Drugs List

Therapeutic Indications

Uses

Polyneuropathy in patients with hereditary transthyretin amyloidosis

Stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR).

Administration

To be administered subcutaneously in the abdomen, upper thigh region, or outer area of the upper arm. Rotate injection sites.

Remove syringe from refrigerated storage at least 30 minutes prior to injection to ensure it reaches room temperature.

Contraindications

Children under 18 years
Platelet count below 100 x 10 to the power of 9 / L at baseline
Urine protein to creatinine ratio equal to or above 113mg/mmol at baseline
Vitamin A deficiency
Breastfeeding
Pregnancy
Renal impairment - eGFR below 45 ml/minute/1.73 m squared
Severe hepatic impairment

Precautions and Warnings

Elderly
Females of childbearing potential
History of significant haemorrhage
Liver transplant

Consider discontinuation if the patient is undergoing liver transplant
Consider use of corticosteroids if adverse reactions occur
Correct vitamin A deficiency before starting treatment
Treatment to be initiated and supervised by a specialist
Avoid injection into areas of active skin disease
Avoid injection into scar tissue
Exclude pregnancy prior to initiation of treatment
Monitor platelets before starting and during treatment
Monitor renal function before treatment and regularly during treatment
If visual disturbances occur, perform ophthalmic evaluation
Monitor hepatic enzymes
Advise on the need to report unusual bleeding
Consider suspending if eGFR falls by more than 30%
Discontinue if glomerulonephritis occurs
Pregnancy confirmed: Discontinue this medication
Suspend if urine protein to creatinine ratio equal to or above 226mg/mmol
Female: Ensure adequate contraception during treatment

Monitor urine protein to creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) at least every 3 months. More frequent monitoring should be considered based on patient history of chronic kidney disease and/or renal amyloidosis. Patients with UPCR twice the upper limit of normal or more, or an eGFR less than 60ml per minute, should be monitored every 4 weeks. Monitor UPCR and eGFR for 8 weeks following discontinuation.

Assess hepatic enzymes 4 months after initiation of treatment, and then annually thereafter, or as clinically indicated.

Monitor for signs and symptoms of transplant rejection during treatment.

Vitamin A supplementation (approximately 3000 units per day) is recommended to reduce the risk of ocular toxicity.

Pregnancy and Lactation

Pregnancy

Inotersen is contraindicated during pregnancy.

The manufacturer does not recommend the use of inotersen during pregnancy unless absolutely necessary. Due to inotersen's effect on vitamin A levels, there is a potential for teratogenic effects.

Patients planning a pregnancy should discontinue inotersen, and vitamin A levels should be monitored to ensure a normal range before attempting conception. Both too high and too low vitamin A levels may increase the risk of foetal malformation.

Lactation

Inotersen is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues inotersen or discontinues breastfeeding. It is not known if inotersen is excreted in human breast milk, but animal studies have shown excretion of inotersen metabolites.

Side Effects

Acute kidney injury
Anaemia
Chills
Contusion
Decreased appetite
Development of neutralising antibodies
Discolouration (injection site)
Eosinophilia
Fatal intracranial haemorrhage
Glomerulonephritis
Haematoma
Headache
Hypersensitivity reactions
Hypotension
Increase in serum transaminases
Influenza-like symptoms
Injection site reactions
Nausea
Orthostatic hypotension
Peripheral oedema
Proteinuria
Pruritus
Pyrexia
Rash
Reduced platelet count
Renal failure
Renal impairment
Swelling
Thrombocytopenia
Vomiting

Presentation

Parenteral formulations of inotersen.

Drugs List

Therapeutic Indications

Uses

Polyneuropathy in patients with hereditary transthyretin amyloidosis

Stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR).

Dosage

Adults

Additional Dosage Information

Administration

To be administered subcutaneously in the abdomen, upper thigh region, or outer area of the upper arm. Rotate injection sites.

Remove syringe from refrigerated storage at least 30 minutes prior to injection to ensure it reaches room temperature.

Contraindications

Children under 18 years
Platelet count below 100 x 10 to the power of 9 / L at baseline
Urine protein to creatinine ratio equal to or above 113mg/mmol at baseline
Vitamin A deficiency
Breastfeeding
Pregnancy
Renal impairment - eGFR below 45 ml/minute/1.73 m squared
Severe hepatic impairment

Precautions and Warnings

Elderly
Females of childbearing potential
History of significant haemorrhage
Liver transplant

Consider discontinuation if the patient is undergoing liver transplant
Consider use of corticosteroids if adverse reactions occur
Correct vitamin A deficiency before starting treatment
Treatment to be initiated and supervised by a specialist
Avoid injection into areas of active skin disease
Avoid injection into scar tissue
Exclude pregnancy prior to initiation of treatment
Monitor platelets before starting and during treatment
Monitor renal function before treatment and regularly during treatment
If visual disturbances occur, perform ophthalmic evaluation
Monitor hepatic enzymes
Advise on the need to report unusual bleeding
Consider suspending if eGFR falls by more than 30%
Discontinue if glomerulonephritis occurs
Pregnancy confirmed: Discontinue this medication
Suspend if urine protein to creatinine ratio equal to or above 226mg/mmol
Female: Ensure adequate contraception during treatment

Monitor urine protein to creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) at least every 3 months. More frequent monitoring should be considered based on patient history of chronic kidney disease and/or renal amyloidosis. Patients with UPCR twice the upper limit of normal or more, or an eGFR less than 60ml per minute, should be monitored every 4 weeks. Monitor UPCR and eGFR for 8 weeks following discontinuation.

Assess hepatic enzymes 4 months after initiation of treatment, and then annually thereafter, or as clinically indicated.

Monitor for signs and symptoms of transplant rejection during treatment.

Vitamin A supplementation (approximately 3000 units per day) is recommended to reduce the risk of ocular toxicity.

Pregnancy and Lactation

Pregnancy

Inotersen is contraindicated during pregnancy.

The manufacturer does not recommend the use of inotersen during pregnancy unless absolutely necessary. Due to inotersen's effect on vitamin A levels, there is a potential for teratogenic effects.

Patients planning a pregnancy should discontinue inotersen, and vitamin A levels should be monitored to ensure a normal range before attempting conception. Both too high and too low vitamin A levels may increase the risk of foetal malformation.

Lactation

Inotersen is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues inotersen or discontinues breastfeeding. It is not known if inotersen is excreted in human breast milk, but animal studies have shown excretion of inotersen metabolites.

Side Effects

Acute kidney injury
Anaemia
Chills
Contusion
Decreased appetite
Development of neutralising antibodies
Discolouration (injection site)
Eosinophilia
Fatal intracranial haemorrhage
Glomerulonephritis
Haematoma
Headache
Hypersensitivity reactions
Hypotension
Increase in serum transaminases
Influenza-like symptoms
Injection site reactions
Nausea
Orthostatic hypotension
Peripheral oedema
Proteinuria
Pruritus
Pyrexia
Rash
Reduced platelet count
Renal failure
Renal impairment
Swelling
Thrombocytopenia
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 2021

Reference Sources

Summary of Product Characteristics: Tegsedi 284mg solution for injection in pre-filled syringe. Akcea Therapeutics UK Ltd. Revised August 2021.