Medical Editor: John P. Cunha, DO, FACOEP
Lutathera (lutetium Lu 177 dotatate) Injection is a radiolabeled somatostatin analog indicated for the treatment of somatostatin receptor-positive gastro-enteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. Common side effects of Lutathera include low level of lymphocytes in the blood (lymphopenia), increased GGT, vomiting, nausea, increased AST, increased ALT, high blood sugar (hyperglycemia), low blood potassium (hypokalemia), fatigue, abdominal pain, diarrhea, decreased appetite, headache, dizziness, swelling or pain in extremities, flushing, back pain, anxiety, kidney failure, hair loss, high blood pressure (hypertension), cough, and constipation.
The dose of Lutathera is 7.4 GBq (200 mCi) administered every 8 weeks for a total of 4 doses. Lutathera may interact with somatostatin analogs. Tell your doctor all medications and supplements you use. Tell your doctor if you are pregnant or plan to become pregnant before using Lutathera; it may harm a fetus. Because of the potential risk for serious adverse reactions in breastfed infants, breastfeeding is not recommended while using Lutathera and for 2.5 months after the final dose.
Our Lutathera (lutetium Lu 177 dotatate) Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
The following serious adverse reactions are described elsewhere in the labeling.
- Myelosuppression [see WARNINGS AND PRECAUTIONS]
- Secondary Myelodysplastic Syndrome and Leukemia [see WARNINGS AND PRECAUTIONS]
- Renal Toxicity [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Neuroendocrine Hormonal Crisis [see WARNINGS AND PRECAUTIONS]
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 substudy 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].
The safety data described below are from NETTER-1, which randomized (1:1) patients with progressive, somatostatin receptor-positive midgut carcinoid tumors to receive 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]. 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. The median duration of follow-up was 24 months for patients receiving LUTATHERA with octreotide and 20 months for patients receiving high-dose octreotide.
Table 4 and Table 5 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 GGT (20%), vomiting (7%), nausea and elevated AST (5% each), and increased ALT, hyperglycemia and hypokalemia (4% each).
Table 4: Adverse Reactions Occurring in ≥ 5%
(All Grades) of Patients Receiving LUTATHERA with Octreotide in NETTER-11
|Adverse Reaction1||LUTATHERA and Long-Acting Octreotide (30 mg)
(N = 111)
|Long-Acting Octreotide (60 mg)
(N = 112)
|All Grades %||Grades 3-4 %||All Grades %||Grades 3-4 %|
|Metabolism and nutrition disorders|
|Musculoskeletal and connective tissue disorders|
|Pain in extremity||11||0||5||0|
|Nervous system disorders|
|Renal and urinary disorders|
|Radiation-related urinary tract toxicity**||8||0||3||0|
|Respiratory, thoracic and mediastinal disorders|
|Skin and subcutaneous tissue disorders|
|1National 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)]
*Includes the terms: Glomerular filtration rate decreased, acute kidney injury, acute prerenal failure, azotemia, renal disorder, renal failure, renal impairment
**Includes the terms: Dysuria, micturition urgency, nocturia, pollakiuria, renal colic, renal pain, urinary tract pain and urinary incontinence
Table 5: Laboratory Abnormalities Occurring in ≥
5% (All Grades) of Patients Receiving LUTATHERA with Octreotide in NETTER-1*1
|Laboratory Abnormality1||LUTATHERA and Long-Acting Octreotide (30 mg)
(N = 111)
|Long-Acting Octreotide (60 mg)
(N = 112)
|All grades %||Grade 3-4 %||All grades %||Grade 3-4 %|
|Alkaline phosphatase increased||65||5||54||9|
|Blood bilirubin increased||30||2||28||0|
|*Values are worst grade observed after randomization
1National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Only displays laboratory abnormalities occurring at a higher incidence in LUTATHERA-treated patients [between arm difference of ≥5% (all grades) or ≥2%(grades 3-4)]
Safety data are available from 1214 patients in ERASMUS, an international, single-institution, single-arm, open-label trial of patients with somatostatin receptor-positive tumors (neuroendocrine and other primaries). Patients received LUTATHERA 7.4 GBq (200 mCi) administered every 6 to 13 weeks with or without octreotide. Retrospective medical record review was conducted on a subset of 811 patients to document serious adverse reactions. Eighty-one (81%) percent of patients in the subset received a cumulative dose ≥ 22.2 GBq (≥ 600 mCi). With a median follow-up time of more than 4 years, the following rates of serious adverse reactions were reported: myelodysplastic syndrome (2%), acute leukemia (1%), renal failure (2%), hypotension (1%), cardiac failure (2%), myocardial infarction (1%), and neuroendocrine hormonal crisis (1%).
Read the entire FDA prescribing information for Lutathera (Lutetium Lu 177 dotatate Injection )