdraw the required volume from vials into syringe; avoid foaming in the syringe. If the volume of solution exceeds one syringe capacity, prepare the required number of syringes in order to replace the syringes quickly during infusion.

Administration

The total volume of infusion is determined by the patient’s actual body weight.

Patients weighing ≤49 kg: administer over a minimum of 60 minutes.

Patients weighing ≥50 kg: administer over maximum of 25 mL/hour.

After administering the last syringe, replace dosing syringe with a 20 mL syringe filled with 0.9% sodium chloride injection; infuse 10 mL of 0.9% sodium chloride injection through the infusion system to ensure that any remaining drug is administered.

Dosage

Pediatric Patients

Alpha Mannosidosis

IV

1 mg/kg (based on actual body weight) once every week as an IV infusion.

If 1 or more doses are missed, restart the treatment as soon as possible, as long as it is at least 3 days from the next scheduled dose. If the missed dose is within 3 days from the next scheduled dose, administer the next dose as scheduled.

Adults

Alpha Mannosidosis

IV

1 mg/kg (actual body weight) administered once every week as an IV infusion.

Dosage Modification for Hypersensitivity and Infusion Reactions

Mild to moderate hypersensitivity reaction or mild to moderate infusion-associated reaction (IAR):Consider temporarily holding the infusion for 15–30 minutes, slowing the infusion rate to 25–50% of recommended rate, and initiating appropriate medical treatment. If symptoms persist after slowing the infusion, stop infusion and monitor patient. If symptoms continue to persist, consider re-initiating infusion within 7–14 days at 25-50% of the recommended rate with appropriate pretreatment. If symptoms subside after holding or slowing the infusion, resume infusion at 25-50% of recommended rate. If tolerated, increase infusion rate by 25% of recommended rate until recommended rate is reached. Closely monitor patient.

Severe hypersensitivity reaction, including anaphylaxis, or severe IAR:Immediately discontinue infusion and initiate appropriate medical treatment.

Special Populations

Hepatic Impairment

No special population dosage recommendations at this time.

Renal Impairment

No special population dosage recommendations at this time.

Geriatric Patients

No special population dosage recommendations at this time.

Cautions for Velmanase Alfa-tycv

Contraindications

None.

Warnings/Precautions

Warnings

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, reported. (See Boxed Warning.)

Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during administration.

Discontinue if severe hypersensitivity reactions occur; initiate appropriate medical treatment.

Other Warnings and Precautions

Infusion-associated Reactions

Infusions-associated reactions (IARs) reported.

Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids. If a severe IAR occurs, discontinue velmanase alfa-tycv immediately and initiate appropriate medical care. If a mild or moderate IAR occurs, consider slowing the infusion rate or temporarily withholding the dose.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm based on animal reproduction studies; skeletal and visceral malformations observed.

Immunogenicity

Anti-drug antibodies (ADAs) detected in controlled trials. IARs, including anaphylaxis and severe hypersensitivity reactions, occurred in a higher incidence in velmanase alfa-tycv-treated patients who developed ADAs, compared to patients who were ADA negative (80 versus 20%).

Specific Populations

Pregnancy

No adequate data on use of velmanase alfa-tycv in pregnant women. Based on animal studies, may cause embryofetal harm.

When deciding whether to continue velmanase alfa during pregnancy, consider patient's need for velmanase alfa, potential drug-related risk to fetus, and potential adverse outcomes from untreated disease.

Lactation

Not known whether velmanase alfa-tycv or its metabolite is distributed into human milk or if the drug has any effects on the breast-fed infant or milk production.

Females and Males of Reproductive Potential

Before initiating velmanase alfa therapy in females of reproductive potential, verify that patient is not pregnant, and advise patient to use effective contraceptive during treatment and for 14 days after last dose if the drug is discontinued.

Pediatric Use

Safety and efficacy established in pediatric patients. In clinical studies, pediatric patients experienced a higher incidence of hypersensitivity reactions compared to adults.

Geriatric Use

Alpha-mannosidosis is largely a disease of pediatric and young adult patients. Safety and efficacy not studied in geriatric patients ≥65 years of age.

Hepatic Impairment

Safety and efficacy not studied in hepatic impairment.

Renal Impairment

Safety and efficacy not studied in renal impairment.

Common Adverse Effects

Most common adverse reactions (>20%): hypersensitivity reactions (including anaphylaxis), nasopharyngitis, pyrexia, headache, arthralgia.

Drug Interactions

No clinical drug interaction studies performed. Velmanase alfa-tycv is not a substrate or inhibitor/inducer of major CYP enzymes, or a substrate or inhibitor of major transporters.

Velmanase Alfa-tycv Pharmacokinetics

Elimination

Metabolism

Metabolic pathway not characterized but expected to be metabolized into small peptides by catabolic pathways.

Half-life

Mean terminal half-life 33.6 hours.

Stability

Storage

Parenteral

Lyophilized Powder

Store refrigerated at 2–8ºC in the original carton to protect from light.

Reconstituted vials may be stored in refrigerator for up to 24 hours, inclusive of infusion time. Reconstituted vials must be used within 10 hours after removal from the refrigerator, inclusive of infusion time. Discard if not used within 10 hours.

Actions

Recombinant form of human alpha-mannosidase enzyme. Acts as an enzyme replacement therapy for the deficient endogenous alpha-mannosidase enzyme in patients with alpha-mannosidosis.
Binds to mannose-6-phosphate receptor on the cell surface; internalized and transported into lysosomes where it is thought to exert enzyme activity.

Advice to Patients

Risk of hypersensitivity reactions including anaphylaxis and infusion-associated reactions (IARs). Advise the patient and caregiver that reactions related to the infusion may occur during and after velmanase alfa-tycv treatment, including anaphylactic reactions, other serious or severe hypersensitivity reactions, and IARs. Inform the patient and caregiver of the signs and symptoms of hypersensitivity reactions and IARs and to seek medical care should signs and symptoms occur.
Velmanase alfa-tycv may cause embryo-fetal harm. Advise pregnant females of the potential risk to the fetus. Advise such female patients or their caregivers to inform their healthcare provider of a known or suspected pregnancy.
Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if velmanase alfa-tycv is discontinued.
Advise patients to inform their clinician if they plan to breast-feed.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Velmanase alfa-tycv is obtained through Chiesi Total Care. For more information about ordering the drug, contact Chiesi Total Care at 855-282-4883.