Cabozantinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of cabozantinib.
Drugs List
Therapeutic Indications
Uses
Hepatocellular carcinoma
Renal cell carcinoma
Unresectable locally advanced or metastatic medullary thyroid carcinoma
Progressive, unresectable locally advanced or metastatic medullary thyroid carcinoma in adults.
Advanced renal cell carcinoma (RCC) in adults, either following prior vascular endothelial growth factor (VEGF)-targeted therapy, or in treatment-naive adults with intermediate or poor risk. Cabozantinib can also be used in combination with nivolumab as first line treatment for RCC in adults.
Hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Cabozantinib tablets and capsules are not bioequivalent, and should not be used interchangeably.
Adults
Medullary thyroid carcinoma
140mg as capsules once daily.
Treatment should continue until disease progression or unacceptable toxicity.
Renal cell carcinoma
60mg as tablets once daily.
OR
40mg as tablets once daily, in combination with intravenous nivolumab at either 240mg once every 2 weeks OR 480mg once every 4 weeks.
Treatment should continue until disease progression or unacceptable toxicity.
Hepatocellular carcinoma
60mg as tablets once daily.
Treatment should continue until disease progression or unacceptable toxicity.
Patients with Hepatic Impairment
Medullary thyroid carcinoma
Mild to moderate hepatic impairment: 60mg once daily.
Additional Dosage Information
Dose adjustments
It is expected that the majority of patients will require one or more dose adjustments due to toxicity.
For persistent events that could become serious or intolerable a dose reduction is recommended. For grade 3 or more toxicities, or intolerable grade 2 toxicities, a dose interruption is recommended.
If palmar-plantar erythrodysaesthesia (PPES) is severe, interrupt treatment until symptoms have returned to grade 1, resume treatment at a reduced dose.
Medullary thyroid carcinoma
If a dose reduction is required the dose should be reduced to 100mg once daily, and further reduced to 60mg once daily if necessary.
Renal Cell and hepatocellular carcinoma
If a dose reduction is required the dose should be reduced to 40mg once daily, and further reduced to 20mg once daily if necessary.
When cabozantinib is administered in combination with nivolumab, it is recommended to reduce the dose to 20mg of cabozantinib once daily, then to 20mg of cabozantinib once every other day. See product literature for more information.
Missed dose
Advise patient that if a dose is missed, to take the missed dose as soon as remembered. However, if it is less than 12 hours until the next scheduled dose, wait until the next scheduled dose.
Contraindications
Children under 18 years
Haemoptysis
Severe haemorrhage
Breastfeeding
Long QT syndrome
Pregnancy
Severe hepatic impairment
Severe renal impairment
Torsade de pointes
Uncontrolled hypertension
Precautions and Warnings
Family history of long QT syndrome
Females of childbearing potential
Patients over 75 years
Predisposition to thromboembolic disease
Recent radiotherapy
Risk of haemorrhage
Tobacco smoking
Behcet's disease
Bradycardia
Cerebrovascular disorder
Diabetes mellitus
Electrolyte imbalance
Galactosaemia
Giant cell arteritis
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of aneurysm
History of long QT syndrome
History of thromboembolic disorder
History of torsade de pointes
Hyperlipidaemia
Hypertension
Inflammatory bowel disease
Ischaemic heart disease
Lactose intolerance
Marfan syndrome
Occlusive peripheral arterial disease
Renal impairment
Takayasu arteritis
Thyroid tumour infiltration of trachea, bronchi or oesophagus
Tumour infiltration of the gastrointestinal tract
Vascular Ehlers-Danlos syndrome
Correct electrolyte disorders before treatment
Reduce dose in patients with hepatic impairment
Suspend treatment if planned surgery within next 28 days
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Consider a dental exam & appropriate preventive dentistry before treatment
Ensure hypertension is controlled prior to treatment
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Monitor closely patient for toxicity during first 8 weeks
Not all formulations are licensed for all uses
Treatment to be initiated by specialist
Some formulations contain lactose
Different oral formulations are not interchangeable (not bioequivalent)
Advise patient to have no food for 2 hours before and 1 hour after dose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Perform liver function tests before commencing therapy
Consider monitoring ECG in patients at risk of QT prolongation
Monitor blood pressure
Monitor for protein in urine
Monitor for signs and symptoms of hepatic encephalopathy
Monitor for signs of osteonecrosis
Monitor for symptoms of gastrointestinal perforation or fistula
Monitor hepatic enzymes
Monitor patients with hepatic impairment for adverse effects
Monitor platelets
Monitor serum electrolytes
Advise patient to report headaches, seizures, confusion, visual disturbance
Consider non-GI fistula if patient presents with mucositis
Consider the use of anti-emetics before and during therapy
Discontinue if osteonecrosis of jaw occurs
Reduce dose for persistent serious or intolerable toxicities
Treatment may adversely affect wound healing
May affect results of some laboratory tests
Discontinue if arterial thromboembolism develops
Discontinue if fistulae develop during treatment
Discontinue if myocardial infarction occurs
Discontinue if nephrotic syndrome occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue permanently if hypertensive crisis occurs
Discontinue treatment if gastrointestinal perforation occurs
Interrupt therapy/reduce dose if palmar-plantar erythrodysaesthesia occurs
Suspend treatment if grade 3 or intolerable grade 2 toxicities
Suspend treatment in severe hypertension that cannot be controlled
Discontinue if wound healing requires medical intervention
Advise patient not to take St John's wort concurrently
Grapefruit juice should not be taken simultaneously
May cause impaired fertility
Male & female: Two methods of contraception required (including barrier)
Male & female:Contraception required during & for 4 months after treatment
Breastfeeding: Do not breastfeed during & for 4 months after treatment
Advise patient how to prevent dehydration
Advise patient of need for high oral hygiene standards
Advise patient on giving up smoking
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.
Clinical judgement should be used to decide when to resume treatment after surgery based on adequate wound healing.
RET mutation status should be established prior to treatment. For patients whose RET status could be negative, a possible lower benefit should be taken into account before individual treatment decisions.
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
Cabozantinib is contraindicated during pregnancy.
Use of cabozantinib during pregnancy is contraindicated by the manufacturer. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Cabozantinib is contraindicated during breastfeeding.
The manufacturer does not recommend breastfeeding whilst taking cabozantinib and for at least 4 months after treatment. The presence of cabozantinib in human breast milk and the effect on exposed infants are unknown.
Side Effects
Abscess
Acute renal failure
Ageusia
Alterations in hepatic enzymes
Alterations in pancreatic enzymes
Amenorrhoea
Anal fissure
Angina pectoris
Anxiety
Arterial thrombosis
Arthralgia
Aspergillosis
Asthenia
Ataxia
Atelectasis
Atrial fibrillation
Attention disturbances
Blood glucose disturbances
Changes of blood pressure
Cheilitis
Chills
Cholelithiasis
Cholestatic hepatitis
Confusion
Convulsions
Cough
Creatine phosphokinase increased
Cysts
Decreased appetite
Dehydration
Delirium
Depression
Dizziness
Dream abnormalities
Dysgeusia
Dysphagia
Dysphonia
Dyspnoea
Dysuria
Ear pain
Electrolyte disturbances
Elevated triglyceride levels
Elevated TSH
Eye disorder
Fatigue
Fistulae
Folliculitis
Fungal infection
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal symptoms
Haematuria
Haemorrhage
Haemorrhoids
Headache
Hepatic encephalopathy
Hypoacusis
Hypoalbuminaemia
Hypothyroidism
Impaired consciousness
Impaired healing
Increase in lactate dehydrogenase
Increase in plasma cholesterol
Increased platelet count
Increases in eosinophils
Infertility
Lymphopenia
Mucosal inflammation
Muscle spasm
Musculoskeletal pain
Myocardial infarction
Neutropenia
Oedema
Oesophagitis
Osteonecrosis (primarily of the jaw)
Pain
Painful extremities
Pallor
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Paraesthesia
Peripheral coldness
Peripheral neuropathy
Pneumonia
Pneumonitis
Posterior reversible encephalopathy syndrome (PRES)
Proteinuria
Pulmonary embolism
Reduced partial thromboplastin time
Rhabdomyolysis
Skin disorder
Speech disturbances
Stroke
Supraventricular tachycardia
Thrombocytopenia
Tinnitus
Tremor
Venous thrombosis
Weight loss
White blood cell count raised
Further Information
Last Full Review Date: December 2019
Reference Sources
Summary of Product Characteristics: Cabometyx 20mg Film-coated tablets. Ipsen Ltd. Revised October 2022.
Summary of Product Characteristics: Cabometyx 40mg Film-coated tablets. Ipsen Ltd. Revised October 2022.
Summary of Product Characteristics: Cabometyx 60mg Film-coated tablets. Ipsen Ltd. Revised October 2022.
Summary of Product Characteristics: Cometriq hard capsules. Ipsen Ltd. Revised April 2020.
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: 12 December 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.