Drugs List

Therapeutic Indications

Uses

Mucopolysaccharidosis I - long term enzyme replacement therapy

Administration

To be administered as an intravenous infusion.

The initial infusion rate of 2 units/kg/hour may be incrementally increased every fifteen minutes, if tolerated, to a maximum of 43 units/kg/hour.

The total volume of the administration should be delivered in approximately 3 to 4 hours.

Contraindications

Elderly
Breastfeeding

Precautions and Warnings

Restricted sodium intake
Hepatic impairment
Pregnancy
Renal impairment
Severe respiratory impairment

Sodium content of formulation may be significant
Consider pre-medication with antihistamines and/or antipyretics
Treatment to be initiated and supervised by a specialist
Resuscitation facilities must be immediately available
Monitor patient for infusion-associated reactions (IARs)
Monitor periodically for IgG antibody formation
Discontinue if severe hypersensitivity reactions occur
Interrupt treatment if severe infusion reaction occurs

Greater risk of IARs in patients with an acute underlying illness at the time of treatment.

Pre-treatment with antihistamine and/or antipyretics may be considered in patients with a history of laronidase IARs or in initial treatment and should be administered approximately 60 minutes prior to infusion. Infusion rates can be reduced by one half of that at which the reaction occurred or up to one quarter in the case of severe IAR.

Based on clinical trial data, almost all patients are expected to develop IgG antibodies to laronidase (mostly within three months of the start of therapy). Re-administer laronidase with caution to patients who have previously developed antibodies or symptoms of IAR.

There is little experience in resuming therapy after prolonged interruption. Re-starting therapy should be approached with caution due to a theoretical increased risk of hypersensitivity reaction after prolonged interruption.

Pregnancy and Lactation

Pregnancy

Laronidase should be used with caution during pregnancy.

There is inadequate data available on the use of laronidase in pregnant women. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal/foetal development, parturition or postnatal development.

The potential risk for humans is unknown. However the benefits of the treatment with laronidase to a pregnant woman with mucopolysaccharidosis appear to outweigh the unknown risks to the embryo and/or foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Laronidase should not be used during breastfeeding.

Laronidase may be excreted in milk. There are no data available in neonates exposed to laronidase via breast milk and as such it is recommended that breastfeeding should be stopped during laronidase therapy.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Alopecia
Anaphylactic reaction
Angioedema
Antibody formation
Arthralgia
Arthropathy
Back pain
Bronchospasm
Chills
Cold sweat
Cough
Cyanosis
Diarrhoea
Dizziness
Dyspnoea
Erythema
Extravasation
Facial oedema
Fatigue
Feeling hot
Flushing
Headache
Hyperhidrosis
Hypotension
Hypoxia
Influenza-like symptoms
Injection site reactions
Laryngeal oedema
Musculoskeletal pain
Nausea
Oxygen saturation decreased
Painful extremities
Pallor
Paraesthesia
Peripheral coldness
Peripheral oedema
Pruritus
Pyrexia
Rash
Respiratory arrest
Respiratory distress
Restlessness
Rise in body temperature
Sensation of cold
Tachycardia
Tachypnoea
Urticaria
Vomiting

Presentation

Concentrate for solution for infusion containing 500 units laronidase in 5ml (approximately 2.9 mg/5 ml)

One unit is defined as activity required to hydrolyse one micromole of substrate (4-MUI) per minute.

Laronidase is produced by recombinant DNA technology using mammalian Chinese Hamster Ovary cell lines.

Drugs List

Therapeutic Indications

Uses

Mucopolysaccharidosis I - long term enzyme replacement therapy

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

To be administered as an intravenous infusion.

The initial infusion rate of 2 units/kg/hour may be incrementally increased every fifteen minutes, if tolerated, to a maximum of 43 units/kg/hour.

The total volume of the administration should be delivered in approximately 3 to 4 hours.

Contraindications

Elderly
Breastfeeding

Precautions and Warnings

Restricted sodium intake
Hepatic impairment
Pregnancy
Renal impairment
Severe respiratory impairment

Sodium content of formulation may be significant
Consider pre-medication with antihistamines and/or antipyretics
Treatment to be initiated and supervised by a specialist
Resuscitation facilities must be immediately available
Monitor patient for infusion-associated reactions (IARs)
Monitor periodically for IgG antibody formation
Discontinue if severe hypersensitivity reactions occur
Interrupt treatment if severe infusion reaction occurs

Greater risk of IARs in patients with an acute underlying illness at the time of treatment.

Pre-treatment with antihistamine and/or antipyretics may be considered in patients with a history of laronidase IARs or in initial treatment and should be administered approximately 60 minutes prior to infusion. Infusion rates can be reduced by one half of that at which the reaction occurred or up to one quarter in the case of severe IAR.

Based on clinical trial data, almost all patients are expected to develop IgG antibodies to laronidase (mostly within three months of the start of therapy). Re-administer laronidase with caution to patients who have previously developed antibodies or symptoms of IAR.

There is little experience in resuming therapy after prolonged interruption. Re-starting therapy should be approached with caution due to a theoretical increased risk of hypersensitivity reaction after prolonged interruption.

Pregnancy and Lactation

Pregnancy

Laronidase should be used with caution during pregnancy.

There is inadequate data available on the use of laronidase in pregnant women. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal/foetal development, parturition or postnatal development.

The potential risk for humans is unknown. However the benefits of the treatment with laronidase to a pregnant woman with mucopolysaccharidosis appear to outweigh the unknown risks to the embryo and/or foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Laronidase should not be used during breastfeeding.

Laronidase may be excreted in milk. There are no data available in neonates exposed to laronidase via breast milk and as such it is recommended that breastfeeding should be stopped during laronidase therapy.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Alopecia
Anaphylactic reaction
Angioedema
Antibody formation
Arthralgia
Arthropathy
Back pain
Bronchospasm
Chills
Cold sweat
Cough
Cyanosis
Diarrhoea
Dizziness
Dyspnoea
Erythema
Extravasation
Facial oedema
Fatigue
Feeling hot
Flushing
Headache
Hyperhidrosis
Hypotension
Hypoxia
Influenza-like symptoms
Injection site reactions
Laryngeal oedema
Musculoskeletal pain
Nausea
Oxygen saturation decreased
Painful extremities
Pallor
Paraesthesia
Peripheral coldness
Peripheral oedema
Pruritus
Pyrexia
Rash
Respiratory arrest
Respiratory distress
Restlessness
Rise in body temperature
Sensation of cold
Tachycardia
Tachypnoea
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: May 2015.

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 13 May 2015.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 13 May 2015.

Summary of Product Characteristics: Aldurazyme 100 U/ml concentrate for solution for infusion. Genzyme Therapeutics. Revised November 2014.