Nintedanib


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Idiopathic pulmonary fibrosis 150 mg bid. Max: 300 mg/day. Locally advanced, metastatic or locally recurrent non-small cell lung carcinoma Combined with docetaxel: 200 mg bid on days 2-21 of a 21-day treatment cycle. Max: 400 mg/day. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Dosage Details
Oral
Idiopathic pulmonary fibrosis
Adult: 150 mg bid. Max: 300 mg daily. Skip the missed dose and wait until the next scheduled dose. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Oral
Locally advanced non-small cell lung carcinoma, Locally recurrent non-small cell lung carcinoma, Metastatic non-small cell lung carcinoma
Adult: In combination with docetaxel: 200 mg bid on days 2 21 of a 21-day treatment cycle. Max: 400 mg daily. Skip the missed dose and wait until the next scheduled dose. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Hepatic Impairment
Oral
Idiopathic pulmonary fibrosis: Mild (Child Pugh A): 100 mg bid, consider treatment interruption, or discontinuation according to individual safety or tolerability (refer to detailed product guideline). Moderate or Severe (Child Pugh B or C): Not recommended.

Locally advanced non-small cell lung carcinoma; Metastatic non-small cell lung carcinoma; Locally recurrent non-small cell lung carcinoma: Moderate or Severe (Child Pugh B or C): Not recommended.
Administration
Should be taken with food. Swallow whole w/ liqd. Do not chew/crush cap because of bitter taste.
Special Precautions
Patient with recent abdominal surgery, history of peptic ulceration, diverticular disease, risk of bleeding, risk factors for liver enzymes elevation, hypertension, high CV risk factors (e.g. coronary artery disease). Smokers. Hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Gastrointestinal disorders (e.g. diarrhoea, nausea, vomiting), dehydration, electrolyte disturbance, venous and arterial thromboembolic events (e.g. MI), hypertension, liver enzyme elevation, hyperbilirubinaemia, febrile neutropaenia, sepsis.
Blood and lymphatic system disorders: Thrombocytopaenia, neutropaenia.
Gastrointestinal disorders: Abdominal pain, mucositis, stomatitis.
Hepatobiliary disorders: Increased gamma-glutamyl transferase.
Infections and infestations: Abscess.
Investigations: Weight loss.
Metabolism and nutrition disorders: Decreased appetite.
Nervous system disorders: Headache, peripheral neuropathy.
Skin and subcutaneous tissue disorders: Rash.
Potentially Fatal: Gastrointestinal perforation, severe liver injury, non-serious and serious bleeding events.
Patient Counseling Information
This drug may cause drowsiness or dizziness, if affected, do not drive or operate machinery.
MonitoringParameters
Obtain CBC with differential, and pregnancy test prior to initiation and during each cycle of treatment. Monitor LFT and at baseline, monthly during the first 3 months of treatment, and periodically thereafter. Monitor blood pressure, gastrointestinal disturbances, and changes in prothrombin time, INR, and bleeding episodes regularly.
Overdosage
Symptoms: Nasopharyngitis, gastrointestinal symptoms, increased liver enzymes. Management: Supportive treatment.
Drug Interactions
Increased risk of gastrointestinal adverse effect with corticosteroids and NSAIDs. Increased plasma concentration with strong P-gp inhibitors (e.g. ketoconazole, erythromycin, ciclosporine). Decreased plasma concentration with strong P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin).
Food Interaction
Reduced plasma concentration with St. John’s wort.
Action
Description: Nintedanib is an inhibitor of multiple receptor tyrosine kinases (RTKs) and nonreceptor tyrosine kinases (nRTKs). It binds competitively to the ATP binding pocket of these receptors and blocks the intracellular signaling which is vital for the proliferation, migration, and transformation of fibroblasts involved in the pathology of pulmonary fibrosis.
Pharmacokinetics:
Absorption: Food, increases exposure and delays absorption. Absolute bioavailability: Approx 5%. Time to peak plasma concentration: 2-4 hours.
Distribution: Volume of distribution: 1,050 L. Plasma protein binding: Approx 98%, mainly to albumin.
Metabolism: Initially metabolised in the liver via hydrolytic cleavage by esterases to a free acid moiety, BIBF 1202, then undergoes glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) enzymes; metabolised by CYP3A4 enzymes (minor).
Excretion: Mainly via faeces (approx 93%); urine (<1%). Terminal elimination half-life: 9-15 hours.
Chemical Structure

Chemical Structure Image
Nintedanib

Source: National Center for Biotechnology Information. PubChem Database. Nintedanib, CID=135423438, https://pubchem.ncbi.nlm.nih.gov/compound/Nintedanib (accessed on Jan. 22, 2020)

Storage
Store at 25°C. Protect from heat and moisture.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration and disposal. Any unused portions should be disposed of in accordance with local requirements.
ATC Classification
L01XE31 - nintedanib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. Used in the treatment of cancer and other indications.
References
Anon. Nintedanib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/03/2018.

Buckingham R (ed). Nintedanib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2018.

Joint Formulary Committee. Nintedanib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2018.

Ofev Capsule (Boehringer Ingelheim Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 06/03/2018.

Disclaimer: This information is independently developed by MIMS based on Nintedanib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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