UVADEX

UVADEX should be administered under the supervision of a health professional experienced with treatment of cutaneous T-cell lymphoma and the use of THERAKOS CELLEX Photopheresis System. 1 Dosing Considerations During treatment with the THERAKOS CELLEX Photopheresis System, the dosage of UVADEX for each treatment will be calculated according to the treatment volume.

2 Recommended Dose and Dosage Adjustment Normal Treatment Schedule: Treatment is given on two consecutive days every four weeks for a minimum of seven treatment cycles (six months).

Accelerated Treatment Schedule:

If the assessment of the patient during the fourth treatment cycle (approximately three months) reveals an increased skin score from the baseline score, the frequency of treatment may be increased to two consecutive treatments every two weeks.

If a 25% improvement i n the skin score is attained after four consecutive weeks, the regular treatment schedule may resume. Patients who are maintained in the accelerated treatment schedule may receive a maximum of 20 cycles. There is no clinical evidence to show that treatment with UVADEX beyond six months provides additional benefit if the patient has not responded within this timeframe or that using a different schedule provides additional benefit.

In Study CTCL 3, 15 of the 17 responses were seen within six months of treatment and only two patients responded to treatment after six months. UVADEX ( methoxsalen) Product Monograph Page 6 of 33 Health Canada has not authorized an indication for pediatric use.

4 Administration UVADEX is administered extracorporeally via the THERAKOS CELLEX Photopheresis System. Read the THERAKOS CELLEX Photopheresis Operator’s Manual before administering the treatment. Do not inject directly into patients.

Each UVADEX treatment involves collection of leukocytes, photoactivation, and reinfusion of photoactivated cells. In the photopheresis process, the patient is connected to the THERAKOS CELLEX instrument via a catheter interface. Red blood cells are separated from the white blood cells and plasma in the centrifuge bowl.

The red blood cells and excess plasma are returned to the patient while the buffy coat (leukocyte-enriched blood) and some plasma are collected into the photoactivation bag located on the side of the instrument. The prescribed amount of UVADEX is injected into the recirculation bag prior to the photoactivation phase (see 11 STORAGE, STABILITY AND DISPOSAL).

1 Adverse Reaction Overview The most common treatment-related adverse events in the clinical study which used UVADEX in conjunction with photopheresis in CTCL in adult patients were loss of venous access (9/51, 10%) and vasovagal spasm (3/51, 3%).

Nausea and vomiting were infrequent following UVADEX/ECP treatment compared to oral methoxsalen/ECP treatment with each event reported in 1/51 patients (2%). See 7 WARNINGS AND PRECAUTIONS. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials therefore may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real world use.

Adverse reaction data was based on 3 open-label, single-arm trials in patients with CTCL. Studies CTCL 1 and CTCL 2 evaluated the use of oral methoxsalen with ECP in 97 patients. 6 mg/kg and treatment frequency was based on clinical response.

2 treatments, with 24 patients completing all treatments. UVADEX was administered at a dose of 200 mcg with a treatment frequency of 2 treatments on 2 consecutive days every 4 weeks, with the option of increasing the frequency to 2 treatments every 2 weeks in patients with worsening skin scores after 3 months, with follow -up of up to 12 months.

Side effects of photopheresis (UVADEX used in conjunction with the THERAKOS Photopheresis System) were primarily related to hypotension secondary to changes in ex tracorporeal volume (>1%). In Study CTCL 3, six serious cardiovascular adverse experiences were reported in five patients (5/51, 10%).

Five of these six events were not related to photopheresis and did not interfere with the scheduled photopheresis treatments. One patient (1/51, 2%) with ischemic heart disease had an arrhythmia after the first day of photopheresis that was resolved the next day.

, General, Driving and Operating Machinery, Carcinogenicity and Mutagenesis 08/2021 7 WARNINGS AND PRECAUTIONS, General, Carcinogenicity and Mutagenesis 08/2021 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed.

1 Pregnant Women .......................................................................................... 2 Breast-feeding............................................................................................... 3 Pediatrics ......................................................................................................

10 8 ADVERSE REACTIONS .................................................................................................. 1 Adverse Reaction Overview................................................................................ 2 Clinical Trial Adverse Reactions ..........................................................................

3 Less Common Clinical Trial Adverse Reactions .................................................... 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data ........................................................................................................

5 Post-Market Adverse Reactions.......................................................................... 11 9 DRUG INTERACTIONS.................................................................................................. 2 Drug Interactions Overview................................................................................

4 Drug-Drug Interactions ...................................................................................... 5 Drug-Food Interactions ...................................................................................... 6 Drug-Herb Interactions ......................................................................................

 UVADEX is contraindicated in patients who are hypersensitive to this drug or any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing of ingredients, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

 Patients possessing a specific history of a light sensitive disease state should not initiate methoxsalen therapy. Diseases associated with photosensitivity include lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism.

 UVADEX is contraindicated in patients with aphakia, because of the significantly increased risk of retinal damage due to the absence of lenses.  UVADEX is contraindicated in patients with severe cardiac disease, severe anemia, white blood cell count greater than 25,000 mm3, previous splenectomy and coagulation disorders.

UVADEX ( methoxsalen) Product Monograph Page 5 of 33  UVADEX is contraindicated in patients with co-existing melanoma, basal cell, or squamous cell skin carcinoma.