DOPACIS Solution for injection Ref.[51143] Active ingredients: Fluorodopa ¹⁸F

Individual benefit/risk justification

For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information.

In patients with reduced kidney function, careful consideration of the indication is required since an increased radiation exposure is possible in these patients.

In patients with a mutation of the succinate dehydrogenase sub-unit B gene, Dopacis is not indicated in diagnosis and localisation of glomus tumors.

Paediatric population

Paediatric population, see section 4.2. or 5.1., as appropriate.

Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11 “Dosimetry”).

Repeated use

Data on repeated use of fluorodopa (¹⁸F) are limited. It is recommended to not inject Dopacis before 5 days after the first administration.

Patient Preparation

Patients should be fasting for at least 4 hours, with unlimited amounts of water, before administering Dopacis.

In order to obtain images of best quality and to reduce the radiation exposure of the bladder, patients should be encouraged to drink sufficient amounts and to empty their bladder prior to, and after the PET examination.

In the neurological indications, it is recommended to stop any antiParkinsonian treatment at least 12 hours before the test.

In the oncological indications, it is recommended to stop any treatment with glucagon at least 12 hours before the test.

In neurological indications, the administration of 200 mg of entacapone one hour prior to the injection of fluorodopa (¹⁸F) is common practice.

General warnings

It is recommended to avoid close physical contact between the patient and young children during the first 12 hours following the injection.

Radiopharmaceuticals should be received, used and administered only by authorized persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licenses of the competent official organisation.

Radiopharmaceuticals should be prepared by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.

Specific warnings

If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.

Warnings related to excipients:

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. is essentially ‘sodium- free’.

Precautions with respect to environmental hazard are in Section 6.6.

Carbidopa, inhibitors of the enzyme catechol-O-methyl transferase (COMT) such as entacapone or nitecapone)

Administration before fluorodopa (¹⁸F) injection can increase the bioavailability of fluorodopa (¹⁸F) in the brain by inhibiting the peripheral decarboxylase and reducing the peripheral metabolism of fluorodopa (¹⁸F) with a formation of 3-O-methyl-6-fluoro (¹⁸F)-L-DOPA. The bioavailability of fluorodopa in the brain can be increased by pre-treatment with either inhibitors of the enzyme aromatic amino acid decarboxylase (AAAD) such as carbidopa which block peripheral conversion of fluorodopa to fluorodopamine, or inhibitors of the enzyme catechol-O-methyl transferase (COMT) such as entacapone and nitecapone which decrease peripheral degradation of fluorodopa to 3-O-methyl-6-fluorodopa.

Carbidopa

A case of congenital hyperinsulinism has been reported where fluorodopa uptake in the pancreas was no longer detectable after carbidopa administration.

Glucagon

Glucagon affects fluorodopa (¹⁸F) uptake in pancreas by interacting with pancreatic betacell function.

Haloperidol

An increase in intracerebral dopamine caused by haloperidol may increase the accumulation of fluorodopa (¹⁸F) in the brain.

Reserpine

Reserpine can empty the contents of intraneuronal vesicles and thus prevent the retention of fluorodopa (¹⁸F) in the brain.

MAO inhibitors (Monoamine Oxidase)

Concomitant use of MAO inhibitors may increase the accumulation of fluorodopa (¹⁸F) in the brain.

Women of childbearing potential

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

Dopacis is contraindicated in pregnancy (see section 4.3).

Available data is insufficient to address the effects of the product during pregnancy. No reproductive studies have been carried out in animals.

Breastfeeding

Fluorodopa (¹⁸F) will be excreted into breast milk.

Before administering radiopharmaceuticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 12 hours and the expressed feeds discarded.

Close contact with infants should be restricted during the first 12 hours following injection.

Dopacis has no or negligible influence on the ability to drive and use machines.

The reported adverse events are presented below by System Organ Class and with a not known frequency (cannot be estimated from the available data):

Pain on injection site was reported to have disappeared in a few minutes, without treatment.

A case of carcinoid crisis related to an injection administrated too fast has been reported in the literature.

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 7 mSv when the maximal recommended activity of 280 MBq (for an individual of 70 kg) is administered these adverse events are expected to occur with a low probability.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the ADR Reporting Website: www.medicinesauthority.gov.mt/adrportal.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.