NETSPOT (Page 3 of 5)

3 DOSAGE FORMS AND STRENGTHS

For Injection: NETSPOT is supplied as a single-dose kit, containing two vials for preparation of Ga 68 dotatate injection:

  • Vial 1 (reaction vial with lyophilized powder): 40 mcg of dotatate, 5 mcg of 1,10-phenanthroline, 6 mcg gentisic acid and 20 mg D-mannitol for injection as a white lyophilized powder in a 10 mL glass vial with light-blue flip-off cap
  • Vial 2 (buffer vial): clear, and colorless reaction buffer solution (60 mg formic acid, 56.5 mg sodium hydroxide in approximately 1 mL volume) in a 10 mL olefin polymer vial with a yellow flip-off cap

Gallium 68 is obtained from one of the following generators:

  • Eckert & Ziegler GalliaPharm Ge 68/Ga 68 generator
  • IRE ELiT Galli Eo (Ge 68/Ga 68) generator

After reconstitution with Ga 68 and pH adjustment with Reaction Buffer, Vial 1 contains a sterile solution of Ga 68 dotatate at a strength of up to 218 MBq/mL (5.89 mCi/mL).

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Radiation Risk

Ga 68 dotatate 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 reconstitution procedures to protect patients and health care workers from unintentional radiation exposure [see Dosage and Administration (2.1)].

Avoid close contact with infants and pregnant women during the first 12 hours after administration of Ga 68 dotatate.

5.2 Hypersensitivity Reactions

Hypersensitivity reactions following administration of somatostatin receptor imaging agents predominantly consisted of cutaneous reactions, such as rash and pruritus. Reactions reversed either spontaneously or with routine symptomatic management. Less frequently hypersensitivity reactions included angioedema or cases with features of anaphylaxis.

5.3 Risk for Image Misinterpretation

The uptake of Ga 68 dotatate reflects the level of somatostatin receptor density in NETs. However, uptake can also be seen in a variety of other tumor types (e.g., those derived from neural crest tissue). Increased uptake might also be seen in sites of splenosis or other pathologic conditions (e.g., thyroid disease or subacute inflammation) or might occur as a normal physiologic variant (e.g., uncinate process of the pancreas). PET images with Ga 68 dotatate should be interpreted visually and the uptake may need to be confirmed by histopathology or other assessments [see Dosage and Administration (2.7)].

A negative scan after the administration of Ga 68 dotatate in patients who do not have a history of NETs, including in patients suspected of ectopic ACTH-secreting tumors, does not rule out the presence of NETs.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Hypersensitivity reactions [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

The safety of Ga 68 dotatate was evaluated in three single center studies [see Clinical Studies (14)] and in a survey of the scientific literature. No serious adverse reactions were identified.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of NETSPOT or other somatostatin receptor imaging agents. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug.

Gastrointestinal Disorders: Nausea and vomiting

General Disorders and Administration Site Conditions: Injection site pain and burning sensation

Immune System Disorders: Hypersensitivity reactions, predominantly rash, pruritus, less frequently angioedema or features of anaphylaxis.

7 DRUG INTERACTIONS

Non-radioactive somatostatin analogs competitively bind to the same somatostatin receptors as Ga 68 dotatate. Image patients with Ga 68 dotatate PET just prior to dosing with long-acting analogs of somatostatin. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with Ga 68 dotatate.

Corticosteroids can down-regulate somatostatin subtype 2 receptors. Repeated administration of high doses of glucocorticoid prior to Ga 68 dotatate administration may result in false negative imaging.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no studies with Ga 68 dotatate in pregnant women to inform any drug-associated risks; however, all radiopharmaceuticals, including Ga 68 dotatate have the potential to cause fetal harm. Animal reproduction studies have not been conducted with Ga 68 dotatate.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

8.2 Lactation

Risk Summary

There is no information on the presence of Ga 68 dotatate in human milk, the effect on the breastfed infant, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Ga 68 dotatate injection and any potential adverse effects on the breastfed child from Ga 68 dotatate injection or from the underlying maternal condition.

Clinical Considerations

Advise a lactating woman to interrupt breastfeeding and pump and discard breast milk for 12 hours after Ga 68 dotatate administration in order to minimize radiation exposure to a breastfed infant.

8.4 Pediatric Use

The efficacy of Ga 68 dotatate PET imaging in pediatric patients with neuroendocrine tumors is based on extrapolation from adult studies, from studies demonstrating the ability of Ga 68 dotatate to bind to somatostatin receptors [see Clinical Pharmacology (12.1)] , and from a published study of Ga 68 dotatate PET imaging in pediatric patients with somatostatin receptor positive tumors. The safety profile of Ga 68 dotatate is similar in adult and pediatric patients with somatostatin receptor positive tumors. The recommended Ga 68 dotatate injection dose in pediatric patients is weight based as in adults [see Dosage and Administration (2.2)].

8.5 Geriatric Use

Clinical studies of Ga 68 dotatate injection did not include sufficient numbers of subjects aged 65 and over, 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.

10 OVERDOSAGE

In the event of a radiation overdose, the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by reinforced hydration and frequent bladder voiding. A diuretic might also be considered. If possible, an estimate of the radioactive dose given to the patient should be performed.

11 DESCRIPTION

NETSPOT is supplied as a sterile, single-dose kit for preparation of Ga 68 dotatate injection for intravenous use.

Dotatate, also known as DOTA-0-Tyr3-Octreotate , is a cyclic 8 amino acid peptide with a covalently bound chelator (dota). The peptide has the amino acid sequence: H-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-OH, and contains one disulfide bond. Dotatate has a molecular weight of 1435.6 Daltons and its chemical structure is shown in Figure 3.

Figure 3. Chemical Structure of dotatate

Figure 3.	Chemical Structure of dotatate
(click image for full-size original)

[(4,7,10-Tricarboxymethyl-1,4,7,10-tetrazacyclododec-1-yl)acetyl]-(D)-Phenylalanyl-(L)Cysteinyl-(L)-Tyrosyl-(D)-Tryptophanyl-(L)-Lysyl-(L)-Threoninyl-(L)-Cysteinyl-(L)-Threonine-cyclic(2-7)disulfide

NETSPOT is a Kit with the following components:

  • Vial 1 (reaction vial with lyophilized powder) contains: 40 mcg dotatate, 5 mcg 1,10-phenanthroline; 6 mcg gentisic acid; 20 mg mannitol.
  • Vial 2 (buffer vial) contains: 60 mg formic acid; 56.5 mg sodium hydroxide and water for injection.

After reconstitution and radiolabeling, [see Dosage and Administration (2.3)] , Ga 68 dotatate injection also contains hydrochloric acid as an excipient derived from the generator eluate. The prepared Ga 68 dotatate injection for intravenous use, is a sterile, pyrogen free, clear, colorless, buffered solution, with a pH between 3.2 — 3.8. Table 5, Table 6, and Table 7 display the principle radiation emission data, radiation attenuation by lead shielding, and physical decay of Ga 68.

Table 5. Principal Radiation Emission Data (> 1%)
Radiation/Emission% DisintegrationMean Energy (MeV)
beta+88%0.8360
beta+1.1%0.3526
gamma178%0.5110
gamma3%1.0770
X-ray2.8%0.0086
X-ray1.4%0.0086
Table 6. Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding
Shield Thickness (Pb) mmCoefficient of Attenuation
60.5
120.25
170.1
340.01
510.001
Table 7. Physical Decay Chart for Gallium Ga 68
MinutesFraction Remaining
01.000
150.858
300.736
600.541
900.398
1200.293
1800.158
3600.025

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