DRAXIMAGE DTPA: Package Insert and Label Information (Page 3 of 4)

3 DOSAGE FORMS AND STRENGTHS

Kit for the preparation of Technetium Tc 99m pentetate injection: multiple-dose 10 mL glass vial contains a non-radioactive (white) lyophilized powder with 20 mg of pentetic acid, 5 mg of p-aminobenzoic acid, 3.73 mg of calcium chloride dihydrate, and not less than 0.25 mg stannous chloride dihydrate and not more than 0.385 mg maximum tin expressed as stannous chloride dihydrate. The lyophilized product is sealed under an atmosphere of nitrogen.

Following reconstitution with the Technetium Tc 99m eluate, the radioactive solution produced is a clear solution not exceeding 9250 MBq/mL (250 mCi/mL) of Tc 99m.

4 CONTRAINDICATIONS

Hypersensitivity to the active ingredient or to any component of the product [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported during post-approval diagnostic use of Technetium Tc 99m pentetate injection. Monitor all patients for hypersensitivity reactions and have access to cardiopulmonary resuscitation equipment and personnel.

5.2 Image Interpretation Risks in Lung Ventilation Studies

In patients with obstructive pulmonary disease there may be deposition of particles in the proximal airways influencing image quality and interfering with diagnostic interpretation, therefore to ensure diagnostic quality, careful use of the nebulizer to assure optimal particle delivery is essential. If interfering particle deposition occurs, consider additional diagnostic options.

5.3 Radiation Exposure Risk

Technetium Tc 99m contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Use the lowest dose of Technetium Tc 99m pentetate necessary for imaging. Encourage patients to drink fluids and void as frequently as possible after intravenous administration [see Dosage and Administration (2.1, 2.3)].

Radiation risks associated with the use of Technetium Tc 99m pentetate are greater in pediatric patients than in adults due to greater radiosensitivity and longer life expectancy.

5.4 Bronchospasm in Lung Ventilation Studies

As with other inhaled medications, inhalation of Technetium Tc 99m pentetate solution may result in acute bronchoconstriction, especially in patients with heightened bronchoreactivity, such as patients with asthma or other lung or allergic disorders. Monitor all patients for bronchoconstriction.

6 ADVERSE REACTIONS

The following adverse reactions have been identified post-approval. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their exact frequency or establish a causal relationship to Technetium Tc 99m pentetate exposure.

Adverse reactions are presented in decreasing order of reported frequency:

  • Immune system disorders: allergic reaction, anaphylactic reaction, angioedema.
  • Skin and subcutaneous tissue disorders: rash, itching, hives, erythema.
  • Respiratory, thoracic and mediastinal disorders: throat irritation, wheezing.
  • Vascular disorders: hypotension, hypertension.
  • Nervous system disorders: headache, fainting, dizziness.
  • General disorders and administration site conditions: chills.
  • Gastrointestinal disorders: nausea, vomiting.
  • Cardiac disorders: cyanosis, tachycardia.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Limited available data with Technetium Tc 99m pentetate use in pregnant women are insufficient to inform a drug associated risk for major birth defects and miscarriage. Technetium Tc 99m pentetate is transferred across the placenta (see Data). No animal reproductive studies have been conducted with Technetium Tc 99m pentetate. All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering Technetium Tc 99m pentetate administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from Technetium Tc 99m pentetate and the gestational timing of exposure.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S., general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

Data

Human Data Limited published literature describes Technetium Tc 99m pentetate crossing the placental barrier. No adverse fetal effects or radiation-related risks have been identified for diagnostic procedures involving less than 50 mGy, which represents less than 10 mGy fetal doses.

8.2 Lactation

Risk Summary

There are limited data available in scientific literature on the presence of Technetium Tc 99m pentetate in human milk. There are no data available on the effects of Technetium Tc 99m pentetate on the breastfed infant or the effects on milk production. Based on the United States Nuclear Regulatory Commission guidelines for breast feeding interruption after exposure to radiopharmaceuticals, breastfeeding interruption is not recommended for Technetium 99m pentetate at levels less than 1000 MBq (30 mCi). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Technetium Tc 99m pentetate, any potential adverse effects on the breastfed child from Technetium Tc 99m pentetate or from the underlying maternal condition.

8.4 Pediatric Use

Technetium Tc 99m pentetate is indicated for lung ventilation and evaluation of pulmonary embolism when paired with perfusion imaging and for renal visualization, assessment of renal perfusion, and estimation of glomerular filtration rate in pediatric patients ages birth to less than 17 years of age. Pediatric use is supported by evidence from controlled studies in adults and dosing and safety are based on clinical experience.

The radiation risk of Technetium Tc 99m pentetate is greater in pediatric patients than adults [See Warnings and Precautions, (5.3)].

8.5 Geriatric Use

No formal studies of Technetium Tc 99m pentetate in the elderly were performed to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

11 DESCRIPTION

11.1 Chemical Characteristics

DRAXIMAGE® DTPA is a kit for the preparation of Technetium Tc 99m pentetate injection, a radioactive diagnostic agent, for intravenous or inhalation use. Each multiple-dose 10 mL glass vial contains a sterile, non-pyrogenic, non-radioactive lyophilized powder of 20 mg of pentetic acid, 5 mg of p-aminobenzoic acid, 3.73 mg of calcium chloride dihydrate, and not less than 0.25 mg stannous chloride dihydrate and not more than 0.385 mg maximum tin expressed as stannous chloride dihydrate. The lyophilized product is sealed under an atmosphere of nitrogen. No bacteriostatic preservative is present. Its chemical name is:

Technetate (1-)99mTc,[N,N-bis[2-[bis(carboxymethyl)amino]ethyl]-glycinato(5-)]-, sodium. The structure of the technetium labeled form is:

structure
(click image for full-size original)

The pH is adjusted with HCl and/or NaOH prior to lyophilization so that the pH range of the reconstituted radiopharmaceutical is 6.5 to 7.5.

11.2 Physical Characteristics

Technetium Tc 99m decays by isomeric transition with a physical half-life of 6 hours. The principal photon that is useful for detection and imaging studies is listed in Table 7.

Table 7 Principal Radiation Emission Data
Radiation Mean % per Disintegration Mean Energy (keV)
Gamma-2 88.5 140.5

The air-kerma-rate (exposure-rate) constant for Technetium Tc 99m is 5.23 m2 ·pGy·(MBq) 1 ·s 1 [0.795 cm2 ·R·(mCi) 1 ·h 1 ]. A range of values for the relative radiation attenuation by the various thicknesses of lead is shown in Table 8. For example, the use of a 3 mm thickness of lead will attenuate the radiation emitted by a factor of about 1,000.

Table 8 Radiation Attenuation by Lead Shielding
Shield Thickness (Pb) cm Coefficient of Attenuation
0.25 0.5
1 10-1
2 10-2
3 10-3
4 10-4

To correct for physical decay of this radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 9.

Table 9 Physical Decay Chart of Technetium 99m Tc, Half Life: 6 Hours
*Calibration Time
Hours Fraction Remaining Hours Fraction Remaining
0* 1.000 5 0.562
1 0.891 6 0.501
2 0.794 8 0.398
3 0.708 10 0.316
4 0.631 12 0.251

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Intravenous Administration

Following intravenous administration for brain and renal imaging, Technetium Tc 99m pentetate is distributed in the vascular compartment. It is cleared by the kidneys, which results in the ability to image the kidney.

Aerosolized Inhalation Administration

Following inhalation of the aerosol, Technetium Tc 99m pentetate deposits on the epithelium of ventilated alveoli.

12.2 Pharmacodynamics

Brain Imaging

Technetium Tc 99m pentetate with intravenous administration tends to accumulate in intra-cranial lesions with excessive neovascularity or an altered blood brain barrier. Technetium Tc 99m pentetate accumulation in the brain is prevented by an intact blood brain barrier. It does not accumulate in the choroid plexus.

Renal Scintigraphy

The first few minutes after intravenous administration, Technetium Tc 99m pentetate is present in the vascular compartment within the renal system.

Lung Ventilation Imaging

In patients with normal lungs, the deposition of Technetium Tc 99m pentetate is homogeneous throughout the lungs. In patients with airway disease, the deposition patterns become inhomogeneous with irregular deposition of Technetium Tc 99m pentetate in the airways and alveolar regions of the lung.

12.3 Pharmacokinetics

After an intravenous administration, the pharmacokinetics of Technetium Tc 99m pentetate were studied by monitoring radioactivity in serial venous blood samples for 7 hours post-administration. The mean plasma clearance rate was 6.8 (L/h) and the mean plasma elimination half-life (t½) was 2.1 hours. The mean volume of distribution at steady state conditions calculated with clearance and mean residence time was 17 L. This relatively low volume of distribution after intravenous administration suggests that Technetium Tc 99m pentetate distributes to the extracellular fluid only. The rate of elimination of Technetium Tc 99m pentetate from the systemic circulation appears to be constant over an approximately 20-fold intravenous dose range.

Absorption

Following inhalation Technetium Tc 99m pentetate was absorbed (Tmax < 2 hours after inhalation) and distributed across the lung epithelium (bioavailability approximately 70%) and into the systemic circulation.

Distribution

Following intravenous administration, Technetium Tc 99m pentetate is distributed throughout the extracellular fluid space and is cleared from the body by the kidney.

The steady-state volume of distribution (Vss) was 17 L following an intravenous administration. Technetium Tc 99m pentetate distribution appears to be limited to the extravascular compartment.

A variable percentage of the Technetium Tc 99m pentetate binds to the serum proteins; this ranges from 3.7% following a single injection to approximately 10% if the material is continuously infused. Although the chelate gives useful information on the glomerular filtration rate, the variable percent which is protein bound leads to a measured renal clearance rate which is lower than that determined by inulin clearance.

Elimination

Metabolism

Technetium Tc 99m pentetate is not metabolized.

Excretion

After either intravenous administration or inhalation, excretion is by glomerular filtration. The mean fraction of intravenously administered Technetium Tc 99m pentetate excreted in urine over 24 hours was 102%.

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