Drugs List

Therapeutic Indications

Uses

X-linked hypophosphataemia

Treatment of X-linked hypophosphataemia with radiographic evidence of bone disease in children aged 1 to 17 years and in adults.

Administration

Burosumab should be injected subcutaneously in the arm, abdomen, buttock or thigh. The maximum volume of medicinal product per injection site is 1.5ml. If more than 1.5ml is required on a given dosing day, the total volume should be split and should be administered at two different injection sites.

Injection sites should be rotated and carefully monitored for signs of potential reactions.

Self or carer administration may be suitable for some patients once no immediate dose modifications are anticipated and the individual has been trained in the injection technique. The first self-administered dose after drug initiation or dose change should be conducted under the supervision of a healthcare professional.

Contraindications

Children under 1 year
Within 1 week of discontinuing active vitamin D analogues
Within 1 week of discontinuing oral phosphate
Breastfeeding
End stage renal disease
Hereditary fructose intolerance
Hyperphosphatemia
Pregnancy
Severe renal impairment

Precautions and Warnings

Females of childbearing potential
Renal impairment

Advise patient dizziness may affect ability to drive or operate machinery
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
For single use only
Record name and batch number of administered product
Monitor parathyroid hormone levels
Monitor serum alkaline phosphatase levels periodically
Monitor serum calcium levels
Monitor serum creatine periodically
Monitor serum phosphate levels periodically
Perform periodic renal ultrasounds
Discontinue if severe hypersensitivity reactions occur
Female: Ensure adequate contraception during treatment

Fasting serum phosphate

After starting the treatment, fasting serum phosphate should be measured every 2 weeks for the first month, every 4 weeks for the following 2 months and thereafter as appropriate. Fasting serum phosphate should also be measured 4 weeks after any dose adjustment. If fasting serum phosphate is within the reference range for age, the same dose should be maintained.

To reduce the risk for ectopic mineralisation, it is advised to target the fasting serum phosphate in the lower end of the normal reference range for age.

Vitamin D replacement or supplementation with inactive forms may be started or continued as per local guidelines under monitoring of serum calcium and phosphate.

Ectopic mineralisation

Ectopic mineralisation, as manifested by nephrocalcinosis has been observed in patients treated with oral phosphate and vitamin D analogues.

Monitoring for signs and symptoms of nephrocalcinosis, e.g. by renal ultrasonography, is recommended at the start of treatment and every 6 months for the first 12 months of treatment, and annually thereafter. Monitoring of plasma alkaline phosphatases, calcium, parathyroid hormone (PTH) and creatinine is recommended every 6 months (every 3 months for children aged 1 to 2 years) or as indicated. Monitoring of urine calcium and phosphate is suggested every 3 months.

Hyperphosphataemia

Due to the risk of hyperphosphataemia, fasting and post prandial serum phosphate levels should be periodically monitored. Dose interruption and/or reduction may be required.

Pregnancy and Lactation

Pregnancy

Burosumab is contraindicated during pregnancy.

The manufacturer does not recommend using burosumab during pregnancy and in women of childbearing potential not using contraception.

Animal studies have shown reproductive toxicity. At the time of writing there is no or limited published information regarding the use of burosumab in pregnancy. Potential risks are unknown.

Lactation

Burosumab is contraindicated in breastfeeding.

The manufacturer recommends that a decision should be made whether to discontinue breastfeeding or to discontinue/abstain from burosumab therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

At the time of writing there is limited published information regarding the excretion of burosumab in human milk. A risk to the newborns/infants cannot be excluded.

LactMed (2018) indicates that due to the high molecular weight of this agent, the amount present in milk is likely to be very low and absorption is unlikely because burosumab is probably destroyed in the infant's gastrointestinal tract.

Side Effects

Antibody formation
Bruising at injection site
Constipation
Cough
Decreased vitamin D
Dental decay
Dermatitis
Diarrhoea
Dizziness
Erythema at injection site
Extremity pain
Facial swelling
Haematoma (injection site)
Headache
Hyperphosphataemia
Hypersensitivity reactions
Injection site reactions
Localised urticaria
Myalgia
Nausea
Pain on injection
Pruritus
Pyrexia
Rash
Rash at injection site
Swelling (injection site)
Tooth abscess
Tooth ache
Tooth infection
Vomiting

Presentation

Injections of burosumab.

Drugs List

Therapeutic Indications

Uses

X-linked hypophosphataemia

Treatment of X-linked hypophosphataemia with radiographic evidence of bone disease in children aged 1 to 17 years and in adults.

Dosage

Children

Additional Dosage Information

Administration

Burosumab should be injected subcutaneously in the arm, abdomen, buttock or thigh. The maximum volume of medicinal product per injection site is 1.5ml. If more than 1.5ml is required on a given dosing day, the total volume should be split and should be administered at two different injection sites.

Injection sites should be rotated and carefully monitored for signs of potential reactions.

Self or carer administration may be suitable for some patients once no immediate dose modifications are anticipated and the individual has been trained in the injection technique. The first self-administered dose after drug initiation or dose change should be conducted under the supervision of a healthcare professional.

Contraindications

Children under 1 year
Within 1 week of discontinuing active vitamin D analogues
Within 1 week of discontinuing oral phosphate
Breastfeeding
End stage renal disease
Hereditary fructose intolerance
Hyperphosphatemia
Pregnancy
Severe renal impairment

Precautions and Warnings

Females of childbearing potential
Renal impairment

Advise patient dizziness may affect ability to drive or operate machinery
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
For single use only
Record name and batch number of administered product
Monitor parathyroid hormone levels
Monitor serum alkaline phosphatase levels periodically
Monitor serum calcium levels
Monitor serum creatine periodically
Monitor serum phosphate levels periodically
Perform periodic renal ultrasounds
Discontinue if severe hypersensitivity reactions occur
Female: Ensure adequate contraception during treatment

Fasting serum phosphate

After starting the treatment, fasting serum phosphate should be measured every 2 weeks for the first month, every 4 weeks for the following 2 months and thereafter as appropriate. Fasting serum phosphate should also be measured 4 weeks after any dose adjustment. If fasting serum phosphate is within the reference range for age, the same dose should be maintained.

To reduce the risk for ectopic mineralisation, it is advised to target the fasting serum phosphate in the lower end of the normal reference range for age.

Vitamin D replacement or supplementation with inactive forms may be started or continued as per local guidelines under monitoring of serum calcium and phosphate.

Ectopic mineralisation

Ectopic mineralisation, as manifested by nephrocalcinosis has been observed in patients treated with oral phosphate and vitamin D analogues.

Monitoring for signs and symptoms of nephrocalcinosis, e.g. by renal ultrasonography, is recommended at the start of treatment and every 6 months for the first 12 months of treatment, and annually thereafter. Monitoring of plasma alkaline phosphatases, calcium, parathyroid hormone (PTH) and creatinine is recommended every 6 months (every 3 months for children aged 1 to 2 years) or as indicated. Monitoring of urine calcium and phosphate is suggested every 3 months.

Hyperphosphataemia

Due to the risk of hyperphosphataemia, fasting and post prandial serum phosphate levels should be periodically monitored. Dose interruption and/or reduction may be required.

Pregnancy and Lactation

Pregnancy

Burosumab is contraindicated during pregnancy.

The manufacturer does not recommend using burosumab during pregnancy and in women of childbearing potential not using contraception.

Animal studies have shown reproductive toxicity. At the time of writing there is no or limited published information regarding the use of burosumab in pregnancy. Potential risks are unknown.

Lactation

Burosumab is contraindicated in breastfeeding.

The manufacturer recommends that a decision should be made whether to discontinue breastfeeding or to discontinue/abstain from burosumab therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

At the time of writing there is limited published information regarding the excretion of burosumab in human milk. A risk to the newborns/infants cannot be excluded.

LactMed (2018) indicates that due to the high molecular weight of this agent, the amount present in milk is likely to be very low and absorption is unlikely because burosumab is probably destroyed in the infant's gastrointestinal tract.

Side Effects

Antibody formation
Bruising at injection site
Constipation
Cough
Decreased vitamin D
Dental decay
Dermatitis
Diarrhoea
Dizziness
Erythema at injection site
Extremity pain
Facial swelling
Haematoma (injection site)
Headache
Hyperphosphataemia
Hypersensitivity reactions
Injection site reactions
Localised urticaria
Myalgia
Nausea
Pain on injection
Pruritus
Pyrexia
Rash
Rash at injection site
Swelling (injection site)
Tooth abscess
Tooth ache
Tooth infection
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: February 2021.

Reference Sources

Summary of Product Characteristics: Crysvita 10mg solution for injection, Crysvita 20mg solution for injection, Crysvita 30mg solution for injection. Kyowa Kirin Limited. Revised August 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 February 2020.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Burosumab. Last revised: 03 December 2018.
Last accessed: 11 February 2020.