Drugs List

Therapeutic Indications

Uses

Aggressive and symptomatic medullary thyroid cancer: treatment

Treatment of aggressive and symptomatic medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease.

Administration

To be swallowed at the same time each day. For patients who have difficulty swallowing, vandetanib tablets may be dispersed in half a glass of non-carbonated water. The tablet should be dropped into the water, without crushing, stirred until dispersed (approximately 10 minutes) and then swallowed immediately. Any residue should be mixed with half a glass of water and swallowed. The liquid may also be administered through a nasogastric or gastrostomy tube.

Contraindications

Children under 5 years
Breastfeeding
Long QT syndrome
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Serum bilirubin above 1.5 times upper limit of normal
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
History of treatment with anthracyclines
Tobacco smoking
Behcet's disease
Cerebral metastases
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Giant cell arteritis
History of aneurysm
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Recent myocardial infarction
Renal impairment - creatinine clearance 30-50ml/minute
Takayasu arteritis
Vascular Ehlers-Danlos syndrome
Ventricular arrhythmias

Correct electrolyte disorders before treatment
Limited data in patients with calcitonin less than 500pg/ml
Reduce dose in patients with moderate renal impairment
Advise visual disturbances may affect ability to drive or operate machinery
Anti-diarrhoeals may be required during treatment
Confirm RET mutation status positive before initiating
Ensure hypertension is controlled prior to treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor ECG at baseline, after 1, 3, 6 & 12 weeks and quarterly thereafter
Monitor serum transaminases (including ALT) before and during therapy
Monitor thyroid stimulating hormone (TSH) before & during treatment
Perform ECG before and during treatment
If QTc increases but stays below 500msec consult cardiologist
Monitor blood pressure regularly
Monitor serum electrolytes
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report new or worsening signs of cardiac failure
Advise patient to seek medical advice if severe skin reaction occurs
Consider discontinuing therapy if significant cardiac failure develops
Discontinue treatment if interstitial lung disease develops
Long half life.Drug interactions possible weeks after treatment has stopped
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Suspend treatment if grade 3 QT prolongation occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if severe skin reaction occurs
Discontinue treatment if QTc exceeds 500msec
Interrupt therapy/reduce dose for mild skin reactions
Suspend treatment if grade 3 or greater diarrhoea occurs
Suspend treatment in severe hypertension that cannot be controlled
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 4 months after treatment
Advise patient on appropriate sun protection methods
Advise patient on giving up smoking
Advise patient that photosensitivity possible
Advise patient to avoid exposure to sunlight and UV rays during treatment
Remind patient of importance of carrying Alert Card with them at all times

Levels of serum potassium, calcium, magnesium and thyroid stimulating hormone (TSH) should be obtained at baseline, at 1, 3, 6 and 12 weeks after starting treatment and every 3 months for at least a year thereafter. This should be repeated after every dose change or interruption of more than 2 weeks, or as clinically indicated during and after this period. Frequent ECG monitoring of the QTc interval should be continued.

Additional monitoring of QTc, electrolytes and renal function are required in the case of diarrhoea, dehydration, electrolyte imbalance and/or impaired renal function.

Patients without RET mutation may have a decreased benefit from vandetanib treatment so its use should be carefully considered if RET status is not confirmed due to the treatment related benefit/risk balance. To establishing RET mutation status, tissue samples should be obtained if possible at the time of initiation of treatment rather than at the time of diagnosis.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

Risk factors for aneurysm and artery dissection
Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.

Pregnancy and Lactation

Pregnancy

Vandetanib is contraindicated during pregnancy.

The manufacturer does not recommend using vandetanib during pregnancy. Treatment should only be continued if the potential benefit to the mother outweighs the risk to the foetus. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out. The effect of concurrent therapies must also be considered.

Lactation

Vandetanib is contraindicated during breastfeeding.

Use of vandetanib when breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of vandetanib in the breast milk, however presence in human breast milk and the effect on exposed infants is unknown. The effect of concurrent therapies must also be considered.

Side Effects

Abdominal pain
Abscess
Alopecia
Anuria
Anxiety
Asthenia
Blurred vision
Cardiac arrest
Cardiac arrhythmias
Cardiac conduction disturbances
Cardiac failure
Cataracts
Cerebral oedema
Cerebrovascular disorders
Cholelithiasis
Chromaturia
Clonus
Colitis
Conjunctivitis
Constipation
Convulsions
Decreased appetite
Dehydration
Depression
Diarrhoea
Disturbances in accommodation
Dizziness
Dry eyes
Dry mouth
Dysaesthesia
Dysgeusia
Dyspepsia
Dysphagia
Dysuria
Elevated amylase levels
Epistaxis
Erythema multiforme
Faecal incontinence
Fatigue
Gastritis
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Glaucoma
Haematuria
Haemoptysis
Headache
Hypercalcaemia
Hyperglycaemia
Hypertension
Hypertensive crisis
Hypocalcaemia
Hypokalaemia
Hyponatraemia
Hypothyroidism
Ileus
Impaired healing
Increase in haemoglobin
Increase in serum ALT/AST
Infections
Influenza
Insomnia
Interstitial lung disease
Keratopathy
Lethargy
Loss of balance
Nail disorders
Nausea
Nephrolithiasis
Oedema
Pain
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Paraesthesia
Peritonitis
Photopsia
Photosensitivity
Pneumonia aspiration
Pneumonitis
Pollakiuria
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Proteinuria
Pyrexia
Rash
Renal failure
Respiratory failure
Reversible posterior leucoencephalopathy syndrome (RPLS)
Serum creatinine increased
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Torsades de pointes
Tremor
Unconsciousness
Ventricular arrhythmias
Visual disturbances
Visual haloes
Vomiting
Weight loss

Presentation

Oral formulations of vandetanib.

Drugs List

Therapeutic Indications

Uses

Aggressive and symptomatic medullary thyroid cancer: treatment

Treatment of aggressive and symptomatic medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Children

Patients with Renal Impairment

Additional Dosage Information

Administration

To be swallowed at the same time each day. For patients who have difficulty swallowing, vandetanib tablets may be dispersed in half a glass of non-carbonated water. The tablet should be dropped into the water, without crushing, stirred until dispersed (approximately 10 minutes) and then swallowed immediately. Any residue should be mixed with half a glass of water and swallowed. The liquid may also be administered through a nasogastric or gastrostomy tube.

Contraindications

Children under 5 years
Breastfeeding
Long QT syndrome
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Serum bilirubin above 1.5 times upper limit of normal
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
History of treatment with anthracyclines
Tobacco smoking
Behcet's disease
Cerebral metastases
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Giant cell arteritis
History of aneurysm
History of torsade de pointes
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Recent myocardial infarction
Renal impairment - creatinine clearance 30-50ml/minute
Takayasu arteritis
Vascular Ehlers-Danlos syndrome
Ventricular arrhythmias

Correct electrolyte disorders before treatment
Limited data in patients with calcitonin less than 500pg/ml
Reduce dose in patients with moderate renal impairment
Advise visual disturbances may affect ability to drive or operate machinery
Anti-diarrhoeals may be required during treatment
Confirm RET mutation status positive before initiating
Ensure hypertension is controlled prior to treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor ECG at baseline, after 1, 3, 6 & 12 weeks and quarterly thereafter
Monitor serum transaminases (including ALT) before and during therapy
Monitor thyroid stimulating hormone (TSH) before & during treatment
Perform ECG before and during treatment
If QTc increases but stays below 500msec consult cardiologist
Monitor blood pressure regularly
Monitor serum electrolytes
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report new or worsening signs of cardiac failure
Advise patient to seek medical advice if severe skin reaction occurs
Consider discontinuing therapy if significant cardiac failure develops
Discontinue treatment if interstitial lung disease develops
Long half life.Drug interactions possible weeks after treatment has stopped
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Suspend treatment if grade 3 QT prolongation occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if severe skin reaction occurs
Discontinue treatment if QTc exceeds 500msec
Interrupt therapy/reduce dose for mild skin reactions
Suspend treatment if grade 3 or greater diarrhoea occurs
Suspend treatment in severe hypertension that cannot be controlled
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 4 months after treatment
Advise patient on appropriate sun protection methods
Advise patient on giving up smoking
Advise patient that photosensitivity possible
Advise patient to avoid exposure to sunlight and UV rays during treatment
Remind patient of importance of carrying Alert Card with them at all times

Levels of serum potassium, calcium, magnesium and thyroid stimulating hormone (TSH) should be obtained at baseline, at 1, 3, 6 and 12 weeks after starting treatment and every 3 months for at least a year thereafter. This should be repeated after every dose change or interruption of more than 2 weeks, or as clinically indicated during and after this period. Frequent ECG monitoring of the QTc interval should be continued.

Additional monitoring of QTc, electrolytes and renal function are required in the case of diarrhoea, dehydration, electrolyte imbalance and/or impaired renal function.

Patients without RET mutation may have a decreased benefit from vandetanib treatment so its use should be carefully considered if RET status is not confirmed due to the treatment related benefit/risk balance. To establishing RET mutation status, tissue samples should be obtained if possible at the time of initiation of treatment rather than at the time of diagnosis.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

Risk factors for aneurysm and artery dissection
Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.

Pregnancy and Lactation

Pregnancy

Vandetanib is contraindicated during pregnancy.

The manufacturer does not recommend using vandetanib during pregnancy. Treatment should only be continued if the potential benefit to the mother outweighs the risk to the foetus. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out. The effect of concurrent therapies must also be considered.

Lactation

Vandetanib is contraindicated during breastfeeding.

Use of vandetanib when breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of vandetanib in the breast milk, however presence in human breast milk and the effect on exposed infants is unknown. The effect of concurrent therapies must also be considered.

Side Effects

Abdominal pain
Abscess
Alopecia
Anuria
Anxiety
Asthenia
Blurred vision
Cardiac arrest
Cardiac arrhythmias
Cardiac conduction disturbances
Cardiac failure
Cataracts
Cerebral oedema
Cerebrovascular disorders
Cholelithiasis
Chromaturia
Clonus
Colitis
Conjunctivitis
Constipation
Convulsions
Decreased appetite
Dehydration
Depression
Diarrhoea
Disturbances in accommodation
Dizziness
Dry eyes
Dry mouth
Dysaesthesia
Dysgeusia
Dyspepsia
Dysphagia
Dysuria
Elevated amylase levels
Epistaxis
Erythema multiforme
Faecal incontinence
Fatigue
Gastritis
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Glaucoma
Haematuria
Haemoptysis
Headache
Hypercalcaemia
Hyperglycaemia
Hypertension
Hypertensive crisis
Hypocalcaemia
Hypokalaemia
Hyponatraemia
Hypothyroidism
Ileus
Impaired healing
Increase in haemoglobin
Increase in serum ALT/AST
Infections
Influenza
Insomnia
Interstitial lung disease
Keratopathy
Lethargy
Loss of balance
Nail disorders
Nausea
Nephrolithiasis
Oedema
Pain
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Paraesthesia
Peritonitis
Photopsia
Photosensitivity
Pneumonia aspiration
Pneumonitis
Pollakiuria
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Proteinuria
Pyrexia
Rash
Renal failure
Respiratory failure
Reversible posterior leucoencephalopathy syndrome (RPLS)
Serum creatinine increased
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Torsades de pointes
Tremor
Unconsciousness
Ventricular arrhythmias
Visual disturbances
Visual haloes
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 2019

Reference Sources

Summary of Product Characteristics: Caprelsa 100mg & 300mg film coated tablets. Genzyme Therapeutics. Revised February 2019.

MHRA Drug Safety Update July 2020
Available at: https://www.gov.uk/drug-safety-update/systemically-administered-vegf-pathway-inhibitors-risk-of-aneurysm-and-artery-dissection
Last accessed: 10 November 2020

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 July 2019