Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Akcea Therapeutics Ireland Ltd., St. James House, 72 Adelaide Road, Dublin 2, D02 Y017, Ireland
Waylivra is indicated as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome (FCS) and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate.
Treatment should be initiated by and remain under the supervision of a physician experienced in the treatment of patients with FCS. Prior to initiating Waylivra, secondary causes of hypertriglyceridemia (e.g. uncontrolled diabetes, hypothyroidism) should be excluded or appropriately addressed.
The recommended starting dose is 285 mg in 1.5 ml injected subcutaneously once weekly for 3 months. Following 3 months, dose frequency should be reduced to 285 mg every 2 weeks.
However, treatment should be discontinued in patients with a reduction in serum triglycerides <25% or who fail to achieve serum triglycerides below 22.6 mmol/L after 3 months on volanesorsen 285 mg weekly.
After 6 months of treatment with volanesorsen, increase of dose frequency to 285 mg weekly should be considered if response has been inadequate in terms of serum triglyceride reduction as evaluated by the supervising experienced specialist and in the condition that platelet counts are in the normal range. Patients should be re-downtitrated to 285 mg every 2 weeks if the higher 285 mg once weekly dose does not provide significant additional triglyceride reduction after 9 months.
Patients should be instructed to give the injection on the same day of the week, according to medically determined frequency of administration.
If a dose is missed and noticed within 48 hours, the patient should be directed to give the missed dose as soon as possible. If not noticed within 48 hours, then the missed dose should be skipped and the next planned injection given.
Before initiation of treatment, platelet count should be measured. If the platelet count is below 140 × 109/L another measurement should be taken approximately a week later to reassess. If platelet count remains below 140 × 109/L upon a second measurement, Waylivra should not be initiated (see section 4.3).
After commencing treatment, patients should have platelet levels monitored at least every two weeks, depending on the platelet levels.
Treatment and monitoring should be adjusted according to laboratory values in line with Table 1.
For any patient dose paused or discontinued due to severe thrombocytopenia, the benefits and risks of returning to treatment once platelet count ≥100 × 109/L should be carefully considered. For discontinued patients, a haematologist should be consulted prior to resuming treatment.
Table 1. Waylivra monitoring and treatment recommendations:
| Platelet Count (x 109/l) | Dose (285 mg prefilled syringe) | Monitoring Frequency |
|---|---|---|
| Normal (≥140) | Starting dose: Weekly After 3 months: Every 2 weeks | Every 2 weeks |
| 100 to 139 | Every 2 weeks | Weekly |
| 75 to 99 | Pause treatment for ≥4 weeks and resume treatment after platelet levels ≥100 × 109/L | Weekly |
| 50 to 74a | Pause treatment for ≥4 weeks and resume treatment after platelet levels ≥100 × 109/L | Every 2-3 days |
| Less than 50a,b | Discontinue treatment Glucocorticoids recommended | Daily |
a See section 4.4 for recommendations regarding use of antiplatelet agents/NSAIDs/anticoagulants
b Consultation of a haematologist is needed to reconsider the benefit/risk for possible further treatment with volanesorsen.
No starting dose adjustment is necessary for elderly patients. There is limited clinical data for patients aged 65 and over (see sections 5.1 and 5.2).
No starting dose adjustment is necessary in patients with mild to moderate renal impairment. The safety and efficacy in patients with severe renal impairment has not been established and these patients should be closely observed.
This medicinal product has not been studied in patients with hepatic impairment. The medicinal product is not metabolised via the cytochrome P450 enzyme system in the liver, therefore dose adjustment is unlikely to be required in patients with hepatic impairment.
The safety and efficacy of this medicinal product in children and adolescents below 18 years of age have not yet been established. No data are available.
This medicinal product is intended for subcutaneous use only. Do not administer intramuscularly or intravenously.
Each pre-filled syringe is for single use only.
Waylivra should be inspected visually prior to administration. The solution should be clear and colourless to slightly yellow. If the solution is cloudy or contains visible particulate matter, the contents must not be injected and the medicinal product should be returned to the pharmacy.
The first injection administered by the patient or caregiver should be performed under the guidance of an appropriately qualified health care professional. Patients and/or caregivers should be trained in the administration of this medicinal product in accordance with the patient information leaflet.
The pre-filled syringe should be allowed to reach room temperature prior to injection. It should be removed from refrigerated storage (2° to 8°C) at least 30 minutes before use. Other warming methods should not be used. It is normal to see a large air bubble. Do not attempt to remove the air bubble.
It is important to rotate sites for injection. Sites for injection include the abdomen, upper thigh region, or outer area of the upper arm. If injected in the upper arm, the injection should be administered by another person. Injection should be avoided at the waistline and other sites where pressure or rubbing may occur from clothing. This medicinal product should not be injected into tattoos, moles, birthmarks, bruises, rashes, or areas where the skin is tender, red, hard, bruised, damaged, burned, or inflamed.
There is no clinical experience with overdose of this medicinal product. In the case of overdose, patients should be carefully observed and supportive care administered, as appropriate. Symptoms of overdose are expected to be limited to constitutional symptoms and injection site reactions.
Haemodialysis is unlikely to be beneficial given that volanesorsen is rapidly distributed into cells.
5 years.
This medicinal product can be removed from refrigeration and stored, in the original carton, at room temperature (below 30°C) for up to 6 weeks. In this 6-week period, it can be kept as needed between refrigerated and room temperature (up to 30°C). This medicinal product must be discarded immediately if not used within the 6 weeks after the first time it is removed from refrigerated storage.
Store in a refrigerator (2°-8°C).
Do not freeze.
Store in the original carton in order to protect from light.
Single-dose, Type I glass pre-filled syringe with a siliconised chlorobutyl rubber stopper and staked needle with shield, filled to deliver 1.5 ml of solution.
Pack sizes of one pre-filled syringe or multipacks containing 4 (4 packs of 1) pre-filled syringes.
Not all pack sizes may be marketed.
This medicinal product should be inspected visually prior to administration. The solution should be clear and colourless to slightly yellow. If the solution is cloudy or contains visible particulate matter, the contents must not be injected and the medicinal product should be returned to the pharmacy. Use each pre-filled syringe only once and then place in a sharps disposal container for disposal according to community guidelines.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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