ibrutinib

ibrutinib

(eye- broo-ti-nib) ,

Imbruvica

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors

Indications

Treatment of mantle cell lymphoma in patients who have not responded to at least one previous therapy.

Action

Bind to and inactivates the BTK enzyme. Inhibits malignant B-cell proliferation.

Therapeutic effects

Decreased progression of mantle cell lymphoma.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: 97.3%
Metabolism and Excretion: Mostly metabolized, primarily by the CYP3A enzyme system. One minor metabolite has antineoplastic activity. Metabolites are mostly eliminated in feces (80%), <10% excreted in urine.
Half-life: 4–6 hr.

Time/action profile (response)

ROUTEONSETPEAKDURATION
PO1.9 mos†unknownunknown
†Median time to response.

Contraindications/Precautions

Contraindicated in: Hepatic impairment;Concurrent use of strong CYP3A4 indcers/inhibitors; Obstetric: May cause fetal harm, pregnancy should be avoided; Lactation: Breast feeding should be avoided.
Use Cautiously in: Moderate inhibitors of CYP3A4 (↓ dose of ibrutinib may be necessary);Concurrent use of antiplatelet agents/anticoagulants (↑ risk of bleeding);Surgical procedures (if possible withhold for 3–7 days pre- and post-operatively;Patients with reproductive potential (effective contraception should be used).

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)

Cardiovascular

  • peripheral edema (most frequent)

Respiratory

  • dyspnea (most frequent)

Gastrointestinal

  • abdominal pain (most frequent)
  • ↓ appetite (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • vomiting (most frequent)

Genitourinary

  • renal toxicity

Ear, Eye, Nose, Throat

  • rash (most frequent)

Hematologic

  • bleeding (life-threatening)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)
  • anemia

Musculoskeletal

  • musculoskeletal pain

Miscellaneous

  • infections (life-threatening)
  • second malignancies

Interactions

Drug-Drug interaction

Chronic concurrent use of strong CYP3A inhibitors including bocepravir, indinavir, ritonavir, nefazodone, nelfinavir, saquinavir, telaprevir significantly ↑ blood levels and should be avoided. If short term use of strong CYP3A inhibitors including clarithromycin, itraconazole, ketoconazole, posiconazole, telithromycin or voriconazole is necessary, ibrutinib may be temporarily interrupted. Moderate CYP3A inhibitors including amprenavir, aprepitant, atazanavir, crizotinib, darunavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib or verapamil ↑ blood levels and the risk of toxicity; if concurrent therapy is necessary, dose ↓ of ibrutinib and careful monitoring for toxicity is required. Strong CYP3A inducers including carbamazepine, phenytoin and rifampin significantly ↓ blood levels and effectiveness and should be avoided.Concurrent use of antiplatelet agents or anticoagulants ↑ risk of bleeding.Concurrent use of St. John's wort ↓ blood levels and effectiveness and should be avoided.Grapefruit juice or Seville oranges↑ blood levels and the risk of toxicity, avoid concurrent ingestion.

Route/Dosage

Oral (Adults) 500 mg once daily (four capsules); Concurrent use of moderate CP3A4 inhibitors—140 mg/day; dose modification required for various levels of toxicity.

Availability

Capsules: 140 mg

Nursing implications

Nursing assessment

  • Assess for signs and symptoms of infection (fever, chills) during therapy.
  • Monitor for signs and symptoms of bleeding (blood in stools or urine, prolonged or uncontrolled bleeding) during therapy.
  • Lab Test Considerations: Monitor CBC monthly; may cause neutropenia, thrombocytopenia, and anemia.
    • Monitor serum creatinine levels periodically during therapy; may cause renal failure.

Potential Nursing Diagnoses

Diarrhea (Side Effects)

Implementation

  • Oral: Administer once daily with a glass of water at the same time each day. Swallow capsule whole; do not open, crush, or chew.
    • If therapy is interrupted for any adverse reactions, once symptoms have resolved to Grade 1 or baseline, reinitiate therapy at starting dose. If toxicity reoccurs, reduce dose by 1 capsule (140 mg/day); restart dose after first toxicity occurrence 560 mg/day; second occurrence at 420 mg/day, third occurrence at 280 mg/day, and if fourth toxicity occurs discontinue therapy.

Patient/Family Teaching

  • Instruct patient to take ibrutinib as directed, at the same time each day. Take missed doses as soon as remembered on same day and return to normal schedule; do not take extra capsules to make up for missed dose.
  • Caution patient to avoid grapefruit, grapefruit juice, and Seville oranges during therapy; may increase amount of ibrutinib in blood.
  • Advise patient to maintain adequate hydration during therapy to prevent renal failure.
  • Instruct patient to notify health care professional if signs and symptoms of infection or bleeding (blood in stools or black stools, pink or brown urine, unexpected bleeding or uncontrollable severe bleeding, vomiting blood or vomit that looks like coffee grounds, coughing up blood or blood clots, increased bruising, dizziness or weakness, confusion, change in speech, headache that last a long time) occur.
  • Inform patient of risk of other types of cancer including skin cancer.
  • Advise patient of common side effects: low blood platelet count, diarrhea, low white blood cell count, low red blood cell count, fatigue, muscle and bone pain, swelling legs and feet, upper respiratory tract infection, nausea, bruising, shortness of breath, constipation, rash, stomach pain, vomiting, decreased appetite. Instruct patient to notify health care professional if diarrhea is persistent.
  • Advise patient to notify health care professional of medication regimen before treatment or surgery.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
  • Advise female patient to use contraception and avoid pregnancy and breastfeeding during therapy; may be harmful to fetus.

Evaluation/Desired Outcomes

  • Decrease in progression of mantle cell lymphoma.
References in periodicals archive ?
benefits such as hospital treatment - drug programs in the field of ibrutinib in the treatment of patients with chronic lymphocytic leukemia
We are excited about the potential opportunity for our lead program, the non-covalent BTK inhibitor vecabrutinib, to help patients who have developed resistance to covalent BTK inhibitors such as ibrutinib, the current standard of care in treating CLL," said Dayton Misfeldt, Interim Chief Executive Officer of Sunesis.
The compound, known as ibrutinib - an inhibitor of Bruton's tyrosoine kinase (BTK) in white blood cells, was first approved by the FDA in 2013 for the treatment of leukemia.
CLINICALLY SIGNIFICANT BLEEDING EVENTS occurred in two elderly men who were taking ibrutinib and underwent Mohs micrographic surgery for squamous cell carcinomas, Cindy E.
Ibrutinib was the only drug out of four the company was developing to receive FDA approval.
RXC005 (reversible BTK inhibitor) is focused on treating patients with chronic lymphocytic leukaemia who have become resistant to ibrutinib, and will be entering studies in the coming months to enable submission of an Investigational New Drug application in 2018.
Adler discusses new targeted therapies like ibrutinib and idelalisib and describes how other treatments, including radiation therapy and stem cell transplants, have been modified, while others have been discontinued.
Pharmaceutical firm Janssen Ireland claims Ibrutinib has been shown to prolong survival and enhance life for adult patients.
Ibrutinib (Imbruvica) - used for a rare, incurable type of non-Hodgkin lymphoma - was approved for very rare and end-of-life conditions.
For example, in a study on 'Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia' [1], the primary question is to find the treatment difference between ibrutinib and chlorambucil for 'previously untreated older patients with CLL or small lymphocytic lymphoma'.
It includes new regimens like antineoplastic and antiemetic agents, advances in radiation therapy, new monoclonal antibodies, a new form of immunological therapy, new targeted therapies like ibrutinib and idelalisib, advances in stem cell transplants, and information on how other treatments have been modified or discontinued.