porfimer (Rx)

>10%

Anemia (32%)

Fever (31%)

Pleural effusion (28%)

Constipation (24%)

Chest pain (22%)

Abd pain (20%)

Dyspnea (18%)

Pneumonia (16%)

Insomnia (14%)

Back pain (11%)

1-10%

Atrial-fib (10%)

Dysphagia (10%)

Pharyngitis (10%)

Resp distress (9%)

Decr wt (9%)

Hematemesis (8%)

Dehydration (7%)

Hypotension (7%)

Peripheral edema (7%)

Cardiac failure (7%)

Tachycardia (6%)

Asthenia (6%)

Hypertension (6%)

Cough (6%)

Diarrhea (5%)

Generalized edema (5%)

Postmarketing Reports

Infusion reactions including urticaria, bradycardia, hypotension, dizziness, and hypertension

Contraindications

Hypersensitivity to porphyrins

Porphyria

Emergency treatment of severe acute respiratory distress when caused by endobronchial lesion

Esophageal or gastric varices

Esophageal ulcers

Tracheoesophageal or bronchoesophageal fistula; tumor erosion into major blood vessel

Cautions

Separate from radiotherapy by 2-4 wk

Avoid sunlight following injection

Esophageal stricture reported within 6 months of initiating treatment (usually within 6 months of treatment)

Inflammation resulting from treatment may obstruct airway (not for use in patients with esophageal tumors eroding into the trachea or bronchial tree

Potentially fatal gastrointestinal and esophageal necrosis and perforation may occur following treatment

May experience substernal chest pain from inflammatory responses within the treatment area

Ocular discomfort reported

Photosensitivity reactions reported in patients exposed to direct sunlight or bright indoor light

Thromboembolism reported, particularly in patients with other risk factors (eg, advanced cancer, postsurgery, prolonged immobilization, CV disease)

Hepatic or renal impairment will likely prolong the elimination of porfimer sodium leading to higher rates of toxicity; inform patients with severe renal impairment or mild to severe hepatic impairment that the period requiring precautionary measures for photosensitivity may be longer than 90 days

Risk of hemorrhage increased in patients esophageal varices or tumors eroding into pulmonary blood vessels; patients with large, centrally located tumors, cavitating tumors, or extensive tumors extrinsic to bronchus are at high risk for fatal massive hemoptysis; assess patients for tumors eroding into a pulmonary blood vessel and esophageal varices; do not administer light directly to an area with esophageal varices because of high risk of hemorrhage

Long-term effect of PDT on high grade dysplasia (HGD) in Barrett’s Esophagus (BE) is unknown; there is always a risk of cancer or abnormal epithelium that is invisible to 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 endoscopic appearance of complete squamous cell reepithelialization

Conduct endoscopic biopsy surveillance every 3 months, until 4 consecutive negative evaluations for HGD have been recorded; further follow-up may be scheduled every 6 to 12 months, as per judgment of healthcare providers; the follow-up period of randomized study at time of analysis was a minimum of 2 years (range 2 to 5.6 years)

If PDT is to be used before or after radiotherapy, allot sufficient time 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; allow 2-4 weeks after PDT before commencing radiotherapy; the acute inflammatory reaction from radiotherapy usually subsides within 4 weeks after completing radiotherapy; allow 4 weeks after completing radiotherapy before commencing PDT

Pregnancy

Based on animal studies, drug may cause embryo-fetal toxicity when administered to a pregnant woman; there are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Verify pregnancy status in females of reproductive potential prior to initiation of therapy

Contraception

• Drug may cause fetal harm when administered to a pregnant woman
• Females: Advise females of reproductive potential to use effective contraception during treatment and for 5 months after final dose
• Males: Advise male patients with female partners of reproductive potential to use condoms during treatment and for 5 months following final dose

Animal data

• Intravenous administration of drug to pregnant rats and rabbits during period of organogenesis at dose levels approximately 0.64 times recommended human dose based on body surface area (BSA) resulted in increased fetal resorptions, decreased litter size, and reduced fetal weight, but did not cause fetal malformations

Lactation

There are no data on presence of drug in human or animal milk, effects on breastfed infant, or on milk production; because of potential for serious adverse reactions in breastfed infant, advise patients that breastfeeding is not recommended during treatment and for 5 months after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Cytotoxic activity dependent on light and oxygen; activated by laser light to produce oxygen free radicals and vascular necrosis via thromboxane A2 release

Pharmacokinetics

Half-Life: 17 days (first dose); 30 days (second dose); retained longest in tumors, skin, and reticuloendothelial organs

Peak Plasma Concentration: 15 mcg/mL

Protein Bound: 90%

Vd: 0.49 L/kg

Clearance: 0.051 mL/min/kg

IV Incompatibilities

Do not mix with other drugs in the same solution

IV Preparation

Reconstitute with 31.8 mL of either D5W or NS resulting in a final concentration of 2.5 mcg/mL & pH of 7-8

Shake well until dissolved

Protect the reconstituted product from bright light & use immediately

Reconstituted porfimer is an opaque solution in which detection of particulate matter by visual inspection is extremely difficult

IV Administration

Administer slow IVP over 3-5 min

Use of gloves & eye protection is recommended

Storage

Store intact vials at controlled room temp 20-25°C (68-77°F)