- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Parenteral formulations of inotersen.
Polyneuropathy in patients with hereditary transthyretin amyloidosis
Stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR).
284mg once a week.
Additional Dosage Information
Platelet count above 100 x 10 to the power of 9 per litre
284mg once a week. Monitor platelets every 2 weeks.
Platelet count between 75 and 100 x 10 to the power of 9 per litre
284mg once every 2 weeks. Monitor platelets once a week.
Platelet count between 50 and 75 x 10 to the power of 9 per litre
Interrupt treatment and monitor platelets twice a week until 3 successive values are above 75 x 10 to the power of 9 per litre, then monitor once a week. When 3 successive platelet counts are above 100 x 10 to the power of 9 per litre, resume treatment at 284mg every 2 weeks.
Platelet count between 25 and 50 x 10 to the power of 9 per litre
Interrupt treatment and monitor platelets twice a week until 3 successive values are above 75 x 10 to the power of 9 per litre, then monitor once a week. Consider monitoring more frequently if patient has additional risk factors for bleeding. When 3 successive platelet counts are above 100 x 10 to the power of 9 per litre, resume treatment at 284mg every 2 weeks. Consider corticosteroids if patient has additional risk factors for bleeding.
Platelet count below 25 x 10 to the power of 9 per litre
Discontinue treatment and administer corticosteroids. Monitor platelets daily until 2 successive platelet counts are above 25 x 10 to the power of 9 per litre, then twice a week until 3 successive values are above 75 x 10 to the power of 9 per litre. Then monitor weekly until stable.
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.
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
Renal impairment - eGFR below 45 ml/minute/1.73 m squared
Severe hepatic impairment
Precautions and Warnings
Females of childbearing potential
History of significant haemorrhage
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
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.
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.
Acute kidney injury
Development of neutralising antibodies
Discolouration (injection site)
Fatal intracranial haemorrhage
Increase in serum transaminases
Injection site reactions
Reduced platelet count
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 ).
Last Full Review Date: August 2021
Summary of Product Characteristics: Tegsedi 284mg solution for injection in pre-filled syringe. Akcea Therapeutics UK Ltd. Revised August 2021.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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