Drugs List

Therapeutic Indications

Uses

Chronic fibrosing interstitial lung disease with progressive phenotype
Idiopathic pulmonary fibrosis (IPF)
Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
Systemic sclerosis associated interstitial lung disease

Locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, in combination with docetaxel.

Idiopathic pulmonary fibrosis (IPF).

Chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype.

Systemic sclerosis associated interstitial lung disease (SSc-ILD).

Contraindications

Children under 18 years
Within 4 weeks of surgery
Breastfeeding
Hepatic impairment - Child-Pugh score greater than 7
Pregnancy
Severe pulmonary hypertension

Precautions and Warnings

History of abdominal surgery
Predisposition to haemorrhage
Predisposition to venous thromboembolism
Tobacco smoking
Weight below 50kg
Behcet's disease
Cardiovascular disorder
Cerebral metastases
Cerebrovascular disorder
Diabetes mellitus
Giant cell arteritis
Hepatic impairment - Child-Pugh score between 5 and 6
History of aneurysm
History of gastrointestinal perforation
History of peptic ulcer
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Pulmonary fibrosis - if treating NSCLC
Recent pulmonary haemorrhage
Renal impairment - creatinine clearance below 30 ml/minute
Takayasu arteritis
Vascular Ehlers-Danlos syndrome

Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Anti-emetics may be required during therapy
Ensure hypertension is controlled prior to treatment
Not all available brands are indicated for all uses
Treatment to be initiated and supervised by a specialist
Contains soya or soya derivative
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Advise patient to report signs of gastrointestinal perforation immediately
Exclude pregnancy prior to initiation of treatment
Idiopathic pulmonary fibrosis: Monitor BP periodically and when indicated
Monitor blood pressure regularly
Monitor for signs and symptoms of ischaemic colitis
Monitor levels of hepatic enzymes and bilirubin
Monitor patients at risk for signs & symptoms of thromboembolism
Monitor patients receiving concurrent anticoagulants
Monitor renal function in patients with risk factors for renal impairment
Monitor serum electrolytes in patients with dehydration or severe diarrhoea
NSCLC: Monitor full blood count regularly
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider discontinuing if thromboembolism occurs
Consider discontinuing treatment if nephrotic syndrome occurs
Consider dose modification in gastrointestinal toxicity
Consider suspending/reducing dose if AST/ALT greater than 2.5 x ULN
Discontinue if jaundice or other clinical symptoms of hepatic injury
Discontinue if symptoms of ischaemic colitis occur
Potential for increased risk of bleeding
Suspend treatment/reduce dose if grade 2 vomiting
Suspend/reduce dose if grade 2 diarrhoea for 7+ days with anti-diarrhoeals
Suspend/reduce dose if grade 3 diarrhoea despite anti-diahorreal treatment
Suspend/reduce dose if grade 3 nausea despite anti-emetic treatment
Treatment may adversely affect wound healing
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombotic microangiopathy
Discontinue if cardiac ischaemia and / or infarction develops
Discontinue treatment if gastrointestinal perforation occurs
NSCLC: Suspend treatment if grade 3 or greater haematological toxicity
Pregnancy confirmed: Discontinue this medication
Reduce dose or discontinue if a significant rise in hepatic enzymes occurs
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Consider dose reduction in renal impairment
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 3 months after treatment
Female: Oral contraception may not be adequate during treatment
Male & female: Two methods of contraception required (including barrier)
Advise patient on giving up smoking

Patients with brain metastases which have been stable for 4 weeks or more prior to treatment should be monitored closely for signs and symptoms of cerebral bleeding. Patients with active brain metastases should not be treated with nintedanib.

Plasma electrolytes should be monitored in patients with gastrointestinal toxicity and electrolytes and fluids administered if dehydration occurs.

Nintedanib may impair wound healing treatment initiation or resumption after surgery should be based on clinical judgement of adequate wound healing.

In the treatment of NSCLC blood counts should be monitored before each treatment cycle, at the nadir and as clinically indicated.

Hepatic enzymes and bilirubin should be investigated before treatment, and periodically during the first month of treatment. Patients should then be monitored at regular intervals over the next two months of treatment, and periodically thereafter at each patient visit, or as clinically indicated.

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

Nintedanib is contraindicated during pregnancy.

The manufacturer does not recommend using nintedanib during pregnancy and for at least 3 months after the last dose.

At the time of writing there no data of the use of nintedanib in pregnant women. Animal studies have shown reproductive toxicity.

Lactation

Nintedanib is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking nintedanib.

At the time of writing it is unknown whether nintedanib is excreted in human breast milk. Studies on rats have shown small amounts of nintedanib and its metabolites are excreted in milk. A risk to neonates cannot be excluded.

Side Effects

Abdominal pain
Abscess
Alanine aminotransferase increased
Aneurysm
Artery dissection
Aspartate aminotransferase increased
Colitis
Decreased appetite
Dehydration
Diarrhoea
Electrolyte disturbances
Febrile neutropenia
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal perforation
Haemorrhage
Hyperbilirubinaemia
Hypertension
Increase in alkaline phosphatase
Mucositis
Myocardial infarction
Nausea
Neutropenia
Pancreatitis
Peripheral neuropathy
Proteinuria
Pruritus
Rash
Renal failure
Sepsis
Thrombocytopenia
Thromboembolism
Vomiting
Weight loss

Presentation

Oral formulations of nintedanib (as esilate).

Drugs List

Therapeutic Indications

Uses

Chronic fibrosing interstitial lung disease with progressive phenotype
Idiopathic pulmonary fibrosis (IPF)
Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
Systemic sclerosis associated interstitial lung disease

Locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, in combination with docetaxel.

Idiopathic pulmonary fibrosis (IPF).

Chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype.

Systemic sclerosis associated interstitial lung disease (SSc-ILD).

Dosage

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

Adults

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Within 4 weeks of surgery
Breastfeeding
Hepatic impairment - Child-Pugh score greater than 7
Pregnancy
Severe pulmonary hypertension

Precautions and Warnings

History of abdominal surgery
Predisposition to haemorrhage
Predisposition to venous thromboembolism
Tobacco smoking
Weight below 50kg
Behcet's disease
Cardiovascular disorder
Cerebral metastases
Cerebrovascular disorder
Diabetes mellitus
Giant cell arteritis
Hepatic impairment - Child-Pugh score between 5 and 6
History of aneurysm
History of gastrointestinal perforation
History of peptic ulcer
Hyperlipidaemia
Hypertension
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Pulmonary fibrosis - if treating NSCLC
Recent pulmonary haemorrhage
Renal impairment - creatinine clearance below 30 ml/minute
Takayasu arteritis
Vascular Ehlers-Danlos syndrome

Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Anti-emetics may be required during therapy
Ensure hypertension is controlled prior to treatment
Not all available brands are indicated for all uses
Treatment to be initiated and supervised by a specialist
Contains soya or soya derivative
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Advise patient to report signs of gastrointestinal perforation immediately
Exclude pregnancy prior to initiation of treatment
Idiopathic pulmonary fibrosis: Monitor BP periodically and when indicated
Monitor blood pressure regularly
Monitor for signs and symptoms of ischaemic colitis
Monitor levels of hepatic enzymes and bilirubin
Monitor patients at risk for signs & symptoms of thromboembolism
Monitor patients receiving concurrent anticoagulants
Monitor renal function in patients with risk factors for renal impairment
Monitor serum electrolytes in patients with dehydration or severe diarrhoea
NSCLC: Monitor full blood count regularly
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider discontinuing if thromboembolism occurs
Consider discontinuing treatment if nephrotic syndrome occurs
Consider dose modification in gastrointestinal toxicity
Consider suspending/reducing dose if AST/ALT greater than 2.5 x ULN
Discontinue if jaundice or other clinical symptoms of hepatic injury
Discontinue if symptoms of ischaemic colitis occur
Potential for increased risk of bleeding
Suspend treatment/reduce dose if grade 2 vomiting
Suspend/reduce dose if grade 2 diarrhoea for 7+ days with anti-diarrhoeals
Suspend/reduce dose if grade 3 diarrhoea despite anti-diahorreal treatment
Suspend/reduce dose if grade 3 nausea despite anti-emetic treatment
Treatment may adversely affect wound healing
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombotic microangiopathy
Discontinue if cardiac ischaemia and / or infarction develops
Discontinue treatment if gastrointestinal perforation occurs
NSCLC: Suspend treatment if grade 3 or greater haematological toxicity
Pregnancy confirmed: Discontinue this medication
Reduce dose or discontinue if a significant rise in hepatic enzymes occurs
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Consider dose reduction in renal impairment
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 3 months after treatment
Female: Oral contraception may not be adequate during treatment
Male & female: Two methods of contraception required (including barrier)
Advise patient on giving up smoking

Patients with brain metastases which have been stable for 4 weeks or more prior to treatment should be monitored closely for signs and symptoms of cerebral bleeding. Patients with active brain metastases should not be treated with nintedanib.

Plasma electrolytes should be monitored in patients with gastrointestinal toxicity and electrolytes and fluids administered if dehydration occurs.

Nintedanib may impair wound healing treatment initiation or resumption after surgery should be based on clinical judgement of adequate wound healing.

In the treatment of NSCLC blood counts should be monitored before each treatment cycle, at the nadir and as clinically indicated.

Hepatic enzymes and bilirubin should be investigated before treatment, and periodically during the first month of treatment. Patients should then be monitored at regular intervals over the next two months of treatment, and periodically thereafter at each patient visit, or as clinically indicated.

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

Nintedanib is contraindicated during pregnancy.

The manufacturer does not recommend using nintedanib during pregnancy and for at least 3 months after the last dose.

At the time of writing there no data of the use of nintedanib in pregnant women. Animal studies have shown reproductive toxicity.

Lactation

Nintedanib is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking nintedanib.

At the time of writing it is unknown whether nintedanib is excreted in human breast milk. Studies on rats have shown small amounts of nintedanib and its metabolites are excreted in milk. A risk to neonates cannot be excluded.

Side Effects

Abdominal pain
Abscess
Alanine aminotransferase increased
Aneurysm
Artery dissection
Aspartate aminotransferase increased
Colitis
Decreased appetite
Dehydration
Diarrhoea
Electrolyte disturbances
Febrile neutropenia
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal perforation
Haemorrhage
Hyperbilirubinaemia
Hypertension
Increase in alkaline phosphatase
Mucositis
Myocardial infarction
Nausea
Neutropenia
Pancreatitis
Peripheral neuropathy
Proteinuria
Pruritus
Rash
Renal failure
Sepsis
Thrombocytopenia
Thromboembolism
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: October 2019

Reference Sources

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

Summary of Product Characteristics: Ofev 100mg & 150mg soft capsules. Boehringer Ingelheim Ltd. Revised July 2020.

Summary of Product Characteristics: Vargatef 100mg & 150mg soft capsules. Boehringer Ingelheim Ltd. Revised December 2021.