Drug Information for PHOTOFRIN (porfimer sodium) for Injection (Axcan Scandipharm Inc.): ADVERSE REACTIONS

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  • Systemically induced effects associated with PDT with PHOTOFRIN® consist of photosensitivity and mild constipation. All patients who receive PHOTOFRIN® will be photosensitive and must observe precautions to avoid sunlight and bright indoor light (see PRECAUTIONS). Photosensitivity reactions occurred in approximately 20% of cancer patients and in 68% of high-grade dysplasia (HGD) in Barrett’s esophagus (BE) patients treated with PHOTOFRIN®. Typically these reactions were mostly mild to moderate erythema but they also included swelling, itching, burning sensation, feeling hot, or blisters. In a single study of 24 healthy subjects, some evidence of photosensitivity reactions occurred in all subjects. Other less common skin manifestations were also reported in areas where photosensitivity reactions had occurred, such as increased hair growth, skin discoloration, skin nodules, increased wrinkles and increased skin fragility. These manifestations may be attributable to a pseudoporphyria state (temporary drug-induced cutaneous porphyria).

    Most toxicities associated with this therapy are local effects seen in the region of illumination and occasionally in surrounding tissues. The local adverse reactions are characteristic of an inflammatory response induced by the photodynamic effect.

    A few cases of fluid imbalance have been reported following the use of PDT with PHOTOFRIN® in patients with overtly disseminated intraperitoneal malignancies. Fluid imbalance is an expected PDT treatment-related event.

    A case of cataracts has been reported in a 51 year-old obese man treated with PHOTOFRIN® PDT for HGD in BE. The patient suffered from a PDT response with development of a deep esophageal ulcer. Within two months post PDT, the patient noted difficulty with his distant vision. A thorough eye examination revealed a change in the refractive error that later progressed to cataracts in both eyes. Both of his parents had a history of cataracts in their 70s. Whether PHOTOFRIN® directly caused or accelerated a familial underlying condition is unknown.

  • Esophageal Carcinoma

  • The following adverse events were reported over the entire follow-up period in at least 5% of patients treated with PHOTOFRIN® PDT, who had completely or partially obstructing esophageal cancer. Table 7 presents data from 88 patients who received the currently marketed formulation. The relationship of many of these adverse events to PDT with PHOTOFRIN® is uncertain.

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    TABLE 7. Adverse Events Reported in 5% or More of PatientsBased on adverse events reported at any time during the entire period of follow-up. with Obstructing Esophageal Cancer
    BODY SYSTEM/ Adverse Event Number (%) of Patients N=88 n (%)
    Patients with at Least One Adverse Event 84 (95)
    AUTONOMIC NERVOUS SYSTEM
    Hypertension 5 (6)
    Hypotension 6 (7)
    BODY AS A WHOLE
    Asthenia 5 (6)
    Back pain 10 (11)
    Chest pain 19 (22)
    Chest pain (substernal) 4 (5)
    Edema generalized 4 (5)
    Edema peripheral 6 (7)
    Fever 27 (31)
    Pain 19 (22)
    Surgical complication 4 (5)
    CARDIOVASCULAR
    Cardiac failure 6 (7)
    GASTROINTESTINAL
    Abdominal pain 18 (20)
    Constipation 21 (24)
    Diarrhea 4 (5)
    Dyspepsia 5 (6)
    Dysphagia 9 (10)
    Eructation 4 (5)
    Esophageal edema 7 (8)
    Esophageal tumor bleeding 7 (8)
    Esophageal stricture 5 (6)
    Esophagitis 4 (5)
    Hematemesis 7 (8)
    Melena 4 (5)
    Nausea 21 (24)
    Vomiting 15 (17)
    HEART RATE/RHYTHM
    Atrial fibrillation 9 (10)
    Tachycardia 5 (6)
    METABOLIC &amp; NUTRITIONAL
    Dehydration 6 (7)
    Weight decrease 8 (9)
    PSYCHIATRIC
    Anorexia 7 (8)
    Anxiety 6 (7)
    Confusion 7 (8)
    Insomnia 12
    RED BLOOD CELL
    Anemia 28 (32)
    RESISTANCE MECHANISM
    Moniliasis 8 (9)
    RESPIRATORY
    Coughing 6 (7)
    Dyspnea 18 (20)
    Pharyngitis 10 (11)
    Pleural effusion 28 (32)
    Pneumonia 16 (18)
    Respiratory insufficiency 9 (10)
    Tracheoesophageal fistula 5 (6)
    SKIN &amp; APPENDAGES
    Photosensitivity reaction 17 (19)
    URINARY
    Urinary tract infection 6 (7)

    Location of the tumor was a prognostic factor for three adverse events: upper-third of the esophagus (esophageal edema), middle-third (atrial fibrillation), and lower-third, the most vascular region (anemia). Also, patients with large tumors (>10 cm) were more likely to experience anemia. Two of 17 patients with complete esophageal obstruction from tumor experienced esophageal perforations, which were considered to be possibly treatment associated; these perforations occurred during subsequent endoscopies.

    Serious and other notable adverse events observed in less than 5% of PDT-treated patients with obstructing esophageal cancer in the clinical studies include the following; their relationship to therapy is uncertain. In the gastrointestinal system, esophageal perforation, gastric ulcer, ileus, jaundice, and peritonitis have occurred. Sepsis has been reported occasionally. Cardiovascular events have included angina pectoris, bradycardia, myocardial infarction, sick sinus syndrome, and supraventricular tachycardia. Respiratory events of bronchitis, bronchospasm, laryngotracheal edema, pneumonitis, pulmonary hemorrhage, pulmonary edema, respiratory failure, and stridor have occurred. The temporal relationship of some gastrointestinal, cardiovascular and respiratory events to the administration of light was suggestive of mediastinal inflammation in some patients. Vision-related events of abnormal vision, diplopia, eye pain and photophobia have been reported.

  • Obstructing Endobronchial Cancer

  • Table 8 presents adverse events that were reported over the entire follow-up period in at least 5% of patients with obstructing endobronchial cancer treated with PHOTOFRIN® PDT or Nd:YAG. These data are based on the 86 patients who received the currently marketed formulation. Since it seems likely that most adverse events caused by these acute acting therapies would occur within 30 days of treatment, Table 8 presents those events occurring within 30 days of a treatment procedure, as well as those occurring over the entire follow-up period. It should be noted that follow-up was 33% longer for the PDT group than for the Nd:YAG group, thereby introducing a bias against PDT when adverse event rates are compared for the entire follow-up period. The extent of follow-up in the 30-day period following treatment was comparable between groups (only 9% more for PDT).

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    TABLE 8. Adverse Events Reported in 5% or More of Patients with Obstructing Endobronchial Cancer
    Number (%) of Patients
    BODY SYSTEM/ Adverse Event Within 30 Daysof Treatment EntireFollow-up PeriodFollow-up was 33% longer for the PDT group than for the Nd:YAG group, introducing a bias against PDT when adverse events are compared for the entire follow-up period.
    PDTN=86n (%) Nd:YAGN=86n (%) PDTN=86n (%) Nd:YAGN=86n (%)
    Patients with at Least One Adverse Event 43 (50) 33 (38) 62 (72) 48 (56)
    BODY AS A WHOLE
    Back pain 3 (3) 1 (1) 3 (3) 5 (6)
    Chest pain 6 (7) 6 (7) 7 (8) 8 (9)
    Edema peripheral 3 (3) 3 (3) 4 (5) 3 (3)
    Fever 7 (8) 7 (8) 14 (16) 8 (9)
    Pain 1 (1) 4 (5) 4 (5) 8 (9)
    CENTRAL NERVOUS SYSTEM
    Dysphonia 3 (3) 2 (2) 4 (5) 2 (2)
    GASTROINTESTINAL
    Constipation 4 (5) 1 (1) 4 2 (2)
    Dyspepsia 1 (1) 4 (5) 2 (2) 5 (6)
    PSYCHIATRIC
    Anxiety 3 (3) 0 (0) 5 (6) 0 (0)
    Insomnia 4 (5) 2 (2) 4 (5) 3 (4)
    RESPIRATORY
    Bronchitis 9 (10) 2 (2) 9 (10) 2 (2)
    Coughing 5 (6) 8 (9) 13 (15) 11 (13)
    Dyspnea 15 (17) 7 (8) 26 (30) 13 (15)
    Hemoptysis 6 (7) 5 (6) 14 (16) 7 (8)
    Pleural effusion 0 (0) 0 (0) 4 (5) 1 (1)
    Pneumonia 5 (6) 4 (5) 10 (12) 5 (6)
    Pneumothorax 0 (0) 0 (0) 0 (0) 4 (5)
    Respiratory insufficiency 0 (0) 0 (0) 5 (6) 1 (1)
    Sputum increased 4 (5) 5 (6) 7 (8) 6 (7)
    SKIN &amp; APPENDAGES
    Photosensitivity reaction 16 (19) 0 (0) 18 (21) 0 (0)