Drugs List

Therapeutic Indications

Uses

Wild-type RAS metastatic colorectal cancer (monotherapy or in combination)

For the treatment of patients with wild-type RAS (at exons 2, 3 and 4 of KRAS and NRAS) metastatic colorectal cancer (mCRC) as:

First line treatment in combination with FOLFOX or FOLFIRI.

Second line treatment in combination with FOLFIRI for patients who have received first line fluoropyrimidine-based chemotherapy, excluding irinotecan.

Monotherapy after failure of fluoropyrimidine, oxaliplatin and irinotecan containing chemotherapy regimens.

Administration

For intravenous infusion after dilution only. The final concentration should not exceed 10 mg/ml.

The recommended infusion time is approximately 60 minutes. If the first infusion is well tolerated then subsequent infusions may be administered over 30 to 60 minutes.

Contraindications

Children under 18 years
Breastfeeding
History of pulmonary fibrosis
Interstitial lung disease
Pregnancy
Pulmonary fibrosis

Precautions and Warnings

Performance status of ECOG greater than or equal to 2
Restricted sodium intake
Wearing of contact lenses
Hepatic impairment
Keratitis
Pulmonary disease
Renal impairment
Severe dry eyes

Refer patients with symptoms of keratitis to an ophthalmology specialist
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Before initiating, ensure patient positive for wild type KRAS or NRAS
Supplemental electrolytes may be required
Treatment to be prescribed under the supervision of a specialist
Consider oral antibiotic/topical steroid to treat dermatologic reactions
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Staff: Not to be handled by pregnant staff
Monitor renal function in patients with dehydration or severe diarrhoea
Monitor serum calcium levels during + for 8 weeks after treatment
Monitor serum magnesium during + for 8 weeks after treatment
Monitor serum potassium levels during and after administration
Patients with new pulmonary symptoms should be investigated
Severe skin reactions should be monitored for inflammation / infection
Advise patient to inform physician if severe diarrhoea occurs
Advise patient to report any blurred vision or any other eye symptoms
Advise patient to report any new or worsening respiratory symptoms
Contact doctor immediately with any signs of hypersensitivity reactions
Discontinue / interrupt treatment if ulcerative keratitis develops
If reactions recur/become intolerable at reduced dose discontinue treatment
Interrupt therapy/reduce dose if grade 3 or worse skin reaction occurs
Discontinue if evidence of interstitial lung disease
Discontinue if severe hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Discontinue permanently if life threatening infusion reactions occur
May cause impaired fertility
Female: Contraception required during and for 2 months after treatment
Breastfeeding: Do not breastfeed during and for 2 months after treatment
Advise patient on appropriate sun protection methods
Advise patient that the use of topical moisturisers may be necessary
Advise patient to report signs / symptoms of infusion related reactions
Advise patient to seek medical advice if delayed adverse event(s) occurs
Avoid direct exposure to sunlight

In the treatment of metastatic colorectal cancer, evidence of wildtype RAS status (at exons 2, 3 and 4 of KRAS and NRAS) is required before initiating treatment with panitumumab alone or in combination with other chemotherapy. Inferior progression-free survival and overall survival have been shown in patients with RAS mutations beyond KRAS exon 2 who have received panitumumab combined with FOLFOX (oxaliplatin-containing) chemotherapy versus FOLFOX alone.

Panitumumab should be permanently discontinued if a severe (NCI-CTC grade 3 and 4) or life-threatening reaction occurs during an infusion or at any time post-infusion. For mild or moderate (NCI-CTC grade 1 and 2) infusion related reactions, the infusion rate should be reduced for the duration of that infusion and this lower infusion rate be maintained in all subsequent infusions. Patients should be informed of the possibility of a late onset reaction (more than 24 hours after infusion) and instructed to contact their doctor if symptoms of a hypersensitivity reaction occur.

Pregnancy and Lactation

Pregnancy

Panitumumab is contraindicated during pregnancy.

The manufacturer recommends that if panitumumab is used during pregnancy or if the patient becomes pregnant while being treated with panitumumab, the patient should be advised of potential risk of loss of the pregnancy or potential hazard to the foetus. At the time of writing, there are no reports of the use of panitumumab in human pregnancy. It is unknown whether panitumumab crosses the placenta (the high molecular weight suggests that it is unlikely), however, human immunoglobulin (IgG) does cross the placenta so it is possible that panitumumab may also cross from the mother to the developing foetus. Panitumumab has the potential to cause harm to the foetus when administered to pregnant women as EGFR has been implicated in the control of prenatal development. Animal studies have shown reproductive toxicity, including abortions and foetal death (Briggs 2015).

Lactation

Panitumumab is contraindicated during breastfeeding.

The manufacturer recommends that the patient does not breastfeed during treatment and for 2 months after the last dose of panitumumab. It is unknown whether panitumumab is excreted in human breast milk, however, because human IgG is secreted into human milk so it is possible panitumumab may also be excreted. The potential for absorption and harm to the infant after ingestion is unknown.

Side Effects

Abdominal pain
Abscess
Acne
Acne-like eruptions
Acute renal failure
Alopecia
Anaemia
Angioedema
Anxiety
Aphthous stomatitis
Asthenia
Back pain
Blepharitis
Blood pressure changes
Blurred vision
Bronchospasm
Cellulitis
Cheilitis
Chest pain
Chills
Conjunctivitis
Constipation
Cough
Crusting of skin
Cyanosis
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Dermatitis
Diarrhoea
Dizziness
Dry eyes
Dry lips
Dry mouth
Dry skin
Dyspepsia
Dyspnoea
Epistaxis
Erythema
Exfoliative dermatitis
Exfoliative rash
Eye infection
Eye irritation
Eye pruritus
Eyelash growth
Eyelid reaction
Fatigue
Flushing
Folliculitis
Gastroesophageal reflux disease
Headache
Hirsutism
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions including anaphylaxis
Hypertrichosis
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Infusion-related symptoms
Insomnia
Interstitial lung disease
Keratitis
Lacrimation
Leukopenia
Local infection
Mucosal inflammation
Nail disorders
Nasal dryness
Nausea
Necrotising fasciitis
Ocular hyperaemia
Onycholysis
Pain
Painful extremities
Palmar-Plantar Erythrodysaesthesia syndrome
Paronychia
Peripheral oedema
Pruritic rash
Pruritus
Pulmonary embolism
Pustular rash
Pyrexia
Rash
Rectal haemorrhage
Sepsis
Skin fissures
Skin lesions
Skin necrosis
Skin ulcer
Stevens-Johnson syndrome
Stomatitis
Tachycardia
Toxic epidermal necrolysis
Ulcerative keratitis
Urinary tract infections
Vomiting
Weight loss

Presentation

Concentrate for solution for infusion containing panitumumab.

Drugs List

Therapeutic Indications

Uses

Wild-type RAS metastatic colorectal cancer (monotherapy or in combination)

For the treatment of patients with wild-type RAS (at exons 2, 3 and 4 of KRAS and NRAS) metastatic colorectal cancer (mCRC) as:

First line treatment in combination with FOLFOX or FOLFIRI.

Second line treatment in combination with FOLFIRI for patients who have received first line fluoropyrimidine-based chemotherapy, excluding irinotecan.

Monotherapy after failure of fluoropyrimidine, oxaliplatin and irinotecan containing chemotherapy regimens.

Dosage

Adults

Additional Dosage Information

Administration

For intravenous infusion after dilution only. The final concentration should not exceed 10 mg/ml.

The recommended infusion time is approximately 60 minutes. If the first infusion is well tolerated then subsequent infusions may be administered over 30 to 60 minutes.

Contraindications

Children under 18 years
Breastfeeding
History of pulmonary fibrosis
Interstitial lung disease
Pregnancy
Pulmonary fibrosis

Precautions and Warnings

Performance status of ECOG greater than or equal to 2
Restricted sodium intake
Wearing of contact lenses
Hepatic impairment
Keratitis
Pulmonary disease
Renal impairment
Severe dry eyes

Refer patients with symptoms of keratitis to an ophthalmology specialist
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Before initiating, ensure patient positive for wild type KRAS or NRAS
Supplemental electrolytes may be required
Treatment to be prescribed under the supervision of a specialist
Consider oral antibiotic/topical steroid to treat dermatologic reactions
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Staff: Not to be handled by pregnant staff
Monitor renal function in patients with dehydration or severe diarrhoea
Monitor serum calcium levels during + for 8 weeks after treatment
Monitor serum magnesium during + for 8 weeks after treatment
Monitor serum potassium levels during and after administration
Patients with new pulmonary symptoms should be investigated
Severe skin reactions should be monitored for inflammation / infection
Advise patient to inform physician if severe diarrhoea occurs
Advise patient to report any blurred vision or any other eye symptoms
Advise patient to report any new or worsening respiratory symptoms
Contact doctor immediately with any signs of hypersensitivity reactions
Discontinue / interrupt treatment if ulcerative keratitis develops
If reactions recur/become intolerable at reduced dose discontinue treatment
Interrupt therapy/reduce dose if grade 3 or worse skin reaction occurs
Discontinue if evidence of interstitial lung disease
Discontinue if severe hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Discontinue permanently if life threatening infusion reactions occur
May cause impaired fertility
Female: Contraception required during and for 2 months after treatment
Breastfeeding: Do not breastfeed during and for 2 months after treatment
Advise patient on appropriate sun protection methods
Advise patient that the use of topical moisturisers may be necessary
Advise patient to report signs / symptoms of infusion related reactions
Advise patient to seek medical advice if delayed adverse event(s) occurs
Avoid direct exposure to sunlight

In the treatment of metastatic colorectal cancer, evidence of wildtype RAS status (at exons 2, 3 and 4 of KRAS and NRAS) is required before initiating treatment with panitumumab alone or in combination with other chemotherapy. Inferior progression-free survival and overall survival have been shown in patients with RAS mutations beyond KRAS exon 2 who have received panitumumab combined with FOLFOX (oxaliplatin-containing) chemotherapy versus FOLFOX alone.

Panitumumab should be permanently discontinued if a severe (NCI-CTC grade 3 and 4) or life-threatening reaction occurs during an infusion or at any time post-infusion. For mild or moderate (NCI-CTC grade 1 and 2) infusion related reactions, the infusion rate should be reduced for the duration of that infusion and this lower infusion rate be maintained in all subsequent infusions. Patients should be informed of the possibility of a late onset reaction (more than 24 hours after infusion) and instructed to contact their doctor if symptoms of a hypersensitivity reaction occur.

Pregnancy and Lactation

Pregnancy

Panitumumab is contraindicated during pregnancy.

The manufacturer recommends that if panitumumab is used during pregnancy or if the patient becomes pregnant while being treated with panitumumab, the patient should be advised of potential risk of loss of the pregnancy or potential hazard to the foetus. At the time of writing, there are no reports of the use of panitumumab in human pregnancy. It is unknown whether panitumumab crosses the placenta (the high molecular weight suggests that it is unlikely), however, human immunoglobulin (IgG) does cross the placenta so it is possible that panitumumab may also cross from the mother to the developing foetus. Panitumumab has the potential to cause harm to the foetus when administered to pregnant women as EGFR has been implicated in the control of prenatal development. Animal studies have shown reproductive toxicity, including abortions and foetal death (Briggs 2015).

Lactation

Panitumumab is contraindicated during breastfeeding.

The manufacturer recommends that the patient does not breastfeed during treatment and for 2 months after the last dose of panitumumab. It is unknown whether panitumumab is excreted in human breast milk, however, because human IgG is secreted into human milk so it is possible panitumumab may also be excreted. The potential for absorption and harm to the infant after ingestion is unknown.

Side Effects

Abdominal pain
Abscess
Acne
Acne-like eruptions
Acute renal failure
Alopecia
Anaemia
Angioedema
Anxiety
Aphthous stomatitis
Asthenia
Back pain
Blepharitis
Blood pressure changes
Blurred vision
Bronchospasm
Cellulitis
Cheilitis
Chest pain
Chills
Conjunctivitis
Constipation
Cough
Crusting of skin
Cyanosis
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Dermatitis
Diarrhoea
Dizziness
Dry eyes
Dry lips
Dry mouth
Dry skin
Dyspepsia
Dyspnoea
Epistaxis
Erythema
Exfoliative dermatitis
Exfoliative rash
Eye infection
Eye irritation
Eye pruritus
Eyelash growth
Eyelid reaction
Fatigue
Flushing
Folliculitis
Gastroesophageal reflux disease
Headache
Hirsutism
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions including anaphylaxis
Hypertrichosis
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Infusion-related symptoms
Insomnia
Interstitial lung disease
Keratitis
Lacrimation
Leukopenia
Local infection
Mucosal inflammation
Nail disorders
Nasal dryness
Nausea
Necrotising fasciitis
Ocular hyperaemia
Onycholysis
Pain
Painful extremities
Palmar-Plantar Erythrodysaesthesia syndrome
Paronychia
Peripheral oedema
Pruritic rash
Pruritus
Pulmonary embolism
Pustular rash
Pyrexia
Rash
Rectal haemorrhage
Sepsis
Skin fissures
Skin lesions
Skin necrosis
Skin ulcer
Stevens-Johnson syndrome
Stomatitis
Tachycardia
Toxic epidermal necrolysis
Ulcerative keratitis
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: July 2021

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 16 July 2021.

Summary of Product Characteristics: Vectibix 20 mg/mL concentrate for solution. Amgen Ltd. Revised September 2019.

MHRA Drug Safety Update September 2013
Available at: https://www.mhra.gov.uk
Last accessed: July 16, 2021