Porfimer

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous, as sodium [preservative free]:

Photofrin: 75 mg (1 ea)

Pharmacology

Mechanism of Action

Porfimer's cytotoxic activity is dependent on light and oxygen. Following administration, the drug is selectively retained in neoplastic tissues. Exposure of the drug to laser light at wavelengths >630 nm results in the production of oxygen free-radicals. Release of thromboxane A₂, leading to vascular occlusion and ischemic necrosis, may also occur.

Pharmacokinetics/Pharmacodynamics

Distribution

Steady state V_d: 0.49 L/kg ± 0.28 L/kg (Pereira 2010)

Half-Life Elimination

First dose: 17 days; Second dose: 30 days

Protein Binding

Plasma: ~90%

Use: Labeled Indications

Barrett esophagus dysplasia (photodynamic therapy): Ablation of high-grade dysplasia in Barrett esophagus (in patients who do not undergo esophagectomy)

Endobronchial cancer (photodynamic therapy): Treatment of microinvasive endobronchial non-small cell lung cancer (NSCLC) in patients for whom surgery and radiation therapy are not indicated; reduction of obstruction and symptom palliation in patients with obstructing (partial or complete) endobronchial NSCLC

Esophageal cancer (photodynamic therapy): Palliation of completely obstructing esophageal cancer, or partially obstructing esophageal cancer in patients who cannot be treated satisfactorily with Nd:YAG laser therapy.

Contraindications

Porphyria

Photodynamic therapy (PDT) is contraindicated in patients with current tracheoesophageal or bronchoesophageal fistula; tumors eroding into a major blood vessel; emergency treatment of severe acute respiratory distress when caused by endobronchial lesion; esophageal or gastric varices; esophageal ulcers >1 cm in diameter

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to porphyrins; photodynamic therapy is contraindicated in patients with papillary bladder cancer who have received prior total bladder radiation or whose functional bladder capacity is <200 mL and in patients with coexisting bladder tumors of stage greater than stage 1 (T1) who have invasive cancer

Dosage and Administration

Dosing: Adult

Esophageal cancer or endobronchial non-small cell lung cancer (photodynamic therapy): IV: 2 mg/kg, followed by endoscopic exposure to the appropriate laser light and debridement; repeat courses must be separated by at least 30 days (delay subsequent treatment for insufficient healing) for a maximum of 3 courses

Barrett esophagus dysplasia (photodynamic therapy): IV: 2 mg/kg, followed by endoscopic exposure to the appropriate laser light; repeat courses must be separated by at least 90 days (delay subsequent treatment for insufficient healing) for a maximum of 3 courses

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Due to the potential for photosensitivity reactions, wear rubber gloves and eye protection and avoid skin and eye contact during preparation and administration. Spills should be wiped with a damp cloth and contaminated material should be disposed of properly. Protect from bright light if overexposure occurs.

Reconstitute each 75 mg vial with 31.8 mL of either D5W or NS injection resulting in a final concentration of 2.5 mg/mL. Shake well until dissolved. Protect the reconstituted product from bright light and use immediately. Use appropriate precautions for handling and disposal.

Administration

IV: Administer slow IV injection over 3 to 5 minutes. Avoid extravasation (if extravasation occurs, protect area from light and sunlight).

Due to the potential for photosensitivity reactions, wear rubber gloves and eye protection and avoid skin and eye contact during administration; if overexposure occurs, protect from bright light. Spills should be wiped with a damp cloth and contaminated material should be disposed of properly.

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F). Reconstituted solutions should be protected from light and used immediately after preparation.

Drug Interactions

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy

Photosensitizing Agents: May enhance the photosensitizing effect of Porfimer. Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Chest pain (8% to 22%)

Central nervous system: Confusion (5% to 24%), pain (5% to 22%), insomnia (5% to 14%)

Dermatologic: Skin photosensitivity (19% to 69%)

Gastrointestinal: Esophageal stenosis (6% to 38%), nausea (24%), constipation (5% to 24%), abdominal pain (20%), vomiting (17%), dysphagia (10%)

Hematologic & oncologic: Anemia (esophageal cancer: 32%)

Neuromuscular & skeletal: Back pain (3% to 11%)

Respiratory: Pleural effusion (5% to 32%), dyspnea (7% to 30%), bronchial obstruction (≤21%; includes bronchial stenosis), bronchial plugs (≤21%), pneumonia (12% to 18%), hemoptysis (16%; massive: 10%), cough (7% to 15%), bronchoconstriction (bronchostenosis: 11%), pharyngitis (11%)

Miscellaneous: Fever (16% to 31%), serous drainage (22%)

1% to 10%:

Cardiovascular: Atrial fibrillation (10%), hypotension (7%), peripheral edema (5% to 7%), cardiac failure (esophageal carcinoma and endobronchial cancer: ≤7%), hypertension (6%), tachycardia (6%), edema (5%), substernal pain (5%), angina pectoris (<5%), bradycardia (<5%), myocardial infarction (<5%), pulmonary embolism (<5%), sick sinus syndrome (<5%), supraventricular tachycardia (<5%), thrombosis (pulmonary: <5%)

Central nervous system: Anxiety (6% to 7%), voice disorder (5%)

Endocrine & metabolic: Weight loss (9%), dehydration (7%)

Gastrointestinal: Anorexia (8%), disease of esophagus (esophageal edema: 8%), hematemesis (8%), tracheoesophageal fistula (6%), dyspepsia (2% to 6%), diarrhea (5%), eructation (5%), esophagitis (5%), melena (5%), esophageal perforation (<5%), gastric ulcer (<5%), intestinal obstruction (<5%), peritonitis (<5%)

Genitourinary: Urinary tract infection (7%)

Hematologic & oncologic: Tumor hemorrhage (8%), pulmonary hemorrhage (<5%)

Hepatic: Jaundice (<5%)

Infection: Candidiasis (9%), abscess (lung: <5%)

Neuromuscular & skeletal: Weakness (6%)

Ophthalmic: Diplopia (<5%), eye pain (<5%), photophobia (<5%), visual disturbance (<5%)

Respiratory: Bronchitis (≤10%), respiratory insufficiency (5% to 10%), airway obstruction (including laryngotracheal edema: <5%), bronchospasm (<5%), pneumonitis (<5%), pulmonary edema (<5%), respiratory failure (<5%), stridor (<5%)

Miscellaneous: Ulcer (bronchial: 9%), postoperative complication (5%)

<1%, postmarketing, and/or case reports: Cataract, cerebrovascular accident, cutaneous nodule, disturbance in fluid balance, fragile skin, gastrointestinal disease (gastroesophageal fistula, gastroesophageal perforation), hemorrhage, hypertrichosis, infusion related reaction (including dizziness and urticaria), pseudoporphyria, sepsis, skin discoloration, thromboembolism, wrinkling of skin

Warnings/Precautions

Concerns related to adverse effects:

• Airway obstruction: Treatment-induced inflammation may obstruct airway. Use with caution in patients with endobronchial tumors, especially if in areas where main airway may be obstructed (long or surrounding tumors). Necrotic debris or mucositis may also cause airway obstruction. Monitor closely between laser therapy and debridement for respiratory distress; may require urgent bronchoscopy to remove secretions or debris.
• Chest pain: Inflammatory responses within the treatment area may result in substernal chest pain.
• Esophageal strictures: Esophageal strictures may occur, usually within 6 months of treatment. May require multiple dilations to resolve. The risk is increased with nodule pretreatment or with re-treatment of the same area.
• Extravasation: Avoid extravasation. If extravasation occurs, protect affected area from light; use of antidotes is of unknown benefit.
• Gastroesophageal fistula/perforation: Serious and potentially fatal gastrointestinal and esophageal necrosis and perforation may occur following treatment. Due to the high risk for fistula, do not use in patients with esophageal tumors eroding into the trachea or bronchial tree/wall. Use is contraindicated in patients with existing tracheoesophageal or bronchoesophageal fistula.
• Hemorrhage: Patients with esophageal varices or tumors eroding into pulmonary blood vessels are at increased risk for hemorrhage, including fatal massive pulmonary hemoptysis (FMH). Other risk factors for FMH include large, centrally-located tumors, cavitating tumors, or extensive tumor extrinsic to the bronchus.
• Ocular photosensitivity: Ocular discomfort has been reported with sun or bright light exposure. For at least 30 days (and until ocular sensitivity resolves), when outdoors, patients should wear dark sunglasses which have an average white light transmittance of <4%.
• Photosensitivity: Photosensitivity reactions are common in patients who are exposed to direct sunlight or bright indoor light (eg fluorescent lights, unshaded light bulbs, examination/operating lights). Conventional ultraviolet (UV) sunscreens are not protective against photosensitivity reactions caused by visible light. Photosensitivity may last 30 to 90 days or more. Encourage exposure to ambient indoor light (aids in gradually inactivating residual porfimer). Patients should be educated to test for residual photosensitivity before resuming exposure to sunlight. Re-exposure to general sunlight should be gradual (expose small area of skin [not the face] for 10 minutes, if no photosensitivity (eg, edema, erythema, blistering) occurs after 24 hours, may gradually resume normal outdoor activities; if photosensitivity occurs then wait 2 weeks and retest).
• Thromboembolism: Thromboembolic events may occur, generally in patients with additional risk factors for thromboembolism (eg, advanced cancer, prolonged immobilization, cardiovascular disease, or following major surgery).

Disease-related concerns:

• Barrett esophagus: In patients with Barrett esophagus, conduct rigorous surveillance (endoscopic biopsy every 3 months until 4 consecutive negative results for high-grade dysplasia followed by further follow-up per physician judgment). The long-term effects of photodynamic therapy in patients with Barrett esophagus is not known. Esophageal strictures are common adverse events associated with photodynamic therapy of Barrett esophagus; esophageal dilation may be required.
• Esophageal/gastric varices: Not suited for treatment of patients with esophageal or gastric varices (due to the high risk for hemorrhage).
• Hepatic impairment: Elimination may be prolonged in hepatic impairment; toxicities may be increased. Photosensitivity may be increased beyond 90 days in patients with mild-to-severe hepatic impairment.
• Renal impairment: Elimination may be prolonged in renal impairment; toxicities may be increased. Photosensitivity may be increased beyond 90 days in patients with severe renal impairment.

Concurrent drug therapy issues:

• Photosensitizing drugs: Concurrent use with other photosensitizing agents may increase the risk for photosensitivity reactions.

Special populations:

• Radiation therapy recipients: Allow 2 to 4 weeks to elapse after phototherapy prior to initiating radiation therapy; 4 weeks should elapse after radiation therapy prior to initiating phototherapy.

Monitoring Parameters

Monitor injection site during infusion (for extravasation); monitor in between laser and debridement for evidence of respiratory distress in patients with endobronchial tumors; monitor for signs/symptoms of photosensitivity, hemorrhage, thromboembolic events, gastroesophageal fistulas/perforation, esophageal strictures.

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat cancer.
• It is used to treat changes in the swallowing tube called Barrett's esophagus.

Frequently reported side effects of this drug

• Hair growth
• Nausea
• Vomiting
• Abdominal pain
• Constipation
• Diarrhea
• Weight loss
• Lack of appetite
• Anxiety
• Skin discoloration
• Skin changes
• Trouble sleeping
• Back pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
• Dehydration like dry skin, dry mouth, dry eyes, increased thirst, fast heartbeat, dizziness, fast breathing, or confusion
• Severe headache
• Severe dizziness
• Passing out
• Vision changes
• Mouth irritation
• Mouth sores
• Throat irritation
• Confusion
• Shortness of breath
• Swelling of arms or legs
• Excessive weight gain
• Fast heartbeat
• Abnormal heartbeat
• Vaginal pain, itching, and discharge
• Trouble swallowing
• Persistent cough
• Severe or persistent skin reaction
• Severe loss of strength and energy
• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
• Bowel problems like black, tarry, or bloody stools; fever; mucus in stools; vomiting; vomiting blood; severe abdominal pain; constipation; or diarrhea
• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.