Photofrin

Before taking Photofrin, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Photofrin, or any of its ingredients
• are allergic to porphyrins
• have porphyria
• have liver problems
• have kidney problems
• have esophageal or stomach varices
• have or have had esophageal ulcers
• are pregnant or breastfeeding
• have a fistula between your esophagus and other organs in the body
• know or have been told you have a tumor protruding into a major blood vessel
• know or have been told you have a tumor blocking your airways

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

You should not receive this medication if you have porphyria, esophageal bleeding, a fistula (abnormal passageway) in the throat or esophagus, or a tumor that affects a large blood vessel.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given into a vein for a period of time.
• This medicine is used with light therapy.
• Follow up with the doctor as you have been told.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
• Signs of dehydration like dry skin, mouth, or eyes; thirst; fast heartbeat; dizziness; fast breathing; or confusion.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Chest pain or pressure or a fast heartbeat.
• A heartbeat that does not feel normal.
• Trouble swallowing.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Cough that does not go away.
• Feeling very tired or weak.
• Vaginal itching or discharge.
• Feeling confused.
• Very bad and sometimes deadly stomach or bowel problems have happened with Photofrin. This includes stomach or bowel bleeding, holes or tears, and tissue death. Call your doctor right away if you have fever or chills; black, tarry, or bloody stools; stomach pain; stomach swelling/throwing up blood or throw up that looks like coffee grounds.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Esophageal Cancer

Photofrin® is indicated for the palliation of patients with completely obstructing esophageal cancer, or of patients with partially obstructing esophageal cancer who, in the opinion of their physician, cannot be satisfactorily treated with Nd:YAG laser therapy.

Endobronchial Cancer

Photofrin is indicated for the treatment of microinvasive endobronchial non-small-cell lung cancer (NSCLC) in patients for whom surgery and radiotherapy are not indicated.

Photofrin is indicated for the reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial NSCLC.

High-Grade Dysplasia in Barrett's Esophagus

Photofrin is indicated for the ablation of high-grade dysplasia in Barrett's esophagus patients who do not undergo esophagectomy.

Photodynamic therapy (PDT) with Photofrin is a two- stage process requiring administration of both drug and light. The first stage of PDT is the intravenous injection of Photofrin at 2 mg/kg. Illumination with laser light 40–50 hours following injection with Photofrin constitutes the second stage of therapy. A second laser light application may be given 96-120 hours after injection [see Dosage and Administration (2.2)]. In clinical studies on endobronchial cancer, debridement via endoscopy was required 2-3 days after the initial light application. Standard endoscopic techniques are used for light administration and debridement. Practitioners should be fully familiar with the patient's condition and trained in the safe and efficacious treatment of esophageal or endobronchial cancer, or high-grade dysplasia (HGD) in Barrett's esophagus (BE) using PDT with Photofrin and associated light delivery devices. PDT with Photofrin should be applied only in those facilities properly equipped for the procedure.

The laser system must be approved for delivery of a stable power output at a wavelength of 630 ± 3 nm. Light is delivered to the tumor by cylindrical OPTIGUIDE™ fiber optic diffusers passed through the operating channel of an endoscope/bronchoscope. Instructions for use of the fiber optic and the selected laser system should be read carefully before use. OPTIGUIDE™ cylindrical diffusers are available in several lengths. The choice of diffuser tip length depends on the length of the tumor or Barrett's mucosa to be treated. Diffuser length should be sized to avoid exposure of nonmalignant tissue to light and to prevent overlapping of previously treated malignant tissue. Refer to the OPTIGUIDE™ instructions for use for complete instructions concerning the fiber optic diffuser.

Photofrin

Photofrin should be administered as a single slow intravenous injection over 3 to 5 minutes at 2 mg/kg of body weight. Reconstitute each vial of Photofrin with 31.8 mL of either 5% Dextrose Injection (USP) or 0.9% Sodium Chloride Injection (USP), resulting in a final concentration of 2.5 mg/mL. Shake well until dissolved. Do not mix Photofrin with other drugs in the same solution. Photofrin, reconstituted with 5% Dextrose Injection (USP) or with 0.9% Sodium Chloride Injection (USP), has a pH in the range of 7 to 8. Photofrin has been formulated with an overage to deliver the 75 mg labeled quantity. The reconstituted product should be protected from bright light and used immediately. Reconstituted Photofrin is an opaque solution, in which detection of particulate matter by visual inspection is extremely difficult. Reconstituted Photofrin, however, like all parenteral drug products, should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Precautions should be taken to prevent extravasation at the injection site. If extravasation occurs, care must be taken to protect the area from light. There is no known benefit from injecting the extravasation site with another substance.

Photoactivation

Esophageal Cancer

Initiate 630 nm wavelength laser light delivery to the patient 40–50 hours following injection with Photofrin. A second laser light treatment may be given as early as 96 hours or as late as 120 hours after the initial injection with Photofrin. No further injection of Photofrin should be given for such retreatment with laser light. Before providing a second laser light treatment, the residual tumor may be debrided. The debridement is optional since the residua will be removed naturally by peristaltic action of the esophagus. Vigorous debridement may cause tumor bleeding.

Photoactivation of Photofrin is controlled by the total light dose delivered. In the treatment of esophageal cancer, a light dose of 300 Joules/cm (J/cm) of diffuser length should be delivered. The total power output at the fiber tip is set to deliver the appropriate light dose using exposure times of 12 minutes and 30 seconds.

For the treatment of esophageal cancer, patients may receive a second course of PDT a minimum of 30 days after the initial therapy; up to three courses of PDT (each separated by a minimum of 30 days) can be given. Before each course of treatment, patients with esophageal cancer should be evaluated for the presence of a tracheoesophageal or bronchoesophageal fistula [see Contraindications (4)]. All patients should be evaluated for the possibility that the tumor may be eroding into a major blood vessel [see Contraindications (4)].

Endobronchial Cancer

Initiate 630 nm wavelength laser light delivery to the patient 40–50 hours following injection with Photofrin. A second laser light treatment may be given as early as 96 hours or as late as 120 hours after the initial injection with Photofrin. No further injection of Photofrin should be given for such retreatment with laser light. Before providing a second laser light treatment, the residual tumor should be debrided. Vigorous debridement may cause tumor bleeding. For endobronchial tumors, debridement of necrotic tissue should be discontinued when the volume of bleeding increases, as this may indicate that debridement has gone beyond the zone of the PDT effect.

Photoactivation of Photofrin is controlled by the total light dose delivered. In the treatment of endobronchial cancer, a light dose of 200 J/cm of diffuser length should be delivered. The total power output at the fiber tip is set to deliver the appropriate light dose using exposure times of 8 minutes and 20 seconds. For noncircumferential endobronchial tumors that are soft enough to penetrate, interstitial fiber placement is preferred to intraluminal activation, since this method produces better efficacy and results in less exposure of the normal bronchial mucosa to light. It is important to perform a debridement 2 to 3 days after each light administration to minimize the potential for obstruction caused by necrotic debris [see Warnings and Precautions (5.8)].

For the treatment of endobronchial cancer, patients may receive a second course of PDT a minimum of 30 days after the initial therapy; up to three courses of PDT (each separated by a minimum of 30 days) can be given. In patients with endobronchial lesions who have recently undergone radiotherapy, sufficient time (approximately 4 weeks) should be allowed between the therapies to ensure that the acute inflammation produced by radiotherapy has subsided prior to PDT [see Warnings and Precautions (5.6)]. All patients should be evaluated for the possibility that the tumor may be eroding into a major blood vessel [see Contraindications (4)].

High-Grade Dysplasia (HGD) in Barrett's Esophagus (BE)

Prior to initiating treatment with Photofrin PDT, the diagnosis of HGD in BE should be confirmed by an expert GI pathologist.

Approximately 40-50 hours after Photofrin administration light should be delivered by a X-Cell Photodynamic Therapy (PDT) Balloon with Fiber Optic Diffuser. The choice of fiber optic/balloon diffuser combination will depend on the length of Barrett's mucosa to be treated (Table 1).

Photoactivation is controlled by the total light dose delivered. The objective is to expose and treat all areas of HGD and the entire length of BE. The light dose administered will be 130 J/cm of diffuser length using a centering balloon. Based on the randomized clinical study, acceptable light intensity for the balloon/diffuser combinations range from 200-270 mW/cm of diffuser length.

To calculate the light dose, the following specific light dosimetry equation applies for all fiber optic diffusers:

Light Dose (J/cm) = Power Output From Diffuser (W) x Treatment Time (s) / Diffuser Length (cm)

Table 2 provides the settings that will be used to deliver the dose within the shortest time (light intensity of 270 mW/cm). A second option (light intensity of 200 mW/cm) has also been included where necessary to accommodate lasers with a total capacity that does not exceed 2.5 W.

Short fiber diffusers (≤2.5 cm) are to be used to pretreat nodules with 50 J/cm of diffuser length prior to regular balloon treatment in the first laser light session or for the treatment of "skip" areas (i.e., an area that does not show sufficient mucosal response) after the first light session. For this treatment, the fiber optic diffuser is used without a centering balloon, and a light intensity of 400 mW/cm should be used. For nodule pretreatment and treatment of skipped areas, care should be taken to minimize exposure to normal tissue as it is also sensitized. Table 3 lists appropriate fiber optic power outputs and treatment times using a light intensity of 400 mW/cm.

A maximum of 7 cm of esophageal mucosa is treated at the first light session using an appropriate size of centering balloon and fiber optic diffuser (Table 1). Whenever possible, the segment selected for the first light application should contain all the areas of HGD. Also, whenever possible, the BE segment selected for the first light application should include normal tissue margin of a few millimeters at the proximal and distal ends.

Nodules are to be pretreated at a light dose of 50 J/cm of diffuser length with a short (≤2.5 cm) fiber optic diffuser placed directly against the nodule followed by standard balloon application as described above.

Repeat Light Application

A second laser light application may be given to a previously treated segment that shows a "skip" area, using a short, ≤2.5 cm, fiber optic diffuser without centering balloon at the light dose of 50 J/cm of the diffuser length. Patients with BE >7 cm, should have the remaining untreated length of Barrett's epithelium treated with a second PDT course at least 90 days later.

The treatment regimen is summarized in Table 4.

For the ablation of HGD in BE, patients may receive an additional course of PDT at a minimum of 90 days after the initial therapy; up to three courses of PDT (each injection separated by a minimum of 90 days) can be given to a previously treated segment which still shows HGD, low-grade dysplasia, or Barrett’s metaplasia, or to a new segment if the initial Barrett's segment was >7 cm in length. Both residual and additional segments may be treated in the same light session(s) provided that the total length of the segments treated with the balloon/diffuser combination is not greater than 7 cm. In the case of a previously treated esophageal segment, if it has not sufficiently healed and/or histological assessment of biopsies is not clear, the subsequent course of PDT may be delayed for an additional 1-2 months.

Gastroesophageal Fistula and Perforation

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.

Serious and sometimes fatal gastrointestinal and esophageal necrosis and perforation can occur following treatment with Photofrin with PDT.

Pulmonary and Gastroesophageal Hemorrhage

Assess patients for tumors eroding into a pulmonary blood vessel [see Contraindications (4)] and esophageal varices. Patients at high risk for fatal massive hemoptysis (FMH) include those with large, centrally located tumors, cavitating tumors or extensive tumors extrinsic to the bronchus. Do not administer light directly to an area with esophageal varices because of the high risk of hemorrhage.

High-Grade Dysplasia (HGD) in Barrett's Esophagus (BE)

The long-term effect of PDT on HGD in BE is unknown. There is always a risk of cancer or abnormal epithelium that is invisible to the endoscopist beneath the new squamous cell epithelium; these facts emphasize the risk of overlooking cancer in such patients and the need for rigorous continuing surveillance despite the endoscopic appearance of complete squamous cell reepithelialization. It is recommended that endoscopic biopsy surveillance be conducted every three months, until four consecutive negative evaluations for HGD have been recorded; further follow-up may be scheduled every 6 to 12 months, as per judgment of physicians. The follow-up period of the randomized study at the time of analysis was a minimum of two years (ranging from 2 to 5.6 years).

Photosensitivity

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 (from examination lamps, including dental lamps, operating room lamps, unshaded light bulbs at close proximity, etc.) for at least 30 days. Some patients may remain photosensitive for up to 90 days or more. The photosensitivity is due to residual drug, which will be present in all parts of the skin. Exposure of the skin to ambient indoor light is, however, beneficial because the remaining drug will be inactivated gradually and safely through a photobleaching reaction. Therefore, patients should not stay in a darkened room during this period and should be encouraged to expose their skin to ambient indoor light. The level of photosensitivity will vary for different areas of the body, depending on the extent of previous exposure to light. Before exposing any area of skin to direct sunlight or bright indoor light, the patient should test it for residual photosensitivity. A small area of skin should be exposed to sunlight for 10 minutes. If no photosensitivity reaction (erythema, edema, blistering) occurs within 24 hours, the patient can gradually resume normal outdoor activities, initially continuing to exercise caution and gradually allowing increased exposure. If some photosensitivity reaction occurs with the limited skin test, the patient should continue precautions for another 2 weeks before retesting. The tissue around the eyes may be more sensitive, and therefore, it is not recommended that the face be used for testing. If patients travel to a different geographical area with greater sunshine, they should retest their level of photosensitivity. 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.

Ocular Sensitivity

Sensitivity to sun, bright lights, or car headlights, causing ocular discomfort, can occur in patients who receive Photofrin. For at least 30 days and until ocular sensitivity resolves, instruct patients when outdoors to wear dark sunglasses which have an average white light transmittance of <4%.

Use Before or After Radiotherapy

If PDT is to be used before or after radiotherapy, sufficient time should be allotted between the two therapies to ensure that the inflammatory response produced by the first treatment has subsided before commencing the second treatment. The inflammatory response from PDT will depend on tumor size and extent of surrounding normal tissue that receives light. It is recommended that 2 to 4 weeks be allowed after PDT before commencing radiotherapy. Similarly, if PDT is to be given after radiotherapy, the acute inflammatory reaction from radiotherapy usually subsides within 4 weeks after completing radiotherapy, after which PDT may be given.

Chest Pain

As a result of PDT treatment, patients may complain of substernal chest pain because of inflammatory responses within the area of treatment. Such pain may be of sufficient intensity to warrant the short-term prescription of opiate analgesics.

Airway Obstruction and Respiratory Distress

Photofrin followed by PDT can cause treatment-induced inflammation and obstruct the main airway. Administer with caution to patients with endobronchial tumors in locations where treatment-induced inflammation can obstruct the main airway, e.g., long or circumferential tumors of the trachea, tumors of the carina that involve both mainstreatm bronchi circumferentially, or circumferential tumors in the mainstream bronchus in patients with prior pneumonectomy.

Monitor patients closely between laser light therapy and the mandatory debridement bronchoscopy for any evidence of respiratory distress. Inflammation, mucositis, and necrotic debris may cause obstruction of the airway. If respiratory distress occurs, the physician should be prepared to carry out immediate bronchoscopy to remove secretions and debris to open the airway.

Esophageal Strictures

Esophageal strictures occurred in 122 of 318 (38%) patients enrolled in three clinical studies of patients who received Photofrin with PDT to the esophagus. Nodule pretreatment and re-treating the same mucosal segment more than once may influence the risk of developing an esophageal stricture. A total of 49% of patients who developed a stricture received nodule pretreatment and 82% who developed a stricture had a mucosal segment treated twice. Overall, esophageal strictures occurred within six months following Photofrin with PDT. Multiple dilations of esophageal strictures may be required, as shown in Table 5.

Hepatic and Renal Impairment

Hepatic or Renal impairment will likely prolong the elimination of porfimer sodium leading to higher rates of toxicity. Patients with severe renal impairment or mild to severe hepatic impairment should be clearly informed that the period requiring the precautionary measures for photosensitivity may be longer than 90 days.

Thromboembolism

Thromboembolic events can occur following photodynamic therapy with Photofrin. Most reported events occurred in patients with other risk factors for thromboembolism including advanced cancer, following major surgery, prolonged immobilization, or cardiovascular disease.

Photofrin (porfimer sodium) for Injection is a photosensitizing agent used in the photodynamic therapy (PDT) of tumors and of high-grade dysplasia (HGD) in Barrett’s esophagus (BE). Following reconstitution of the freeze-dried product with 5% Dextrose Injection (USP) or 0.9% Sodium Chloride Injection (USP), it is injected intravenously. This is followed 40–50 hours later by illumination of the tumor or the esophageal segment with HGD in BE with laser light (630 nm wavelength). Photofrin is not a single chemical entity; it is a mixture of oligomers formed by ether and ester linkages of up to eight porphyrin units. It is a dark red to reddish brown cake or powder. Each vial of Photofrin contains 75 mg of porfimer sodium as a sterile freeze-dried cake or powder. Hydrochloric Acid and/or Sodium Hydroxide may be added during manufacture to adjust the pH to within 7.2-7.9. There are no preservatives or other additives. The structural formula below is representative of the components present in Photofrin.

Figure 1 Structure of Porfimer Sodium

Mechanism of Action

Cellular damage caused by photodynamic therapy (PDT) with Photofrin is a consequence of the propagation of radical reactions. Radical initiation may occur after porfimer sodium absorbs light to form a porphyrin excited state. Spin transfer from porfimer sodium to molecular oxygen may then generate singlet oxygen. Subsequent radical reactions can form superoxide and hydroxyl radicals. Tumor death also occurs through ischemic necrosis secondary to vascular occlusion that appears to be partly mediated by thromboxane A2 release. As opposed to a thermal effect, the laser treatment with porfimer sodium induces a photochemical effect. The necrotic reaction and associated inflammatory responses may evolve over several days.

Pharmacodynamics

The cytotoxic and antitumor actions of Photofrin are light and oxygen dependent. PDT with Photofrin is a two-stage process. The first stage is the intravenous injection of Photofrin. Clearance from a variety of tissues occurs over 40-72 hours, but tumors, skin, and organs of the reticuloendothelial system (including liver and spleen) retain Photofrin for a longer period. Illumination with 630 nm wavelength laser light constitutes the second stage of therapy. Tumor selectivity in treatment occurs through a combination of selective retention of Photofrin and selective delivery of light.

Pharmacokinetics

The pharmacokinetics of Photofrin were studied in 18 cancer patients who received two doses of Photofrin, 2 mg/kg each, administered 30 to 45 days apart as slow IV injection over 3 to 5 minutes. The mean Cmax values were comparable after the first and second administrations (43.1 ± 10.5 mcg/mL and 41.3 ± 8.7 mcg/mL, respectively). However, the mean AUC0-inf of porfimer was about 34% higher after the second administration than that after the first administration (3937 ± 1034 mcg.h/mL and 2937 ± 627 mcg.hour/mL, respectively), indicating some accumulation upon repeated administration. The elimination half-life of porfimer increased from 410 to 725 hours after the first and second administrations, respectively.

Photofrin was approximately 90% protein bound in human serum, studied in vitro. The binding was independent of concentration over the concentration range of 20–100 mcg/mL.

Effect of Gender:

The effect of gender was determined in 18 patients (8 males and 10 females) who received two administrations of Photofrin 2 mg/kg within 30-45 days apart as slow IV injection over 3 to 5 minutes. The mean Cmax and AUC values were comparable between males and females following either the first or the second administrations.

Effect of Hepatic and Renal Impairment:

The effect of hepatic and renal impairment has not been studied.

Photofrin vial label

Photofrin carton

Photofrin is used to treat non-small cell lung and esophageal cancer (cancer in the tube that connects your throat to your stomach). This drug is also used to treat high-grade dysplasia in Barrett’s esophagus (cancer at the end of the esophagus that connects with the stomach).

This drug comes as a solution that’s injected into one of your veins by a healthcare provider. You must also receive light therapy 40–50 hours after your injection.

Photofrin is a brand name for the drug porfimer. It isn’t available as a generic drug.

The more common side effects of this drug can include chest pain, trouble breathing, and discomfort and injury of the esophagus. They can also include nausea, vomiting, constipation, and stomach pain. Your eyes and skin will also be very sensitive to light for at least 30 days after you receive this drug.

In some cases, Photofrin can cause serious side effects. These include chest pain, bleeding, blood clots, and trouble breathing.

• Fistula See Details

• Vision problems See Details

• Sensitivity to sunlight See Details

What is Photofrin?

This drug is a prescription drug. It’s available in an intravenous (IV) form, which is only given by a healthcare provider. You won’t give yourself this drug at home. 

Photofrin is a brand name for the drug porfimer. It isn’t available as a generic drug.

Why it's used

This drug is used to treat non-small cell lung cancer. It’s given when other treatments cannot be used and when the cancer blocks your airway. 

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How it works

This drug belongs to a class of drugs called photosensitizing agents. A class of drugs is a group of medications that work in a similar way.

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