Afinitor (Page 3 of 12)

5 WARNINGS AND PRECAUTIONS

5.1 Non-infectious Pneumonitis

Non-infectious pneumonitis is a class effect of rapamycin derivatives. Non-infectious pneumonitis was reported in up to 19% of patients treated with AFINITOR/AFINITOR DISPERZ in clinical trials, some cases were reported with pulmonary hypertension (including pulmonary arterial hypertension) as a secondary event. The incidence of Grade 3 and 4 non-infectious pneumonitis was up to 4% and up to 0.2%, respectively [see Adverse Reactions (6.1)]. Fatal outcomes have been observed.

Consider a diagnosis of non-infectious pneumonitis in patients presenting with non-specific respiratory signs and symptoms. Consider opportunistic infections, such as pneumocystis jiroveci pneumonia (PJP) in the differential diagnosis. Advise patients to report promptly any new or worsening respiratory symptoms.

Continue AFINITOR/AFINITOR DISPERZ without dose alteration in patients who develop radiological changes suggestive of non-infectious pneumonitis and have few or no symptoms. Imaging appears to overestimate the incidence of clinical pneumonitis.

For Grade 2 to 4 non-infectious pneumonitis, withhold or permanently discontinue AFINITOR/AFINITOR DISPERZ based on severity [see Dosage and Administration (2.9)]. Corticosteroids may be indicated until clinical symptoms resolve. Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required. The development of pneumonitis has been reported even at a reduced dose.

5.2 Infections

AFINITOR/AFINITOR DISPERZ has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections, including infections with opportunistic pathogens [see Adverse Reactions (6.1)]. Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections, invasive fungal infections (e.g., aspergillosis, candidiasis, or PJP), and viral infections (e.g., reactivation of hepatitis B virus) have occurred. Some of these infections have been severe (e.g., sepsis, septic shock, or resulting in multisystem organ failure) or fatal. The incidence of Grade 3 and 4 infections was up to 10% and up to 3%, respectively. The incidence of serious infections was reported at a higher frequency in patients < 6 years of age [see Use in Specific Populations (8.4)].

Complete treatment of preexisting invasive fungal infections prior to starting treatment. Monitor for signs and symptoms of infection. Withhold or permanently discontinue AFINITOR/AFINITOR DISPERZ based on severity of infection [see Dosage and Administration (2.9)].

Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required.

5.3 Severe Hypersensitivity Reactions

Hypersensitivity reactions to AFINITOR/AFINITOR DISPERZ have been observed and include anaphylaxis, dyspnea, flushing, chest pain, and angioedema (e.g., swelling of the airways or tongue, with or without respiratory impairment) [see Contraindications (4)]. The incidence of Grade 3 hypersensitivity reactions was up to 1%. Permanently discontinue AFINITOR/AFINITOR DISPERZ for the development of clinically significant hypersensitivity.

5.4 Angioedema with Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors

Patients taking concomitant ACE inhibitors with AFINITOR/AFINITOR DISPERZ may be at increased risk for angioedema (e.g., swelling of the airways or tongue, with or without respiratory impairment). In a pooled analysis of randomized double-blind oncology clinical trials, the incidence of angioedema in patients taking AFINITOR with an ACE inhibitor was 6.8% compared to 1.3% in the control arm with an ACE inhibitor. Permanently discontinue AFINITOR/AFINITOR DISPERZ for angioedema.

5.5 Stomatitis

Stomatitis, including mouth ulcers and oral mucositis, has occurred in patients treated with AFINITOR/AFINITOR DISPERZ at an incidence ranging from 44% to 78% across clinical trials. Grades 3-4 stomatitis was reported in 4% to 9% of patients [see Adverse Reactions (6.1)]. Stomatitis most often occurs within the first 8 weeks of treatment. When starting AFINITOR/AFINITOR DISPERZ, initiating dexamethasone alcohol-free oral solution as a swish and spit mouthwash reduces the incidence and severity of stomatitis [see Adverse Reactions (6.1)]. If stomatitis does occur, mouthwashes and/or other topical treatments are recommended. Avoid alcohol-, hydrogen peroxide-, iodine-, or thyme- containing products, as they may exacerbate the condition. Do not administer antifungal agents, unless fungal infection has been diagnosed.

5.6 Renal Failure

Cases of renal failure (including acute renal failure), some with a fatal outcome, have occurred in patients taking AFINITOR. Elevations of serum creatinine and proteinuria have been reported in patients taking AFINITOR/AFINITOR DISPERZ [see Adverse Reactions (6.1)]. The incidence of Grade 3 and 4 elevations of serum creatinine was up to 2% and up to 1%, respectively. The incidence of Grade 3 and 4 proteinuria was up to 1% and up to 0.5%, respectively. Monitor renal function prior to starting AFINITOR/AFINITOR DISPERZ and annually thereafter. Monitor renal function at least every 6 months in patients who have additional risk factors for renal failure.

5.7 Risk of Impaired Wound Healing

Impaired wound healing can occur in patients who receive drugs that inhibit the VEGF signaling pathway. Therefore, AFINITOR/AFINITOR DISPERZ have the potential to adversely affect wound healing.

Withhold AFINITOR/AFINITOR DISPERZ for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of treatment upon resolution of wound healing complications has not been established.

5.8 Geriatric Patients

In the randomized hormone receptor-positive, HER2-negative breast cancer study (BOLERO-2), the incidence of deaths due to any cause within 28 days of the last AFINITOR dose was 6% in patients ≥ 65 years of age compared to 2% in patients < 65 years of age. Adverse reactions leading to permanent treatment discontinuation occurred in 33% of patients ≥ 65 years of age compared to 17% in patients < 65 years of age. Careful monitoring and appropriate dose adjustments for adverse reactions are recommended [see Dosage and Administration (2.9), Use in Specific Populations (8.5)].

5.9 Metabolic Disorders

Hyperglycemia, hypercholesterolemia, and hypertriglyceridemia have been reported in patients taking AFINITOR/AFINITOR DISPERZ at an incidence up to 75%, 86%, and 73%, respectively. The incidence of these Grade 3 and 4 laboratory abnormalities was up to 15% and up to 0.4%, respectively [see Adverse Reactions (6.1)]. In non-diabetic patients, monitor fasting serum glucose prior to starting AFINITOR/AFINITOR DISPERZ and annually thereafter. In diabetic patients, monitor fasting serum glucose more frequently as clinically indicated. Monitor lipid profile prior to starting AFINITOR/AFINITOR DISPERZ and annually thereafter. When possible, achieve optimal glucose and lipid control prior to starting AFINITOR/AFINITOR DISPERZ. For Grade 3 to 4 metabolic events, withhold or permanently discontinue AFINITOR/AFINITOR DISPERZ based on severity [see Dosage and Administration (2.9)].

5.10 Myelosuppression

Anemia, lymphopenia, neutropenia, and thrombocytopenia have been reported in patients taking AFINITOR/AFINITOR DISPERZ. The incidence of these Grade 3 and 4 laboratory abnormalities was up to 16% and up to 2%, respectively [see Adverse Reactions (6.1)]. Monitor complete blood count (CBC) prior to starting AFINITOR/AFINITOR DISPERZ every 6 months for the first year of treatment and annually thereafter. Withhold or permanently discontinue AFINITOR/AFINITOR DISPERZ based on severity [see Dosage and Administration (2.9)].

5.11 Risk of Infection or Reduced Immune Response with Vaccination

The safety of immunization with live vaccines during AFINITOR/AFINITOR DISPERZ therapy has not been studied. Due to the potential increased risk of infection, avoid the use of live vaccines and close contact with individuals who have received live vaccines during treatment with AFINITOR/AFINITOR DISPERZ. Due to the potential increased risk of infection or reduced immune response with vaccination, complete the recommended childhood series of vaccinations according to American Council on Immunization Practices (ACIP) guidelines prior to the start of therapy. An accelerated vaccination schedule may be appropriate.

5.12 Radiation Sensitization and Radiation Recall

Radiation sensitization and recall, in some cases severe, involving cutaneous and visceral organs (including radiation esophagitis and pneumonitis) have been reported in patients treated with radiation prior to, during, or subsequent to AFINITOR/AFINITOR DISPERZ treatment [see Adverse Reactions (6.2)].

Monitor patients closely when AFINITOR/AFINITOR DISPERZ is administered during or sequentially with radiation treatment.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.