Important Safety Information

LUTATHERA^® 0.37 GBq/mL solution for infusion

Important note: Before prescribing, consult full prescribing information.

Presentation: One mL of solution contains 0.37 GBq of lutetium (177Lu) oxodotreotide at the date and time of calibration.

Indications: Lutathera is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Dosage and administration:

Adults: ♦The recommended treatment regimen of Lutathera in adults consists of 4 infusions of 7.4 GBq each. ♦For renal protection purpose, an amino acid solution must be initiated 30 minutes before administering Lutathera. The amino acid infusion should continue during, and for at least 3 hours after the Lutathera infusion. ♦Antiemetics should be administered prior to the amino acid solution.

Special populations: ♦Renal impairment: No dose adjustment is necessary in patients with creatinine clearance (CrCl) ≥40 mL/min. Patients with CrCl <40 mL/min should not be treated with Lutathera. ♦Hepatic impairment: Mild or moderate: No dose adjustment is necessary. Severe: careful benefit-risk assessment. ♦Geriatrics (≥65 years): No dose adjustment is required. ♦Pediatrics (≤18 years): Safety and efficacy have not been established.

Contraindications:

♦Established or suspected pregnancy or when pregnancy has not been excluded.

Warnings and precautions:

♦Radiation exposure: Lutathera contributes to a patient’s overall long-term radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Radiation exposure should be minimized to patients, medical personnel, and household contacts after treatment for at least 7 days. ♦Hematological toxicity: Hematological evaluation of patients must be performed at baseline and prior to every dose. Treatment initiation in patients with severely impaired hematological function at baseline is not recommended. ♦Secondary myelodysplastic syndrome (MDS) and leukemia: Late onset MDS and acute leukaemia have been reported after treatment with Lutathera. ♦Renal toxicity: Renal dysfunction can develop during and after treatment with Lutathera. Cases were reported following several years of treatment. Concurrent administration of amino acid solution is recommended, to help decrease in the radiation exposure to the kidneys. Treatment with Lutathera in patients with baseline CrCl <40 mL/min is not recommended. More frequent monitoring of renal function is recommended in renally impaired patients with CrCl>40 mL/min. For patients with CrCl <50mL/min, a increased risk for transient hyperkalemia due to the amino acid solution should also be taken into consideration. ♦Hepatobiliary toxicity: Patients with baseline liver impairment should only be treated with Lutathera after careful benefit-risk assessment. ♦Endocrine and metabolism: Patients should be monitored for signs and symptoms of tumor-related hormonal release. Somatostatin analogs, fluids, corticosteroids, and electrolytes should be administered as clinically indicated. Overnight hospitalization of patients should be considered in some cases for observation (e.g. patients with poor pharmacologic control of symptoms).

Warnings and precautions regarding the renal protective amino acid solution:

♦Hyperkalemia: Serum potassium levels must be tested before each treatment with amino acid solutions. In case of hyperkalemia, patient’s history of hyperkalemia and concomitant medication should be checked, and hyperkalemia should be corrected accordingly before starting the infusion. A second monitoring is recommended prior to the amino acid infusion, to confirm the hyperkalaemia has been successfully corrected. The patient should be monitored closely for signs and symptoms of hyperkalemia. An ECG should be performed prior to patient discharge. ♦Heart failure: Care should be taken with use of arginine and lysine in patients with severe heart failure. In patients with severe heart failure, should only be treated after careful benefit-risk assessment. ♦Metabolic acidosis: Metabolic acidosis has been observed with complex amino-acid solutions administered as part of total parenteral nutrition (TPN) protocols.

Pregnancy, lactation, females and males of reproductive potential

♦Pregnancy: Lutathera, being a radiopharmaceutical, has the potential to cause fetal harm. ♦Lactation: Women receiving Lutathera should not breastfeed. If Lutathera treatment is started during breastfeeding, breastfeeding should be discontinued. ♦Females and males of reproductive potential: ♦Pregnancy testing: The pregnancy status should be verified prior to initiating treatment with Lutathera. ♦Contraception: Females of reproductive potential should use effective contraception during treatment and for 6 months following the last dose of Lutathera. Males with female partners of reproductive potential should use effective contraception during and for 4 months following the last dose of Lutathera. ♦Infertility: Ionizing radiations of lutetium (177Lu) oxodotreotide may cause temporary infertility in males and females.

Adverse drug reactions:

Very common (≥10%): Thrombocytopenia, lymphopenia, anaemia, pancytopenia, decreased appetite, nausea, vomiting, fatigue.

Common (≥1 to <10%): Refractory cytopenia with multilineage dysplasia (myelodysplastic syndrome), leukopenia, neutropenia, secondary hypothyroidism, hyperglycaemia, dehydration, hypomagnesaemia, hyponatremia, sleep disorders, dizziness, dysgeusia, headache, lethargy, syncope, electrocardiogram QT prolonged, hypertension, flushing, hot flush, hypotension, dyspnoea, abdominal distension, diarrhoea, abdominal pain, constipation, abdominal pain upper, dyspepsia, gastritis, hyperbilirubinaemia, alopecia, musculoskeletal pain, muscle spasms, acute kidney injury, haematuria, renal failure, proteinuria, injection site reaction, oedema peripheral, administration site pain, chills, influenza like illness, blood creatinine increased, GGT increased, ALT increased, AST increased, blood ALP increased, transfusion.

Uncommon (≥0.1 to <1%): Conjunctivitis, respiratory tract infection, cystitis, pneumonia, herpes zoster, ophthalmic herpes zoster, influenza, staphylococcal infections, streptococcal bacteraemia, acute myeloid leukaemia, acute leukaemia, chronic myelomonocytic leukaemia, refractory cytopenia with unilineage dysplasia, nephrogenic anaemia, bone marrow failure, thrombocytopenic purpura, hypersensitivity, hypothyroidism, diabetes mellitus, carcinoid crisis, hyperparathyroidism, hypoglycaemia, hypernatraemia, hypophosphataemia, tumour lysis syndrome, hypercalcaemia, hypocalcaemia, hypoalbuminaemia, metabolic acidosis, anxiety, hallucination, disorientation, formication, hepatic encephalopathy, paraesthesia, parosmia, somnolence, spinal cord compression, eye disorders, vertigo, atrial fibrillation, palpitations, myocardial infarction, angina pectoris, cardiogenic shock, vasodilatation, peripheral coldness, pallor, orthostatic hypotension, phlebitis, oropharyngeal pain, pleural effusion, sputum increased, chocking sensation, dry mouth, flatulence, ascities, gastrointestinal pain, stomatitis, haematochezia, abdominal discomfort, intestinal obstruction, colitis, pancreatitis acute, rectal haemorrhage, melaena, abdominal pain lower, haematemesis, haemorrhagic ascites, ileus, pancreatic enzymes decreased, hepatocellular injury, cholestasis, hepatic congestion, hepatic failure, rash, dry skin, swelling face, hyperhidrosis, pruritus generalised, leukocyturia, urinary incontinence, glomerular filtration rate decreased, renal disorder, acute prerenal failure, renal impairment, injection site mass, chest discomfort, chest pain, pyrexia, malaise, pain, death, feeling abnormal, blood potassium decreased, blood urea increased, glycosylated haemoglobin increased, haematocrit decreased, protein urine, weight decreased, blood creatine phosphokinase increased, blood lactate dehydrogenase increased, blood catecholamines, C-reactive protein increased, clavicle fracture, abdominal cavity drainage, dialysis, gastrointestinal tube insertion, stent placement, abscess drainage, bone marrow harvest, polypectomy, physical ability.

Interactions:

♦Long-acting somatostatin analogs should be discontinued at least 4 weeks prior to the administration of Lutathera. Short-acting somatostatin analogs should be administered as needed and should be discontinued at least 24 hours prior to Lutathera administration. ♦Repeated administration of high-doses of glucocorticosteroids should be avoided during treatment with Lutathera. Patients with a history of chronic use of glucocorticosteroids should be carefully evaluated for sufficient somatostatin receptor expression.

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