mTOR Inhibitor Pregnancy: Contraindicated — embryotoxic; effective contraception required during and for 8 weeks after treatment

Everolimus (RCC)

Brand names: Afinitor

Adult dose

Dose: 10 mg once daily continuously

Route: Oral

Frequency: Once daily (with or without food — consistent timing)

Max: 10 mg/day

mRCC after VEGFR-TKI failure; pNET; tuberous sclerosis complex (TSC) — angiomyolipoma, SEGA; avoid strong CYP3A4 inhibitors; take same time each day; swallow whole

Paediatric dose

Dose: TSC indications: 4.5 mg/m² once daily titrated to target trough 5–15 ng/mL mg/m²/kg

Route: Oral

Frequency: Once daily

Max: 10 mg/day

Licensed for TSC-associated SEGA ≥1 year; TSC-related renal angiomyolipoma ≥18 years

Dose adjustments

Renal

No dose adjustment required

Hepatic

Mild: no adjustment; moderate (Child-Pugh B): reduce to 5 mg; severe (Child-Pugh C): avoid

Paediatric weight-based calculator

Patient weight (kg)

Licensed for TSC-associated SEGA ≥1 year; TSC-related renal angiomyolipoma ≥18 years

Clinical pearls

RECORD-1 trial (Motzer et al. NEJM 2008): everolimus vs placebo in mRCC after VEGFR-TKI failure — PFS 4.0 vs 1.9 months; established everolimus as standard second-line; now largely replaced by cabozantinib/nivolumab which show superior outcomes post-TKI
Non-infectious pneumonitis: class effect of mTOR inhibitors — occurs in up to 14%; ranges from asymptomatic radiological infiltrates to life-threatening respiratory failure; CT shows ground-glass opacities; bronchoscopy with BAL to exclude infection; treat with corticosteroids if symptomatic grade ≥2
Stomatitis/oral ulcers: common and distressing — topical steroid mouthwash (dexamethasone 0.5 mg/5 mL) significantly reduces severity vs standard mouthwash; prophylactic use from cycle 1 is recommended in some centres (SWISH trial)
Tuberous sclerosis complex (TSC): everolimus is disease-modifying — mTOR is constitutively activated in TSC due to TSC1/2 mutations; everolimus shrinks TSC-related angiomyolipomas, SEGAs, and pulmonary lymphangioleiomyomatosis; therapeutic drug monitoring (trough 5-15 ng/mL) guided dosing in TSC
Drug interactions are clinically critical: CYP3A4 inhibitors (including grapefruit juice) can increase everolimus trough 3-4×; clarithromycin prescribed for stomatitis treatment is itself a strong CYP3A4 inhibitor — use azithromycin instead

Contraindications

Known hypersensitivity to everolimus, sirolimus, or excipients
Uncontrolled infections

Side effects

Non-infectious pneumonitis (class effect — up to 14%; monitor)
Stomatitis/mouth ulcers
Infections (PCP, aspergillosis)
Hyperglycaemia
Dyslipidaemia (triglycerides, cholesterol)
Anaemia
Fatigue
Wound healing impairment

Interactions

Strong CYP3A4/P-gp inhibitors (itraconazole, clarithromycin, ritonavir) — markedly increase everolimus levels; avoid or reduce dose to 2.5 mg
Strong CYP3A4 inducers (rifampicin) — reduce levels; increase to 20 mg
ACE inhibitors — additive angioedema risk

Monitoring

Chest imaging (CT) at baseline and if respiratory symptoms
Fasting glucose and lipids (each cycle)
FBC, LFTs, creatinine
Stomatitis assessment (each visit)
Drug level monitoring (TSC indications)

Reference: BNFc; BNF 90; RECORD-1 trial (Motzer et al. NEJM 2008); SWISH trial (stomatitis); EXIST-2 trial (TSC-AML); MHRA SPC Afinitor; NICE TA432; EAU RCC Guidelines 2024. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Drugs

Pathways