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Porfimer


General


Pronunciation

(POR fi mer)


Brand Names: U.S.

  • Photofrin

Indications


Use: Labeled Indications

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

Endobronchial cancer: 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: Palliation of obstructing (partial or complete) esophageal cancer (in patients who cannot be treated satisfactorily with laser therapy)

Canadian labeling: Additional use (not in US labeling: Second-line treatment of recurrent, superficial papillary bladder cancer


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


Dosing and Administration


Dosing: Adult

Photodynamic therapy in esophageal cancer or endobronchial non-small cell lung cancer: 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

Photodynamic therapy in Barrett esophagus dysplasia: 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

Photodynamic therapy in papillary bladder cancer (Canadian labeling; not in U.S. labeling): IV: 2 mg/kg, followed by cystoscopic exposure to the appropriate laser light. Note: Repeat dosing is not recommended due to increased risk of bladder contracture.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).


Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (meets NIOSH 2014 criteria).

U.S. labeling: 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.

Canadian labeling: Reconstitute each 75 mg vial with 31.8 mL of D5W (only) resulting in a final concentration of 2.5 mg/mL. Reconstitute each 15 mg vial with 6.6 mL of D5W only 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

Administer slow IV injection over 3 to 5 minutes. Avoid contact with skin during administration. Avoid extravasation (if extravasation occurs, protect area from light and sunlight). Hazardous agent; use appropriate precautions for handling and disposal (meets NIOSH 2014 criteria).


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.


Dosage Forms/Strengths


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)


Compatibility

Do not mix porfimer with other drugs in the same solution.


Drug Interactions

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. 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


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.


Adverse Reactions


>10%:

Cardiovascular: Chest pain (5% to 31%), edema (3% to 18%)

Central nervous system: Fever (8% to 31%), pain (1% to 22%), insomnia (5% to 14%)

Dermatologic: Photosensitivity reaction (19% to 69%)

Gastrointestinal: Esophageal stricture/stenosis (6% to 38%), nausea (24% to 37%), vomiting (17% to 31%), constipation (5% to 24%), dysphagia (10% to 24%), mucositis ( ≤20%), abdominal pain (5% to 20%)

Hematologic: Anemia (32% in esophageal cancer patients)

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

Respiratory: Pleural effusion (5% to 32%), dyspnea (7% to 30%), bronchial obstruction/mucus plug (21%), pneumonia (6% to 18%), hemoptysis (7% to 16%), cough (5% to 15%), bronchostenosis (11%), pharyngitis (11%)

5% to 10%:

Cardiovascular: Atrial fibrillation, cardiac failure (esophageal cancer), hyper-/hypotension, tachycardia

Central nervous system: Anxiety, confusion, dysphonia

Endocrine & metabolic: Dehydration

Gastrointestinal: Anorexia, diarrhea, dyspepsia, eructation, esophageal edema, esophageal pain, esophagitis, hematemesis, melena, odynophagia, weight loss

Genitourinary: Urinary tract infection

Neuromuscular & skeletal: Weakness

Respiratory: Bronchial ulceration, bronchitis, fatal massive hemoptysis, respiratory insufficiency, tracheoesophageal fistula

Miscellaneous: Hiccups, moniliasis, tumor hemorrhage, surgical complication

Common adverse reactions observed in papillary bladder cancer (Canadian labeling; not an approved use in the U.S.):

Cardiovascular: Peripheral edema

Central nervous system: Anxiety, insomnia, pain

Gastrointestinal: Constipation, nausea

Genitourinary: Bladder contracture (irreversible), dysuria, genital edema, micturition frequency, nocturia, suprapubic pain, urinary incontinence, urinary tract infection, urinary urgency

Renal: Hematuria

<5% (Limited to important or life-threatening): Airway obstruction, angina, bradycardia, bronchospasm, cardiac failure, cataracts, cerebrovascular accident, diplopia, erythema, esophageal perforation, eye pain, fluid imbalance, gastric ulcer, gastroesophageal fistula/perforation, hemorrhage, ileus, infusion reactions, jaundice, laryngotracheal edema, lung abscess, MI, ocular sensitivity, peritonitis, photophobia, pneumonitis, pruritus, pseudoporphyria state, pulmonary edema, pulmonary embolism, pulmonary hemorrhage, pulmonary thrombosis, respiratory distress/failure, sepsis, sick sinus syndrome, skin blistering, skin discoloration, skin fragility, skin nodules, skin wrinkles, stridor, supraventricular tachycardia, thromboembolic events, urticaria


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.

- 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.

Special handling:

- Hazardous agent: Use appropriate precautions for handling and disposal (meets NIOSH 2014 criteria).

Other warnings/precautions:

- Extravasation: Avoid extravasation. If extravasation occurs, protect affected area from light; use of antidotes is of unknown benefit.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Effective contraception is recommended for women of childbearing potential.


Actions


Pharmacology

Porfimers 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.


Distribution

Steady state Vd: 0.49 L/kg


Half-Life Elimination

First dose: 17 days; Second dose: 30 days


Protein Binding

Plasma: ~90%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, abdominal pain, constipation mouth irritation, pharyngitis, skin discoloration, skin irritation, insomnia, or back pain. Have patient report immediately to prescriber signs of infection, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), shortness of breath; angina; tachycardia; arrhythmia; dysphagia; persistent cough; bruising; bleeding; coughing up blood; black, tarry, or bloody stools; vomiting blood; injection site irritation; vision changes; severe loss of strength and energy; dry mouth; dry eyes; or jaundice (HCAHPS).

- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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