TABLE 2.

Guidelines for use of sirolimus in vascular anomalies

Oral sirolimus/rapamycin in head and neck vascular anomalies
Indications
KHE/TA complicated by Kasabach–Merritt phenomenon
Low‐flow vascular malformation: LM & VM
Exceptionally: IHs, High‐flow malformation
Prior therapy
Search for contraindication: active infections (teeth), cancer, anemia and/or leucopenia, liver insufficiency, peanut allergy (oral solution), pregnancy
Ensure that vaccinations are up‐to‐date
Do: Blood count with platelets, extensive coagulation workup, renal and hepatic functions, lipids and glycemia, and depending on the patient situation: beta‐hCG, HIV, and hepatitis serology, QuantiFERON (+ chest X‐ray)
Initiation and monitoring
Initial dose of 0.08 to 0.1 mg/kg/day or 1.6 mg/m2/day, one dose in adults and two doses in children at a fixed time
Residual concentration of sirolimus must be dosed after 2 weeks, then every month; threshold value of the residual concentration is estimated between 4 and 12 ng/ml
Monitor children monthly: clinical evaluation
Ensure a good tolerance of treatment every month: blood count, renal and hepatic functions, lipids and glycemia
In case of lymphopenia, Pneumocystis prophylaxis is advised
Warning: bioavailability of the product is low, and it interacts with many molecules (e.g., grapefruit juice, antifungals, clarithromycin, rifampicin)
Expected side effects
At each visit, patient should be educated concerning the risk of infections
Most common side effects: oral mucositis, acne, digestive disorders (abdominal pain, anorexia), headaches, and asthenia
Anemia with microcytosis, lymphopenia, hyperlipidemia, hyperglycemia
Rare cases of hypersensitivity pneumonitis, arterial hypertension, and induced lymphoedema

Abbreviations: Beta‐hCG, beta human chorionic gonadotropin; HIV, human immunodeficiency virus; IH, infantile hemangioma; KHE, kaposiform hemangioendothelioma; LM, lymphatic malformation; TA, tufted angioma; VM, venous malformation.