REVTORPYK gedatolisib 180 mg Injection, Powder, For Solution, 1 vial
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
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🧪 Inactive Ingredients / Excipients
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780 mg
UNII 1I96OHX6EK
A cyclic carbohydrate derived from plant starch that acts as a solubilizer and stabilizer. It helps dissolve poorly water-soluble drugs and protects active ingredients from degradation in the formulation.
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48.6 mg
UNII 33X04XA5AT
Lactic acid is a naturally occurring organic acid derived from milk or plant sources. It lowers and maintains pH in formulations, helps preserve the product, and can enhance ingredient stability and absorption.
2 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Revtorpyk 180 mgthis 84577-0751-01 | Celcuity | 1 vial | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Jul 14, 2031 |
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🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 84577-0751-01 You're viewing this | 1 VIAL, GLASS in 1 CARTON (84577-751-01) / 1 INJECTION, POWDER, FOR SOLUTION in 1 VIAL, GLASS | 2026-07-14 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE REVTORPYK is indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting [see Dosage and Administration (2.1) and Clinical Studies (14) ] . REVTORPYK is a kinase inhibitor indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting.
(1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended dosage : 180 mg intravenously as a 30-minute infusion once weekly on Days 1, 8, and 15 of a 28-day cycle ( 2.2 ) Prophylactically initiate steroid-containing alcohol-free mouthwash to reduce the incidence and severity of stomatitis. ( 2.3 ) See Full Prescribing Information for dosage modifications due to adverse reactions. ( 2.4 ) See Full Prescribing Information for instructions on preparation and administration.
( 2.5 )
2.1Patient Selection Select patients for treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer with REVTORPYK based on the absence of detected PIK3CA mutations in breast cancer [see Clinical Studies (14) ] . An FDA-authorized test for the determination of PIK3CA mutation status in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer is not available.
2.2Recommended Dosage and Administration The recommended dosage of REVTORPYK is 180 mg as an intravenous infusion over 30 minutes once weekly on Days 1, 8, and 15 of every 28-day cycle, in combination with fulvestrant, with or without palbociclib, until disease progression or unacceptable toxicity. If a planned dose is delayed or missed, administer as soon as possible thereafter. Do not wait until the next planned dose in the cycle.
Adjust the timing of the subsequent dose to maintain the 3 weeks on followed by 1 week off schedule. Refer to the Prescribing Information for fulvestrant and palbociclib administered in combination with REVTORPYK for additional dosing information.
2.3Stomatitis Prophylaxis Initiate steroid-containing alcohol-free mouthwash when starting REVTORPYK. Continue to administer steroid-containing alcohol-free mouthwash 4 times daily for the first 8 weeks of treatment and longer if needed [see Warnings and Precautions (5.1) and Patient Counseling Information (17) ] .
2.4Dosage Modifications for Adverse Reactions The recommended dosage reduction levels for adverse reactions are listed in Table 1. Table 1: Recommended Dosage Reductions of REVTORPYK for Adverse Reactions Dose Reductions Recommended Dose First 150 mg Second 130 mg Permanently discontinue REVTORPYK in patients who are unable to tolerate 130 mg intravenously once weekly on Days 1, 8, and 15 of every 28-day cycle. The recommended dosage modifications for adverse reactions are described in Table 2.
Table 2: Recommended Dosage Modifications of REVTORPYK for Adverse Reactions Abbreviations: FBG, fasting blood glucose; FPG, fasting plasma glucose; ULN, upper limit of normal. Adverse Reaction Severity Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dosage Modification Stomatitis [see Warnings and Precautions (5.1) ] Grade 3 Withhold REVTORPYK until recovery to Grade ≤2.
Resume at next lower dose. Grade 4 Permanently discontinue REVTORPYK. Hematologic Toxicities [see Adverse Reactions (6.1) ] Grade 4 Withhold REVTORPYK until recovery to Grade ≤2.
Resume at next lower dose. Dermatologic Adverse Reactions [see Warnings and Precautions (5.2) ] Grade 3 rash (both maculopapular and acneiform) Withhold REVTORPYK until recovery to Grade ≤1. Resume at next lower dose.
For recurrent Grade 3, permanently discontinue REVTORPYK. Grade 4 rash (acneiform) Permanently discontinue REVTORPYK. Any Grade of Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) or other SJS/TEN-like severe skin reactions Permanently discontinue REVTORPYK.
Hyperglycemia (Fasting Glucose [FG]) [see Warnings and Precautions (5.3) ] FG levels (FPG or FBG) > ULN-160 mg/dL (>ULN-8.9 mmol/L) No adjustment of REVTORPYK required. Initiate dietary modifications and ensure adequate hydration. Consider initiating or intensifying oral anti-hyperglycemic treatment as clinically indicated.
FG levels 161-250 mg/dL (9-13.9 mmol/L) No adjustment of REVTORPYK required. Initiate dietary modifications, ensure adequate hydration, and consider initiat…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS REVTORPYK is supplied as a sterile, white to off-white lyophilized powder for injection containing 180 mg gedatolisib in a single-dose vial for reconstitution and further dilution. For Injection:180 mg gedatolisib in a lyophilized powder in a single-dose vial. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Stomatitis: REVTORPYK can cause severe stomatitis, including mouth ulcers. Initiate steroid-containing alcohol-free mouthwash prior to starting treatment. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity.
( 2.3 , 2.4 , 5.1 ) Dermatologic Adverse Reactions: REVTORPYK can cause severe rash. Monitor patients for rash and infectious sequelae. Instruct patients to limit sun exposure during REVTORPYK treatment.
Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity. ( 2.4 , 5.2 ) Hyperglycemia: REVTORPYK can cause severe hyperglycemia. Evaluate blood glucose levels and hemoglobin A1c prior to starting and at regular intervals during treatment.
Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity. ( 2.4 , 5.3 ) Embryo-Fetal Toxicity: REVTORPYK can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
Refer to the Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information. ( 5.4 , 8.1 , 8.3 )
5.1Stomatitis REVTORPYK can cause severe stomatitis, including ulcers and oral mucositis. In Study 1 of VIKTORIA-1, stomatitis occurred in 72% of patients treated with REVTORPYK with fulvestrant and palbociclib, including Grade 3 events in 22% of patients. Prophylactic steroid-containing alcohol-free mouthwash was required for a minimum of 8 weeks.
The median time to onset was 7 days (range: 1 to 457 days). Stomatitis led to REVTORPYK dose reduction in 19% and permanent discontinuation in 3.8% of patients. Stomatitis occurred in 58% of patients treated with REVTORPYK with fulvestrant, including Grade 3 events in 12% of patients.
The median time to onset was 4 days (range: 1 to 524 days). Stomatitis led to REVTORPYK dose reduction in 9% and permanent discontinuation in 1.5% of patients. Prophylactically initiate steroid-containing alcohol-free mouthwash to reduce the incidence and severity of stomatitis [see Dosage and Administration (2.3) ] .
If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity [see Dosage and Administration (2.4) ] .
5.2Dermatologic Adverse Reactions REVTORPYK can cause severe rash. In Study 1 of VIKTORIA-1, rash occurred in 30% of patients treated with REVTORPYK in combination with fulvestrant and palbociclib, including Grade 3 events in 6% of patients. The median time to onset was 21 days (range: 3 to 260 days) after starting REVTORPYK.
Rash led to REVTORPYK dose reduction in 5% and permanent discontinuation in 0.8% of patients. Rash occurred in 40% of patients treated with REVTORPYK in combination with fulvestrant, including Grade 3 events in 5% of patients. Rash led to REVTORPYK dose reduction in 6% and permanent discontinuation in 0.8% of patients.
The median time to onset was 31.5 days (range: 2 to 407 days) after starting REVTORPYK. Monitor patients receiving REVTORPYK for rash and infectious sequelae. Instruct patients to limit sun exposure during REVTORPYK treatment.
Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity [see Dosage and Administration (2.4) ] .
5.3Hyperglycemia Severe hyperglycemia can occur in patients treated with REVTORPYK. Hyperglycemia is associated with drugs that inhibit the PI3K/AKT/mTOR pathway. In Study 1 of VIKTORIA-1, increased fasting glucose (FG) from baseline occurred in 46% of patients treated with REVTORPYK in combination with fulvestrant and palbociclib, including Grade 1 (FG >ULN to 160 mg/dL) in 36% of patients, Grade 2 (FG >160 to 250 mg/dL) in 8% of patients and Grade 3 (FG >250 to 500 mg/dL) in 0.9% of patients.
Increased fasting glucose from baseline occurred in 57% of patients treated with REVTORPYK in combination with fulvestrant, including Grade 1 in 44% of patients, Grade 2 in 11% of patients and Grade 3 in 1.8% of pati…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Stomatitis [see Warnings and Precautions (5.1) ] Dermatologic adverse reactions [see Warnings and Precautions (5.2) ] Hyperglycemia [see Warnings and Precautions (5.3) ] The most common (≥20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant and palbociclib were decreased white blood cells, decreased neutrophils, decreased hemoglobin, decreased lymphocytes, stomatitis, nausea, decreased platelets, increased fasting glucose, fatigue, vomiting, rash, constipation, diarrhea, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), musculoskeletal pain, decreased sodium, and increased eosinophils.
( 6.1 ) The most common (≥20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant were stomatitis, increased fasting glucose, increased eosinophils, decreased hemoglobin, nausea, rash, increased ALT, fatigue, musculoskeletal pain, decreased lymphocytes, vomiting, increased AST, pruritus, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Celcuity Inc. at 1-877-4-CELCUITY (1-877-423-5284) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of REVTORPYK was evaluated in 383 adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a detectable PIK3CA mutation in Study 1 of VIKTORIA-1 [see Clinical Studies (14) ] .
Patients received either Arm A: REVTORPYK 180 mg intravenously once weekly for 3 weeks on followed by 1 week off (Days 1, 8, 15 for each 28-day cycle) in combination with fulvestrant 500 mg intramuscularly on cycle 1 Days 1 and 15, and then at Day 1 of each subsequent 28-day cycle and palbociclib 125 mg orally once daily for 21 days followed by 7 days off treatment for each 28-day cycle (n = 130); or Arm B: REVTORPYK in combination with fulvestrant (n = 130); or Arm C: fulvestrant alone (n = 123). The dose, route of administration, and frequency of each drug in Arms B and C were the same as Arm A.
The median duration of exposure for REVTORPYK plus fulvestrant and palbociclib was 6.2 months (range: 0.5 to 25 months) and 5.7 months (range: 0 to 26 months) for REVTORPYK plus fulvestrant. REVTORPYK in Combination with Fulvestrant and Palbociclib Serious adverse reactions occurred in 25% of patients who received REVTORPYK in combination with fulvestrant and palbociclib. Serious adverse reactions in ≥1% of patients included pneumonia (3.8%), thrombosis (3.8%), and stomatitis (1.5%).
Fatal adverse reactions occurred in 2.3% of patients who received REVTORPYK in combination with fulvestrant and palbociclib, including (0.8% each) pneumonia, multiorgan failure, and hepatic failure. Permanent discontinuation of REVTORPYK due to an adverse reaction occurred in 12% of patients receiving REVTORPYK in combination with fulvestrant and palbociclib. Adverse reactions that resulted in permanent discontinuation of REVTORPYK were stomatitis, nausea, rash, pneumonitis, diplopia, hypertension, vomiting, breast ulceration, and squamous cell carcinoma of the lung.
Dosage interruptions of REVTORPYK due to an adverse reaction occurred in 64% of patients receiving REVTORPYK in combination with fulvestrant and palbociclib. Adverse reactions which required dosage interruption of REVTORPYK in ≥2% of patients included neutropenia, stomatitis, decreased neutrophil count, fatigue, anemia, leukopenia, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), pyrexia, rash, thrombosis, pneumonia, diarrhea, hyperglycemia, thrombocytopenia, upper…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary REVTORPYK is used in combination with fulvestrant, with or without palbociclib. Refer to the Prescribing Information for fulvestrant and palbociclib for pregnancy information. When used in combination with REVTORPYK, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.
Based on its mechanism of action, REVTORPYK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data in pregnant women to inform the drug-associated risk. Animal reproductive toxicity studies have not been conducted with REVTORPYK.
Inhibition of PI3K and mTOR pathways have been associated with adverse embryo-fetal growth and lethality in animals ( see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data PIK3CA knockout mice experienced developmental delay at embryonic day 9.5 and mortality between embryonic day 9.5 and 10.5. mTOR knockout mice experienced early lethality by embryonic day 7.5.
In both animal models, early embryonic death was a result of impaired cell proliferation and structural development.
8.2Lactation Risk Summary REVTORPYK is used in combination with fulvestrant, with or without palbociclib. Refer to the Prescribing Information for fulvestrant and palbociclib for lactation information. When used in combination with REVTORPYK, advise patients to not breastfeed during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.
There are no data on the presence of gedatolisib or its metabolites in human milk, its effects on milk production, or a breastfed child. Because of the potential for serious adverse reactions in a breastfed child, advise lactating women to not breastfeed during treatment with REVTORPYK and for 2 weeks after the last dose.
8.3Females and Males of Reproductive Potential REVTORPYK is used in combination with fulvestrant, with or without palbociclib. Refer to the Prescribing Information for fulvestrant and palbociclib for contraception and infertility information. When used in combination with REVTORPYK, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.
Based on its mechanism of action, REVTORPYK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with REVTORPYK. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose.
Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose. Infertility Based on animal studies, REVTORPYK may impair fertility in females and males of reproductive potential. Findings in animals were reversible [see Nonclinical Toxicology (13.1) ] .
8.4Pediatric Use The safety and efficacy of REVTORPYK in pediatric patients have not been established.
8.5Geriatric Use Of 260 patients who received REVTORPYK, 55 patients (21%) were ≥65 and <75 years of age and 17 patients (6.5%) were ≥75 years of age [see Clinical Studies (14) ] . In patients treated with REVTORPYK in combination with fulvestrant and palbociclib, the incidence of Grade ≥3 stomatitis and rash was higher in patients ≥65 years of age (37% and 11%, respectively) compared to younger patients (16% and 4.3%, respectively).…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary REVTORPYK is used in combination with fulvestrant, with or without palbociclib. Refer to the Prescribing Information for fulvestrant and palbociclib for pregnancy information. When used in combination with REVTORPYK, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.
Based on its mechanism of action, REVTORPYK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data in pregnant women to inform the drug-associated risk. Animal reproductive toxicity studies have not been conducted with REVTORPYK.
Inhibition of PI3K and mTOR pathways have been associated with adverse embryo-fetal growth and lethality in animals ( see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data PIK3CA knockout mice experienced developmental delay at embryonic day 9.5 and mortality between embryonic day 9.5 and 10.5. mTOR knockout mice experienced early lethality by embryonic day 7.5.
In both animal models, early embryonic death was a result of impaired cell proliferation and structural development.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and efficacy of REVTORPYK in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of 260 patients who received REVTORPYK, 55 patients (21%) were ≥65 and <75 years of age and 17 patients (6.5%) were ≥75 years of age [see Clinical Studies (14) ] . In patients treated with REVTORPYK in combination with fulvestrant and palbociclib, the incidence of Grade ≥3 stomatitis and rash was higher in patients ≥65 years of age (37% and 11%, respectively) compared to younger patients (16% and 4.3%, respectively). In patients treated with REVTORPYK in combination with fulvestrant, the incidence of Grade ≥3 stomatitis and rash was higher in patients ≥65 years of age (18% and 12%, respectively) compared to younger patients (10% and 3.1%, respectively).
No overall differences in effectiveness of REVTORPYK were observed between patients ≥65 years of age and younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Gedatolisib is a kinase inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2, resulting in downstream inhibition of multiple effectors, including AKT. In estrogen receptor (ER)-positive breast cancer cell lines and xenograft models harboring wild-type or mutant PIK3CA , gedatolisib induced apoptosis and anti-proliferative effects in vitro and reduced tumor cell growth in vivo . In a human ER-positive breast cancer xenograft model harboring a PIK3CA mutation, the combination of gedatolisib with palbociclib and fulvestrant increased tumor growth inhibition compared to each treatment alone or the doublet combinations.
12.2Pharmacodynamics Exposure-Response Relationships The exposure-response relationship and time course of pharmacodynamic response for the effectiveness of gedatolisib have not been fully characterized. An increased incidence of stomatitis or mucositis (Grade 3 and 4), nausea, vomiting, hyperglycemia, and adverse reaction leading to dosage modification or discontinuation was observed with higher gedatolisib exposure at the dose range of 10 mg to 319 mg (0.06 to 1.8 times the approved recommended dose). Cardiac Electrophysiology At weekly doses up to 319 mg (1.8 times the recommended dose), clinically significant QTc interval prolongation was not observed.
12.3Pharmacokinetics Gedatolisib pharmacokinetic parameters were observed at the approved recommended dosage in patients with breast cancer and are presented as mean (% coefficient of variation [%CV]), unless otherwise specified. Gedatolisib maximum plasma concentration (C max ) is 13,700 (29%) ng/mL and area under the curve (AUC) is 21,400 (21%) ng·h/mL. Gedatolisib C max and AUC values increase dose proportionally in the dose range 10 mg to 319 mg (0.06 to 1.8 times the recommended dose).
No accumulation of gedatolisib is observed after once-weekly administration. Distribution Gedatolisib plasma protein binding is 98%, and is not concentration dependent, in vitro. Gedatolisib blood-to-plasma ratio is 0.87, in vitro.
Gedatolisib volume of distribution is 393 L. Elimination Gedatolisib elimination half-life (t 1/2 ) is 36 hours with an estimated clearance of 8 (23%) L/hour. Excretion After a single dose of radiolabeled gedatolisib 89 mg to healthy subjects, approximately 67.4% of the dose was recovered in feces (67% unchanged) and 12.2% in urine (11.6% unchanged).
Specific Populations No clinically significant effects on the pharmacokinetics of gedatolisib were observed based on age (21 to 84 years), sex, race (White [78%], Asian [9.1%], Black or African American [4.1%]) body weight (35 to 168 kg), mild hepatic impairment (total bilirubin ≤1.5 × ULN and any AST) or estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m 2 (MDRD equation). The effect of moderate (total bilirubin >1.5 to 3 times ULN with any AST) or severe (total bilirubin >3 x ULN with any AST) hepatic impairment, eGFR <45 mL/min/1.73 m 2 , or dialysis on gedatolisib pharmacokinetics is unknown.
Drug Interactions Clinical Studies and Model-Informed Approaches No clinically significant differences in the pharmacokinetics of the following drugs were observed when used concomitantly with gedatolisib: metformin (MATE1, MATE2-K, and OCT1 substrate), rosuvastatin (BCRP substrate), or repaglinide (CYP2C8 sensitive substrate). In Vitro Studies CYP450 Enzymes: Gedatolisib is not an inhibitor of CYP1A2, CYP2A6, or CYP2B6. The ability of gedatolisib to induce CYP450 enzymes is unknown given the results of the vitro studies were inconclusive due to decreased viability of hepatocytes.
Transporter Systems: Gedatolisib is a substrate of P-gp and BCRP and is not a substrate for OATP1B1, OATP1B3, OCT1, NTCP, MRP2, or MRP3. Gedatolisib did not inhibit P-gp, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, and BSEP.
🧬 Mechanism of Action ▾
12.1Mechanism of Action Gedatolisib is a kinase inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2, resulting in downstream inhibition of multiple effectors, including AKT. In estrogen receptor (ER)-positive breast cancer cell lines and xenograft models harboring wild-type or mutant PIK3CA , gedatolisib induced apoptosis and anti-proliferative effects in vitro and reduced tumor cell growth in vivo . In a human ER-positive breast cancer xenograft model harboring a PIK3CA mutation, the combination of gedatolisib with palbociclib and fulvestrant increased tumor growth inhibition compared to each treatment alone or the doublet combinations.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied REVTORPYK for injection is a white to off-white lyophilized powder supplied as: Carton Content NDC One 180 mg single-dose vial NDC 84577-751-01 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted 15°C to 30°C (59°F to 86°F). Store vial in original carton until time of reconstitution.
📋 Description ▾
11 DESCRIPTION REVTORPYK for injection contains gedatolisib, a kinase inhibitor. The chemical name of gedatolisib is 1-[4-(4-dimethylaminopiperidine-1-carbonyl)phenyl]-3-[4-(4,6-dimorpholin-4-yl-[1,3,5]triazin2-yl)phenyl]urea. The molecular formula for gedatolisib is C 32 H 41 N 9 O 4 and the molecular weight is 615.74 g/mol.
Gedatolisib is a white to off-white crystalline solid that is insoluble in water. The chemical structure of gedatolisib is shown below: REVTORPYK for injection is a sterile, preservative-free, lyophilized white to off-white cake or powder with cake supplied in a single-dose vial. Each vial delivers 180 mg of gedatolisib.
The lyophilized powder also contains 720 mg of hydroxypropyl β cyclodextrin and 48.6 mg of lactic acid and may include hydrochloric acid and/or sodium hydroxide for pH adjustment. Chemical structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Stomatitis Inform patients of the risk of stomatitis. Advise patients to contact their healthcare provider if they experience any symptoms (e.g., painful redness, swelling, or sores in the mouth).
Inform patients to use steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct patients not to eat or drink for at least 1 hour after administration of the steroid-containing mouthwash [see Warnings and Precautions (5.1) ] . Dermatologic Adverse Reactions Inform patients of the risks of dermatologic adverse reactions, including rash.
Advise patients to limit sun exposure during treatment. Advise patients to contact their healthcare provider immediately if they develop a new rash [see Warnings and Precautions (5.2) ] . Hyperglycemia Inform patients of the risks of hyperglycemia and the need for monitoring of fasting blood glucose and HbA1c periodically during treatment.
Advise patients to contact their healthcare provider immediately for signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often, blurred vision, confusion, difficulty breathing, or increased appetite with weight loss) [see Warnings and Precautions (5.3) ] . Embryo-Fetal Toxicity Inform pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ] .
Advise females of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose [see Use in Specific Populations (8.3) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose [see Use in Specific Populations (8.3) ] . Refer to the Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information.
When used in combination with REVTORPYK, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products. Lactation Advise women not to breastfeed during treatment with REVTORPYK and for 2 weeks after the last dose [see Use in Specific Populations (8.2) ] . Refer to the Prescribing Information of palbociclib and fulvestrant for lactation information.
When used in combination, advise patients not to breastfeed during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products. Infertility Advise females and males of reproductive potential that REVTORPYK may impair fertility [see Use in Specific Populations (8.3) ] . Refer to the Prescribing Information of palbociclib and fulvestrant for infertility information.
This product's labeling may have been updated. For full prescribing information, please visit www.celcuity.com . Manufactured for: Celcuity Inc.
2800 Campus Dr, Suite 140 Minneapolis, MN 55441