nin-TED-a-nib

Therapeutic Classification: pulmonary fibrosis agents

Pharmacologic Classification: kinase inhibitors

• Idiopathic pulmonary fibrosis (IPF).
• Chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype.
• Systemic sclerosis-associated ILD (SSc-ILD)

• Inhibits tyrosine kinases which may be responsible for proliferation, migration and transformation of fibroblasts in pulmonary fibrosis.

• Slowed progression of pulmonary impairment.

Absorption: 4.7% absorbed following oral administration (substantial first-pass effect).

Distribution: Unknown.

Protein Binding: 97.8%.

Metabolism/Excretion: Undergoes extensive metabolism and subsequent fecal/biliary elimination (93.4%). Minimal amounts excreted in urine.

Half-life: 9.5 hr.

(effects on pulmonary function)

Contraindicated in:

• Moderate or severe hepatic impairment
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Recent GI surgery, history of diverticular disease, or current use of corticosteroids or NSAIDs (↑ risk of GI perforation; use only if expected benefit outweighs potential risk)
• Known cardiovascular risk factors including coronary artery disease
• Cigarette smoking (may ↓ levels and effectiveness)
• Known risk of bleeding (use only if expected benefit outweighs potential risk)
• Severe renal impairment/end-stage renal disease (safety and effectiveness not established)
• Low body weight (<65 kg), Asian, and female patients (↑ risk of hepatotoxicity)
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may have ↑ risk of adverse reactions.

CV: ARTERIAL THROMBOEMBOLIC EVENTS (INCLUDING MI) , hypertension.

Endo: hypothyroidism.

GI: GASTROINTESTINAL PERFORATION, HEPATOTOXICITY, abdominal pain, ↓appetite, diarrhea, ↑bilirubin, ↑liver enzymes, nausea, vomiting, ↓ weight.

Hemat: bleeding.

Neuro: headache.

Drug-Drug:

• Concurrent use of oral P-glycoprotein and CYP3A4 inhibitors including erythromycin and ketoconazole↑ blood levels and the risk of adverse reactions; close monitoring is recommended.
• Concurrent use of oral P-glycoprotein and CYP3A4 inducers including carbamazepine, phenytoin and rifampin↓ blood levels and may ↓ effectiveness; concurrent use should be avoided.
• Cigarette smoking ↓blood levels and may ↓ effectiveness, encourage cessation prior to treatment.
• Anticoagulants and antiplatelet agents may ↑ risk of bleeding.

Drug-Natural Products:

• St. John's wort↓ blood levels and may ↓ effectiveness; concurrent use should be avoided.

• PO (Adults): 150 mg twice daily; may be ↓ to 100 mg twice daily if adverse reactions occur.

• Capsules: 100 mg; 150 mg;

• Monitor for signs and symptoms of lung disease (dyspnea, decreased forced vital capacity (FVC), diffuse pulmonary infiltrates on chest x-ray) during therapy.
• Monitor for diarrhea, nausea and vomiting during therapy. Diarrhea usually occurs during first 3 mo. Treat diarrhea, nausea and vomiting with adequate hydration and antidiarrheal (loperamide) and antiemetic medications. Consider interruption of therapy if diarrhea or nausea and vomiting continues. Therapy may be resumed at full dose or at reduced dose and increased to full dose. Discontinue therapy if diarrhea, nausea, and vomiting is severe and persists despite symptomatic therapy.

• Verify negative pregnancy test prior to starting therapy.
  • Obtain liver function tests (AST, ALT, bilirubin) prior to starting therapy, at regular intervals for 3 mo, and periodically thereafter as clinically indicated. Risk may be increased in patients with a low body weight (<65 kg) and Asian and female patients. If AST or ALT ↑ >3 times to <5 times upper limit of normal without signs of liver damage, interrupt therapy or reduce dose to 100 mg twice daily. Once liver enzymes have returned to baseline, may reintroduce nintedanib at a reduced dose (100 mg twice daily), which may increase to full dose (150 mg twice daily). Discontinue nintedanib if AST or ALT ↑ >5 times upper limit of normal or >3 times upper limit of normal with signs and symptoms of liver damage.

• PO: Administer with food and liquid once every 12 hrs. DNC: Swallow capsule whole; do not open, crush, or chew, contents taste bitter.

• Instruct patient to take nintedanib as directed. If a dose is missed, omit and take next dose at scheduled time; do not double doses. Advise patient to read Patient Information sheet prior to starting therapy and with each Rx refill in case of changes.
• Advise patient that diarrhea nausea, and vomiting are common side effects and advise to maintain hydration and take antidiarrheal or antiemetic medication as needed. Notify health care professional if diarrhea, nausea, or vomiting is persistent or severe.
• Encourage patient to stop smoking before therapy and to avoid smoking during therapy.
• Advise patient to notify health care professional immediately if signs and symptoms of liver dysfunction (fatigue, anorexia, skin or whites or eyes turn yellow, urine turns dark or brown (tea colored), pain on right side of stomach, unusual bleeding or bruising, lethargy), arterial thrombotic events such as heart attack (chest pain or pressure; pain in arms, back, neck, or jaw; shortness of breath) or stroke (numbness or weakness on 1 side of body, trouble talking, headache, dizziness), or gastric perforation (pain or swelling in stomach area), occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep: May cause fetal harm. Advise females or reproductive potential to use highly effective contraception during and for at least 3 mo following therapy and to avoid breastfeeding during therapy. Patients with vomiting and/or diarrhea during therapy may have decreased efficacy if an oral hormonal contraceptive is used; may require an alternate form of highly effective contraception where drug absorption may be reduced. Notify health care professional promptly if pregnancy is suspected.
• Emphasize the importance of follow up blood tests to determine liver function.

• Decrease in rate of decline in forced vital capacity (FVC) and extension in time to first exacerbation of pulmonary fibrosis.

Ofev

NDC Code^*

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0143- Ofev
    • 0597-0143-60- 1 BOTTLE in 1 CARTON (0597-0143-60) > 60 CAPSULE in 1 BOTTLE

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0145- Ofev
    • 0597-0145-60- 1 BOTTLE in 1 CARTON (0597-0145-60) > 60 CAPSULE in 1 BOTTLE