Lutetium Lu 177 Dotatate
FDA Drug Information • Also known as: Lutathera
- Brand Names
- Lutathera
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Lutetium Lu 177 dotatate is a radiolabeled somatostatin analog. The drug substance lutetium Lu 177 dotatate is a cyclic peptide linked with the covalently bound chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to a radionuclide. Lutetium Lu 177 dotatate is described as lutetium (Lu 177)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl) acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic (2-7) disulfide. The molecular weight is 1609.6 Daltons and the structural formula is as follows: LUTATHERA (lutetium Lu 177 dotatate) 370 MBq/mL (10 mCi/mL) Injection is a sterile, clear, colorless to slightly yellow solution for intravenous use. Each single-dose vial contains acetic acid (0.48 mg/mL), sodium acetate (0.66 mg/mL), gentisic acid (0.63 mg/mL), sodium hydroxide (0.64 mg/mL), ascorbic acid (2.8 mg/mL), diethylene triamine pentaacetic acid (0.05 mg/mL), sodium chloride (6.85 mg/mL), and Water for Injection (ad 1 mL). The pH range of the solution is 4.5 to 6. Lutetium Lu 177 dotatate structural formula 11.1 Physical Characteristics Lutetium-177 decays to stable hafnium-177 with a half-life of 6.647 days, by emitting beta-minus radiation with a maximum energy of 0.498 MeV (79%) and photonic radiation (γ) of 0.208 MeV (11%) and 0.113 MeV (6.2%). The main radiations of lutetium-177 are detailed in Table 7. Table 7. Lutetium-177 Main Radiations Radiation Energy (keV) Iβ - % Iγ% β - 176.5 12.2 β - 248.1 0.05 β - 384.9 9.1 β - 497.8 78.6 γ 71.6 0.15 γ 112.9 6.20 γ 136.7 0.05 γ 208.4 11.0 γ 249.7 0.21 γ 321.3 0.22 11.2 External Radiation Table 8 summarizes the radioactive decay properties of lutetium-177. Table 8. Physical Decay Chart: Lutetium-177 Physical Half-Life = 6.647 Days Hours Fraction remaining Hours Fraction remaining 0 1.000 48 (2 days) 0.812 1 0.996 72 (3 days) 0.731 2 0.991 168 (7 days) 0.482 5 0.979 336 (14 days) 0.232 10 0.958 720 (30 days) 0.044 24 (1 day)...
What Is Lutetium Lu 177 Dotatate Used For?
1 INDICATIONS AND USAGE LUTATHERA is indicated for the treatment of adult and pediatric patients 12 years and older with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors. LUTATHERA is a radiolabeled somatostatin analog indicated for the treatment of adult and pediatric patients 12 years and older with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Verify pregnancy status of females of reproductive potential prior to initiating LUTATHERA. ( 2.1 ) Administer 7.4 GBq (200 mCi) every 8 weeks (± 1 week) for a total of 4 doses. ( 2.2 ) Administer long-acting octreotide 30 mg intramuscularly 4 to 24 hours after each LUTATHERA dose and short-acting octreotide for symptomatic management. ( 2.3 ) Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing LUTATHERA until disease progression or for 18 months following treatment initiation. ( 2.3 ) Administer antiemetics before recommended amino acid solution. ( 2.3 ) Initiate recommended intravenous amino acid solution 30 minutes before LUTATHERA infusion; continue during and for at least 3 hours after LUTATHERA infusion. Do not decrease dose of amino acid solution if LUTATHERA dose is reduced. ( 2.3 ) 2.1 Important Safety Instructions LUTATHERA is a radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions ( 5.1 )] . Use waterproof gloves and effective radiation shielding when handling LUTATHERA. Radiopharmaceuticals, including LUTATHERA, should be used by or under the control of healthcare providers who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals. Verify pregnancy status of females of reproductive potential prior to initiating LUTATHERA [see Use in Specific Populations ( 8.1 , 8.3 )] . Monitor patients closely for signs and symptoms of hypersensitivity reactions during and following the LUTATHERA administration for a minimum of 2 hours in a setting where cardiopulmonary resuscitation medication and equipment are available [see Warnings and Precautions ( 5.6 )] . 2.2 Recommended Dosage The recommended LUTATHERA dosage for adult and pediatric patients 12 years and older is 7.4 GBq (200 mCi) every 8 weeks (± 1 week) for a total of 4 doses. Administer premedications and concomitant medications as recommended [see Dosage and Administration ( 2.3 )] . 2.3 Premedications and Concomitant Medications Somatostatin Analogs Before initiating LUTATHERA treatment: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) at least 4 weeks prior to initiating LUTATHERA. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating LUTATHERA [see Drug Interactions ( 7.1 )] . During LUTATHERA treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each LUTATHERA dose. Do not administer long-acting octreotide within 4 weeks prior to each subsequent LUTATHERA dose. Short-acting octreotide may be given for symptomatic management during LUTATHERA treatment but must be withheld at least 24 hours before each LUTATHERA dose. Following LUTATHERA treatment: Continue...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions ( 5.2 )] Secondary Myelodysplastic Syndrome and Leukemia [see Warnings and Precautions ( 5.3 )] Renal Toxicity [see Warnings and Precautions ( 5.4 )] Hepatotoxicity [see Warnings and Precautions ( 5.5 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] Neuroendocrine Hormonal Crisis [see Warnings and Precautions ( 5.7 )] Most common Grade 3-4 adverse reactions (≥ 4% with a higher incidence in LUTATHERA arm) are lymphopenia, increased GGT, vomiting, nausea, increased AST, increased ALT, hyperglycemia and hypokalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical 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 data in WARNINGS AND PRECAUTIONS reflect exposure to LUTATHERA in 111 patients with advanced, progressive midgut neuroendocrine tumors (NETTER-1). Safety data in WARNINGS AND PRECAUTIONS were also obtained in an additional 22 patients in a non-randomized pharmacokinetic sub-study of NETTER-1 and in a subset of patients (811 of 1214) with advanced somatostatin receptor-positive tumors enrolled in ERASMUS [see Warnings and Precautions ( 5 )] . Adult Population NETTER-1 The safety data of LUTATHERA with octreotide was evaluated in NETTER-1 [see Clinical Studies ( 14.1 )] . Patients with progressive, somatostatin receptor-positive midgut carcinoid tumors received LUTATHERA 7.4 GBq (200 mCi) administered every 8 to 16 weeks concurrently with the recommended amino acid solution and with long-acting octreotide (30 mg administered by intramuscular injection within 24 hours of each LUTATHERA dose) (N = 111), or high-dose octreotide (defined as long-acting octreotide 60 mg by intramuscular injection every 4 weeks) (N = 112) [see Clinical Studies ( 14.1 )] . Among patients receiving LUTATHERA with octreotide, 79% received a cumulative dose > 22.2 GBq (> 600 mCi) and 76% of patients received all four planned doses. Six percent (6%) of patients required a dose reduction and 13% of patients discontinued LUTATHERA. Five patients discontinued LUTATHERA for renal-related events and 4 discontinued for hematological toxicities. Table 5 and Table 6 summarize the incidence of adverse reactions and laboratory abnormalities, respectively. The most common Grade 3-4 adverse reactions occurring with a greater frequency among patients receiving LUTATHERA with octreotide compared to patients receiving high-dose octreotide include: lymphopenia (44%), increased gamma-glutamyltransferase (GGT) (20%), vomiting (7%), nausea and increased aspartate aminotransferase (AST) (5% each), and increased alanine aminotransferase (ALT), hyperglycemia and hypokalemia (4% each). Table 5. Adverse Reactions Occurring at Higher Incidence in Patients Receiving LUTATHERA with Long-Acting Octreotide Compared to High-Dose Long-Acting Octreotide (Between Arm Difference of ≥ 5% All Grades or ≥ 2% Grades 3-4) a a National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Only displays adverse reactions occurring at a higher incidence in LUTATHERA-treated patients [between arm difference of ≥ 5% (all Grades) or ≥ 2% (Grades 3-4)]. b Includes the terms: Glomerular filtration rate decreased, acute kidney injury, acute prerenal failure, azotemia, renal disorder, renal failure, renal impairment. c Includes the terms: Dysuria, micturition urgency, nocturia, pollakiuria, renal colic, renal pain, urinary tract pain and urinary incontinence. Adverse reaction a LUTATHERA with long-acting Octreotide (30 mg) (N = 111)...
Drug Interactions
7 DRUG INTERACTIONS Somatostatin Analogs : Discontinue long-acting analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to each LUTATHERA dose. ( 2.3 , 7.1 ) 7.1 Somatostatin Analogs Somatostatin and its analogs competitively bind to somatostatin receptors and may interfere with the efficacy of LUTATHERA. Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to each LUTATHERA dose. Administer short- and long-acting octreotide during LUTATHERA treatment as recommended [see Dosage and Administration ( 2.3 )] . 7.2 Glucocorticoids Glucocorticoids can induce down-regulation of subtype 2 somatostatin receptors (SSTR2). Avoid repeated administration of high doses of glucocorticoids during treatment with LUTATHERA.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on its mechanism of action, LUTATHERA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on LUTATHERA use in pregnant women. No animal studies using lutetium Lu 177 dotatate have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, radioactive emissions, including those from LUTATHERA, can cause fetal harm. Advise pregnant women of the potential risk to a fetus. 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING LUTATHERA Injection containing 370 MBq/mL (10 mCi/mL) of lutetium Lu 177 dotatate is a sterile, preservative-free and clear, colorless to slightly yellow solution for intravenous use supplied in a clear, colorless Type I glass 30 mL single-dose vial containing 7.4 GBq (200 mCi) ± 10% of lutetium Lu 177 dotatate at the time of injection (NDC# 69488-003-01). The solution volume in the vial ranges between 20.5 to 25 mL to provide a total of 7.4 GBq (200 mCi) of radioactivity. The product vial is enclosed within a lead shielded container (NDC# 69488-003-01) placed in a plastic sealed container. The product is shipped in a Type A package. Store below 25°C (77°F). Do not freeze LUTATHERA. Store in the original package to protect from ionizing radiation (lead shielding). The shelf life is 72 hours from the date and time of calibration. Discard appropriately at 72 hours. Lutetium-177 for LUTATHERA may be prepared using two different sources of stable nuclides (either lutetium-176 or ytterbium-176) resulting in different waste management. Consult the documentation provided before using LUTATHERA to ensure appropriate waste management.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.