IMMUCOTHEL®: Drug Product

Summary of Product Characteristics

1. Name of The Medicinal Product

IMMUCOTHEL® 1 mg
IMMUCOTHEL® 10 mg

2. Qualitative and Quantitative Composition

IMMUCOTHEL® 1 mg: 1 vial with 54.63 mg powder for injections contains 1 mg biotechnically obtained, chromatographically uniform, molecularly standardized immunocyanin. Each vial is accompanied by 1 ampoule with 1 ml solvent.
IMMUCOTHEL® 10 mg: 1 vial with 546.3 mg powder for intravesical instillations contains 10 mg of biotechnically obtained, chromatographically uniform, molecularly standardized immunocyanin. Each vial is accompanied by 1 ampoule with 10 ml solvent.

3. Pharmaceutical Form

IMMUCOTHEL® 1 mg: Powder for injections + solvent.
IMMUCOTHEL® 10 mg: Powder for intravesical instillations + solvent.

4. Clinical Particulars

4.1 Therapeutic Indications

Prevention of bladder carcinoma recurrence after transurethral resection and after failure of established therapies for this indication.

4.2 Posology and Method of Administration

Posology: The treatment splits up into an initial therapy with IMMUCOTHEL® 1 mg and a maintenance therapy with IMMUCOTHEL® 10 mg.
Initial therapy: In the initial therapy, the patient is tested for hypersensitivity with a subcutaneous or intracutaneous injection of 1 mg immunocyanin into the left forearm (in case of left-handedness, into the right forearm). If a noticeable erythema fails to appear within 4 days at the most, proving a primary immune response, the injection of IMMUCOTHEL® 1 mg is repeated up to 2 times at intervals of 2 to 4 days.
Maintenance therapy: After the development of an erythema, bladder instillations are begun. During the first 6 weeks 2 x 10 mg (20 mg) IMMUCOTHEL® once weekly, followed by 2 x 10 mg (20 mg) IMMUCOTHEL® once monthly for 1 year.

4.3 Contraindications

Immunosuppression.
Known hypersensitivity to proteins foreign to the body.

4.4 Special Warnings and Special Precautions for Use

None

4.5 Interaction With Other Medicaments and Other Forms of Interaction

Specific interactions with other drugs were not observed. However, the immunostimulating effect of IMMUCOTHEL® may be impaired by a concurrent immunosuppressive radio- or chemotherapy or by simultaneous administration of corticosteroids.
Concurrent immunosuppressive treatment (radiation, cytostatics, corticosteroids) should be avoided to ensure an optimum therapeutic effect.

4.6 Pregnancy and Lactation

The safety of this drug during pregnancy or lactation in man has hot been sufficiently evaluated to judge possible risks. Likewise, the results obtained from animal studies are not sufficient to judge possible risks. IMMUCOTHEL® should therefore only be used after careful consideration by the doctor.

4.7 Effects On Ability to Drive and Use Machines

IMMUCOTHEL® has no effect on the ability to drive and use machines.

4.8 Undesirable Effects

Subfebrile temperatures are sometimes reported but are reversible after 3 days. Rarely increase of γ[gamma]-glutamyl transferase and of glutamate pyruvate transaminase. Urgency, feeling of pressure or pain. Allergic reactions of the bladder manifesting as sterile leukocyturia.
A distinct reddening and swelling of the skin (approximately 2 cm) at the site of injection during initial therapy is a desired effect. Patients with a susceptibility to allergic reactions may develop an allergic erythema in rare cases. If necessary, a corticosteroid-containing ointment may be administered topically. Systemic administration of corticosteroids is indicated in the event of systemic allergic reactions.
Slight cystitis, which may occur after intravesical instillation of IMMUCOTHEL® 10 mg, is a desired therapeutic effect; cystic convulsion should only be treated locally or systemically with light analgesics. At the same time, diuresis should be stimulated. Systemic allergic reactions occuring after bladder instillations should be treated with antihistamines or eventually corticosteroids.

4.9 Overdose

In the event of allergic hypersensitivity reactions the dose is to be reduced. The termination of the therapy may be indicated.
Further therapy measures may consist of artificial respiration, oxygen inhalation, the administration of calcium and of antihistamines.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Immunotherapeutic agent for oncotherapy.
Pharmacodynamic effects: The active ingredient immunocyanin is a stable modification of the blood pigment hemocyanin from a sea snail (Megathura crenulata). Hemocyanin (synonym: KLH = keyhole limpet hemocyanin) is one of the largest proteins known and, thus, a multigenic, allosteric protein complex with multi-epitopic antigen structures. This means that man is confronted with several hundred xenogeneic epitopes activating the immune system.

IMMUCOTHEL® activates the cellular and humoral immune system in the bladder mucosa.

It is assumed that IMMUCOTHEL® exhibits an immunologic action mechanism in the prophylaxis of recurrent superficial bladder carcinoma.

5.2 Pharmacokinetic Properties

At present, science does not dispose of methods (e. g. radioactive labelling) sensitive enough to characterize the biological half-life, the metabolism, or the elimination of this substance. The protein immunocyanin is only administered locally. It is step-by step degraded to peptides and amino acids by the proteinases and peptidases present in the tissue.
Subcutaneous immunization triggers the formation of hemocyanin-specific IgM antibodies, followed by IgG antibodies. These antibodies may be detected by means of monoclonal antibodies up to 1 year later.
After intravesical instillation immunocyanin attaches to the bladder wall and induces an immune response. Consecutively, it is diluted by the urine and excreted.

5.3 Preclinical Safety Data

No special features.

6. Pharmaceutical Particulars

6.1 List of Excipients

Powder for injections and powder for intravesical instillations: Glycine, sodium hydroxide, sodium chloride, sucrose.
Solvent: Water for injections.

6.2 Cases of Incompatibilities

With regard to possible incompatibilities IMMUCOTHEL® should not be mixed with other medicaments.

6.3 Shelf Life

The shelf life is 2 years for IMMUCOTHEL® 1 mg and 3 years for IMMUCOTHEL® 10 mg. The clear solution must be used at once.

6.4 Special Precautions for Storage

IMMUCOTHEL® should be stored at room temperature (15–25 °C).

6.5 Nature and Contents of Container

IMMUCOTHEL® 1 mg: Package with 1 vial of 1 mg immunocyanin and 1 ampoule with 1 ml solvent.
IMMUCOTHEL® 10 mg: Package with 1 vial of 10 mg immunocyanin and 1 ampoule with 10 ml solvent.

6.6 Instructions for use/handling

IMMUCOTHEL® 1 mg: To make up the ready-for-use injection solution, the contents of a solvent ampoule is injected under sterile conditions into the corresponding injection vial containing powder for injections, thus dissolving the powder. The ready injection solution is transferred into a tuberculin syringe and injected intracutaneously or subcutaneously.
IMMUCOTHEL® 10 mg: To make up the ready-for-use instillation solution, the contents of a solvent ampoule is injected under sterile conditions into the corresponding injection vial containing powder for intravesical instillations, thus dissolving the powder. The solution is colourless. The ready instillation solution is transferred into a suitable syringe and instilled into the empty bladder via a disposable catheter, and left in the bladder as long as possible. Afterwards the patient may pass urine as usual. IMMUCOTHEL® is biologically degradable and needs no special treatment of wastes.

Marketing Authorization Holder

biosyn Arzneimittel GmbH
Schorndorfer Strasse 32
D–70734 Fellbach
GERMANY