PACKAGE LEAFLET

TECHNESCAN HDP 3 mg kit for radiopharmaceutical preparation

Sodium hydroxymethylenediphosphonate
NAME OF THE MEDICINAL PRODUCT
TECHNESCAN HDP 3 mg kit for radiopharmaceutical preparation
PHARMACOTHERAPEUTIC CATEGORY
Pharmacotherapeutic category: radiopharmaceuticals for diagnostic use.
ATC Code: V09BA01.
THERAPEUTIC INDICATIONS
Medicinal product for diagnostic use only.
After radiolabelling with an injectable solution of sodium pertechnetate ( Tc), the technetium ( Tc) hydroxymethylenediphosphonate solution is indicated for bone scintigraphy, allowing localization of areas with altered osteogenesis.
CONTRAINDICATIONS
Hypersensitivity to the active substance or to any of the excipients listed in the Composition section or to any of the components of the labelled radiopharmaceutical.
SPECIAL PRECAUTIONS FOR USE
Pregnancy and lactation, see section Fertility, Pregnancy and Lactation.
Potential anaphylactic or anaphylactoid reactions
If anaphylactic or anaphylactoid reactions occur, administration of the medicinal product must be immediately discontinued and intravenous treatment initiated, if necessary.
To allow immediate intervention in case of emergency, necessary medications and equipment, such as endotracheal tube and ventilator, must be immediately available.
Benefit/risk ratio justification
For each patient, exposure to ionizing radiation must be justified based on the potential benefit. The administered activity must be such as to ensure the lowest reasonably achievable radiation dose to obtain the desired diagnostic information.
Renal/hepatic impairment
The administered activity must be carefully evaluated in patients with renal impairment, as these patients are at risk of increased radiation exposure.
In patients with high bone uptake and/or severe renal impairment, careful assessment of the benefit/risk ratio is required, as increased radiation exposure may occur in these patients.
This must be taken into consideration when calculating the administered activity (see Dosimetry section).
Image defects
Abnormal accumulation may occur in the liver (e.g. in case of liver metastases), spleen, adrenal glands, or heart (e.g. infarction, pericarditis), resulting in image defects (see also section Interactions).
Paediatric population
For information on use in the paediatric population, see section Dosage, method and time of administration.
In neonates and children, particular attention must be paid to the relatively high radiation exposure to the epiphyses of growing bones, as the product is taken up by the epiphyseal growth plate.
A careful benefit/risk assessment is required, as the effective dose per MBq in children is higher than in adults (see Dosimetry section).
Patient preparation
The patient should be well hydrated before the examination and encouraged to void before the examination and as frequently as possible during the first few hours after the examination, in order to reduce radiation exposure to the bladder.
To avoid radioisotope accumulation in the muscles, patients should be advised to avoid strenuous physical exercise immediately after injection until satisfactory images are obtained.
After the procedure
Close contact with children and pregnant women should be limited during the first 4 hours.
Specific warnings
It is important to avoid accidental subcutaneous administration of technetium ( Tc) hydroxymethylenediphosphonate, as cases of perivascular inflammation have been reported.
For precautions regarding environmental risk, see section Special precautions for disposal and handling.
INTERACTIONS
Inform your doctor or nuclear medicine specialist if you have recently taken any other medicinal products, including those without a prescription.
The uptake of technetium ( Tc) hydroxymethylenediphosphonate in the skeleton, and consequently the quality of the scintigraphic procedure, may be reduced by treatment with:

chelating agents
diphosphonates
tetracyclines
iron-containing drugs.

Regular treatment with aluminium-containing drugs (particularly antacids) may cause excessive uptake of technetium-99m in the liver, presumably due to the formation of labelled colloids.
SPECIAL WARNINGS
Pregnancy, lactation and fertility
Consult your doctor or nuclear medicine specialist before taking any medicinal product.
Women of childbearing potential
When administering radiopharmaceuticals to women of childbearing potential, information on possible pregnancy should always be obtained. Unless otherwise proven, any woman who has missed a menstrual period should be considered pregnant. In case of doubt regarding possible pregnancy (e.g. missed menstrual period, very irregular cycle, etc.), alternative techniques not involving ionizing radiation should be proposed to the patient (if available).
Pregnancy
Procedures using radionuclides in pregnant women result in radiation exposure also to the fetus. Radionuclide investigations during pregnancy should be performed only when absolutely necessary and when the expected benefit outweighs the risk to both mother and fetus.
Administration of 700 MBq of technetium ( Tc) hydroxymethylenediphosphonate to a patient with normal bone uptake corresponds to a uterus absorbed dose of 4.41 mGy. The dose is reduced to 2.03 mGy in patients with high bone uptake and/or severely impaired renal function.
Doses exceeding 5 mGy should be considered potentially hazardous to the fetus.
Lactation
Before administering radiopharmaceuticals to a breastfeeding woman, consideration should be given to the possibility of postponing the investigation until the end of breastfeeding, and it should be verified that the most appropriate radiopharmaceutical has been selected, taking into account the secretion of activity into breast milk. If administration is considered necessary, breastfeeding should be suspended for 4 hours and the milk produced during this period should be discarded. Close contact with infants should be limited during this period.
Fertility
The effect of administration of technetium ( T099m) hydroxymethylenediphosphonate on fertility and in pregnant women is unknown.
Effects on the ability to drive and use machines
No effects on the ability to drive and use machines are known.
Important information on some excipients
This medicinal product contains 12 mg of sodium per vial. Depending on the time of administration, the sodium content may in some cases exceed 1 mmol (23 mg).
This should be taken into consideration in individuals on a low-sodium diet.
DOSAGE, METHOD AND TIME OF ADMINISTRATION
Posology
Adults
In an adult weighing 50–70 kg, the recommended average activity to be administered per single intravenous injection is 500 MBq (range 300–700 MBq). Other activities may be justified.
Elderly
No dose adjustment is anticipated in elderly patients.
Renal impairment/high bone uptake
Careful evaluation of the administered activity is required, as these patients may be subject to higher radiation exposure.
Patients with high bone uptake and/or severe renal impairment
Dose adjustment may be required (see sections Precautions for use and Dosimetry).
Paediatric population
Use in children and adolescents should be carefully considered based on clinical need and benefit/risk assessment in this patient group.
The activity to be administered to children and adolescents corresponds to a fraction of the adult dose according to the recommendations of the European Association of Nuclear Medicine (EANM - Dosage Card 2008). This activity can be calculated using the formula below and a factor corresponding to the child's or adolescent's body weight (see Table 1):
Recommended activity [MBq] = 35 MBq × factor (Table 1)
Weight Factor Weight Factor Weight Factor
3 kg = 1 22 kg = 5.29 42 kg = 9.14
4 kg = 1.14 24 kg = 5.71 44 kg = 9.57
6 kg = 1.71 26 kg = 6.14 46 kg = 10.00
8 kg = 2.14 28 kg = 6.43 48 kg = 10.29
10 kg = 2.71 30 kg = 6.86 50 kg = 10.71
12 kg = 3.14 32 kg = 7.29 52–54 kg = 11.29
14 kg = 3.57 34 kg = 7.72 56–58 kg = 12.00
16 kg = 4.00 36 kg = 8.00 60–62 kg = 12.71
18 kg = 4.43 38 kg = 8.43 64–66 kg = 13.43
20 kg = 4.86 40 kg = 8.86 68 kg = 14.00
In very young children (up to one year of age), a minimum radioactivity dose of 40 MBq is required to obtain satisfactory image quality.
Method of administration
For multidose use.
After radiolabelling, the medicinal product is administered as a single intravenous injection.
Precautions to be taken before handling or administering the medicinal product
This medicinal product must be reconstituted before administration to the patient.
For instructions on reconstitution of the medicinal product before administration, see section Instructions for use.
For patient preparation, see section Precautions for use.
Image acquisition

Images acquired immediately after injection (e.g. using the so-called "three-phase bone scintigraphy" method) reflect only partially the metabolic activity of the bone. The final phase of static scintigraphy should be performed no earlier than 2 hours after injection.

OVERDOSAGE
In case of administration of an excessive dose of radioactivity of technetium ( Tc) hydroxymethylenediphosphonate, the dose administered to the patient should be reduced by increasing elimination of the radionuclide as much as possible through forced diuresis with frequent micturition.
In case of accidental ingestion/intake, immediately inform the doctor or nuclear medicine specialist.
ADVERSE REACTIONS
Adverse reactions are extremely rare after administration of technetium ( Tc) hydroxymethylenediphosphonate (less than 1 in 200,000 administrations): anaphylactic and anaphylactoid reactions, rash, nausea, hypotension and sometimes arthralgia. Symptoms may occur even 4–24 hours after administration.
The frequency of adverse reactions is defined as follows:
Very common (≥ 1/10)
Common (≥1/100, <1/10)
Uncommon (≥1/1,000, <1/100)
Rare (≥1/10,000, <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from available data)
The table below lists the adverse reactions observed according to MedDRA system organ class classification.
System organ class according to Adverse reaction Frequency
MedDRA
Immune system disorders Anaphylactic or anaphylactoid Very rare
reactions, angioedema
Vascular disorders Hypotension Very rare
Gastrointestinal disorders Nausea, vomiting, diarrhoea, Not known
abdominal pain
Skin and subcutaneous tissue Rash Very rare
disorders
Nervous system disorders Severe vegetative reactions such as Not known
circulatory collapse or syncope.
Vasovagal reactions such as
headache or dizziness
Musculoskeletal and connective Arthralgia Very rare
tissue disorders
General disorders and Reactions at injection site (e.g. Not known
administration site conditions cellulitis, inflammation, pain,
erythema, swelling), chills
Exposure to ionizing radiation is associated with cancer induction and potential occurrence of heritable defects. As the effective dose is 4.0 mSv when the maximum recommended activity of 700 MBq is administered, such adverse effects are expected to occur with low probability.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after marketing authorization of the medicinal product is important, as it allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system at http://www.agenziafarmaco.gov.it/it/responsabili.
EXPIRY DATE AND STORAGE
Shelf life: 2 years.
The expiry date is indicated on the secondary packaging and on each vial.
The expiry date refers to the product in intact packaging correctly stored.
Kit in intact packaging: store at a temperature not exceeding 25°C.
After radiolabelling, store the product at a temperature not exceeding 25°C and use within 8 hours.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the shelf life and storage conditions during use are the responsibility of the user.
Storage of radiopharmaceuticals must comply with national regulations on radioactive materials.
COMPOSITION
Each vial contains 3 mg of sodium hydroxymethylenediphosphonate (hydroxymethylene diphosphonate or HMDP).
TECHNESCAN HDP must be radiolabelled with injectable sodium pertechnetate ( Tc) solution.
The radionuclide is not included in this kit.
Excipients:
Stannous chloride dihydrate
Gentisic acid
Sodium chloride
Sodium hydroxide (to adjust pH)
Hydrochloric acid 37% (to adjust pH).
PHARMACEUTICAL FORM AND CONTENT
Kit for radiopharmaceutical preparation.
White to slightly yellowish lyophilized powder.
10 ml glass vial of type I closed with a bromobutyl rubber stopper, aluminium cap.
Packaging: 5 multidose vials
MARKETING AUTHORISATION HOLDER
Mallinckrodt Medical B.V.
Westerduinweg 3
1755 LE Petten
The Netherlands
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
Mallinckrodt Medical B.V. - Westerduinweg 3, 1755 LE Petten - The Netherlands
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
{DD Month YYYY}
REVISION OF THE PACKAGE LEAFLET BY THE ITALIAN MEDICINES AGENCY
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THE FOLLOWING INFORMATION IS INTENDED EXCLUSIVELY FOR HEALTHCARE PROFESSIONALS
Instructions for use
Withdrawals must be performed under aseptic conditions. Vials must not be opened. The solution should be withdrawn through the stopper using a single-use syringe and appropriate shielding, and a sterile disposable needle or an authorized automated dispensing system.
The product must not be used if the integrity of the vial is compromised during preparation.
Preparation method
Preparation for multidose use
Under aseptic conditions, add to a vial of Technescan HDP the required amount of sodium pertechnetate ( Tc) solution (fissionable/non-fissionable) with a maximum activity of 20 GBq in a volume of 3–10 ml.
Shake for 30 seconds to dissolve the contents. The preparation is then ready for injection.
Dilution is preferably performed with 0.9% sodium chloride solution.
In a single patient, a maximum of 1 mg of HDP (1/3 of a vial) may be injected.
Properties after radiolabelling
After radiolabelling, the solution is colourless and ranges from clear to slightly opalescent.
Quality control
Perform thin-layer chromatography (TLC) on silica gel-coated glass fibre plates.

Develop 5–10 µl in 13.6% sodium acetate R and technetium hydroxymethylenediphosphonate. Pertechnetate ions migrate near the solvent front, while hydrolysed technetium and colloidal technetium remain at the origin.
Develop 5–10 µl in methyl ethyl ketone R. Pertechnetate ions migrate to the solvent front, while the technetium hydroxymethylenediphosphonate complex and colloidal technetium remain at the origin. For details, consult the European Pharmacopoeia (Monograph 641).

Individual and total impurities must not exceed 5%.
Incompatibilities
This medicinal product must not be mixed with other products except those mentioned in the Instructions for use section.
SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING
General warnings
Radiopharmaceuticals must be received, used and administered only by authorized personnel in specially designated clinical facilities.
Receipt, storage, use, transfer and disposal must be carried out in accordance with regulations and/or appropriate authorizations from the competent local authorities.
Radiopharmaceuticals must be prepared to comply with radiation protection standards and pharmaceutical quality requirements. Appropriate aseptic precautions must be taken.
The vial contents are intended solely for the preparation of an injectable solution of technetium ( Tc) hydroxymethylenediphosphonate and must not be administered directly to the patient without prior preparation.
For instructions on radiolabelling the product before administration, see section Preparation method.
If at any time during preparation the integrity of the vial is compromised, the vial must not be used.
The contents of the kit before extemporaneous preparation are not radioactive. However, after addition of the injectable sodium pertechnetate ( Tc) solution, the final preparation must be adequately shielded.
Administration procedures must be performed to minimize the risk of contamination of the medicinal product and irradiation of operators. Adequate shielding is mandatory.
Administration of radiopharmaceuticals poses risks to other persons due to external irradiation or contamination from excretion of urine, vomit, etc. Therefore, radiation protection measures must be taken in accordance with national regulations.
Unused medicinal product and waste derived from this medicinal product must be disposed of in accordance with applicable local regulations.
DOSIMETRY
Sodium pertechnetate ( Tc) is produced by a generator ( Mo/ Tc) and decays with emission of gamma radiation with an average energy of 140 keV and a half-life of 6.02 hours to technetium ( Tc), which, due to its long half-life of 2.13 x 10 years, can be considered practically stable.
Dosimetry data were derived from ICRP (International Commission on Radiological Protection) publications 53 and 80 on phosphonates and are calculated based on the following assumptions:
Main uptake occurs in bone, with minor additional uptake in the kidneys, and excretion occurs via the renal system. It is assumed that a fraction of 0.5 of the injected activity is taken up by bone with a half-life of 15 minutes, and retained with T½ of 2 hours (0.3) and 3 days (0.7). In children, uptake occurs predominantly in the metaphyseal growth zones.
Renal uptake is set at 0.02 with retention identical to that of the whole body characterized by T½ (fractional retention) of 0.5 hours (0.3), 2 hours (0.3) and 3 days (0.4).
In pathological conditions, higher uptake and/or longer retention in bone may occur, especially in renal diseases. Whole-body retention at 24 hours, normally amounting to 30%, has been reported to be 40% in osteomalacia, 50% in primary hyperparathyroidism, 60% in Paget's disease and 90% in renal osteodystrophy. For absorbed dose calculation in pathological cases, an average bone uptake of 70% is assumed, without excretion.
Organ absorbed doses and effective absorbed doses for normal bone were recalculated in ICRP publication 80.
Radiation exposure (normal bone uptake) - ICRP 80
Absorbed dose/administered activity (mGy/MBq)
Organ
Adult 15 years 10 years 5 years 1 year
Adrenal glands 0.0021 0.0027 0.0039 0.0058 0.011
Bladder wall 0.048 0.06 0.088 0.073 0.13
Bone surface 0.063 0.082 0.13 0.22 0.53
Brain 0.0017 0.0021 0.0028 0.0043 0.0061
Breast 0.00071 0.00089 0.0014 0.0022 0.0042
Gallbladder 0.0014 0.0019 0.0035 0.0042 0.0067
Gastrointestinal tract
Stomach wall 0.0012 0.0015 0.0025 0.0035 0.0066
Small intestine 0.0023 0.0029 0.0044 0.0053 0.0095
Colon 0.0027 0.0034 0.0053 0.0061 0.011
Ascending colon wall 0.0019 0.0024 0.0039 0.0051 0.0089
Descending colon wall 0.0038 0.0047 0.0072 0.0075 0.013
Heart 0.0012 0.0016 0.0023 0.0034 0.006
Kidneys 0.0073 0.0088 0.012 0.018 0.032
Liver 0.0012 0.0016 0.0025 0.0036 0.0066
Lungs 0.0013 0.0016 0.0024 0.0036 0.0068
Muscles 0.0019 0.0023 0.0034 0.0044 0.0079
Oesophagus 0.001 0.0013 0.0019 0.003 0.0053
Ovaries 0.0036 0.0046 0.0066 0.007 0.012
Pancreas 0.0016 0.002 0.0031 0.0045 0.0082
Red bone marrow 0.0092 0.01 0.017 0.033 0.067
Skin 0.001 0.0013 0.002 0.0029 0.0055
Spleen 0.0014 0.0018 0.0028 0.0045 0.0079
Testes 0.0024 0.0033 0.0055 0.0058 0.011
Thymus 0.001 0.0013 0.0019 0.003 0.0053
Thyroid 0.0013 0.0016 0.0023 0.0035 0.0056
Uterus 0.0063 0.0076 0.012 0.011 0.018
Other tissues 0.0019 0.0023 0.0034 0.0045 0.0079
Effective dose (mSv/MBq) 0.0057 0.007 0.011 0.014 0.027
The effective dose resulting from administration of 700 MBq of technetium ( Tc) hydroxymethylenediphosphonate to a 70 kg adult is approximately 4.0 mSv.
For administration of 700 MBq, the radiation dose to the target organ (bone) is 44.1 mGy, while the dose to the critical organ (bladder wall) is 33.6 mGy.
Radiation exposure (high bone uptake or severe renal impairment) - ICRP 53
ORGAN Absorbed dose/administered activity (mGy/MBq)
Adult 15 years 10 years 5 years 1 year
Adrenal glands 0.0035 0.005 0.0072 0.011 0.021
Bladder wall 0.0025 0.0035 0.0054 0.0074 0.015
Bone surface 0.12 0.16 0.26 0.43 1.0
Breast 0.0021 0.0021 0.0032 0.0051 0.0096
Stomach wall 0.0026 0.0032 0.0051 0.0073 0.014
Small intestine 0.0031 0.0038 0.0057 0.0085 0.016
Ascending colon wall 0.0029 0.0036 0.0053 0.0086 0.015
Descending colon wall 0.0034 0.0042 0.0065 0.0096 0.018
Kidneys 0.003 0.0037 0.0056 0.0087 0.016
Liver 0.0027 0.0033 0.0049 0.0075 0.014
Lungs 0.003 0.0037 0.0053 0.0081 0.015
Ovaries 0.0029 0.0041 0.0059 0.0089 0.016
Pancreas 0.0032 0.004 0.0059 0.0089 0.016
Red bone marrow 0.018 0.023 0.037 0.072 0.14
Spleen 0.0026 0.0034 0.0051 0.0078 0.015
Testes 0.0023 0.0027 0.0039 0.006 0.011
Thyroid 0.0024 0.0037 0.0054 0.0083 0.014
Uterus 0.0029 0.0037 0.0054 0.0082 0.015
Other tissues 0.003 0.0036 0.0053 0.0081 0.015
Equivalent effective dose (mSv/MBq) 0.0082 0.011 0.017 0.028 0.061
In cases of high bone uptake and/or severe renal impairment, the effective dose resulting from administration of 700 MBq of radioactivity is normally 5.7 mSv. The typical radiation dose to the target organ (bone) is 84 mGy and the typical radiation dose to the critical organ (red bone marrow) is 12.6 mGy.