Porfimer sodium parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Powder for solution for injection formulations of porfimer
Drugs List
Therapeutic Indications
Uses
Palliative treatment of obstructing non small cell lung Ca (with PDT)
Palliative treatment of obstructing oesophageal cancer (with PDT)
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Photodynamic therapy (PDT) with porfimer is a two-stage process requiring administration of both drug and light.
The first stage of PDT is the intravenous injection of porfimer at a dose of 2 mg/kg body weight.
The second stage of therapy is illumination with laser light 40 to 50 hours following injection with porfimer. Patients may receive a second laser light application 96 to 120 hours after drug administration.
Therefore, one course of PDT consists of one injection plus one or two light applications. Up to 2 more courses of drug and light may be given, with each injection separated by a minimum of 30 days.
Elderly
(See Dosage; Adult).
Additional Dosage Information
Porfimer sodium should be reconstituted before use administered as a single slow intravenous injection over 3 to 5 minutes.
As with all intravenous injections, care should be taken to prevent extravasation at the injection site.
If extravasation does occur, the area should be protected from light for a minimum of 30 days.
There is no known benefit from injecting the extravasation site with another substance.
Photo activation of porfimer:
Porfimer is activated by light in the spectral region of 630 nm. Approximately 40 to 50 hours after porfimer administration, laser light should be delivered to the tumour by a cylindrical fibre optic diffuser or a microlens fibre optic passed through the operating channel of an endoscope/bronchoscope.
Light Doses:
Photo activation of porfimer is controlled by the total light energy (light dose) delivered to the tumour site and depends on the indication and the means of light delivery, as follows:
For endobronchial tumours, the cylindrical diffuser will be suitable for most tumours. The light dose for endobronchial tumours using the cylindrical diffuser is 200 joules/cm of tumour length. Alternatively, the microlens fibre optic may be appropriate for small, flat, non-circumferential tumours. The light dose using the microlens fibre optic is 100 joules/cm squared.
For oesophageal tumours, a light dose of 300 joules/cm of tumour length should be delivered using a cylindrical diffuser.
Cylindrical Diffuser (Endobronchial or Oesophageal Lesions):
The cylindrical diffuser uniformly distributes laser light radially in a cylindrical pattern over the entire length of the fibre optic tip. The following light dosimetry equation applies:
Light dose (J/cm) = Total power output from diffuser (W) x Treatment time (seconds) divided by
Diffuser length (cm)
For example, the total power output from the diffuser, as measured by a suitable integrating sphere power meter, could be set to (400 mW/cm x length of diffuser in cm) which will deliver the appropriate dose using exposure times of either 8 minutes, 20 seconds (endobronchial tumours, 200 J/cm) or 12 minutes, 30 seconds (oesophageal tumours, 300 J/cm).
Cylindrical diffusers are available in several lengths and the diffuser tip length should be chosen to match the length of the tumour. Tumours with lengths that differ from available diffuser lengths may require multiple use of a single diffuser or the use of two or more diffusers of differing lengths. Diffuser length should be sized to avoid exposure of non-malignant tissue to light and to prevent overlapping of previously treated malignant tissue. Diffusers or combinations of diffusers should be selected to minimise patient treatment time.
The cylindrical diffusers may be used either interstitially or intraluminally. For non-circumferential endobronchial tumours that are soft enough to penetrate, interstitial fibre placement is preferred to intraluminal activation, since this method produces better efficacy and results in less exposure of normal bronchial mucosa to the light. When the interstitial technique is used, up to 90% of the length of the diffuser should be inserted into the tumour mass.
Microlens (Endobronchial lesions only):
The microlens fibre optic delivers a diverging, forward-directed beam of light similar to that produced by a torch. It is used to treat small lesions by positioning the microlens tip so that the lesion is uniformly illuminated by a circular spot. The diameter of the spot can be increased or decreased by moving the microlens tip further from or nearer to the lesion. The following light dosimetry equation applies:
Light dose (J/cm squared) = Total power output at fibre tip (W) x Treatment time (seconds) divided by
Treatment are (cm squared)
For example, the power output at the microlens fibre tip, as measured by a power meter, could be set to (200 mW/cm squared x tumour area in cm squared). This will deliver the dose of 100 J/cm squared of tumour using an exposure time of 8 minutes, 20 seconds per area treated.
Debridement and Retreatment:
In patients with endobronchial tumours, debridement is mandatory to remove necrotic tumour debris and clear secretions or mucous plugs, thereby preventing possible dyspnoea, obstruction, atelectasis and infection. For oesophageal cancer, debridement is optional since the residua will be removed naturally by peristaltic action. Debridement of residua should be performed 2 days after light treatment. Patients with residual tumour may be retreated with laser light at the time of debridement at the same dose as used for the initial treatment. The second light dose should be administered 96 to 120 hours after the porfimer injection.
Patients may receive a second course of PDT a minimum of 30 days after the initial therapy; up to three courses of PDT (each injection separated by a minimum of 30 days) can be given. Before each course of treatment, patients should be evaluated for the presence of a tracheo-oesophageal or broncho-oesophageal fistula or for the possibility that the tumour may be eroding into a major blood vessel.
Contraindications
Children under 18 years
Erosion of major blood vessels
Suspected erosion of major blood vessels
Breastfeeding
Broncho-oesophageal fistula
Oesophagotracheal fistula
Porphyria
Pregnancy
Severe hepatic impairment
Severe renal impairment
Precautions and Warnings
Concurrent radiotherapy
Major surgery
History of cardiovascular disorder
Lung cancer invading deeply into the bronchial wall
Oesophageal cancer invading into the bronchial tree
Oesophageal cancer invading into the trachea
Oesophageal varices
Consult local policy on the safe use of anti-cancer drugs
Resuscitation facilities must be immediately available
To be used only in experienced centres or clinics
Treatment to be administered by or under supervision of specialist
Ensure negative pregnancy test in week preceding initiation of treatment
Monitor patient for signs and symptoms of respiratory distress
If photosensitivity occurs with skin test avoid light for further 2 weeks
Treatment induced inflammation may cause airway obstruction
Discontinue if allergic reaction occurs
Female: Contraception required during and for 3 months after treatment
Advise patient to avoid exposure of skin/eyes to bright indoor light 30days
Advise patient to avoid exposure of skin/eyes to direct sunlight for 30days
Patient should test skin area for photosensitivity before exposure to light
Some patients may remain photosensitive for up to 90 days
UV sunscreens not effective in protecting against photosensitivity reaction
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 photo bleaching 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, oedema, blistering) occurs within 24 hours, the patient can gradually resume normal outdoor activities, initially continuing to exercise caution and gradually allowing increased exposure.
Pregnancy and Lactation
Pregnancy
Porfimer is contraindicated in pregnancy.
There are no adequate clinical data on exposed pregnancies available for porfimer sodium.
Reproduction studies with porfimer have been conducted in rats. In pregnant rate, an IV dose 0.64 times the human clinical dose based on the BSA given daily during organogenesis did not cause congenital malformations but did result in maternal and foetal toxicity (resorptions, decreased litter size, delayed ossification, and reduced foetal weight) (Briggs, 2011).
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Porfimer is contraindicated during breastfeeding.
At the time of writing no reports of the use of porfimer during human breastfeeding have been located. The long elimination half-life, may be excreted into breast milk. The effect of this potential exposure on a nursing infant is unknown (Briggs, 2011).
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal pain
Abnormal vision
Anaemia
Angina pectoris
Angioedema
Anorexia
Anxiety
Asthenia
Asthenopia
Atrial fibrillation
Back pain
Bladder spasm
Blood urea increased
Bradycardia
Bronchitis
Candidiasis
Cardiac failure
Cataracts
Chest pain
Confusion
Constipation
Cough
Deep vein thrombosis (DVT)
Dehydration
Diarrhoea
Diplopia
Dizziness
Dry skin
Dyspepsia
Dysphagia
Dyspnoea
Erythema
Erythrocytopenia
Eye pain
Fever
First degree AV block
Gastric ulceration
Haematemesis
Haemoglobin decrease
Haemoptysis
Hydronephrosis
Hypertension
Hypoaesthesia
Hypocalcaemia
Hypotension
Ileus
Increased sputum
Inflammatory reactions
Insomnia
Jaundice
Leukocytosis
Lung abscess
Moniliasis
Myocardial infarction
Nausea
Nocturia
Ocular hyperaemia
Oedema
Oesophageal oedema
Oesophageal perforation
Oesophageal stricture
Oesophageal tumour bleeding
Oesophagitis
Pain
Pancreatitis
Peritonitis
Pharyngitis
Phlebitis
Photophobia
Photosensitivity
Pleural effusion
Pneumonia
Pneumonitis
Prothrombin time increased
Pseudoporphyria
Pulmonary embolism
Pulmonary haemorrhage
Pulmonary oedema
Pulmonary thrombosis
Pyrexia
Raised C-reactive protein
Respiratory distress
Respiratory failure
Respiratory insufficiency
Sepsis
Sick-sinus syndrome
Stridor
Sunburn
Supraventricular tachycardia
Tachycardia
Tracheo-oesophageal fistula
Urinary retention
Urinary tract infections
Vomiting
Weight loss
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: November 2013
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Photofrin 15. Axcan Pharma. Revised June 2001.
Summary of Product Characteristics: Photofrin 75 mg powder for solution for injection. Axcan Pharma Inc. Revised October 2013.
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