Drugs List

Therapeutic Indications

Uses

Paediatric-onset hypophosphatasia

Administration

To be administered as a subcutaneous injection only.

The maximum volume of medicinal product per injection should not exceed 1ml. If more than 1ml is required, multiple injections may be administered at the same time.

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

Patients can self-inject only if they have properly been trained on administration procedures.

Contraindications

Breastfeeding
Pregnancy

Precautions and Warnings

Adults aged 18 years and above
Hepatic impairment
Hyperparathyroidism
Raised intracranial pressure
Renal impairment

Supplements of calcium and vitamin D may be required
Treatment to be initiated and supervised by a specialist
Never rechallenge treatment after a severe hypersensitivity reaction
Record name and batch number of administered product
Rotate injection sites within a given area to avoid lipodystrophy
Monitor for hypersensitivity reactions - risk of severe reactions
Monitor for increased intracranial pressure regularly
Monitor ophthalmic function
Monitor parathyroid hormone levels
Monitor serum calcium levels
Perform periodic renal ultrasounds
Antibodies to ingredient may develop
May cause weight gain
May interfere with certain laboratory measurements
Discontinue if serious allergic or anaphylactic reaction occurs
Dietary restrictions should be maintained
Female: Ensure adequate contraception during treatment

Ophthalmic (conjunctival and corneal) calcification and nephrocalcinosis have been reported in patients with hypophosphatasia. There is insufficient data to establish a causal relationship between asfotase alfa and ectopic calcification. Periodic ophthalmology examination and renal ultrasounds are recommended.

Craniosynostosis and worsening of pre-existing craniosynostosis have been reported in hypophosphatasia patients less than 5 years of age. There is insufficient data to establish a causal relationship between asfotase alfa and progression of craniosynostosis. Craniosynostosis can lead to increased intracranial pressure. In patients under the age of 5 years with hypophosphatasia, periodic monitoring (including fundoscopy or signs of papilloedema) and prompt intervention for increased intracranial pressure is recommended.

Consider pre-medication for patients with a history of reactions to asfotase alfa.

There have been no adverse reactions related to anti-asfotase alfa antibody status in clinical trials.

Patients confirmed positive for antibodies have not shown signs of hypersensitivity or tachyphylaxis with asfotase alfa administration.

Asfotase alfa has been shown to interfere with routine measurement of serum alkaline phosphatase used in laboratory assays. The laboratory should be informed and alternative assays considered.

Pregnancy and Lactation

Pregnancy

Asfotase alfa is contraindicated during pregnancy.

The manufacturer recommends that asfotase alfa should not be used during pregnancy and in women of childbearing potential not using contraception.

At the time of writing there is limited published data regarding the use of asfotase alfa in pregnancy. Following repeated subcutaneous administration to pregnant mice in the therapeutic dose range (greater than 0.5mg/kg), asfotase alfa levels were quantifiable in foetuses at all doses tested, suggesting cross-placental transport of asfotase alfa. Animal studies are insufficient with respect to reproductive toxicity. The potential risk is unknown.

Lactation

Asfotase alfa is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding should be discontinued during treatment with asfotase alfa. At the time of writing there is limited published data regarding the excretion of asfotase alfa in human milk. A risk to the newborns/infants cannot be excluded.

Side Effects

Anaphylactoid reaction
Anaphylaxis
Antibody formation
Bruising
Cellulitis (injection site)
Chills
Contusion
Cough
Discolouration (injection site)
Erythema
Erythema at injection site
Haematoma (injection site)
Haemorrhage (injection site)
Headache
Heat and redness (injection site)
Hot flushes
Hypersensitivity reactions
Hypocalcaemia
Induration (injection site)
Inflammation (injection site)
Injection site reactions
Irritability
Lipoatrophy at injection site
Lipodystrophy (injection site)
Lipohypertrophy
Myalgia
Nausea
Nephrolithiasis
Nodules (injection site)
Oral hypoaesthesia
Pain on injection
Painful extremities
Pruritus
Pyrexia
Rash at injection site
Scar
Skin discolouration
Skin disorder
Swelling (injection site)
Tachycardia
Vomiting

Presentation

Injections of asfotase alfa.

These products have been produced by recombinant DNA technology using Chinese Hamster Ovary (CHO) cell lines.

Drugs List

Therapeutic Indications

Uses

Paediatric-onset hypophosphatasia

Dosage

Adults

Children

Administration

To be administered as a subcutaneous injection only.

The maximum volume of medicinal product per injection should not exceed 1ml. If more than 1ml is required, multiple injections may be administered at the same time.

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

Patients can self-inject only if they have properly been trained on administration procedures.

Contraindications

Breastfeeding
Pregnancy

Precautions and Warnings

Adults aged 18 years and above
Hepatic impairment
Hyperparathyroidism
Raised intracranial pressure
Renal impairment

Supplements of calcium and vitamin D may be required
Treatment to be initiated and supervised by a specialist
Never rechallenge treatment after a severe hypersensitivity reaction
Record name and batch number of administered product
Rotate injection sites within a given area to avoid lipodystrophy
Monitor for hypersensitivity reactions - risk of severe reactions
Monitor for increased intracranial pressure regularly
Monitor ophthalmic function
Monitor parathyroid hormone levels
Monitor serum calcium levels
Perform periodic renal ultrasounds
Antibodies to ingredient may develop
May cause weight gain
May interfere with certain laboratory measurements
Discontinue if serious allergic or anaphylactic reaction occurs
Dietary restrictions should be maintained
Female: Ensure adequate contraception during treatment

Ophthalmic (conjunctival and corneal) calcification and nephrocalcinosis have been reported in patients with hypophosphatasia. There is insufficient data to establish a causal relationship between asfotase alfa and ectopic calcification. Periodic ophthalmology examination and renal ultrasounds are recommended.

Craniosynostosis and worsening of pre-existing craniosynostosis have been reported in hypophosphatasia patients less than 5 years of age. There is insufficient data to establish a causal relationship between asfotase alfa and progression of craniosynostosis. Craniosynostosis can lead to increased intracranial pressure. In patients under the age of 5 years with hypophosphatasia, periodic monitoring (including fundoscopy or signs of papilloedema) and prompt intervention for increased intracranial pressure is recommended.

Consider pre-medication for patients with a history of reactions to asfotase alfa.

There have been no adverse reactions related to anti-asfotase alfa antibody status in clinical trials.

Patients confirmed positive for antibodies have not shown signs of hypersensitivity or tachyphylaxis with asfotase alfa administration.

Asfotase alfa has been shown to interfere with routine measurement of serum alkaline phosphatase used in laboratory assays. The laboratory should be informed and alternative assays considered.

Pregnancy and Lactation

Pregnancy

Asfotase alfa is contraindicated during pregnancy.

The manufacturer recommends that asfotase alfa should not be used during pregnancy and in women of childbearing potential not using contraception.

At the time of writing there is limited published data regarding the use of asfotase alfa in pregnancy. Following repeated subcutaneous administration to pregnant mice in the therapeutic dose range (greater than 0.5mg/kg), asfotase alfa levels were quantifiable in foetuses at all doses tested, suggesting cross-placental transport of asfotase alfa. Animal studies are insufficient with respect to reproductive toxicity. The potential risk is unknown.

Lactation

Asfotase alfa is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding should be discontinued during treatment with asfotase alfa. At the time of writing there is limited published data regarding the excretion of asfotase alfa in human milk. A risk to the newborns/infants cannot be excluded.

Side Effects

Anaphylactoid reaction
Anaphylaxis
Antibody formation
Bruising
Cellulitis (injection site)
Chills
Contusion
Cough
Discolouration (injection site)
Erythema
Erythema at injection site
Haematoma (injection site)
Haemorrhage (injection site)
Headache
Heat and redness (injection site)
Hot flushes
Hypersensitivity reactions
Hypocalcaemia
Induration (injection site)
Inflammation (injection site)
Injection site reactions
Irritability
Lipoatrophy at injection site
Lipodystrophy (injection site)
Lipohypertrophy
Myalgia
Nausea
Nephrolithiasis
Nodules (injection site)
Oral hypoaesthesia
Pain on injection
Painful extremities
Pruritus
Pyrexia
Rash at injection site
Scar
Skin discolouration
Skin disorder
Swelling (injection site)
Tachycardia
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 2020

Reference Sources

Summary of Product Characteristics: Strensiq 40mg/ml solution for injection. Alexion Pharma UK Ltd. Revised April 2020.

Summary of Product Characteristics: Strensiq 100mg/ml solution for injection. Alexion Pharma UK Ltd. Revised April 2020.