Consumer medicine information

Gallium (Ga 67) Citrate Injection

Gallium (67Ga) citrate

BRAND INFORMATION

Brand name

Gallium (Ga67) Citrate Injection

Active ingredient

Gallium (67Ga) citrate

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Gallium (Ga 67) Citrate Injection.

What is in this leaflet

This leaflet answers some of the common questions about Gallium (Ga 67) Citrate Injection. It does not contain all of the available information about Gallium (Ga 67) Citrate Injection. It does not replace talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you or your child receiving Gallium (Ga 67) Citrate Injection against the benefits he or she expects it will have.

If you have any concerns about having this medicine, ask your doctor.

Keep this leaflet.

You may need to read it again.

What is Gallium (Ga 67) Citrate Injection

Gallium (Ga 67) Citrate Injection contains the active ingredient called Gallium Ga 67 and belongs to a group of medicines called radiopharmaceutical agents, which are all radioactive.

Gallium (Ga 67) Citrate Injection comes in a 10 mL vial and is available in three different radioactivities. It is ready for intravenous injection as packaged.

What Gallium (Ga 67) Citrate Injection is used for

Gallium (Ga 67) Citrate Injection is used to diagnose, stage and/or manage malignant lymphomas such as Hodgkin’s and non-Hodgkin’s lymphoma. Gallium (Ga 67) Citrate Injection may also help in the diagnosis of lung cancer.

Gallium (Ga 67) Citrate Injection can also be used to diagnose specific lung inflammatory lesions.

Your doctor may have prescribed Gallium (Ga 67) Citrate Injection for another purpose. Ask your doctor if you have any questions about why Gallium (Ga 67) Citrate Injection has been prescribed for you. If you have any concerns, you should discuss these with your doctor.

This medicine is only available with a doctor's prescription.

Before you are given Gallium (Ga 67) Citrate Injection

Before you are given Gallium (Ga 67) Citrate Injection your doctor will explain to you the procedure you are about to undergo, and the radioactive medicine you will be given. You must discuss any concerns you have with your doctor.

Gallium (Ga 67) Citrate Injection is not recommended for patients less than 3 years of age. If your doctor believes it is necessary to give Gallium (Ga 67) Citrate Injection to a patient under 18, he or she will discuss the benefits and risks with you.

You must tell your doctor if you have allergies to:

  • any other medicines
  • any other substances such as foods, preservatives or dyes

Tell your doctor if you are or plan to become pregnant.

Like most medicines Gallium (Ga 67) Citrate Injection is not recommended for use during pregnancy. If there is a need to consider Gallium (Ga 67) Citrate Injection during your pregnancy, your doctor will discuss the benefits and risks of giving it to you.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Like most medicines Gallium (Ga 67) Citrate Injection is not recommended while you are breastfeeding. However if you are breastfeeding, formula feedings should be substituted for breastfeeding for 24 hours following the administration of Gallium (Ga 67) Citrate Injection. Breast milk produced within that time should be discarded.

Tell your doctor if you have any other medical conditions especially if you suffer from heart disease.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from pharmacy, supermarket or health food shop.

How Gallium (Ga 67) Citrate Injection is given

How much is given

Your doctor will decide how much you will be given. This depends on your condition and other factors, such as weight.

If you are being given Gallium (Ga 67) Citrate Injection for cancer or inflammatory lesion imaging you will be given one injection.

How it is given

Gallium (Ga 67) Citrate Injection is given as an injection into a vein. Gallium (Ga 67) Citrate Injection should only be given by a doctor or a nurse.

When you are given Gallium (Ga 67 Citrate Injection

Things you must do

There is nothing in particular you must do once given Gallium (Ga-67) Citrate Injection.

Things you must not do

Do not take any other medicines unless advised by your doctor.

Things to be careful of

Gallium (Ga 67) Citrate Injection should not affect your ability to drive or operate machinery.

Gallium is eliminated from the body in the intestines and kidneys. Because activity in the intestines may interfere with the interpretation of your scan, the physician may ask you to take a laxative or have an enema to help eliminate the Gallium from the intestines.

Side effects

Tell your doctor as soon as possible if you do not feel well after being given Gallium (Ga 67) Citrate Injection.

All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some side effects.

Tell your doctor if you experience any of the following and they worry you

  • warm sensation
  • Warmth or redness of skin (Flushing)
  • Painful skin redness (Cutaneous erythema)
  • Itching (Pruritis)
  • Hives (Urticaria)

These side effects are usually mild.

Tell your doctor or a nurse immediately if you notice any of the following:

  • chest pain or a feeling of tightness, pressure or heaviness in the chest
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • changes in your heart rate
  • feeling faint
  • vomiting
  • abdominal pain
  • rash, itching or hives (itchy swellings on the skin)
  • allergic reaction - shortness of breath or difficulty breathing, slow heart rate, dizziness or light-headedness, feeling unusually tired or weak
  • fever

These are serious side effects for which you may need urgent medical treatment.

Do not be alarmed by this list of side effects.

You may not experience any of them.

Product Description

What it looks like

Gallium (Ga 67) Citrate Injection is a clear sterile solution which is supplied in a glass vial. An injection is prepared from the vial immediately before it is injected.

Ingredients

Active ingredient:
Gallium Ga 67 Citrate

Inactive Ingredients:
Sodium Citrate dihydrate
Sodium Chloride
Benzyl Alcohol

BRAND INFORMATION

Brand name

Gallium (Ga67) Citrate Injection

Active ingredient

Gallium (67Ga) citrate

Schedule

Unscheduled

 

Name of the medicine

Gallium (Ga67) citrate.

Excipients.

Sodium citrate, benzyl alcohol, sodium chloride and water for injection.

Description

Mallinckrodt Medical catalogue number: DRN 3103. CAS: 41183-64-6.

Qualitative and quantitative composition.

Composition per mL at activity reference date and time 67Ga as gallium citrate 37 MBq. The qualitative composition is in conformity with the monograph 555 of the European Pharmacopoeia. Gallium (67Ga) is a radionuclide (Atomic number 31; atomic weight 67) and has a physical half-life of 3.3 days (78.3 hours). It decays to stable zinc by electron capture emitting gamma energies of 93 keV (38%), 185 keV (21%) and 300 keV (16.8%). A small, but clinically insignificant amount of 66Ga is present as a natural contaminant (see dosimetry). For excipients, see List of excipients.

Pharmaceutical form.

Solution for injections.

List of excipients.

Sodium citrate, benzyl alcohol, sodium chloride and water for injection.
The pH of the product is 6-8.

Incompatibilities.

Incompatibilities are not known to exist.

Pharmacology

Pharmacodynamic properties.

Pharmacotherapeutic group: Other radiopharmaceuticals for inflammation and infection detection. ATC code: V09H X01.
The accumulation of gallium in tumour tissue and in sites of inflammation is thought to be due to its behavioural similarity to iron. Incorporation of gallium in transferrin, ferritin and lactoferrin has been demonstrated in-vivo and, with respect to transferrin, also in-vitro.
In the chemical dosages administered in man for imaging procedures (< 10-7 mg/kg) it is not envisaged that gallium would have clinically important pharmacodynamic effects. High doses of gallium are known to interact with body tissues and the effects of its decay product zinc (> 2 g) are described in man as toxic.

Pharmacokinetic properties.

During the first 24 hours after administration 15 to 25% of the administered dose is excreted via the kidneys. The remaining activity is slowly excreted via the intestinal tract (t1/2 of 25 days). By day 7 post injection, the body usually retains about 65% of the administered dose. The skeleton is the major site for gallium retention (25% of administered dose). Other organs that visibly retain activity are liver, spleen, kidneys, lachrymal and salivary glands, nasopharynx and the breast (especially when lactating).

Preclinical safety data.

Single-dose intravenous toxicity of gallium (67Ga) citrate is species dependent being significantly more toxic in dogs than rats. Gallium possesses cumulative toxic effects. Total doses of 6.5 to 20 mg/kg administered over periods of several weeks can be lethal. These doses are about 1000 times more than the maximal human dose of 67Ga administered for diagnostic purposes (i.e. < 1 microgram/70 kg).

Indications

Gallium Citrate Ga 67 may be useful to demonstrate the presence and extent of Hodgkin's disease, lymphoma, and broncogenic carcinoma. Positive Gallium Ga 67 uptake in the absence of prior symptoms warrants follow-up as an indication of potential disease state. Gallium Citrate Ga 67 may be useful as an aid in detecting some acute inflammatory lesions.

Contraindications

This product contains 9 mg/mL benzyl alcohol. This product should not be given to premature babies or neonates.

Precautions

Special warning and special precautions for use.

This medicinal product contains less than 1 mmoL sodium (23 mg) per dose.
This radiopharmaceutical may be received, used and administered only by authorised persons in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the local competent official organisations.
Care must be exercised in interpreting images of the lung fields at 24-48 hours when non-specific uptake of gallium (67Ga) citrate may occur. Such findings may not indicate interstitial lung disease. The appearance of gallium (67Ga) conjugates in the intestines, resulting from its accumulation in the liver and subsequent biliary excretion, can reduce its diagnostic usefulness in detecting intra-abdominal lesions. In such cases the administration of a laxative in advance of imaging may be helpful. The administration of laxatives in insulin dependent diabetics should be undertaken with due caution.

Paediatric use.

This product contains 9 mg/mL benzyl alcohol. Benzyl alcohol may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old.
Gallium (67Ga) is a bone-seeking radionuclide. Therefore, particular care should be exercised in young children where irradiation of the end-plates in growing bone and haemopoietic tissues may require special consideration (see dosimetry).

Use in the elderly.

No data available.

Effects on fertility.

No data available.

Carcinogenicity and genotoxicity.

No data are available about possible mutagenic or carcinogenic effects of gallium. Gallium is known to be teratogenic when administered in high dosages but insufficient data are available in order to estimate the risk.

Use in pregnancy.

When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. Where uncertainty exists it is important that radiation exposure should be the minimum consistent with achieving the desired clinical information. Alternative techniques which do not involve ionising radiation, should be considered.
All radionuclide procedures carried out on pregnant women involve radiation doses to the fetus. Radiogallium is not suitable for use during any stage of pregnancy although its administration may be justifiable in exceptional circumstances e.g. curable neoplastic disease requiring routine chemo- or radiotherapy with undisputed teratogenic potential. In such cases special consideration of dosimetry will be necessary. In particular, the potential risks to be incurred by both the mother and fetus will need to be carefully debated. An absorbed dose of greater than 0.5 mGy is normally considered hazardous to the developing fetus. Higher dosages may occasionally be justifiable later in pregnancy. However, it should be noted that when administering an activity of 185 MBq the absorbed dose to the uterus in a 15 year old (70 kg) pregnant female will be in the order of 19 mGy.

Use in lactation.

Gallium (67Ga) should only be administered to lactating females after breast-feeding has been discontinued.

Effects on the ability to drive and use machines.

Administration of diagnostic activities of gallium (67Ga) citrate involves amounts which are unlikely to result in effects on the ability to drive or to use machines.

Interactions

The biodistribution of gallium (67Ga) may be affected by a wide range of pharmacological substances including cytotoxic agents, immunosuppressants (including steroids), radiocontrast agents, phenothiazines, tricyclic antidepressants, metoclopramide, reserpine, methyl dopa, oral contraceptives and stilboestrol.
Pre-treatment with some cytotoxic agents may lead to an increased uptake of radiogallium in the bony skeleton, accompanied by a reduced accumulation in the liver, in soft tissues and also in tumour.
Non-specific, non-pathological 67Ga lung uptake has been described in patients who have received contrast media for contrast-enhanced radiolymphangiography.
Significant uptake of gallium in the thymus gland may be observed in children who have undergone chemotherapy and radiotherapy. This is non-pathological and is as a consequence of secondary hyperplasia.
Drugs causing increases in plasma prolactin levels may lead to increased gallium uptake in the mammary tissues.
Alteration in 67Ga radiokinetics and tissue binding may occur after iron therapy. Therefore, the possibility of false positive results should always be borne in mind.

Adverse Effects

For each patient, exposure to ionising radiation must be justifiable on the basis of likely benefit. The activity administered must be such that the resulting radiation dose is as low as reasonably achievable bearing in mind the need to obtain the intended diagnostic or therapeutic result.
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. For diagnostic nuclear medicine investigations the current evidence suggests that these adverse effects will occur with low frequency because of the low radiation doses incurred.
For most diagnostic investigations using a nuclear medicine procedure the radiation dose delivered (effective dose/EDE) is less than 20 mSv. Higher doses may be justified in some clinical circumstances.
The following frequencies are used to classify the adverse events: very common: > 10%; common: 1%-10%; uncommon: 0.1% - 1%; rare: 0.01% - 0.1%; very rare: < 0.01%.
Very rare: intravenous administration of Gallium (67Ga) citrate has been reported to provoke adverse reactions of an anaphylactoid nature. The symptoms are generally mild being characterised as a warm sensation, generalised flushing, cutaneous erythema, pruritus and/or urticaria.

Dosage and Administration

Radiation dosimetry.

For this product the effective dose equivalent resulting from an administered activity of 185 MBq is typically 22 mSv assuming a weight of 70 kg. The absorbed doses to bone surfaces would be in the order of 109 mGy with a 10-fold reduction of the activities required in children of 1 year in order to achieve similar absorbed doses.
The contribution of the contaminant 66Ga to the delivered radiation dose is less than 0.5% at the time of delivery of the product, and diminishes rapidly afterwards due to the short physical half-life of this isotope (9 hours). 66Ga is a positron and gamma emitter.
Table 1 shows the dosimetry tables (ICRP53) stating the absorbed doses to the seven standard organs and five additional organs according dose retention (marked with *).

Adults/elderly.

Recommended activity range 74-185 MBq. Activities of 37 MBq may be adequate for the sequential follow up of disease activity in patients with interstitial lung disease. Higher activities in SPECT may be required for tumour imaging (up to 260 MBq). This is most commonly encountered when staging mediastinal lymphomas.

Children.

Limited experience is recorded for children. Where alternative non-ionising diagnostic methods are unavailable gallium (67Ga) citrate may be used but the activities should be scaled down according to body weight-1.85 MBq/kg is recommended.
Gallium (67Ga) citrate may only be administered by intravenous injection. Imaging may be undertaken 24 and 92 hours after administration although preferably on the 2nd or 3rd day for tumours. When investigating inflammatory lesions early scintigraphy, possibly as little as 4 hours after administration, may also be of value.

Instructions for use and handling and disposal.

The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spills of urine, vomiting, etc. Therefore, radiation protection precautions in accordance with national regulations must be taken.

Overdosage

Gallium (67Ga) citrate should only be administered intravenously by qualified personnel in authorised settings. Therefore, the possibility of a pharmacological overdose is remote.
In the unlikely event of inadvertent excess of activity being administered, the overall radiation to critical organs may be reduced by the intravenous administration of appropriate chelating agents (as for other heavy metals). In addition, increased fluids by mouth and the intensive use of laxatives may be indicated when it is necessary to promote excretion of the radiolabel.

Presentation

10 mL glass vial (Type 1 Ph.Eur) closed with a bromobutyl rubber stopper sealed with an aluminium crimp cap. Gallium (Ga67) Citrate Injection is supplied in the following activity amounts at activity reference date and time:
Gallium (Ga67) citrate 82 MBq/2.2 mL;
Gallium (Ga67) citrate 123 MBq/3.3 mL;
Gallium (Ga67) citrate 205 MBq/5.5 mL.

Storage

Do not store Gallium (Ga67) Citrate Injection above 25°C. Store at 2°C to 8°C after first use. If multi-dose use is intended, each aliquot should be removed under aseptic conditions, and within one working day.

Shelf-life.

Gallium (Ga67) Citrate Injection expires 10 days after the activity reference date and time. Activity reference date and time and expiry date and time are stated on the label of the shielding and in the shipping papers accompanying each shipment. After opening of the vial the shelf-life of the product is 8 hours.

Poison Schedule

Unscheduled.