Other Possible Side Effects¹

Other potential side effects of PHOTOFRIN^®, occurring in 10% or less of patients, include the following:

Treatment of the lung

When cancer obstructs (or blocks) the airway:

Constipation, pain in the chest, pain (general), swelling of the tissues in the lower limbs due to large fluid volume, difficulty speaking, difficulty sleeping, anxiety, bronchitis, productive cough, difficulty breathing, fluid around the lungs, blood clot in the lung, blockage of the main artery of the lung or one of its branches, destruction of lung tissue due to infection, cardiac failure, bacterial infection of the blood, stroke.

When cancer slightly invades surrounding tissues:

Ulcers leading to the main airways of the lungs, cough, shortness of breath, inflammation of the digestive tract lining, life- threatening shortness of breath, narrowing of the main airway to the lungs that requires stent placement, coughing up life- threatening amounts of blood.

Treatment of the esophagus

Abnormal heart rhythm, cardiac failure, faster than normal heart rate, difficulty swallowing, swelling of tissue of the esophagus due to large fluid volume, vomiting blood, indigestion, esophageal narrowing, diarrhea, inflammation of the esophagus, belching, blood in stool, swelling of tissue in the lower limbs due to large fluid volume, weakness, chest pain below the breastbone, swelling of tissue due to large fluid volume (general), fungal infection, urinary tract infection, post-procedural complication, weight loss, loss of appetite, dehydration, bleeding tumor, confusion, anxiety, difficulty breathing, cough, abnormal connection between the esophagus and windpipe, low blood pressure, high blood pressure, hole in the esophagus, stomach ulcer, blockage of the intestine due to paralysis of intestinal muscles, yellowing of the skin, inflammation of abdominal lining, bacterial infection of the blood, chest pain, slow heart rate, heart attack, various abnormal heart rhythms, fast heart rate, bronchitis, abnormal contraction of main airway leading to lungs, fluid build-up in the windpipe and voice box, inflammation of

lung tissue, bleeding from the lungs, fluid build-up in the lungs, respiratory failure, abnormal high-pitched breathing sound, inflammation of the middle section of the chest cavity, abnormal vision, double-vision, eye pain and excessive eye sensitivity to light.

You are encouraged to report negative side effects of prescription drugs to Pinnacle Biologics, Inc. or the FDA. Call Pinnacle Biologics, Inc. at 1.847.283.7690, visit http://www.fda.gov/medwatch/ or call 1-800-FDA-1088.

Important Safety Information

Contraindications

PHOTOFRIN^® is contraindicated in patients with porphyria
Photodynamic therapy (PDT) is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula
PDT is contraindicated in patients with tumors eroding into a major blood vessel
PDT is not suitable for emergency treatment of patients with severe acute respiratory distress caused by an obstructing endobronchial lesion because 40 to 50 hours are required between injection with PHOTOFRIN^® and laser light treatment
PDT is not suitable for patients with esophagealor gastricvarices, or patients with esophagealulcers >1 cm in diameter

Warnings and Precautions

Do not initiate PHOTOFRIN^® with PDT in patients with esophageal tumors eroding into the trachea or bronchial tree or bronchial wall because of the high likelihood of tracheoesophageal or bronchoesophageal fistula
Gastrointestinal perforation can occur
High risk of bleeding in patients with esophageal varices
High risk for fatal massive hemoptysis with endobronchial tumors that are large, centrally located; cavitating; extensive, extrinsic to the bronchus
All patients who receive PHOTOFRIN^® will be photosensitive and must observe precautions to avoid exposure of skin and eyes to direct sunlight or bright indoor light for at least 30 days. Ocular sensitivity is also possible; instruct patients when out doors to edema, bronchostenosis wear dark sunglasses. See full Prescribing Information
Allow 2-4 weeks between PDT and subsequent radiotherapy• Substernalchestpainmayoccuraftertreatmentbecause of inflammatory responses within the area of treatment
Treatment-induced inflammation can cause airway obstruction. Administer with caution to patients with tumors in locations where treatment-induced inflammation can obstruct the main airway
Patients with hepatic or renal impairment may need longer precautionary measures for photosensitivity• Thromboembolic events can occur following photodynamic therapy with PHOTOFRIN^®

Adverse Reaction Profile

Most toxicities associated with PHOTOFRIN^® therapy are local effects seen in the area of illumination and occasionally in surrounding tissues and are characteristic of an inflammatory response
All patients who receive PHOTOFRIN^® will be photosensitive and must observe precautions listed in the Prescribing Information
Photosensitivity reactions occurred in approximately 20% of cancer patients treated with PHOTOFRIN^® in clinical studies
Typically these reactions were mostly mild to moderate erythema but they also included swelling, pruritus, 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)
Conventional ultraviolet (UV) sunscreens will only protect against UV light-related photosensitivity and will be of no value in protecting against induced photosensitivity reactions caused by visible light

Most Common Adverse Reactions

The following adverse reactions were reported in >10% of patients:

Esophageal Cancer: Anemia, pleuraleffusion, pyrexia, constipation, nausea, chestpain, pain, abdominal pain, dyspnoea, photosensitivity reaction, pneumonia, vomiting, insomnia, back pain, pharyngitis
Obstructing Endobronchial Cancer: Dyspnea, photosensitivity reaction, hemoptysis, pyrexia, cough, pneumonia
Superficial Endobronchial Tumors: Exudate, photosensitivity reaction, bronchial obstruction, edema, bronchostenosis

Other Possible Side Effects1