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Porfimer
DRUG NAME: Porfimer
SYNONYM(S): Dihaematoporphyrin ether,1 porphyrins2
COMMON TRADE NAME(S): PHOTOFRIN®
CLASSIFICATION: Miscellaneous
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
MECHANISM OF ACTION:
Porfimer, a mixture of porphyrins, is a photosensitizing agent with cytotoxic activity dependent on oxygen and light.2
Tumour selectivity occurs as a result of selective retention of porfimer in tumour tissue and by selective delivery of
2
light. Photodynamic therapy (PDT) is a 2-stage process involving porfimer and laser light. PDT-induced cytotoxicity
may be due to free radical generation and the production of singlet oxygen.2 Tumour death also occurs through
2
ischemic necrosis secondary to vascular occlusion, mediated by thromboxane A 2 release.
PHARMACOKINETICS:
Oral Absorption
Distribution
Metabolism
Excretion
Sex
no information found
slow distribution phase
cross blood brain barrier?
yes3
4
volume of distribution
0.49 L/kg
plasma protein binding
90%
in tissues via slow photodestruction (photobleaching)5
active metabolite(s)
no information found
inactive metabolite(s)5
yes
primarily hepatic, elimination occurs over 40-72 h from a variety of tissues;
tumour, skin, and organs of the reticuloendothelial system (including liver and spleen)
retain porfimer longer
urine
no information found
feces
primarily
terminal half life
17-22 d (range: 11-28 d)
clearance4
0.051 mL/min/kg
6
no significant differences
2
Adapted from standard reference unless specified otherwise.
USES:
Primary uses:
*Endobronchial non-small cell lung cancer
*Esophageal cancer
*High-grade dysplasia associated with Barrett’s esophagus
*Superficial papillary bladder cancer
Other uses:
4
Gastric cancer
4
Rectal cancer
*Health Canada approved indication
BC Cancer Agency Cancer Drug Manual©
Developed: September 1994
Revised: 1 October 2007
Page 1 of 7
Porfimer
Porfimer
SPECIAL PRECAUTIONS:
Contraindications2:
 porphyria or a history of hypersensitivity reaction to porphyrins
 tumours eroding into a major blood vessel (due to the risk of fatal massive hemoptysis)
 tracheoesophageal or bronchoesophageal fistula
 prior total bladder radiation or functional bladder capacity less than 200 mL (due to the risk of irreversible bladder
contractures from increased fibrosis)
 coexisting bladder tumours of stage greater than T1 with invasive cancer
 emergency treatment of severe acute respiratory distress caused by obstruction (due to delay required between
porfimer administration and laser light treatment)
 esophageal or gastric varices or esophageal ulcers >1 cm in diameter; esophageal tumour eroding into the
trachea or bronchial tree (due to risk of fistula formation)
Caution2:
 photosensitivity; avoid contact with the skin and eyes during preparation and administration due to the risk of
irritation; if exposure occurs protect area from light; see paragraph following the Side Effects table
 endobronchial tumour treatment may result in an obstructed airway due to treatment induced inflammation;
debridement of the treated area, approximately 24 hours after treatment,7 is mandatory to remove exudates and
necrotic tissue
 large centrally located tumours, cavitating tumours, or tumours extrinsic to the bronchus (due to risk of fatal
hemoptysis)
 radiation; see Dosage Guidelines
Carcinogenicity: No information found.
Mutagenicity: Porfimer is not mutagenic in Ames test with and without light irradiation.2 Porfimer with light
irradiation is mutagenic in some mammalian in vitro mutation tests.2 Only after light irradiation did porfimer induce a
2
marginally positive response for clastogenicity in the mammalian in vitro chromosome test. Porfimer without light
2
irradiation is not clastogenic in the mammalian in vivo chromosome tests. The overall mutagenicity risk of porfimer
2
is considered minimal.
Fertility: No impairment of fertility in rats at doses equivalent to two times the maximum recommended human dose
based on body weight and one-half the human dose based on body-surface area.2 No evidence of teratogenicity in
2
animals at doses equivalent to 2-4 times the maximum recommended human dose based on body weight.
Pregnancy: FDA Pregnancy Category C.4 Animal studies have shown fetal risks and there are no controlled studies
in women. Drugs should be given only if the potential benefit justifies the potential risk to the fetus. Animal studies
have shown maternal and fetal toxicity but no major malformations.4
4
Breastfeeding is not recommended due to the potential secretion into breast milk.
SIDE EFFECTS:
The table includes adverse events that presented during drug treatment but may not necessarily have a causal
relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event
rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they
were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be
7
clinically important. When placebo-controlled trials are available, adverse events are included if the incidence is
>5% higher in the treatment group.
BC Cancer Agency Cancer Drug Manual©
Developed: September 1994
Revised: 1 October 2007
Page 2 of 7
Porfimer
Porfimer
ORGAN SITE
SIDE EFFECT
Clinically important side effects are in bold, italics
Many side effects are limited to the tumour site or organ system being treated. These are identified in italics.
BE= High-grade dysplasia associated with Barrett’s esophagus, ENSCLC= Endobronchial non-small cell lung cancer
allergy/immunology
hypersensitivity reaction8,9
blood/bone marrow/
febrile neutropenia
cardiovascular
(arrhythmia)
constitutional symptoms
anemia (26%); secondary to tumour bleeding,
dermatology/skin
gastrointestinal
10
with treatment for esophageal cancer
atrial fibrillation (3-8%); with treatment for BE and esophageal cancer; likely a
manifestation of a local/regional inflammatory reaction
insomnia (7-20%)
fever (15-33%); with treatment for esophageal, endobronchial cancer, or BE; likely a
manifestation of a local/regional inflammatory reaction or the endoscopic procedure7
extravasation hazard: irritant11; if extravasation occurs, protect the area from light for a
minimum of 30 days
photosensitivity; (<100%) typically mild to moderate, see paragraph following the
Side Effects table
emetogenic potential: rare12,13
constipation (5-27%); typically mild to moderate
diarrhea (16%); with treatment for BE
dysphagia (19%); with treatment for BE
esophageal edema (6%); with treatment for esophageal cancer; likely a manifestation
of a local/regional inflammatory reaction
esophageal stenosis/stricture (40%); with treatment for BE; typically mild to moderate
and occurs during the second course of treatment; esophageal dilation may be required
nausea (12-21%)
vomiting (16-38%); with treatment for BE and esophageal cancer
hemorrhage
infection
hematemesis (11%); with treatment for esophageal cancer
non-fatal hemoptysis (12%), fatal massive hemoptysis (10%); however, 3% treatmentassociated events within 30 days of treatment; with treatment for ENSCLC; see
Caution section
bronchitis (11%); with treatment for ENSCLC; typically mild to moderate and occurs
within 1 week of treatment; typically resolves within 10 days with antibiotic treatment
pneumonia (13-16%); with treatment for BE, esophageal cancer, and ENSCLC
lymphatics
peripheral edema (16%); with treatment for bladder cancer
metabolic/laboratory
neurology
elevated serum transaminases and alkaline phosphatase levels14 (~10%)14; typically
mild to moderate14
anxiety (5-12%)
ocular/visual
cataracts (<1%); accelerated development
fluid imbalance (<1%); with disseminated intraperitoneal malignancies
ocular sensitivity; see paragraph following the Side Effects table
pain
abdominal pain (19-20%); with treatment for BE and esophageal cancer
chest pain (9-25%); with treatment for BE, esophageal cancer, and ENSCLC
non-specific pain (12-22%)
pulmonary
cough (17%); with treatment for ENSCLC
BC Cancer Agency Cancer Drug Manual©
Developed: September 1994
Revised: 1 October 2007
Page 3 of 7
Porfimer
Porfimer
ORGAN SITE
SIDE EFFECT
Clinically important side effects are in bold, italics
Many side effects are limited to the tumour site or organ system being treated. These are identified in italics.
BE= High-grade dysplasia associated with Barrett’s esophagus, ENSCLC= Endobronchial non-small cell lung cancer
dyspnea (10-32%); with treatment for BE, esophageal cancer, and ENSCLC; typically
transient and self-limiting
hiccups (11%); with treatment for BE
increased sputum (9%); with treatment for ENSCLC
pleural effusion (6-28%); with treatment for BE and esophageal cancer; typically mild to
moderate; likely a manifestation of a local/regional inflammatory reaction
respiratory insufficiency (7-10%, severe 3%); with treatment for ENSCLC and
esophageal cancer
renal/genitourinary
irritative bladder symptoms; with treatment for bladder cancer; may occur for several
weeks and includes: increased micturition (60%), hematuria (56%), dysuria (36%),
urgency (32%), strangury (32%), genital edema (24%), suprapubic pain (20%), urinary
incontinence (20%), nocturia (12%), urinary tract infection (12%), and transient
reduction in bladder capacity; irreversible bladder contracture (20%), typically occurs
several months post-PDT2
2
Adapted from standard reference unless specified otherwise.
Toxicities associated with PDT, except for photosensitivity and constipation, occur primarily within the same
physiological system as the tumour or in the immediate area that received laser light.2 Toxicities occasionally extend
2
into adjacent tissues. Local reactions are consistent with an inflammatory reaction induced by the photodynamic
2
effect. The necrotic reaction and associated inflammatory responses may evolve over several days.2
2
Photosensitivity, caused by residual drug in the skin, typically occurs for >30 days after treatment. Symptoms
2
include mild to moderate erythema, swelling, itching, burning sensations, blisters, or feeling hot. Ocular discomfort,
2
commonly described as sensitivity to sun, bright lights, or car headlights has also been reported. Other less
common skin manifestations, in areas where photosensitivity reactions occurred, include increased hair growth, skin
discolouration, skin nodules, increased wrinkles, and increased skin fragility which may be attributed to a temporary
drug induced cutaneous porphyria.2
Protection: Avoid exposure of skin and eyes to direct sunlight or brightly focused indoor light (from examination
lamps, dental lamps, operating room lamps, floodlights, halogen lamps, etc.).2 Conventional UV sunscreens are not
2
effective at protecting against photosensitivity reactions as photoactivation is caused by visible light. For >30 days,
2
when outdoors, wear protective clothing and dark sunglasses. Patients should not stay in a darkened room, but
should be encouraged to expose their skin to ambient indoor light as porfimer will be inactivated gradually and safely
through a photobleaching reaction.2 The level of photosensitivity will vary for different areas of the body depending
2
on the extent of previous exposure to light.
Testing: Before exposing any area of skin to direct sunlight or bright indoor light, test for residual photosensitivity
beginning 30 days after porfimer treatment.2 A small area of skin should be exposed to sunlight for 10 minutes2 by
cutting a 2 inch hole in a brown paper bag and placing a hand in the bag.15 Expose only the unprotected patch to
15
sunlight. The tissue around the eyes may be more sensitive; therefore, it is not recommended that the face be
used for testing.2 If no photosensitivity reaction occurs within 24 hours, gradually resume exposure to sunlight,
2
continuing to exercise caution and gradually increasing exposure. If any photosensitivity reaction occurs, such as
7,15
redness, burning sensation, itch, blisters, or swelling,
continue precautions for another two weeks before
2
2
retesting. Photosensitivity may persist for >90 days. Patients travelling to a different geographical area with more
sunshine should retest their level of photosensitivity.2 Short courses of oral corticosteroids have been used to
16
manage symptoms of photosensitivity.
BC Cancer Agency Cancer Drug Manual©
Developed: September 1994
Revised: 1 October 2007
Page 4 of 7
Porfimer
Porfimer
INTERACTIONS:
2,17
Medications known to cause photosensitivity reactions may increase the photosensitivity reaction of porfimer.
2,10,18
Due to inhibition of thromboxane A 2 corticosteroids given prior and concurrently may inhibit the effect of PDT
Animal and in vitro data suggest that the efficacy of porfimer may be altered by drugs which alter blood flow; cause
2,17
vasoconstriction; decrease clotting, platelet aggregation, or availability of oxygen or free radicals.
SUPPLY AND STORAGE:
Injection: Axcan Pharma Inc. supplies porfimer as preservative-free 15 and 75 mg vials of freeze-dried cake or
powder. Store at room temperature.2
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation
and Stability Chart in Appendix.
SOLUTION PREPARATION AND COMPATIBILITY:
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation
and Stability Chart in Appendix.
2
Compatibility of selected drugs: Do not mix with other drugs in the same solution.
PARENTERAL ADMINISTRATION:
Intermittent infusion
Continuous infusion
Intraperitoneal
Intrapleural
Intrathecal
Intra-arterial
BCCA administration guideline noted in bold, italics
no information found
no information found
by physician only19; over 3-5 minutes2 into tubing of
running IV; see Prevention and Management of
Extravasation of Chemotherapy
no information found
no information found
no information found
no information found
no information found
no information found
Intravesical
no information found
Subcutaneous
Intramuscular
Direct intravenous
BC Cancer Agency Cancer Drug Manual©
Developed: September 1994
Revised: 1 October 2007
Page 5 of 7
Porfimer
Porfimer
DOSAGE GUIDELINES:
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease,
response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count
(ANC). Dosage may be reduced, delayed or discontinued in patients with bone marrow depression due to
cytotoxic/radiation therapy or with other toxicities.
Adults:
BCCA usual dose noted in bold, italics
Intravenous:
Cycle Length:
n/a2:
2 mg/kg IV for one dose on day 1 followed by illumination with
appropriate laser light approximately 40-50 hours after
injection of porfimer
Depending on the indication:

a second laser light application 96-120 hours after drug
2
administration may be given

treatment may be repeated a minimum of 30 days after
2
initial therapy (90 days for BE)
Concurrent radiation:
Sufficient time between radiation and PDT is required to ensure that the
inflammatory response produced by one treatment has subsided before
commencing the other treatment.

It is recommended that two to four weeks be allowed after PDT before
radiation is initiated; the inflammatory response from PDT will depend on
tumour size and the extent of surrounding tissue that receives light.2

The acute inflammatory reaction from radiation usually subsides within four
weeks after completing radiation.2
Dosage in myelosuppression:
modify according to protocol by which patient is being treated; if no guidelines
available, refer to Appendix 6 "Dosage Modification for Myelosuppression"
Dosage in renal failure:
no adjustment required2
Dosage in hepatic failure:
no information found
Dosage in dialysis:
not dialyzable2
Children:
2
safety and efficacy have not been established
REFERENCES:
1. MARTINDALE- The Complete Drug Reference (database on the Internet). Porfimer sodium. Thomson MICROMEDEX®, 2007.
Available from http://www.micromedex.com/ Accessed 24 August 2007.
2. Axcan Pharma Inc. PHOTOFRIN® Product Monograph. Mont-Saint-Hilaire, Quebec; 16 May 2005.
3. Schmidt MH, Meyer GA, Reichert KW, et al. Evaluation of photodynamic therapy near functional brain tissue in patients with
recurrent brain tumors. Journal of Neuro-Oncology 2004;67(1-2):201-7.
4. Rose BD, editor. Porfimer. Waltham, Massachusetts: UpToDate 15.2; 2007.
BC Cancer Agency Cancer Drug Manual©
Developed: September 1994
Revised: 1 October 2007
Page 6 of 7
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Porfimer
5. DRUGDEX® Evaluations (database on the Internet). Porfimer. Thompson MICROMEDEX®, 2007. Available from
http://www.micromedex.com/ Accessed 16 August 2007.
6. Houle JM, Clervoix N, Bain S, et al. Lack of effect of sex and disease state on the pharmacokinetics of porfimer sodium. Clin
Pharmacokinet 2006;45(9):923-30.
7. Stephen Lam, MD. BC Cancer Agency Lung Tumour Group. Personal communication. Vancouver, British Columbia;18
September 2007.
8. Karasic DS, Pearson VE, Karasic DS, et al. Urticaria and respiratory distress due to porfimer sodium. Ann Pharmacother
2000;34(10):1208-9.
9. Koehler IK, Koehler IK. Acute immediate urticarialike reaction to i.v. injected photofrin. Lasers Surg Med 1997;20(1):97-8.
10. Axcan Scandipharm Inc. PHOTOFRIN® for Injection U.S. Package Insert. Birmingham, Alabama; 29 September 2005.
11. BC Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and
management of extravasation of chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 September 2006.
12. Stephen Lam, MD. BC Cancer Agency Lung Tumour Group. Personal communication. Vancouver, British Columbia;24 August
2007.
13. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in
Adults. Vancouver, British Columbia: BC Cancer Agency; 1 November 2005.
14. Shaw JW, Solimando DA, Jr. Updates of letrozole and porfimer sodium. Hosp Pharm 1998;33(3):264-9.
15. Axcan Scandipharm Inc. Patient Guide PHOTOFRIN®. Birmingham, Alabama; 2003.
16. Wolfsen HC, Hemminger LL, Wallace MB, et al. Clinical experience of patients undergoing photodynamic therapy for Barrett's
dysplasia or cancer. Alim Pharmacol Ther 2004;20(10):1125-31.
17. Drug Facts and Comparisons 4.0 (database on the Internet). Porfimer Sodium. Facts and Comparisons 4.0, 2007. Available
from http://online.factsandcomparisons.com. Accessed 1 August 2007.
18. USPDI® Drug Information for the Health Care Professional (database on the Internet). Porfimer (Systemic). Thompson
MICROMEDEX®, 2007. Available from http://www.micromedex.com/ Accessed 16 August 2007.
19. BC Cancer Agency Provincial Systemic Therapy Program. BCCA-Approved Parenteral Routes-Antineoplastic Drugs.
Vancouver, British Columbia: BC Cancer Agency; 15 July 2004.
BC Cancer Agency Cancer Drug Manual©
Developed: September 1994
Revised: 1 October 2007
Page 7 of 7
Porfimer