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Antisense oligonucleotide (apoC-III) Pregnancy: There are no data on the use of volanesorsen in pregnant women; animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid use during pregnancy. Breast-feeding: milk levels were very low in lactating mice and systemic exposure from nursing is considered unlikely because of poor oral bioavailability, but it is unknown whether volanesorsen or its metabolites are excreted in human milk and a risk to the newborn infant cannot be excluded — decide whether to discontinue breast-feeding or therapy. Fertility: no human data; volanesorsen had no effect on fertility in mice.

Volanesorsen

Brand names: Waylivra

Volanesorsen is an antisense oligonucleotide used as an adjunct to diet in adults with familial chylomicronaemia syndrome who are at high risk of pancreatitis. It is given by subcutaneous injection to lower very high triglyceride levels.

Adult dose

Dose: Familial chylomicronaemia syndrome (FCS): 285 mg in 1.5 mL by subcutaneous injection once weekly for 3 months, then reduce the dose frequency to 285 mg every 2 weeks
Route: Subcutaneous injection only — must not be given intramuscularly or intravenously. Rotate injection sites: abdomen, upper thigh region, or outer area of the upper arm (an upper-arm injection should be given by another person). Avoid the waistline and other sites subject to pressure or rubbing from clothing, and do not inject into tattoos, moles, birthmarks, bruises, rashes, or skin that is tender, red, hard, bruised, damaged, burned or inflamed.
Frequency: Once weekly for the first 3 months, then every 2 weeks. Patients should inject on the same day of the week.
Max: 285 mg once weekly — the highest labelled dose frequency. After 6 months of treatment, an increase of dose frequency back to 285 mg weekly should be considered if the triglyceride response has been inadequate as evaluated by the supervising experienced specialist AND platelet counts are in the normal range; patients should be re-downtitrated to 285 mg every 2 weeks if the weekly dose does not provide significant additional triglyceride reduction after 9 months.
Treatment should be initiated by, and remain under the supervision of, a physician experienced in treating patients with FCS. Before initiating, exclude or appropriately address secondary causes of hypertriglyceridaemia (e.g. uncontrolled diabetes, hypothyroidism). STOPPING RULE: discontinue in patients with a reduction in serum triglycerides of less than 25%, or who fail to achieve serum triglycerides below 22.6 mmol/L, after 3 months on volanesorsen 285 mg weekly. MISSED DOSE: if noticed within 48 hours, give the missed dose as soon as possible; if not noticed within 48 hours, skip it and give the next planned injection. PLATELETS AND DOSE ADJUSTMENT (SPC Table 1) — measure platelet count before initiation; if it is below 140 x 10^9/L, repeat approximately a week later, and if it remains below 140 x 10^9/L do not initiate. After starting, monitor platelets at least every two weeks. Platelets 140 x 10^9/L or above (normal): starting dose weekly, after 3 months every 2 weeks, monitoring every 2 weeks. Platelets 100-139: dose every 2 weeks, monitor weekly. Platelets 75-99: pause treatment for at least 4 weeks and resume after platelets are 100 x 10^9/L or above, monitor weekly. Platelets 50-74: pause treatment for at least 4 weeks and resume after platelets are 100 x 10^9/L or above, monitor every 2-3 days. Platelets below 50: discontinue treatment, glucocorticoids recommended, monitor daily, and consult a haematologist to reconsider the benefit/risk of any further treatment. For any patient paused or discontinued for severe thrombocytopenia, carefully consider the benefits and risks of returning to treatment once the platelet count is 100 x 10^9/L or above; for discontinued patients consult a haematologist before resuming. SPECIAL POPULATIONS: elderly — no starting dose adjustment, but limited clinical data in patients aged 65 and over; renal impairment — no starting dose adjustment in mild to moderate impairment, safety and efficacy not established in severe impairment (observe closely); hepatic impairment — not studied, but dose adjustment is unlikely to be required as the product is not metabolised by cytochrome P450. PAEDIATRIC: safety and efficacy in children and adolescents below 18 years have not been established and no data are available — verify any under-18 use against a children's formulary. ADMINISTRATION: the first injection by the patient or caregiver should be performed under the guidance of an appropriately qualified healthcare professional; allow the pre-filled syringe to reach room temperature by removing it from refrigerated storage (2 to 8 degrees C) at least 30 minutes before use and do not use other warming methods; each syringe is single use; do not inject if the solution is cloudy or contains visible particles; a large air bubble is normal and should not be removed. ⚠ SOURCE COMPLETENESS: section 4.2 was retrieved complete and is the basis of the dosing above; sections 4.4 and 4.8 are truncated at the source-fetch limit, so the warnings and adverse-reaction lists are partial. Source product: Waylivra 285 mg solution for injection in pre-filled syringe (UK SPC).

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
  • Chronic or unexplained thrombocytopenia
  • Do not initiate treatment in patients with thrombocytopenia (platelet count below 140 x 10^9/L)

Side effects

  • Platelet count decreased (29% of patients in the pivotal studies) and thrombocytopenia (21%)
  • Injection site reactions (82% of patients) — including injection site erythema, pain, swelling, discolouration, induration, pruritus and bruising (very common)
  • Immune thrombocytopenic purpura, spontaneous haematoma, leukopenia, lymphopenia, eosinophilia (common)
  • Headache (very common); dizziness, tremor, syncope, presyncope, hypoaesthesia, retinal migraine (common)
  • Hypersensitivity, immunisation reaction and serum sickness-like reaction (common)
  • Nausea, diarrhoea, vomiting, abdominal pain and distension, gingival bleeding, mouth haemorrhage (common)
  • Erythema, pruritus, rash, urticaria, petechiae, ecchymosis (common)
  • Myalgia, arthralgia, pain in extremity, arthritis, musculoskeletal and back pain (common)
  • Haematuria and proteinuria (common)
  • Hypertension, haemorrhage, haematoma, hot flush (common)
  • Dyspnoea, pharyngeal oedema, wheezing, epistaxis, cough, nasal congestion (common)
  • Diabetes mellitus, insomnia, chills, pyrexia, asthenia, fatigue, malaise, oedema (common)

Interactions

  • Antiplatelet medicinal products, NSAIDs and anticoagulants — discontinuation should be considered at platelet levels below 75 x 10^9/L, and treatment with these medicines must be discontinued at platelet levels below 50 x 10^9/L

Monitoring

  • Measure platelet count before initiation; if below 140 x 10^9/L repeat approximately a week later, and do not initiate if it remains below 140 x 10^9/L
  • After starting treatment, monitor platelet levels at least every two weeks, adjusting treatment and monitoring frequency per SPC Table 1
  • Patients with lower body weight (less than 70 kg) may be more prone to thrombocytopenia
  • Instruct patients to report immediately any signs of bleeding — petechiae, spontaneous bruising, subconjunctival bleeding, nosebleeds, bleeding gums, blood in stools, unusually heavy menstrual bleeding, neck stiffness, atypical severe headache or any prolonged bleeding
  • Monitor for nephrotoxicity by routine urine dipstick quarterly; if positive, perform a broader assessment including serum creatinine and a 24-hour collection to quantify proteinuria and assess creatinine clearance. Discontinue if proteinuria is 500 mg/24 hours or more, if serum creatinine rises by 0.3 mg/dL (26.5 micromol/L) or more above the upper limit of normal, or if CKD-EPI creatinine clearance is 30 mL/min/1.73 m2 or below
  • Monitor serum liver enzymes and bilirubin quarterly. Discontinue for a single increase in ALT or AST above 8 x ULN, an increase above 5 x ULN persisting for 2 weeks or more, or lesser ALT/AST increases associated with total bilirubin above 2 x ULN or INR above 1.5
  • LDL-C levels may rise during treatment but usually remain within the normal range

Clinical monograph

How it works

It is an antisense oligonucleotide that binds apolipoprotein C-III messenger RNA, reducing its translation; lowering apoC-III decreases plasma triglycerides through clearance pathways that are partly independent of lipoprotein lipase.

Prescribing in practice

  • It commonly causes thrombocytopenia, which can be severe, so platelet counts must be monitored regularly before and throughout treatment, with treatment adjusted or stopped according to the count.
  • Injection-site reactions are very common, and bleeding events can occur in association with low platelets.
  • Renal function and the development of antibodies should be considered, and it is used under specialist lipid supervision in a confirmed diagnosis.

Monitoring

Monitor platelet counts regularly, together with serum triglycerides, liver and renal function, and observe for injection-site reactions and any signs of bleeding.

Counselling the patient

  • Regular blood tests are essential to check your platelet count during treatment.
  • Report any unusual bruising, bleeding, or a rash of small red or purple spots straight away.
  • Continue your prescribed low-fat diet, as this remains central to managing the condition.

Evidence & guidelines

Triglyceride-lowering efficacy in familial chylomicronaemia syndrome was shown in a randomised placebo-controlled trial supporting its approval for this rare condition.

Reference: NICE TA784; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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