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PHOTOFRIN
Overview
What is PHOTOFRIN?
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 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.
What does PHOTOFRIN look like?
What are the available doses of PHOTOFRIN?
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What should I talk to my health care provider before I take PHOTOFRIN?
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How should I use PHOTOFRIN?
Photodynamic therapy with PHOTOFRIN is indicated for:
Photodynamic therapy 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, preceded by gentle debridement of residual tumor (see ). In clinical studies on esophageal and endobronchial cancers, 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 in Barrett’s esophagus using photodynamic therapy with PHOTOFRIN and associated light delivery devices.
For the treatment of esophageal and 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. Before each course of treatment, patients with esophageal cancer should be evaluated for the presence of a tracheoesophageal or bronchoesophageal fistula (see ). 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 , ). All patients should be evaluated for the possibility that the tumor may be eroding into a major blood vessel (see ).
For the ablation of high-grade dysplasia in Barrett’s esophagus, 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 high-grade dysplasia, 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.
What interacts with PHOTOFRIN?
PHOTOFRIN is contraindicated in patients with porphyria or in patients with known allergies to porphyrins.
Photodynamic therapy is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula.
Photodynamic therapy is contraindicated in patients with tumors eroding into a major blood vessel.
Photodynamic therapy 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.
Photodynamic therapy is not suitable for patients with esophageal or gastric varices, or patients with esophageal ulcers >1 cm in diameter.
What are the warnings of PHOTOFRIN?
PRIOR TO CATHETER INSERTION, THE PHYSICIAN SHOULD BE FAMILIAR WITH PATIENT CONDITIONS (SUCH AS INFECTION AT THE INJECTION SITE, BLEEDING DIATHESIS, ANTICOAGULANT THERAPY, ETC.) WHICH CALL FOR SPECIAL EVALUATION OF THE BENEFIT VERSUS RISK POTENTIAL.
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 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 ). 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.
Photodynamic therapy 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 pivotal study at the time of analysis was a minimum of two years (ranging from 2 to
3.6 years).
What are the precautions of PHOTOFRIN?
General Precautions and Information for Patients
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.
Ocular Sensitivity
Ocular discomfort, commonly described as sensitivity to sun, bright lights, or car headlights, has been reported in patients who received PHOTOFRIN. 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 events. 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 6. 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 pre-treatment prior to developing the event (49%)
and/or had a mucosal segment treated twice (82%). Therefore, nodule pre-treatment and re-treating the same mucosal segment more than once may influence the
risk of developing an esophageal stricture.
Prior to initiating treatment with PHOTOFRIN PDT, the diagnosis of HGD in BE should be confirmed by an expert GI pathologist. Photodynamic therapy with PHOTOFRIN should be applied by physicians trained in the endoscopic use of PDT with PHOTOFRIN, and only in those facilities properly equipped for the procedure.
Avoidance of Pregnancy
Women of childbearing potential should practice an effective method of contraception during therapy (see ).
| Number of Dilations | Number of Patients with Strictures, N=122 | Percentage of Patients with Strictures | |||
| 1 − 2 Dilations | 38 | 31% | |||
| 3 − 5 Dilations | 33 | 27% | |||
| 6 − 10 Dilations | 26 | 21% | |||
| > 10 Dilations | 25 | 20% |
Drug Interactions
There have been no formal interaction studies of PHOTOFRIN and any other drugs. However, it is possible that concomitant use of other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, and fluoroquinolones) could increase the risk of photosensitivity reaction.
PHOTOFRIN PDT causes direct intracellular damage by initiating radical chain reactions that damage intracellular membranes and mitochondria. Tissue damage also results from ischemia secondary to vasoconstriction, platelet activation and aggregation and clotting. Research in animals and in cell culture has suggested that many drugs could influence the effects of PDT, possible examples of which are described below. There are no human data that support or rebut these possibilities.
Compounds that quench active oxygen species or scavenge radicals, such as dimethyl sulfoxide, β-carotene, ethanol, formate and mannitol would be expected to decrease PDT activity. Preclinical data also suggest that tissue ischemia, allopurinol, calcium channel blockers and some prostaglandin synthesis inhibitors could interfere with PHOTOFRIN PDT. Drugs that decrease clotting, vasoconstriction or platelet aggregation, e.g., thromboxane A inhibitors, could decrease the efficacy of PDT. Glucocorticoid hormones given before or concomitant with PDT may decrease the efficacy of the treatment.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term studies have been conducted to evaluate the carcinogenic potential of PHOTOFRIN. , PHOTOFRIN 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. PHOTOFRIN 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. PHOTOFRIN PDT caused an increase in thymidine kinase mutants and DNA-protein cross-links in mouse L5178Y cells, but not mouse LYR83 cells. PHOTOFRIN PDT caused a light-dose dependant increase in DNA-strand breaks in malignant human cervical carcinoma cells, but not in normal cells. PHOTOFRIN was negative in a Chinese hamster ovarian cells (CHO/HGPRT) mutation test. , PHOTOFRIN did not cause chromosomal aberrations in the mouse micronucleus test.
PHOTOFRIN given to male and female rats intravenously, at 4 mg/kg/d (0.32 times the clinical dose on a mg/m basis) before conception and through Day 7 of pregnancy caused no impairment of fertility. In this study, long-term dosing with PHOTOFRIN caused discoloration of testes and ovaries and hypertrophy of the testes. PHOTOFRIN also caused decreased body weight in the parent rats.
Pregnancy: Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. PHOTOFRIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
PHOTOFRIN given to rat dams during fetal organogenesis intravenously at 8 mg/kg/d (0.64 times the clinical dose on a mg/m 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. PHOTOFRIN caused no major malformations when given to rabbits intravenously during organogenesis at 4 mg/kg/d (0.65 times the clinical dose on a mg/m basis) for 13 days. This dose caused maternal toxicity resulting in increased resorptions, decreased litter size, and reduced fetal body weight.
PHOTOFRIN given to rats during late pregnancy through lactation intravenously at 4 mg/kg/d (0.32 times the clinical dose on a mg/m basis) for at least 42 days caused a reversible decrease in growth of offspring. Parturition was unaffected.
Nursing Mothers
It is not known whether this drug 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, women receiving PHOTOFRIN must not breast feed.
Pediatric Use
Safety and effectiveness in children have not been established.
Use in Elderly Patients
Approximately 70% of the patients treated with PDT using PHOTOFRIN 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.
What are the side effects of PHOTOFRIN?
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 ). 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.
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.
| 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 & NUTRITIONAL | ||
| Dehydration | 6 | (7) |
| Weight decrease | 8 | (9) |
| PSYCHIATRIC | ||
| Anorexia | 7 | (8) |
| Anxiety | 6 | (7) |
| Confusion | 7 | (8) |
| Insomnia | 12 | (14) |
| 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 & APPENDAGES | ||
| Photosensitivity reaction | 17 | (19) |
| URINARY | ||
| Urinary tract infection | 6 | (7) |
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).
Transient inflammatory reactions in PDT-treated patients occur in about 10% of patients and manifest as fever, bronchitis, chest pain, and dyspnea. The incidences of bronchitis and dyspnea were higher with PDT than with Nd:YAG. Most cases of bronchitis occurred within 1 week of treatment and all but one were mild or moderate in intensity. The events usually resolved within 10 days with antibiotic therapy. Treatment-related worsening of dyspnea is generally transient and self-limiting. Debridement of the treated area is mandatory to remove exudate and necrotic tissue. Life-threatening respiratory insufficiency likely due to therapy occurred in 3% of PDT-treated patients and 2% of Nd:YAG-treated patients (see and ).
There was a trend toward a higher rate of fatal massive hemoptysis (FMH) occurring on the PDT arm (10%) versus the Nd:YAG arm (5%), however, the rate of FMH occurring within 30 days of treatment was the same for PDT and Nd:YAG (4% total events, 3% treatment-associated events). Patients who have received radiation therapy have a higher incidence of FMH after treatment with PDT and after other forms of local therapy than patients who have not received radiation therapy, but analyses suggest that this increased risk may be due to associated prognostic factors such as having a centrally located tumor. The incidence of FMH in patients previously treated with radiotherapy was 21% (6/29) in the PDT group and 10% (3/29) in the Nd:YAG group. In patients with no prior radiotherapy, the overall incidence of FMH was less than 1%. Characteristics of patients at high risk for FMH are described in and .
Other serious or notable adverse events were observed in less than 5% of PDT-treated patients with endobronchial cancer; their relationship to therapy is uncertain. In the respiratory system, pulmonary thrombosis, pulmonary embolism, and lung abscess have occurred. Cardiac failure, sepsis, and possible cerebrovascular accident have also been reported in one patient each.
| Number (%) of Patients | |||||||||
| 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 | (5) | 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 & APPENDAGES | |||||||||
| Photosensitivity reaction | 16 | (19) | 0 | (0) | 18 | (21) | 0 | (0) |
Superficial Endobronchial Tumors
The following adverse events were reported over the entire follow-up period in at least 5% of patients with superficial tumors (microinvasive or carcinoma ) who received the currently marketed formulation.
In patients with superficial endobronchial tumors, 44 of 90 patients (49%) experienced an adverse event, two-thirds of which were related to the respiratory system. The most common reaction to therapy was a mucositis reaction in one-fifth of the patients, which manifested as edema, exudate, and obstruction. The obstruction (mucus plug) is easily removed with suction or forceps. Mucositis can be minimized by avoiding exposure of normal tissue to excessive light (see ). Three patients experienced life-threatening dyspnea: one was given a double dose of light, one was treated concurrently in both mainstem bronchi and the other had had prior pneumonectomy and was treated in the sole remaining main airway (see ). Stent placement was required in 3% of the patients due to endobronchial stricture. Fatal massive hemoptysis occurred within 30 days of treatment in one patient with superficial tumors (1%).
| Adverse Event | |||
| Patients with at Least One Adverse Event | 44 | (49%) | |
| Photosensitivity reaction | 20 | (22%) | |
| Coughing | 8 | (9%) | |
| Dyspnea | 6 | (7%) | |
| Edema | 16 | (18%) | |
| Exudate | 20 | (22%) | |
| Obstruction | 19 | (21%) | |
| Stricture | 10 | (11%) | |
| Ulceration | 8 | (9%) |
High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)
Table 10 presents adverse events that were reported, regardless of the relationship to treatment, over the follow-up period in at least 5% of patients with HGD in BE in either controlled or uncontrolled clinical trials.
In the PHOTOFRIN PDT + OM group, severe treatment-associated adverse events included chest pain of non-cardiac origin, dysphagia, nausea, vomiting, regurgitation, and heartburn. The severity of these symptoms decreased within 4 to 6 weeks following treatment.
The majority of the photosensitivity reactions occurred within 90 days following PHOTOFRIN injection and was of mild (69%) or moderate (24%) intensity. Almost all (98%) of the photosensitivity reactions were considered to be associated with treatment. Fourteen (10%) patients reported severe reactions, all of which resolved. The typical reaction was described as skin disorder, sunburn or rash, and affected mostly the face, hands, and neck. Associated symptoms and signs were swelling, pruritis, erythema, blisters, itching, burning sensation, and feeling of heat.
The majority of esophageal stenosis and strictures reported in the PHOTOFRIN PDT + OM group were of mild (55%) or moderate (37%) intensity, while approximately 8% were of severe intensity. The majority of esophageal strictures were reported during Course 2 of treatment. All esophageal strictures were considered to be associated with treatment. Most esophageal strictures were manageable through dilations (see ).
Laboratory Abnormalities
In patients with esophageal cancer, PDT with PHOTOFRIN may result in anemia due to tumor bleeding. No significant effects were observed for other parameters in patients with endobronchial carcinoma or with HGD in BE.
| Treatment Groups | ||||
| BODY SYSTEM/ Adverse Event | Total PHOTOFRIN PDT N=318 n (%) | |||
| Patients with at Least One Adverse Event | 217 (99) | 51 (74) | 99 (100) | 316 (99) |
| GASTROINTESTINAL | 180 (82) | 25 (36) | 87 (88) | 267 (84) |
| Nausea | 61 (28) | 5 (7) | 63 (64) | 124 (39) |
| Esophageal Stricture | 85 (39) | 0 | 37 (37) | 122 (38) |
| Vomiting | 72 (33) | 4 (6) | 35 (35) | 107 (34) |
| Dysphagia | 50 (23) | 1 (1) | 27 (27) | 77 (24) |
| Esophageal Narrowing | 60 (27) | 4 (6) | 16 (16) | 76 (24) |
| Constipation | 45 (21) | 5 (7) | 9 (9) | 54 (17) |
| Abdominal Pain (Upper, lower, NOS) | 32 (15) | 4 (6) | 8 (8) | 40 (12) |
| Diarrhea | 22 (10) | 7 (10) | 6 (6) | 28 (9) |
| Esophageal Pain | 15 (7) | 0 | 9 (9) | 24 (8) |
| Hiccup | 18 (8) | 0 | 1 (1) | 19 (6) |
| Dyspepsia | 12 (5) | 3 (4) | 6 (6) | 18 (6) |
| Odynophagia | 13 (6) | 0 | 4 (4) | 17 (5) |
| Eructation | 11 (5) | 0 | 4 (4) | 15 (5) |
| GENERAL and ADMINISTRATION SITE CONDITIONS | 135 (62) | 17 (25) | 66 (67) | 201 (63) |
| Chest Pain | 71 (32) | 8 (12) | 40 (40) | 111 (35) |
| Pyrexia | 47 (21) | 3 (4) | 13 (13) | 60 (19) |
| Chest Discomfort | 14 (6) | 1 (1) | 21 (21) | 35 (11) |
| Pain | 17 (8) | 2 (3) | 7 (7) | 24 (8) |
| Fatigue | 13 (6) | 2 (3) | 0 | 13 (4) |
| SKIN and SUBCUTANEOUS TISSUE | 120 (55) | 8 (12) | 29 (29) | 149 (47) |
| Photosensitivity Reaction | 101 (46) | 0 | 16 (16) | 117 (37) |
| Rash | 14 (6) | 3 (4) | 7 (7) | 21 (7) |
| Pruritis | 13 (6) | 1 (1) | 1 (1) | 14 (4) |
| RESPIRATORY, THORACIC and MEDIASTINAL | 67 (31) | 21 (30) | 22 (22) | 89 (28) |
| Pleural Effusion | 25 (11) | 0 | 15 (15) | 40 (13) |
| Dyspnea | 16 (7) | 3 (4) | 4 (4) | 20 (6) |
| INFECTIONS and INFESTATIONS | 58 (26) | 22 (32) | 8 (8) | 66 (21) |
| Sinusitis | 11 (5) | 3 (4) | 2 (2) | 13 (4) |
| Bronchitis | 10 (5) | 3 (4) | 2 (2) | 12 (4) |
| METABOLISM and NUTRITION | 53 (24) | 9 (13) | 16 (16) | 69 (22) |
| Dehydration | 24 (11) | 2 (3) | 8 (8) | 32 (10) |
| Anorexia | 6 (3) | 2 (3) | 8 (8) | 14 (4) |
| NERVOUS SYSTEM | 51 (23) | 14 (20) | 11 (11) | 62 (19) |
| Headache | 17 (8) | 6 (9) | 2 (2) | 19 (6) |
| INJURY, POISONING and PROCEDURAL | 42 (19) | 10 (14) | 19 (19) | 61 (19) |
| Post Procedural Pain | 16 (7) | 1 (1) | 14 (14) | 30 (9) |
| Sunburn | 8 (4) | 0 | 6 (6) | 14 (4) |
| MUSCULOSKELETAL and CONNECTIVE TISSUE | 46 (21) | 18 (26) | 9 (9) | 55 (17) |
| Back Pain | 15 (7) | 4 (6) | 1 (1) | 16 (5) |
| Arthralgia | 10 (5) | 6 (9) | 1 (1) | 11 (3) |
| INVESTIGATIONS | 41 (19) | 5 (7) | 14 (14) | 55 (17) |
| Weight Decreased | 17 (8) | 2 (3) | 3 (3) | 20 (6) |
| Body Temperature Increased | 8 (4) | 0 | 8 (8) | 16 (5) |
| PSYCHIATRIC | 37 (17) | 8 (12) | 4 (4) | 41 (13) |
| Insomnia | 11 (5) | 3 (4) | 1 (1) | 12 (4) |
| Depression | 10 (5) | 3 (4) | 0 | 10 (3) |
| Anxiety | 10 (5) | 1 (1) | 0 | 10 (3) |
| VASCULAR | 25 (11) | 6 (9) | 4 (4) | 29 (9) |
| Hypertension | 10 (5) | 1 (1) | 0 | 10 (3) |
What should I look out for while using PHOTOFRIN?
PHOTOFRIN is contraindicated in patients with porphyria or in patients with known allergies to porphyrins.
Photodynamic therapy is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula.
Photodynamic therapy is contraindicated in patients with tumors eroding into a major blood vessel.
Photodynamic therapy 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.
Photodynamic therapy is not suitable for patients with esophageal or gastric varices, or patients with esophageal ulcers
>1 cm in diameter.
Following injection with PHOTOFRIN precautions must be taken to avoid exposure of skin and eyes to direct sunlight or bright indoor light (see , ).
What might happen if I take too much PHOTOFRIN?
How should I store and handle PHOTOFRIN?
Store the kit at 2°-8°C (36°-46°F) and protect from light.ArrayStore the kit at 2°-8°C (36°-46°F) and protect from light.Array PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005 PHOTOFRIN (porfimer sodium) for Injection is supplied as a freeze-dried cake or powder as follows: NDC 58914-155-75 — 75 mg vial PHOTOFRIN freeze-dried cake or powder should be stored at Controlled Room Temperature 20−25°C (68−77°F) [see USP].Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations.Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.Manufactured byWYETH-AYERST LEDERLE PARENTERALS, INC.Carolina, Puerto Rico 00987forAxcan Scandipharm Inc.Birmingham, AL 35242For inquiries call Axcan Scandipharm Inc. at:1-800-742-6706September 29, 2005
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
The cytotoxic and antitumor actions of PHOTOFRIN are light and oxygen dependent. Photodynamic therapy 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. Cellular damage caused by PHOTOFRIN PDT is a consequence of the propagation of radical reactions. Radical initiation may occur after PHOTOFRIN absorbs light to form a porphyrin excited state. Spin transfer from PHOTOFRIN 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 A release. The laser treatment induces a photochemical, not a thermal, effect. The necrotic reaction and associated inflammatory responses may evolve over several days.
Non-Clinical Toxicology
PHOTOFRIN is contraindicated in patients with porphyria or in patients with known allergies to porphyrins.Photodynamic therapy is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula.
Photodynamic therapy is contraindicated in patients with tumors eroding into a major blood vessel.
Photodynamic therapy 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.
Photodynamic therapy is not suitable for patients with esophageal or gastric varices, or patients with esophageal ulcers >1 cm in diameter.
Following injection with PHOTOFRIN precautions must be taken to avoid exposure of skin and eyes to direct sunlight or bright indoor light (see , ).
There have been no formal interaction studies of PHOTOFRIN and any other drugs. However, it is possible that concomitant use of other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, and fluoroquinolones) could increase the risk of photosensitivity reaction.
PHOTOFRIN PDT causes direct intracellular damage by initiating radical chain reactions that damage intracellular membranes and mitochondria. Tissue damage also results from ischemia secondary to vasoconstriction, platelet activation and aggregation and clotting. Research in animals and in cell culture has suggested that many drugs could influence the effects of PDT, possible examples of which are described below. There are no human data that support or rebut these possibilities.
Compounds that quench active oxygen species or scavenge radicals, such as dimethyl sulfoxide, β-carotene, ethanol, formate and mannitol would be expected to decrease PDT activity. Preclinical data also suggest that tissue ischemia, allopurinol, calcium channel blockers and some prostaglandin synthesis inhibitors could interfere with PHOTOFRIN PDT. Drugs that decrease clotting, vasoconstriction or platelet aggregation, e.g., thromboxane A inhibitors, could decrease the efficacy of PDT. Glucocorticoid hormones given before or concomitant with PDT may decrease the efficacy of the treatment.
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.
Ocular Sensitivity
Ocular discomfort, commonly described as sensitivity to sun, bright lights, or car headlights, has been reported in patients who received PHOTOFRIN. 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 events. 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 6. 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 pre-treatment prior to developing the event (49%) and/or had a mucosal segment treated twice (82%). Therefore, nodule pre-treatment and re-treating the same mucosal segment more than once may influence the risk of developing an esophageal stricture.
Prior to initiating treatment with PHOTOFRIN PDT, the diagnosis of HGD in BE should be confirmed by an expert GI pathologist. Photodynamic therapy with PHOTOFRIN should be applied by physicians trained in the endoscopic use of PDT with PHOTOFRIN, and only in those facilities properly equipped for the procedure.
Avoidance of Pregnancy
Women of childbearing potential should practice an effective method of contraception during therapy (see ).
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 ). 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.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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Interactions
Interactions
A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).