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Photofrin

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Photofrin

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Esophageal Cancer

If the esophageal tumor is eroding into the trachea or bronchial tree, the likelihood of tracheoesophageal or bronchoesophageal fistula resulting from treatment is sufficiently high that photodynamic therapy (PDT) is not recommended.

Patients with esophageal varices should be treated with extreme caution. Light should not be given directly to the variceal area because of the high risk of bleeding.

Endobronchial Cancer

Patients should be assessed for the possibility that a tumor may be eroding into a pulmonary blood vessel [see CONTRAINDICATIONS]. Patients at high risk for fatal massive hemoptysis (FMH) include those with large, centrally located tumors, those with cavitating tumors or those with extensive tumor extrinsic to the bronchus.

If the endobronchial tumor invades deeply into the bronchial wall, the possibility exists for fistula formation upon resolution of tumor.

PDT should be used with extreme caution for endobronchial tumors in locations where treatment-induced inflammation could obstruct the main airway, e.g., long or circumferential tumors of the trachea, tumors of the carina that involve both mainstem bronchi circumferentially, or circumferential tumors in the mainstem bronchus in patients with prior pneumonectomy.

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 (porfimer sodium) 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

Ocular discomfort, commonly described as sensitivity to sun, bright lights, or car headlights, has been reported in patients who received PHOTOFRIN (porfimer sodium) . For 30 days, when outdoors, patients should 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.

Respiratory Distress

Patients with endobronchial lesions must be closely monitored between the 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 as a result of PDT of HGD in BE are common adverse reactions. An esophageal stricture was defined as a fixed lumen narrowing with solid food dysphagia and requiring dilation.

Regardless of the indication, esophageal strictures were reported in 122 of the 318 (38%) patients enrolled in the three clinical studies. Overall, esophageal strictures occurred within six months following PDT and were manageable through dilations. Multiple dilations of esophageal strictures may be required, as shown in Table 5. Special care should be taken during dilation to avoid perforation of the esophagus.

A high proportion of patients who developed an esophageal stricture received a nodule pretreatment prior to developing the event (49%) and/or had a mucosal segment treated twice (82%). Therefore, nodule pretreatment and re-treating the same mucosal segment more than once may influence the risk of developing an esophageal stricture.

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.

TABLE 5: Esophageal Dilations in Patients with Treatment-Related Strictures

Number of Dilations Number of Patients with Strictures
N=114
Percentage of Patients with Strictures
1 – 2 Dilations 32 28%
3 – 5 Dilations 32 28%
6 – 10 Dilations 24 21%
> 10 Dilations 26 23%

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, and Impairment of Fertility

No long-term studies have been conducted to evaluate the carcinogenic potential of porfimer sodium.

In the presence of light, in vitro , porfimer sodium PDT did not cause mutations in the Ames test, nor did it cause chromosome aberrations or mutations (HGPRT locus) in Chinese hamster ovary (CHO) cells. Porfimer sodium PDT caused < 2-fold, but significant, increases in sister chromatid exchange in CHO cells irradiated with visible light and a 3-fold increase in Chinese hamster lung fibroblasts irradiated with near UV light. Porfimer sodium PDT caused an increase in thymidine kinase mutants and DNA-protein cross-links in mouse L5178Y cells, but not mouse LYR83 cells Porfimer sodium PDT caused a light-dose dependant increase in DNA-strand breaks in malignant human cervical carcinoma cells, but not in normal cells. In the absence of light, porfimer sodium was negative in a Chinese hamster ovarian cells (CHO/HGPRT) mutation test. In vivo, porfimer sodium did not cause chromosomal aberrations in the mouse micronucleus test.

Porfimer sodium given to male and female rats intravenously, at 4 mg/kg/d (0.32 times the clinical dose on a mg/m² basis) before conception and through Day 7 of pregnancy caused no impairment of fertility. In this study, long-term dosing with porfimer sodium caused discoloration of testes and ovaries and hypertrophy of the testes. Porfimer sodium also caused decreased body weight in the parent rats.

Use In Specific Populations

Pregnancy

Pregnancy Category C. Porfimer sodium has been shown to have an embryocidal effect in rats and rabbits when given in doses 0.64 times the recommended human dose on a mg/m² basis. Porfimer sodium given to rat dams during fetal organogenesis intravenously at 0.64 times the clinical dose on a mg/m² basis for 10 days caused no major malformations or developmental changes. This dose caused maternal and fetal toxicity resulting in increased resorptions, decreased litter size, delayed ossification, and reduced fetal weight. Porfimer sodium caused no major malformations when given to rabbits intravenously during organogenesis at 0.65 times the clinical dose on a mg/m² basis for 13 days. This dose caused maternal toxicity resulting in increased resorptions, decreased litter size, and reduced fetal body weight.

Porfimer sodium given to rats during late pregnancy through lactation intravenously at 0.32 times the clinical dose on a mg/m² basis for at least 42 days caused a reversible decrease in growth of offspring. Parturition was unaffected.

There are no adequate and well-controlled studies of PHOTOFRIN (porfimer sodium) in pregnant women. PHOTOFRIN (porfimer sodium) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether PHOTOFRIN (porfimer sodium) is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from PHOTOFRIN (porfimer sodium) , a decision should be made whether not to treat or to discontinue breastfeeding, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in children have not been established.

Geriatric Use

Approximately 70% of the patients treated with PDT using PHOTOFRIN (porfimer sodium) in clinical trials were over 60 years of age. There was no apparent difference in effectiveness or safety in these patients compared to younger people. Dose modification based upon age is not required.

Last reviewed on RxList: 5/19/2011
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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