- Approval Id
- 46f1e074c6a4bfea
- Drug Name
- PLUVICTO SOLUTION FOR INJECTION/INFUSION 1000 MBq/mL
- Product Name
- PLUVICTO SOLUTION FOR INJECTION/INFUSION 1000 MBq/mL
- Approval Number
- SIN16917P
- Approval Date
- 2023-12-18
- Registrant
- NOVARTIS (SINGAPORE) PTE LTD
- Licence Holder
- NOVARTIS (SINGAPORE) PTE LTD
- Drug Type
- Therapeutic
- Forensic Classification
- Prescription Only
- Dosage Form
- INJECTION, SOLUTION (RADIOPHARMACEUTICAL)
- Dosage
- <p><strong>4 Dosage regimen and administration</strong></p>
<p><strong>Important safety instructions</strong></p>
<p>Pluvicto is a radiopharmaceutical and should be handled with appropriate safety measures to minimize radiation exposure (see section 6 Warnings and precautions – <em>please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information</em>). Waterproof gloves and effective radiation shielding should be used when handling Pluvicto.</p>
<p>Radiopharmaceuticals, including Pluvicto, 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.</p>
<p><strong>Patient identification</strong></p>
<p>Patients should be identified for treatment by PSMA imaging.</p>
<p><strong>Dosage regimen</strong></p>
<p>The recommended Pluvicto dose is 7.4 GBq (200 mCi) intravenously every 6 weeks (± 1 week) for a total of 6 doses.</p>
<p><strong>Treatment monitoring</strong></p>
<p>Laboratory tests should be performed before and during treatment with Pluvicto.</p>
<ul>
<li>Hematology (hemoglobin, white blood cell count, absolute neutrophil count, platelet count)</li>
<li>Kidney function (serum creatinine, calculated creatinine clearance [CLcr])</li>
<li>Liver function (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood serum albumin, total blood bilirubin)</li>
</ul>
<p><strong>Dose modifications for adverse drug reactions</strong></p>
<p>Recommended dose modifications of Pluvicto for adverse drug reactions are provided in Table 4-1. Management of severe or intolerable adverse drug reactions may require temporary dose interruption, dose reduction or permanent discontinuation of treatment with Pluvicto. If a treatment delay due to an adverse drug reaction persists for >4 weeks, treatment discontinuation with Pluvicto may be considered. The dose of Pluvicto may be reduced by 20% to 5.9 GBq (160 mCi) once; the dose should not be re-escalated. If a patient has further adverse drug reactions that would require an additional dose reduction, treatment with Pluvicto must be discontinued.</p>
<img src="/TGIF/Pluvicto-Table4-1_130225.png" alt="Pluvicto Dosage Table 4-1" /><br><br>
<p><strong>Special populations</strong></p>
<p><strong>Renal impairment</strong></p>
<p>Exposure of Pluvicto is expected to increase with the degree of renal impairment. Patients with mild or moderate renal impairment may be at greater risk of toxicity. No dose adjustment is recommended for patients with mild renal impairment (baseline CLcr 60 to 89 mL/min by Cockcroft-Gault); however, insufficient data are available for drawing a conclusion for patients with moderate renal impairment (CLcr 30 to 59 mL/min). Renal function and adverse reactions should be monitored frequently in patients with mild to moderate renal impairment. The pharmacokinetic profile and safety of Pluvicto have not been studied in patients with severe (CLcr 15 to 29 mL/min) renal impairment or end-stage renal disease.</p>
<p><strong>Hepatic impairment</strong></p>
<p>No dose adjustment is recommended for patients with hepatic impairment.</p>
<p><strong>Pediatric patients (below 18 years of age)</strong></p>
<p>The safety and effectiveness of Pluvicto in pediatric patients have not been established.</p>
<p><strong>Geriatric patients (65 years of age or older)</strong></p>
<p>No dose adjustment is recommended in patients 65 years of age or older.</p>
<p><strong>Method of administration</strong></p>
<p><strong>Preparation instructions</strong></p>
<ul>
<li>Use aseptic technique and radiation shielding when handling or administering Pluvicto, using tongs as needed to minimize radiation exposure.</li>
<li>Visually inspect the product under a shielded screen for particulate matter and discoloration prior to administration. Discard the vial if particulates and/or discoloration are present.</li>
<li>Pluvicto is a ready-to-use solution for single use only. Do not inject the Pluvicto solution directly into any other intravenous solution.</li>
<li>Confirm the amount of radioactivity of Pluvicto delivered to the patient with an appropriately calibrated dose calibrator prior to and after each Pluvicto administration.</li>
<li>Dispose of any unused medicinal product or waste material in accordance with national regulations.</li>
</ul>
<p><strong>Administration instructions</strong></p>
<p>The recommended dose of Pluvicto may be administered intravenously as an injection using the syringe method, as an infusion using the gravity method, or as an infusion using the peristaltic pump method.</p>
<p>When using the gravity or peristaltic pump method, infuse Pluvicto directly from its original container.</p>
<p>Use the syringe method or the peristaltic pump method when administering a reduced dose of Pluvicto following a dose modification for an adverse drug reaction. When using the gravity method for a reduced dose, adjust the Pluvicto dose before the administration to avoid the delivery of an incorrect volume of Pluvicto.</p>
<p>Prior to administration, flush the intravenous catheter used exclusively for Pluvicto administration with ≥10 mL of 0.9% sterile sodium chloride solution to ensure patency and to minimize the risk of extravasation. Manage cases of extravasation as per institutional guidelines.</p>
<p><strong>Intravenous methods of administration</strong></p>
<p><strong>Instructions for the syringe method</strong></p>
<ul>
<li>Withdraw an appropriate volume of Pluvicto solution to deliver the desired radioactivity by using a disposable syringe fitted with a syringe shield and a disposable sterile needle that is 9 cm, 18 gauge (long needle). To aid the withdrawal of the solution, a filtered 2.5 cm, 20 gauge needle (short venting needle) can be used to reduce the resistance from the pressurized vial. Ensure that the short needle does not touch the Pluvicto solution in the vial.</li>
<li>If using a syringe pump, fit the syringe into the shielded pump and include a 3-way stopcock valve between the syringe and an intravenous catheter primed with 0.9% sterile sodium chloride solution and used for Pluvicto administration to the patient.</li>
<li>Administer Pluvicto to the patient by slow intravenous push within approximately 1 to 10 minutes (either with a syringe pump or manually without a syringe pump) via an intravenous catheter that is primed with 0.9% sterile sodium chloride solution and that is used exclusively for Pluvicto administration to the patient.</li>
<li>When the desired Pluvicto radioactivity has been delivered, stop the syringe pump and then change the position of the 3-way stopcock valve to flush the syringe with 25 mL of 0.9% sodium chloride solution. Restart the syringe pump.</li>
<li>After the flush of the syringe has been completed, perform an intravenous flush of ≥10 mL of 0.9% sterile sodium chloride solution through the intravenous catheter to the patient.</li>
</ul>
<p><strong>Instructions for the gravity method</strong></p>
<ul>
<li>Insert a 2.5 cm, 20 gauge needle (short needle) into the Pluvicto vial and connect via a catheter to 500 mL 0.9% sterile sodium chloride solution (used to transport the Pluvicto solution during the infusion). Ensure that the short needle does not touch the Pluvicto solution in the vial and do not connect the short needle directly to the patient. Do not allow the 0.9% sterile sodium chloride solution to flow into the Pluvicto vial prior to the initiation of the Pluvicto infusion and do not inject the Pluvicto solution directly into the 0.9% sterile sodium chloride solution.</li>
<li>Insert a second needle that is 9 cm, 18 gauge (long needle) into the Pluvicto vial, ensuring that the long needle touches and is secured to the bottom of the Pluvicto vial during the entire infusion. Connect the long needle to the patient by an intravenous catheter that is primed with 0.9% sterile sodium chloride solution and that is used exclusively for the Pluvicto infusion into the patient.</li>
<li>Use a clamp or an infusion pump to regulate the flow of the 0.9% sterile sodium chloride solution via the short needle into the Pluvicto vial (the 0.9% sterile sodium chloride solution entering the vial through the short needle will carry the Pluvicto solution from the vial to the patient via the intravenous catheter connected to the long needle within approximately 30 minutes).</li>
<li>During the infusion, ensure that the level of solution in the Pluvicto vial remains constant.</li>
<li>Disconnect the vial from the long needle line and clamp the 0.9% sterile sodium chloride solution line once the level of radioactivity is stable for at least five minutes.</li>
<li>Follow the infusion with an intravenous flush of ≥10 mL of 0.9% sterile sodium chloride solution through the intravenous catheter to the patient.</li>
</ul>
<p><strong>Instructions for the peristaltic pump method</strong></p>
<ul>
<li>Insert a filtered 2.5 cm, 20 gauge needle (short venting needle) into the Pluvicto vial. Ensure that the short needle does not touch the Pluvicto solution in the vial and do not connect the short needle directly to the patient or to the peristaltic pump.</li>
<li>Insert a second needle that is 9 cm, 18 gauge (long needle) into the Pluvicto vial, ensuring that the long needle touches and is secured to the bottom of the Pluvicto vial during the entire infusion. Connect the long needle and a 0.9% sterile sodium chloride solution to a 3-way stopcock valve via appropriate tubing.</li>
<li>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.</li>
<li>Prime the line by opening the 3-way stopcock valve and pumping the Pluvicto solution through the tubing until it reaches the exit of the valve.</li>
<li>Prime the intravenous catheter which will be connected to the patient by opening the 3-way stopcock valve to the 0.9% sterile sodium chloride solution and pumping the 0.9% sterile sodium chloride solution until it exits the end of the catheter tubing.</li>
<li>Connect the primed intravenous catheter to the patient and set the 3-way stopcock valve such that the Pluvicto solution is in line with the peristaltic pump.</li>
<li>Infuse an appropriate volume of Pluvicto solution at approximately 25 mL/h to deliver the desired radioactivity.</li>
<li>When the desired Pluvicto radioactivity has been delivered, stop the peristaltic pump and then change the position of the 3-way stopcock valve so that the peristaltic pump is in line with the 0.9% sterile sodium chloride solution. Restart the peristaltic pump and infuse an intravenous flush of ≥10 mL of 0.9% sterile sodium chloride solution through the intravenous catheter to the patient.</li>
</ul>
<p><strong>Radiation dosimetry</strong></p>
<p>Dosimetry of lutetium (<sup>177</sup>Lu) vipivotide tetraxetan was collected in 29 patients in the Phase III VISION sub-study, in order to calculate whole body and organ radiation dosimetry. The mean and standard deviation (SD) of the estimated radiation absorbed doses to different organs for adult patients receiving Pluvicto are shown in Table 4-2. The organs with the highest radiation absorbed doses are lacrimal glands and salivary glands.</p>
<p>The maximum penetration of lutetium-177 in tissue is approximately 2 mm and the mean penetration is 0.67 mm.</p>
<img src="/TGIF/Pluvicto-Table4-2_261225.png" alt="Pluvicto Dosage Table 4-2" /><br><br>
- Route Of Administration
- INTRAVENOUS
- Indication Info
- <p><strong>3 Indications</strong></p>
<p>Pluvicto® is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibitor and taxane-based chemotherapy.</p>
- Contraindications
- <p><strong>5 Contraindications</strong></p>
<p>Hypersensitivity to the active substance or to any of the excipients listed in Section 2 Description and composition – <em>please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information</em>.</p>
- Atc Code
- V10XX05
- Atc Item Name
- lutetium (177Lu) vipivotide tetraxetan
- Pharma Manufacturer Name
- NOVARTIS (SINGAPORE) PTE LTD
