Drugs List

Therapeutic Indications

Uses

Mucopolysaccharidosis VI - long term enzyme replacement therapy

Dosage

The recommended dose is 1mg/kg body weight administered once every week as an intravenous infusion over 4 hours.

It is of primary importance especially in severe forms of the disorder to initiate treatment as early as possible before appearance of non-reversible clinical manifestations of the disease.

Administration

For intravenous infusion after dilution with sodium chloride 0.9% solution for infusion.

The initial infusion rate is adjusted so that approximately 2.5% of the total solution is infused during the first hour, with infusion of the remaining volume over the next 3 hours. In patients that are susceptible to fluid volume overload and weigh less than 20kg, the dilution volume and infusion rate (ml/minute) should be decreased so that the total duration remains not less than 4 hours.

Contraindications

None known

Precautions and Warnings

Children under 1 year
Febrile disorder
Patients over 65 years
Restricted sodium intake
Breastfeeding
Hepatic impairment
Pregnancy
Renal impairment
Respiratory impairment

Sodium content of formulation may be significant
Pre-medicate with antihistamines with or without antipyretics
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Delay treatment if acute febrile illness
Delay treatment if respiratory illness
Dilute and use as an infusion
Resuscitation facilities must be immediately available
Slow infusion and treat non life threatening allergic reactions accordingly
Use recommended diluent only- no other drugs to be added to solution
Antibodies to ingredient may develop
Spinal cord compression may occur
Discontinue if serious allergic or anaphylactic reaction occurs

It is expected that the majority of patients will develop IgG antibodies to galsulfase within 4 to 8 weeks of treatment initiation.
Caution should be used in the management and treatment of patients with compromised airways by limitation or careful monitoring of antihistamine and other sedative medication use. In clinically appropriate situations, consider institution of positive-airway pressure during sleep or potential tracheostomy. The use of antihistamines and or antipyretics are recommended approximately 30 to 60 minutes prior to the start of infusion in order to minimise the potential occurrence of infusion associated reactions (IAR). In cases of a mild or moderate IAR treat with antihistamines and paracetamol and/or a reduction in infusion rate to half of the rate at which the reaction occurred. In the case of a single severe IAR, stop the infusion until the symptoms are resolved and consider treatment with antihistamines and paracetamol. The infusion should be restarted with a reduction of the infusion rate to 50% to 25% of the rate at which the reaction occurred. In the case of a recurrent moderate IAR or re-challenge after a single severe IAR, pre-treat with antihistamines and paracetamol and/or corticosteroids and reduce the infusion rate to 50% to 25% of the rate at which the previous reaction occurred.

Spinal/ cervical cord compression (SCC) is a serious complication of Mucopolysaccharidosis VI (MPS VI), it has been reported that patients treated with galsulfase experience the onset or worsening of SCC, requiring surgery. Patients should be monitored for signs and symptoms of SCC and given appropriate care.

Pregnancy and Lactation

Pregnancy

Use galsulfase with caution during pregnancy.

The manufacturer recommends galsulfase is not used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryonal/foetal development when exposed to galsulfase. No clinical studies on exposed pregnancies are available.

It is not known if galsulfase crosses the human placenta. A molecular weight of approximately 56,000 and a short half life suggests the exposure to embryo or foetus would be minimal, if any (Briggs, 2015).

Lactation

Use galsulfase with caution during breastfeeding.

The manufacturer advises that it is not known whether galsulfase is excreted in breast milk and that mothers should not breastfeed during treatment with galsulfase.

The Specialist Pharmacy Service (SPS) states, however, that due to the drug's properties, low levels are anticipated in milk which are likely to be degraded in the infant's GI tract.

Side Effects

Abdominal pain
Anaphylactoid reaction
Anaphylaxis
Angioedema
Antibody formation
Apnoea
Areflexia
Arthralgia
Asthma
Bradycardia
Bronchospasm
Chest pain
Conjunctivitis
Corneal opacities
Cough
Cyanosis
Dyspnoea
Ear pain
Erythema
Fever
Gastro-enteritis
Headache
Hearing disturbances
Hypersensitivity reactions
Hypertension
Hypotension
Hypoxia
Laryngeal oedema
Malaise
Nasal congestion
Nausea
Pain
Pallor
Paraesthesia
Pharyngitis
Pruritus
Rash
Respiratory distress
Rigors
Shock
Tachycardia
Tachypnoea
Tremor
Umbilical hernia
Urticaria
Vomiting

Presentation

Concentrate for solution for infusion containing galsulfase.

Drugs List

Therapeutic Indications

Uses

Mucopolysaccharidosis VI - long term enzyme replacement therapy

Dosage

The recommended dose is 1mg/kg body weight administered once every week as an intravenous infusion over 4 hours.

It is of primary importance especially in severe forms of the disorder to initiate treatment as early as possible before appearance of non-reversible clinical manifestations of the disease.

Administration

For intravenous infusion after dilution with sodium chloride 0.9% solution for infusion.

The initial infusion rate is adjusted so that approximately 2.5% of the total solution is infused during the first hour, with infusion of the remaining volume over the next 3 hours. In patients that are susceptible to fluid volume overload and weigh less than 20kg, the dilution volume and infusion rate (ml/minute) should be decreased so that the total duration remains not less than 4 hours.

Contraindications

None known

Precautions and Warnings

Children under 1 year
Febrile disorder
Patients over 65 years
Restricted sodium intake
Breastfeeding
Hepatic impairment
Pregnancy
Renal impairment
Respiratory impairment

Sodium content of formulation may be significant
Pre-medicate with antihistamines with or without antipyretics
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Delay treatment if acute febrile illness
Delay treatment if respiratory illness
Dilute and use as an infusion
Resuscitation facilities must be immediately available
Slow infusion and treat non life threatening allergic reactions accordingly
Use recommended diluent only- no other drugs to be added to solution
Antibodies to ingredient may develop
Spinal cord compression may occur
Discontinue if serious allergic or anaphylactic reaction occurs

It is expected that the majority of patients will develop IgG antibodies to galsulfase within 4 to 8 weeks of treatment initiation.
Caution should be used in the management and treatment of patients with compromised airways by limitation or careful monitoring of antihistamine and other sedative medication use. In clinically appropriate situations, consider institution of positive-airway pressure during sleep or potential tracheostomy. The use of antihistamines and or antipyretics are recommended approximately 30 to 60 minutes prior to the start of infusion in order to minimise the potential occurrence of infusion associated reactions (IAR). In cases of a mild or moderate IAR treat with antihistamines and paracetamol and/or a reduction in infusion rate to half of the rate at which the reaction occurred. In the case of a single severe IAR, stop the infusion until the symptoms are resolved and consider treatment with antihistamines and paracetamol. The infusion should be restarted with a reduction of the infusion rate to 50% to 25% of the rate at which the reaction occurred. In the case of a recurrent moderate IAR or re-challenge after a single severe IAR, pre-treat with antihistamines and paracetamol and/or corticosteroids and reduce the infusion rate to 50% to 25% of the rate at which the previous reaction occurred.

Spinal/ cervical cord compression (SCC) is a serious complication of Mucopolysaccharidosis VI (MPS VI), it has been reported that patients treated with galsulfase experience the onset or worsening of SCC, requiring surgery. Patients should be monitored for signs and symptoms of SCC and given appropriate care.

Pregnancy and Lactation

Pregnancy

Use galsulfase with caution during pregnancy.

The manufacturer recommends galsulfase is not used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryonal/foetal development when exposed to galsulfase. No clinical studies on exposed pregnancies are available.

It is not known if galsulfase crosses the human placenta. A molecular weight of approximately 56,000 and a short half life suggests the exposure to embryo or foetus would be minimal, if any (Briggs, 2015).

Lactation

Use galsulfase with caution during breastfeeding.

The manufacturer advises that it is not known whether galsulfase is excreted in breast milk and that mothers should not breastfeed during treatment with galsulfase.

The Specialist Pharmacy Service (SPS) states, however, that due to the drug's properties, low levels are anticipated in milk which are likely to be degraded in the infant's GI tract.

Side Effects

Abdominal pain
Anaphylactoid reaction
Anaphylaxis
Angioedema
Antibody formation
Apnoea
Areflexia
Arthralgia
Asthma
Bradycardia
Bronchospasm
Chest pain
Conjunctivitis
Corneal opacities
Cough
Cyanosis
Dyspnoea
Ear pain
Erythema
Fever
Gastro-enteritis
Headache
Hearing disturbances
Hypersensitivity reactions
Hypertension
Hypotension
Hypoxia
Laryngeal oedema
Malaise
Nasal congestion
Nausea
Pain
Pallor
Paraesthesia
Pharyngitis
Pruritus
Rash
Respiratory distress
Rigors
Shock
Tachycardia
Tachypnoea
Tremor
Umbilical hernia
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: August 2019.

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Naglazyme 1mg/ml concentrate for solution for infusion. Biomarin Europe Ltd. Revised January 2011.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 10 August 2019.

Specialist Pharmacy Service (SPS)
Available at: https://www.sps.nhs.uk/
Naglazyme Last revised: 17 May 2019
Last accessed: 10 August 2019.