Poltech dtpa

INSTRUCTIONS for medical use of the medicinal product Poltech DTPA (PoltechDTPA)

Composition:

Active substance: sodium diethylenetriaminepentaacetate, monohydrate;

One vial contains sodium diethylenetriaminepentaacetate monohydrate 13.25 mg;

Excipients: tin chloride, dihydrate; sodium chloride; nitrogen.

Radioactive nuclides are not part of the kit.

Pharmaceutical form. Kit for the preparation of a radiopharmaceutical agent.

Main physicochemical properties: white powder.

Pharmacotherapeutic group.

Diagnostic radiopharmaceuticals with technetium (99mTc).

ATC code V09C A01.

Pharmacological properties.

Pharmacodynamics.

99mTc-DTPA and excipients, at doses used for diagnostic purposes, do not exhibit any pharmacodynamic effect.

Pharmacokinetics.

Distribution

Less than 5% of the administered dose binds to plasma proteins. There is also minimal binding of 99mTc-DTPA to erythrocytes. After administration, 99mTc-DTPA does not cross the intact blood-brain barrier, but is weakly excreted into breast milk.

Elimination

Plasma clearance is multiphasic exponential, with a predominant rapid component. The complex remains stable in vivo, with over 98% of radioactivity excreted in urine in the form of the chelate.

Approximately 90% of the administered dose is excreted in urine within the first 24 hours, primarily via glomerular filtration. There is no accumulation of radioactivity in the kidneys.

Plasma clearance may be reduced in patients with renal disease. After intravenous administration, 99mTc-DTPA is rapidly cleared from the blood.

Clinical characteristics.

Indications.

This medicinal product is intended for diagnostic use only.

The radiopharmaceutical preparation 99mTc-DTPA is indicated for renal scintigraphy (dynamic renal scintigraphy to measure glomerular filtration rate of each kidney and to assess urinary excretion disorders), measurement of glomerular filtration rate from plasma samples, as well as cerebral angiography and brain scanning.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Safety precautions.

In case of hypersensitivity or anaphylactic reactions, administration of the medicinal product must be immediately discontinued and, if necessary, intravenous treatment initiated. To ensure prompt emergency management, appropriate medications and equipment, such as an intubation tube and artificial ventilator, should be prepared in advance.

Justification of individual benefit/risk

For each patient, radiation exposure must be justified by the expected diagnostic benefit. The radioactive dose should always be as low as reasonably achievable while still obtaining the necessary diagnostic information.

In patients with impaired renal function, indications should be carefully considered, as increased radiation exposure may occur in such patients. This should be taken into account when calculating the administered activity.

Patient preparation

The patient should drink plenty of fluids before the examination and void the bladder as frequently as possible during the first hours after the procedure to reduce radiation exposure.

Close contact with infants and pregnant women should be limited for 24 hours after the procedure.

The contents of the vial are intended solely for the preparation of the radiopharmaceutical 99mTc-DTPA and must be administered to the patient only after completion of the labeling procedure.

Special warning

Radiopharmaceuticals may be received, used, and prescribed only by authorized personnel holding appropriate permits for working with radiopharmaceuticals in clinical settings. Their receipt, storage, use, transfer, and disposal are regulated by applicable regulations and/or licenses issued by the relevant local authorities.

Radiopharmaceuticals must be prepared by the user in a manner ensuring appropriate radiological safety and pharmaceutical quality.

Appropriate aseptic precautions must be taken.

The contents of the kit are non-radioactive prior to preparation. However, after addition of sodium pertechnetate (99mTc), appropriate radiation protection measures for the finished product must be observed.

Administration of radiopharmaceuticals creates a risk of ionizing radiation exposure or contamination from spills of urine, vomit, and other biological fluids to other individuals. Precautions must be taken to minimize radiation exposure in accordance with current regulations.

Any unused medicinal product or waste material must be disposed of in accordance with applicable regulatory requirements.

Dosimetry

Technetium (99mTc) is obtained from a radionuclide generator (99Mo/99mTc) and decays with emission of gamma rays of energy 140 keV and a half-life of 6.02 hours to technetium (99Tc), which, due to its long half-life (2.13 × 105 years), can be considered quasi-stable.

Estimated radiation doses to patient organs and tissues following intravenous administration of 99mTc-DTPA are presented in Tables 1 and 2.

The data in Table 1 are taken from ICRP Publication 80 (International Commission on Radiological Protection, Radiation Doses to Patients from Radiopharmaceuticals, Pergamon Press, 1998).

Table 1

Patients with normal renal function

The effective equivalent dose received from the administered activity of 555 MBq for a patient weighing 70 kg is 2.7 mSv.

Table 2 shows the dosimetry calculated according to Publication 53 of the ICRP (International Commission on Radiological Protection, Radiation Doses to Patients from Radiopharmaceuticals, Pergamon Press, 1987).

Table 2

Patients with impaired kidney function

Interaction with other medicinal products and other forms of interaction.

Many medicinal products can affect the function of the organ under investigation and alter the uptake of 99mTc-DTPA.

Diagnostic use of captopril. Dynamic renal scintigraphy performed under controlled conditions one hour after oral administration of captopril (25–50 mg) may reveal hemodynamic changes in kidneys affected by renal artery stenosis. Blood pressure should be carefully monitored, as patients with vascular diseases are at risk of severe hypotension and impaired renal function.

Diagnostic use of furosemide. Intravenous administration of furosemide during dynamic renal scintigraphy accelerates the excretion of 99mTc-DTPA, which may help differentiate the presence of true obstruction in dilated urinary tracts from one that has already been relieved.

Cerebral angiography. Psychotropic drugs increase blood flow in the external carotid artery basin. This may lead to rapid retention of the radiopharmaceutical agent in the nasopharyngeal region during the arterial and capillary phases (the "hot nose" phenomenon).

Special precautions for use.

This medicinal product contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is practically sodium-free.

Use during pregnancy or breastfeeding.

Women of childbearing potential

When administering radiopharmaceuticals to women of childbearing potential, it is essential to determine whether such a woman is pregnant. Any woman with a delayed menstruation should be considered pregnant until proven otherwise.

Studies involving radiopharmaceuticals in women of childbearing potential should be performed within the first 10 days of the menstrual cycle.

If there is uncertainty regarding possible pregnancy (e.g. in women with delayed menstruation and highly irregular cycles), the patient should be offered alternative diagnostic methods (if available) that do not involve ionizing radiation.

Pregnancy

Radionuclide procedures performed during pregnancy also deliver radiation doses to the fetus. Therefore, such procedures should only be carried out during pregnancy when the potential benefit clearly outweighs the risk to both the mother and the fetus.

Administration of 555 MBq of 99mTc-DTPA to a patient results in a uterine dose of up to 4.4 mGy. Doses exceeding 0.5 mGy should be considered as a potential risk to the fetus.

Breastfeeding

Before administering a radiopharmaceutical to a breastfeeding woman, consideration should be given to the possibility of postponing radionuclide administration until breastfeeding has ceased. Additionally, radiopharmaceuticals should be carefully selected, taking into account the excretion of radioactivity into breast milk.

If administration of the radiopharmaceutical is necessary, breastfeeding should be interrupted for 4 hours, and the expressed milk should be discarded.

Ability to affect reaction speed when driving or operating machinery.

The radiopharmaceutical does not affect the ability to drive or operate machinery.

Method of Administration and Dosage

The medicinal product is intended for intravenous administration.

This radiopharmaceutical must be administered only by a specialist authorized to handle radiopharmaceuticals. Strict adherence to safety procedures when handling this radiopharmaceutical is required.

Radioactive 99mTc-DTPA is administered intravenously after labeling with sodium pertechnetate-99mTc solution obtained from a 99Mo/99mTc radionuclide generator, according to the preparation instructions.

For radiolabeling of one vial, 5 mL of sodium pertechnetate (99mTc) solution (eluate from the 99Mo/99mTc radionuclide generator) with an activity of 740–1500 MBq should be used.

This amount is sufficient for examination of several adult patients.

Image Acquisition

Renal scintigraphy with measurement of glomerular filtration rate: sequential imaging should begin at the moment of injection. The optimal time for static imaging is 1 hour after injection.

Brain scanning: sequential dynamic imaging should begin immediately after injection. Static images are obtained 1 hour after injection and, if necessary, several hours after injection.

Dosage

Adults

The recommended activity for renal scintigraphy in an adult patient ranges from 74–370 MBq; for measurement of glomerular filtration rate from plasma, 1.8–3.7 MBq; for angiography and brain scanning diagnosis, 370–555 MBq. However, depending on the indication, other activity levels may be justified.

Children

Dosage for children is adjusted according to body weight or body surface area:

Pediatric (child) activity (MBq) = adult dose (MBq) × child's body weight (kg) / 70

Pediatric (child) activity (MBq) = adult dose (MBq) × child's body surface area (m²) / 1.73

The activity to be administered to children and adolescents may be calculated according to the recommendations of the Paediatric Dosage Card of the European Association of Nuclear Medicine (EANM); the activity administered to children and adolescents may also be calculated by multiplying the baseline activity (for calculation purposes) by the weight-based coefficient:

The minimum dose of 20 MBq is required to obtain images of sufficient quality in very young children (under 1 year of age) when the medicinal product is used for kidney imaging.

Patients with impaired renal function

The administered activity must be carefully calculated, as increased radiation exposure may occur in these patients.

Instructions for preparation of the radiopharmaceutical

Radiopharmaceuticals must be prepared by a specialist in a manner that meets both radiation safety and pharmaceutical requirements. Appropriate aseptic precautions must be taken. As with any pharmaceutical product, if the integrity of the vial is compromised at any time during preparation, the product must not be used. Therefore, the vial must be carefully inspected for damage, including cracks, prior to the radiolabelling procedure.

Politekh DTPA is intended for labelling with a solution of sodium pertechnetate-99mTc obtained from a 99Mo/99mTc radionuclide generator. The labelling procedure must ensure sterility of the product and include safety measures to minimize radiation exposure by using appropriate shielding.

Labelling procedure

1. Place the vial containing the powder into an appropriate lead protective container.
2. Using a syringe, inject (through the rubber stopper) approximately 5 mL of 99mTc sodium pertechnetate eluate (or eluate of desired activity previously diluted with sterile physiological saline) into the vial containing DTPA.
3. Using the same syringe, withdraw an equivalent volume of air to relieve excess pressure in the vial.
4. Shake the vial contents until the powder is completely dissolved (approximately 2 minutes). The vial must remain in the lead container throughout the procedure.
5. The resulting solution is the ready-to-use injectable solution.

The 99mTc-DTPA preparation should be used within 6 hours after completion of the labelling procedure.

During handling and administration of the product, strict adherence to radiation safety recommendations regarding ionizing radiation exposure is mandatory.

Quality control instructions for the radiopharmaceutical 99mTc-DTPA

Measurement of radiochemical purity by thin-layer chromatography: two chromatographic systems according to the European Pharmacopoeia, Monograph 0642.

Impurity A

1. ITLC-SG plates (glass-fibre sheets coated with silica gel).
2. Mobile phase preparation: 9 g/L sodium chloride solution.
3. Sample application: apply approximately 2 µL of the test solution (with radioactivity between 50 MBq/mL and 200 MBq/mL) onto a chromatographic plate (1.5 cm × 12 cm), approximately 1.5 cm from the bottom edge.
4. Development: immediately, until the solvent front reaches approximately 4/5 of the plate.
5. Drying: in air.
6. Detection: appropriate radiation detector.

Conditions:

• Unbound, reduced colloidal forms of 99mTc and 99mTc (impurity A) remain at the origin (Rf = 0.0–0.1);
• 99mTc-DTPA and free pertechnetate ion 99mTcO4- migrate with the solvent front (Rf = 0.9–1.0).

Impurity B

1. ITLC-SG plates (glass-fibre sheets coated with silica gel).
2. Mobile phase preparation: methyl ethyl ketone (MEK).
3. Sample application: apply approximately 2 µL of the test solution (with radioactivity between 50 MBq/mL and 200 MBq/mL) onto a chromatographic plate (1.5 cm × 12 cm), approximately 1.5 cm from the bottom edge.
4. Development: immediately, until the solvent front reaches approximately 4/5 of the plate.
5. Drying: in air.
6. Detection: appropriate radiation detector.

Conditions:

• Free pertechnetate ion 99mTcO4- (impurity B) migrates with the mobile phase (Rf = 0.9–1.0);
• 99mTc-DTPA and 99mTc-colloidal forms remain at the origin (Rf = 0.0–0.1).

Radiochemical purity of the 99mTc-DTPA kit: not less than 95% of total technetium-99m. Calculate the % radioactivity of the 99mTc-DTPA kit as:

100 - (A + B),

where:

A – percentage of radioactivity of impurity A, determined in the impurity A test;

B – percentage of radioactivity of impurity B, determined in the impurity B test.

Children

Use in children and adolescents should be carefully considered based on clinical need and assessment of the risk-benefit ratio for this patient group, as the effective dose per MBq is higher than in adults.

Overdose

In case of radiation overdose with 99mTc-DTPA, the absorbed dose should be reduced as much as possible by promoting defecation, forced diuresis, and frequent bladder voiding.

Adverse reactions.

Adverse reactions reported following administration of the drug are presented in Table 3.

Table 3

* Associated with ionizing radiation

For each patient, exposure to ionizing radiation should be justified by the expected benefit. The administered activity should be as low as reasonably achievable, taking into account obtaining the desired diagnostic outcome.

Exposure to ionizing radiation is associated with cancer induction and potential development of hereditary defects. Data from diagnostic nuclear medicine studies indicate that these adverse reactions are expected to occur with low probability.

For most diagnostic procedures using nuclear medicine techniques, the radiation dose (effective dose) is less than 20 mSv. Higher doses may be justified in certain clinical circumstances.

According to published data, the following adverse reactions have been observed after intravenous administration of the radiopharmaceutical 99mTc-DTPA: fever, nausea, vomiting, flushing, erythema, pruritus, urticaria, headache, hypertension, and aseptic meningitis.

Shelf life.

Kit – 1 year.

After radioactive labelling with sodium pertechnetate (99mTc) solution – 6 hours.

Storage conditions.

Store in a refrigerator at a temperature of 2 °C to 8 °C.

During transport (for no more than 7 days) at a temperature not exceeding 35 °C.

After radioactive labelling with sodium pertechnetate (99mTc) solution, store at a temperature not exceeding 25 °C in an appropriate lead container.

Packaging.

10 ml glass vial, 6 vials per cardboard pack.

Supply category.

Prescription only in hospital settings.

Supplied only to specialized medical facilities authorized to handle radiopharmaceuticals.

Manufacturer.

National Centre for Nuclear Research.

Manufacturer's address and location of operations.

ul. Andrzeja Sołtana 7, Otwock, 05-400, Poland.