QUADRAMET

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QUADRAMET

Classes

Other Therapeutic Radiopharmaceuticals

Administration

Hazardous Drugs Classification
Lutetium Lu 177 dotatate is a radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure. Store in original packaging to protect from ionizing radiation (lead shielding).
Use waterproof gloves and effective radiation shielding when handling lutetium Lu 177 dotatate.
Lutetium Lu 177 dotatate should be used by or under the control of physicians 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.
Emetic Risk
Moderate
Administer antiemetics before initiating the recommended amino acid solution infusion 30 minutes prior to each lutetium Lu 177 dotatate dose.

Injectable Administration Intravenous Administration

Do not inject lutetium Lu 177 dotatate directly into any other intravenous solution.
Premedicate against hypersensitivity reactions in those patients with a history of grade 1 or 2 hypersensitivity reactions to lutetium Lu 177; do not rechallenge patients with a history of grade 3 or 4 hypersensitivity reactions.
Administer antiemetics before the start of the recommended amino acid solution infusion.
Initiate a sterile IV amino acid solution infusion 30 minutes before the start of a lutetium Lu 177 dotatate infusion, using either a three-way valve with the same venous access as lutetium Lu 177 dotatate, or through a separate venous access in the patient's other arm. Continue the amino acid infusion during and for at least 3 hours after completion of the lutetium Lu 177 dotatate infusion.
Lutetium Lu 177 dotatate may be infused using the gravity method, peristaltic pump method, or syringe pump method; do not administer as an IV bolus.
Use the peristaltic pump method or the syringe method when administering a reduced dose of lutetium Lu 177 dotatate due to an adverse reaction. When using the gravity method for a reduced dose, adjust the lutetium Lu 177 dotatate dose before administration to avoid delivery of an incorrect volume.
 
Amino Acid Solution Specifications:
L-lysine HCl content: between 18 and 25 g (equivalent to 14.4 to 20 g L-lysine).
L-arginine HCl content: between 18 and 25 g (equivalent to 14.9 to 20.7 g L-arginine).
Volume: 1 to 2 L.
Osmolality: less than 1,200 mOsmol/kg.
 
Preparation:
Use aseptic technique and radiation shielding during handling and administration of lutetium Lu 177 dotatate. Use tongs when handling vial to minimize radiation exposure.
Inspect the product visually for particulate matter and discoloration prior to administration under a shielded screen. Discard vial if particulates or discoloration are present.
Confirm the amount of radioactivity of lutetium Lu 177 dotatate to be delivered to the patient with an appropriate dose calibrator prior to (and after) each administration. The shelf-life is 72 hours from the date and time of calibration.
 
Intravenous infusion, gravity method:
Infuse lutetium Lu 177 dotatate directly from the original container.
Insert a 2.5 cm, 20 gauge needle (short needle) into the lutetium Lu 177 dotatate vial; ensure the needle does not touch the lutetium Lu 177 dotatate solution in th vial. Do not connect this short needle directly to the patient.
Via catheter, connect the lutetium Lu 177 dotatate vial to 500 mL 0.9% Sodium Chloride Injection (used to transport the lutetium Lu 177 dotatate solution during the infusion). Do not allow the 0.9% Sodium Chloride Injection to flow into the lutetium Lu 177 dotatate vial prior to the initiation of the infusion, and do not inject lutetium Lu 177 dotatate directly into the 0.9% Sodium Chloride Injection solution.
Insert a second needle that is 9 cm, 18 gauge (long needle) into the lutetium Lu 177 dotatate vial. This long needle should touch and be secured to the bottom of the lutetium Lu 177 dotatate vial during the entire infusion. Connect the long needle to the patient by an IV catheter that is prefilled with 0.9% sterile sodium chloride.
Use a clamp or infusion pump to regulate the flow of the 0.9% Sodium Chloride Injection solution via the short needle into the lutetium Lu 177 dotatate vial at 50 mL/hour to 100 mL/hour for 5 to 10 minutes; then increase the rate to 200 mL/hour to 300 mL/hour for an additional 25 to 30 minutes (the 0.9% Sodium Chloride Injection solution entering the vial through the short needle will carry the lutetium Lu 177 dotatate from the vial to the patient via the catheter connected to the long needle over a total duration of 30 to 40 minutes).
During the infusion, ensure that the level of 0.9% Sodium Chloride Injection in the lutetium Lu 177 dotatate vial remains constant.
Disconnect the vial from the long needle line and clamp the saline line once the level of radioactivity is stable for at least 5 minutes.
Flush the IV catheter with 25 mL of 0.9% Sodium Chloride Injection.
Confirm the amount of radioactivity of lutetium Lu 177 dotatate delivered to the patient with an appropriate dose calibrator after each administration.
Dispose of any unused medicinal product or waste material in accordance with local and federal laws.
 
Intravenous infusion, peristaltic pump method:
Infuse lutetium Lu 177 dotatate directly from the original container.
Insert a filtered 2.5 cm, 20 gauge needle (short venting needle) into the lutetium Lu 177 dotatate vial; ensure the needle does not touch the lutetium Lu 177 dotatate solution in th vial. Do not connect this short needle directly to the patient or to the peristaltic pump.
Insert a second needle that is 9 cm, 18 gauge (long needle) into the lutetium Lu 177 dotatate vial. This long needle should touch and be secured to the bottom of the lutetium Lu 177 dotatate vial during the entire infusion. Connect the long needle and a 0.9% Sodium Chloride Injection solution to a 3-way stopcock valve using appropriate tubing.
Connect the output of the 3-way stopcock valve to tubing installed on the input side of the peristaltic pump according to manufacturer's instructions.
Prime the line by opening the 3-way stopcock valve and pumping the lutetium Lu 177 dotatate solution through the tubing until it reaches the exit of the valve.
Prime the IV catheter that will be connected to the patient by opening the 3-way stopcock valve to the 0.9% Sodium Chloride Injection solution and pumping this solution until it reaches the exit of the valve.
Connect the primed IV catheter to the patient and set the 3-way stopcock valve so that the lutetium Lu 177 dotatate solution is in line with the peristaltic pump.
Infuse an appropriate volume of lutetium Lu 177 dotatate solution over a 30- to 40-minute period to deliver the desired radioactivity.
Stop the peristaltic pump and change the position of the 3-way stopcock valve so that the pump is in line with the 0.9% Sodium Chloride Injection solution.
Restart the peristaltic pump and infuse an IV flush of 25 mL of 0.9% Sodium Chloride Injection solution through the IV catheter to the patient.
Confirm the amount of radioactivity of lutetium Lu 177 dotatate delivered to the patient with an appropriate dose calibrator after each administration.
Dispose of any unused medicinal product or waste material in accordance with local and federal laws.
 
Intravenous infusion, syringe pump method:
Using a disposable syringe fitted with a syringe shield and a sterile 9 cm, 18 gauge disposable needle (long needle), withdraw an appropriate volume of lutetium Lu 177 dotatate solution to deliver the desired radioactivity. A filtered 2.5 cm, 20 gauge needle (short venting needle) can be used to reduce the resistance from the pressurized vial to aid in withdrawal. Ensure the short needle does not touch the lutetium Lu 177 dotatate solution in the vial.
Fit the syringe into the shielded pump, including a 3-way stopcock valve between the syringe and an IV catheter pre-filled with 0.9% Sodium Chloride Injection.
Infuse an appropriate volume of lutetium Lu 177 dotatate solution over a 30- to 40-minute period to deliver the desired radioactivity.
Stop the syringe pump and change the position of the 3-way stopcock valve to flush the syringe with 25 mL of 0.9% Sodium Chloride Injection solution.
Restart the syringe pump.
After the flush of the syringe has been completed, flush the IV catheter to the patient with 25 mL of 0.9% Sodium Chloride Injection solution.
Confirm the amount of radioactivity of lutetium Lu 177 dotatate delivered to the patient with an appropriate dose calibrator after each administration.
Dispose of any unused medicinal product or waste material in accordance with local and federal laws.

Adverse Reactions
Severe

lymphopenia / Delayed / 44.0-44.0
elevated hepatic enzymes / Delayed / 4.0-20.0
hyperkalemia / Delayed / 19.0-19.0
vomiting / Early / 7.0-7.0
hyperuricemia / Delayed / 6.0-6.0
nausea / Early / 5.0-5.0
hyperglycemia / Delayed / 4.0-4.0
hypokalemia / Delayed / 4.0-4.0
neutropenia / Delayed / 3.0-3.0
renal failure (unspecified) / Delayed / 0-3.0
diarrhea / Early / 3.0-3.0
abdominal pain / Early / 3.0-3.0
new primary malignancy / Delayed / 0.5-2.3
leukopenia / Delayed / 2.0-2.0
hyperbilirubinemia / Delayed / 2.0-2.0
back pain / Delayed / 2.0-2.0
hypertension / Early / 2.0-2.0
heart failure / Delayed / 0-2.0
thrombocytopenia / Delayed / 1.0-1.0
flushing / Rapid / 1.0-1.0
neuroendocrine hormonal crisis / Early / 0-1.0
bronchospasm / Rapid / 0-1.0
anxiety / Delayed / 1.0-1.0
cough / Delayed / 1.0-1.0
atrial fibrillation / Early / 1.0-1.0
myocardial infarction / Delayed / 0-1.0
fatigue / Early / 1.0-1.0
azotemia / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

anemia / Delayed / 81.0-81.0
hypocalcemia / Delayed / 32.0-32.0
hypernatremia / Delayed / 17.0-17.0
peripheral edema / Delayed / 16.0-16.0
hypoglycemia / Early / 15.0-15.0
constipation / Delayed / 10.0-10.0
hypotension / Rapid / 0-1.0
cholestasis / Delayed / Incidence not known
colic / Delayed / Incidence not known
urethral pain / Early / Incidence not known
urinary incontinence / Early / Incidence not known
dysuria / Early / Incidence not known

Mild

anorexia / Delayed / 21.0-21.0
dizziness / Early / 17.0-17.0
headache / Early / 17.0-17.0
alopecia / Delayed / 12.0-12.0
dysgeusia / Early / 8.0-8.0
fever / Early / 8.0-8.0
myalgia / Early / 5.0-5.0
nocturia / Early / Incidence not known
pelvic pain / Delayed / Incidence not known

Common Brand Names

Lutathera

Dea Class

Rx

Description

A radiolabeled somatostatin analog
Used for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults
Use appropriate safety measures to minimize radiation exposure

Dosage And Indications
For the treatment of somatostatin receptor-positive gastroenteropancreatic malignant neuroendocrine tumor (NET), including foregut, midgut, and hindgut neuroendocrine tumors. Intravenous dosage Adults

7.4 GBq (200 mCi) IV infusion, at a rate of 50 to 100 mL/hour for 5 to 10 minutes and then 200 to 300 mL/hour for an additional 25 to 30 minutes, every 8 weeks (+/- 1 week) for a total of 4 doses. Beginning 30 minutes prior to the start of a lutetium Lu 177 dotatate infusion, initiate an IV infusion of a sterile amino acid solution containing lysine HCl (18 g to 24 g) and arginine HCl (18 g to 24 g); continue this infusion during and for at least 3 hours after completion of the lutetium Lu 177 dotatate infusion. Do not decrease the dose of the amino acid solution even if the dose of lutetium Lu 177 dotatate is reduced. Administer long-acting octreotide 30 mg IM between 4 to 24 hours after each lutetium Lu 177 dotatate dose; do not administer long-acting octreotide within 4 weeks prior to each subsequent lutetium Lu 177 dotatate dose. After completion of lutetium Lu 177 dotatate, continue long-acting octreotide every 4 weeks until disease progression, or for 18 months following the initiation of treatment at the physician's discretion. In a multicenter, randomized, open-label, active-controlled trial (NETTER-1), treatment with lutetium Lu 177 dotatate plus long-acting octreotide (30 mg IM) significantly improved median progression-free survival (PFS) (not reached vs. 8.5 months) and objective response rate (13% vs. 4%) in patients with progressive, well-differentiated, locally advanced/inoperable or metastatic somatostatin receptor-positive midgut carcinoid tumors. There was not a significant difference in overall survival (OS) between treatment arms in the final OS analysis. In patients with foregut, midgut, and hindgut gastroenteropancreatic neuroendocrine tumors (GEP-NETs), treatment with lutetium Lu 177 dotatate resulted in an ORR of 16%, with 3 complete responses (n = 360); the median duration of response was 35 months.

Dosing Considerations
Hepatic Impairment

Baseline Hepatic Impairment
Mild to moderate hepatic impairment (total bilirubin less than or equal to 3 times the upper limit of normal): No dosage adjustment necessary.
Severe hepatic impairment (total bilirubin greater than 3 times the upper limit of normal and any AST): The safety of lutetium Lu 177 dotatate has not been studied in this population; specific guidelines for dosage adjustments are not available.
 
Treatment-Related Hepatotoxicity
Grade 3 or 4 hyperbilirubinemia (bilirubin greater than 3 times the upper limit of normal), or serum albumin less than 30 g/L with international normalized ratio (INR) greater than 1.5: Hold lutetium Lu 177 dotatate therapy. Upon resolution or return to baseline within 16 weeks, resume lutetium Lu 177 dotatate at a reduced dose of 3.7 GBq (100 mCi). If this dose does not result in hepatotoxicity, increase the dose of lutetium Lu 177 dotatate to 7.4 GBq (200 mCi) for the next dose. Permanently discontinue lutetium Lu 177 dotatate for hepatotoxicity that requires a treatment delay resulting in a dosing interval beyond 16 weeks.
Recurrent grade 3 or 4 hyperbilirubinemia, or serum albumin less than 30 g/L with INR greater than 1.5: Permanently discontinue lutetium Lu 177 dotatate therapy.

Renal Impairment

Baseline Renal Impairment
Mild to moderate renal impairment (Creatinine clearance (CrCl) 30 to 89 mL/min): No dosage adjustment necessary.
Severe renal impairment (CrCl less than 30 mL/min) or end-stage renal impairment: The safety of lutetium Lu 177 dotatate has not been studied in this population; specific guidelines for dosage adjustments are not available.
 
Treatment-Related Nephrotoxicity
CrCl less than 40 mL/min using actual body weight, 40% increase in baseline serum creatinine, or a 40% decrease in baseline CrCl using actual body weight: Hold lutetium Lu 177 dotatate therapy. Upon resolution or return to baseline within 16 weeks, resume lutetium Lu 177 dotatate at a reduced dose of 3.7 GBq (100 mCi). If this dose does not result in nephrotoxicity, increase the dose of lutetium Lu 177 dotatate to 7.4 GBq (200 mCi) for the next dose. Permanently discontinue lutetium Lu 177 dotatate for nephrotoxicity that requires a treatment delay resulting in a dosing interval beyond 16 weeks.
Recurrent CrCl less than 40 mL/min using actual body weight, 40% increase in baseline serum creatinine, or a 40% decrease in baseline CrCl using actual body weight: Permanently discontinue lutetium Lu 177 dotatate therapy.

Drug Interactions

Albuterol; Budesonide: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Betamethasone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Budesonide: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Budesonide; Formoterol: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Corticosteroids (systemic): (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Cortisone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Deflazacort: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Dexamethasone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Fludrocortisone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Hydrocortisone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Lanreotide: (Major) Discontinue long-acting lanreotide at least 4 weeks prior to beginning treatment with lutetium Lu 177 dotatate. A short-acting somatostatin analog may be administered as-needed, but must be discontinued at least 24 hours prior to each lutetium Lu 177 dotatate dose. Somatostatin and its analogs, such as lanreotide, competitively bind to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate.
Methylprednisolone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Octreotide: (Major) Discontinue long-acting octreotide at least 4 weeks prior to beginning treatment with lutetium Lu 177 dotatate. Short-acting octreotide may be administered as-needed; discontinue at least 24 hours prior to each lutetium Lu 177 dotatate dose. Somatostatin and its analogs, such as octreotide, competitively bind to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate.
Prednisolone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Prednisone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Triamcinolone: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

How Supplied

Lutathera Intravenous Inj Sol: 1mL, 370MBq

Maximum Dosage
Adults

7.4 GBq (200 mCi) IV.

Geriatric

7.4 GBq (200 mCi) IV.

Mechanism Of Action

Lutetium Lu 177 dotatate binds to somatostatin receptors, including those on malignant somatostatin receptor-positive tumors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2). After binding, it is internalized and the beta-minus emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells.

Pharmacokinetics

Lutetium Lu 177 dotatate is administered intravenously. The non-radioactive lutetium Lu 175 dotatate is 43% bound to human plasma proteins. The mean volume of distribution (Vd) for lutetium Lu 177 dotatate is 460 L (CV, 54%). Within 4 hours of the infusion, lutetium Lu 177 dotatate distributes in kidneys, liver, spleen, and in some patients, pituitary gland and thyroid. The maximum radiation penetration in tissue is 2.2 mm; the mean penetration is 0.67 mm. The coadministration of amino acids reduced the median radiation dose to the kidneys by 47% (range, 34% to 59%). The mean clearance (CL) is 4.5 L/h (CV, 31%); coadministration of amino acids increased the mean beta-phase blood clearance of lutetium Lu 177 dotatate by 36%. Lutetium Lu 177 dotatate decays to stable hafnium (Hf 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 (gamma) of 0.208 MeV (11%) and 0.113 MeV (6.2%). The mean terminal half-life is 71 (+/- 28) hours.
 
Lutetium Lu 177 dotatate is primarily renally eliminated, with cumulative excretion of 44% within 5 hours, 58% within 24 hours, and 65% within 48 hours following administration. The fraction of radiation remaining after 2 hours is 99.1%; 90.1% of radiation remains after 24 hours, 81.2% after 2 days, 73.1% after 3 days, 48.2% after 7 days, 23.2% after 14 days, 4.4% after 30 days, and 0.9% after 45 days. Prolonged elimination of lutetium Lu 177 dotatate in the urine is expected; however, based on the half-life of lutetium 177 and terminal half-life of lutetium Lu 177 dotatate, greater than 99% of the administered radioactivity will be eliminated within 14 days after administration.
 
Affected cytochrome P450 isoenzymes and drug transporters: None

Intravenous Route

The mean AUC of lutetium Lu 177 dotatate at the recommended dose is 41 ng*h/mL (CV, 36%); the mean Cmax is 10 ng/mL (CV, 50%), generally occurring at the end of the infusion.

Pregnancy And Lactation
Pregnancy

Pregnancy should be avoided by females of reproductive potential during lutetium Lu 177 dotatate treatment and for at least 7 months after the last dose. Although there are no adequately controlled studies in pregnant animals or humans, lutetium Lu 177 dotatate, as with other radioactive emissions, can cause fetal harm when administered during pregnancy based on its mechanism of action. Women who are pregnant or who become pregnant while receiving lutetium Lu 177 dotatate should be apprised of the potential hazard to the fetus.

Counsel patients about the reproductive risk and contraception requirements during lutetium Lu 177 dotatate treatment. Lutetium Lu 177 dotatate can cause fetal harm if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 7 months after treatment with lutetium Lu 177 dotatate. Males with female partners of reproductive potential should use effective contraception during treatment and for 4 months after the last dose of lutetium Lu 177 dotatate. Females of reproductive potential should undergo pregnancy testing prior to initiation of lutetium Lu 177 dotatate. Women who become pregnant while receiving lutetium Lu 177 dotatate should be apprised of the potential hazard to the fetus. The recommended cumulative dose of lutetium Lu 177 dotatate results in a radiation absorbed dose to the testis and ovaries within the range where temporary or permanent infertility can be expected following external beam radiotherapy.