Poltech mdp

INSTRUCTION for medical use of the medicinal product Poltech MDP (PoltechMDP)

Composition:

Active substance: methylenediphosphonic acid;

1 vial contains 5 mg of methylenediphosphonic acid in the form of 6.25 mg of sodium methylenediphosphonate;

Excipients: tin chloride dihydrate; ascorbic acid; nitrogen.

Radioactive nuclides are not part of the kit.

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

Main physicochemical properties: white powder.

Pharmacotherapeutic group.

Diagnostic radiopharmaceuticals. Medicinal products for diagnosis of skeletal diseases.

ATC code V09B A02.

Pharmacological Properties

Pharmacodynamics

99mTc-MDP and excipients, at the doses used for diagnostic purposes, do not exhibit any pharmacodynamic effects.

Pharmacokinetics

Within the first 3 minutes after administration of 99mTc-MDP, uptake by soft tissues and accumulation in the kidneys occurs. As clearance from these compartments progresses, gradual skeletal accumulation is first observed in the lumbar vertebrae and pelvic region.

Blood clearance occurs in three phases:

1. Fast phase (t½ = 3.5 min)
2. Intermediate phase (t½ = 27 min)
3. Slow phase (t½ = 144 min)

The fast phase represents transfer of the radioactive substance from the bloodstream into the extravascular space. The intermediate phase includes skeletal uptake. The slow phase is likely associated with release of 99mTc-MDP from protein-bound complexes. Approximately 50% of the administered dose accumulates in the skeleton.

Maximum bone uptake is achieved within 1 hour after administration and remains virtually unchanged up to 72 hours. Unbound complexes are eliminated via the kidneys. Peak renal activity is reached approximately 20 minutes after injection.

With normal renal function, about 32% of the total amount of unbound complexes is excreted via glomerular filtration within 1 hour, 47.5% within 2 hours, and 60% within 6 hours.

The level of skeletal uptake depends on blood flow and the degree of regeneration of the underlying bone tissue. Body retention values are: 31.6 ± 5% in healthy individuals, 38.2 ± 7% in patients with extensive metastases, 49 ± 11% in primary hyperparathyroidism, and 45% in osteoporosis.

Clinical characteristics.

Indications.

This medicinal product is intended exclusively for diagnostic use.

The radiopharmaceutical agent 99mTc-MDP is intended for bone scintigraphy utilizing the radioactive properties of technetium-99m and the affinity of methylenediphosphonic acid for hydroxyapatite crystals, which form the inorganic structure of bone tissue.

Contraindications.

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

Safety precautions.

In the event of hypersensitivity or anaphylactic reactions, administration of the medicinal product must be immediately discontinued and, if necessary, intravenous treatment initiated. To ensure timely emergency intervention, appropriate medicinal products and equipment, such as an intubation tube and a mechanical ventilator, should be prepared in advance.

Justification of individual benefit/risk

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

Patient preparation

No special patient preparation is required for the examination.

To obtain images of adequate quality, it is recommended that the patient empty the bladder prior to the start of the examination.

The vial contents are intended solely for the preparation of the radiopharmaceutical agent 99mTc-MDP and may be administered to the patient only after the labeling procedure is complete.

When deciding on the examination, increased sensitivity of the epiphyses of growing bones to ionizing radiation should be taken into account.

To minimize bladder irradiation, the patient should drink plenty of fluids and void the bladder as frequently as possible.

Increased radiation exposure may occur in patients with renal insufficiency. This should be considered when calculating the administered activity.

Special warnings

Preclinical safety data
The product is not intended for regular or continuous administration.

The very low toxicity of the medicinal product (LD50 = 190 mg/kg) allows safe administration of diagnostic doses. No immunization effects have been observed.

Special warning

Radiopharmaceuticals may be obtained, used, and prescribed only by authorized personnel licensed to work with radiopharmaceuticals in appropriate clinical settings. Their receipt, storage, use, transfer, and disposal are regulated by regulations and/or appropriate licenses issued by the relevant local authorities.

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

Appropriate aseptic precautions must be taken.

The contents of the kit are not radioactive prior to reconstitution. However, after addition of sodium pertechnetate (99mTc), appropriate shielding of the final product must be ensured.

Administration of radiopharmaceuticals creates a risk of ionizing radiation exposure and potential contamination from spills of urine, vomit, and other biological fluids to other individuals. Appropriate radiation protection precautions must be taken in accordance with applicable regulations when handling ionizing radiation.

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

Dosimetry

Technetium (99mTc) is obtained from a radionuclide generator (99Mo/99mTc) and decays with emission of gamma rays of 140 keV energy 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-MDP are provided in Tables 1 and 2.

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

Table 1

Patients with normal bone uptake.

The effective equivalent dose received from the administered activity of 740 MBq, for a patient with a body weight of 70 kg, is 4.22 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 high skeletal uptake and/or severe renal impairment

Interaction with other medicinal products and other forms of interactions.

Increased extraosseous accumulation of radiotracers has been reported when used concomitantly with iron-containing compounds, single-dose administration of diphosphonates, certain cytostatic and immunosuppressive agents, aluminum-containing antacids, radiographic contrast agents, antibiotics, anti-inflammatory substances, calcium gluconate injections, calcium heparin, and γ-aminocaproic acid.

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 the woman is pregnant. Any woman with a delayed menstruation should be considered pregnant until proven otherwise.

Studies involving the use of 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 irregular cycles), alternative diagnostic methods not involving ionizing radiation should be offered to the patient, if available.

Pregnancy

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

Administration of 700 MBq of 99mTc-MDP to a patient with normal skeletal uptake results in a uterine absorbed dose of 4.27 mGy. This dose decreases to 2.03 mGy in patients with high skeletal uptake and/or severe renal impairment. 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 postponing the radionuclide administration until breastfeeding has ended. Additionally, radiopharmaceuticals should be carefully selected based on their excretion 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

No data available.

Method of Administration and Dosage

The medicinal product is intended for intravenous administration.

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

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

To radiolabel one vial, 5 mL of sodium pertechnetate (99mTc) solution with an activity of 1100–18500 MBq should be used.

Image acquisition

High-quality scintigraphic images (e.g., in three-phase scintigraphy) are obtained using so-called static late-phase scintigraphy, i.e., performing the examination no sooner than 2 hours after intravenous administration of the radiopharmaceutical. Performing the examination earlier may result in images that only partially reflect bone metabolic activity. Slow injection of the radiopharmaceutical over approximately 30 seconds is recommended.

Dosage

Adults

The recommended activity for a single skeletal system examination in adult patients ranges from 370 to 740 MBq; however, depending on the indication, other activity levels may be justified.

Children and adolescents

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 administered activity is calculated by multiplying the baseline activity (for calculation purposes) by a weight-based coefficient:

The minimum dose of 40 MBq is required to obtain images of sufficient quality in very young children (under 1 year of age).

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, prior to the radiolabelling procedure, the vial must be carefully inspected for damage, including cracks.

Polytech MDP 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

Fill the vial with a solution of sodium pertechnetate-99mTc with an activity of 1100–18500 MBq.

1. Place the vial containing the powder into an appropriate lead-shielded container.
2. Using a syringe, inject approximately 5 mL of sodium pertechnetate-99mTc eluate (or eluate of required activity previously diluted with sterile physiological saline in a vial) through the rubber stopper.
3. Using the same sy游戏副本

Adverse reactions.

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

Table 3

Rarely (approximately 1 in 200,000 investigations), hypersensitivity reactions may occur after intravenous administration of 99mTc-MDP, including very rare life-threatening anaphylactic reactions. Cases of local rash or generalized rash with itching and skin irritation have been reported. Reactions usually begin several hours after administration and may last up to 48 hours. Treatment with a non-sedating H1 histamine antagonist is effective.

Other reported reactions include hypotension and its symptoms, nausea, vomiting, cutaneous vasodilation, headache, malaise, limb edema, and arthralgia.

For each patient, exposure to ionizing radiation must be justified based on the expected benefit. The administered activity should be as low as reasonably achievable to obtain the desired diagnostic outcome, while keeping the radiation dose as low as possible.

Exposure to ionizing radiation is associated with cancer induction and the potential risk of developing genetic defects. Data from diagnostic nuclear medicine procedures indicate that the probability of such adverse reactions is low.

For most diagnostic nuclear medicine procedures, 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-MDP: chills, injection site pain, fever, nausea, vomiting, erythema, back pain, abdominal pain, headache, dizziness, sweating, hypersensitivity reactions, fatigue, photophobia, erythema, skin rash, pruritus, seizures, metallic taste, and cardiac arrest (one fatal case has been reported due to secondary cardiac arrhythmia).

Shelf life.

Kit – 1 year.

After radioactive labeling with sodium pertechnetate (99mTc) solution – 8 hours.

Storage conditions.

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

During transport (for up to 7 days) at a temperature not exceeding 35 °C.

After radioactive labeling 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.

Prescription status.

For hospital use only.

Supplied exclusively to specialized medical facilities authorized to handle radiopharmaceuticals.

Manufacturer.

National Centre for Nuclear Research / Narodowe Centrum Badań Jądrowych.

Manufacturer's address and location of operations.

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