Pralsetinib
GAVRETO
What it isAn oral selective RET receptor tyrosine kinase inhibitor active against oncogenic RET fusions and mutations.
Why this oneIt treats RET fusion-positive non-small cell lung cancer and RET-altered thyroid cancers, giving high response rates in a molecularly defined niche.
What limits itA boxed warning for serious and opportunistic infections, plus interstitial lung disease/pneumonitis, hypertension, and hemorrhage, constrain its use.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| RET fusion-positive NSCLC (metastatic) | Adults | 400 mg QD | 400 mg QD until progression/unacceptable toxicity | 400 mg QD |
| RET fusion-positive thyroid cancer | Adults and peds ≥12 yrs | 400 mg QD | 400 mg QD until progression/unacceptable toxicity | 400 mg QD |
Renal Undefined
Hepatic No adjustment needed
Instructions
- Confirm RET gene fusion before treatment
- Take on an empty stomach: no food ≥2 h before and ≥1 h after dose
- Missed dose: take same day, resume schedule next day; if vomiting after a dose, do not re-dose — take next scheduled dose
- Toxicity dose reductions: 300 → 200 → 100 mg QD; discontinue if 100 mg QD not tolerated
- Avoid CYP3A and/or P-gp inhibitors; if unavoidable reduce dose per label (e.g., 400→200 mg QD with combined P-gp + strong CYP3A inhibitor; 400→300 mg QD with strong/moderate CYP3A or P-gp inhibitor), resume prior dose 3-5 half-lives after inhibitor stops
- Avoid strong/moderate CYP3A inducers; if unavoidable increase dose from Day 7 of coadministration (e.g., 400→800 mg QD strong; 400→600 mg QD moderate), resume prior dose ≥14 days after inducer stops
- Hold ≥5 days before elective surgery; do not give for ≥2 weeks after major surgery and until adequate wound healing
Cautions
- Serious/opportunistic infections (boxed) — infections in 72% (7% fatal) in AcceleRET-Lung; monitor and treat; withhold/reduce/discontinue by severity
- ILD/pneumonitis (12%, can be fatal) — withhold and investigate new/worsening respiratory symptoms; permanently discontinue if recurrent or Grade 3-4
- Hypertension (35%; Grade 3 in 18%) — do not initiate with uncontrolled BP; optimize BP first; monitor at 1 week then at least monthly
- Hepatotoxicity — monitor AST/ALT at baseline, q2 weeks x3 months, then monthly
- Hemorrhagic events (Grade ≥3 in 4.1%) — permanently discontinue for severe/life-threatening hemorrhage
- Tumor lysis syndrome (reported in MTC) — monitor at-risk patients; consider hydration/prophylaxis
- Impaired wound healing (VEGF-pathway effect)
- Embryo-fetal toxicity — effective NON-hormonal contraception (may render hormonal contraceptives ineffective)
- Adolescents: monitor open growth plates; consider interruption/discontinuation for abnormalities
Adverse reactions
- Musculoskeletal pain
- Constipation
- Hypertension
- Diarrhea
- Fatigue
- Edema
- Pyrexia
- Cough
- Grade 3-4 labs: lymphopenia, neutropenia, anemia, thrombocytopenia, leukopenia; low phosphate/sodium/calcium/potassium; high AST/ALT/ALP/bilirubin/potassium
Pregnancy Can cause fetal harm (animal malformations/embryolethality below human exposure); verify pregnancy status before starting; non-hormonal contraception during and 2 weeks after (females); males with partners of reproductive potential: contraception during and 1 week after; may impair fertility
Lactation Do not breastfeed during treatment and for 1 week after last dose
⚠ BOXED WARNING
- Serious infections, including opportunistic infections
Principal riskBoxed warning: increased risk of serious bacterial, fungal, viral, and opportunistic infections that can lead to hospitalization or death (added 12/2025).
Cost, est. cash$5,000–$30,000+/month or cycle
Generic entry2039 est.
Classes and tags
Clinical profile
Legacy pregnancy categoryNot assigned — PLLR-era drug
Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.
Mechanism of action: Pralsetinib ballicule
