Alunbrig Special Precautions

Pulmonary adverse reactions: Severe, life-threatening, and fatal pulmonary adverse reactions, including those with features consistent with ILD/pneumonitis, can occur in patients treated with Alunbrig (see Adverse Reactions).
Most pulmonary adverse reactions were observed within the first 7 days of treatment. Grade 1-2 pulmonary adverse reactions resolved with interruption of treatment or dose modification. Increased age and shorter interval (less than 7 days) between the last dose of crizotinib and the first dose of Alunbrig were independently associated with an increased rate of these pulmonary adverse reactions. These factors should be considered when initiating treatment with Alunbrig. Patients with a history of ILD or drug-induced pneumonitis were excluded from the pivotal trials.
Some patients experienced pneumonitis later in treatment with Alunbrig.
Patients should be monitored for new or worsening respiratory symptoms (e.g., dyspnoea, cough, etc.), particularly in the first week of treatment. Evidence of pneumonitis in any patient with worsening respiratory symptoms should be promptly investigated. If pneumonitis is suspected, the dose of Alunbrig should be withheld, and the patient evaluated for other causes of symptoms (e.g., pulmonary embolism, tumour progression, and infectious pneumonia). The dose should be modified accordingly (see Dosage & Administration).
Hypertension: Hypertension has occurred in patients treated with Alunbrig (see Adverse Reactions).
Blood pressure should be monitored regularly during treatment with Alunbrig. Hypertension should be treated according to standard guidelines to control blood pressure. Heart rate should be monitored more frequently in patients if concomitant use of a medicinal product known to cause bradycardia cannot be avoided. For severe hypertension (≥ Grade 3), Alunbrig should be withheld until hypertension has recovered to Grade 1 or to baseline. The dose should be modified accordingly (see Dosage & Administration).
Bradycardia: Bradycardia has occurred in patients treated with Alunbrig (see Adverse Reactions). Caution should be exercised when administering Alunbrig in combination with other agents known to cause bradycardia. Heart rate and blood pressure should be monitored regularly.
If symptomatic bradycardia occurs, treatment with Alunbrig should be withheld and concomitant medicinal products known to cause bradycardia should be evaluated. Upon recovery, the dose should be modified accordingly (see Dosage & Administration). In case of life-threatening bradycardia, if no contributing concomitant medication is identified or in case of recurrence, treatment with Alunbrig should be discontinued (see Dosage & Administration).
Visual Disturbance: Visual disturbance adverse reactions have occurred in patients treated with Alunbrig (see Adverse Reactions). Patients should be advised to report any visual symptoms. For new or worsening severe visual symptoms, an ophthalmologic evaluation and dose reduction should be considered (see Dosage & Administration).
Creatine Phosphokinase (CPK) Elevation: Elevations of CPK have occurred in patients treated with Alunbrig (see Adverse Reactions). Patients should be advised to report any unexplained muscle pain, tenderness, or weakness. CPK levels should be monitored regularly during Alunbrig treatment. Based on the severity of the CPK elevation, and if associated with muscle pain or weakness, treatment with Alunbrig should be withheld, and the dose modified accordingly (see Dosage & Administration).
Elevations of pancreatic enzymes: Elevations of amylase and lipase have occurred in patients treated with Alunbrig (see Adverse Reactions). Lipase and amylase should be monitored regularly during treatment with Alunbrig. Based on the severity of the laboratory abnormalities, treatment with Alunbrig should be withheld, and the dose modified accordingly (see Dosage & Administration).
Hepatotoxicity: Elevations of hepatic enzymes (aspartate aminotransferase, alanine aminotransferase) and bilirubin have occurred in patients treated with Alunbrig (see Adverse Reactions). Liver function, including AST, ALT and total bilirubin should be assessed prior to the initiation of Alunbrig and then every 2 weeks during the first 3 months of treatment. Thereafter, monitoring should be performed periodically. Based on the severity of the laboratory abnormalities, treatment should be withheld, and the dose modified accordingly (see Dosage & Administration).
Hyperglycemia: Elevations of serum glucose have occurred in patients treated with Alunbrig. Fasting serum glucose should be assessed prior to initiation of Alunbrig and monitored periodically thereafter. Antihyperglycaemic treatment should be initiated or optimised as needed. If adequate hyperglycaemic control cannot be achieved with optimal medical management, Alunbrig should be withheld until adequate hyperglycaemic control is achieved; upon recovery reducing the dose as described in Table 5 may be considered or Alunbrig may be permanently discontinued.
Drug-drug interactions: The concomitant use of Alunbrig with strong CYP3A inhibitors should be avoided. If concomitant use of strong CYP3A inhibitors cannot be avoided, the dose of Alunbrig should be reduced from 180 mg to 90 mg, or from 90 mg to 60 mg. After discontinuation of a strong CYP3A inhibitor, Alunbrig should be resumed at the dose that was tolerated prior to the initiation of the strong CYP3A inhibitor.
The concomitant use of Alunbrig with strong and moderate CYP3A inducers should be avoided (see Interactions). If concomitant use of moderate CYP3A inducers cannot be avoided, the dose of Alunbrig may be increased in 30 mg increments after 7 days of treatment with the current Alunbrig dose as tolerated, up to a maximum of twice the Alunbrig dose that was tolerated prior to the initiation of the moderate CYP3A inducer. After discontinuation of a moderate CYP3A inducer, Alunbrig should be resumed at the dose that was tolerated prior to the initiation of the moderate CYP3A inducer.
Photosensitivity and photodermatosis: Photosensitivity to sunlight has occurred in patients treated with Alunbrig (see Adverse Reactions). Patients should be advised to avoid prolonged sun exposure while taking Alunbrig, and for at least 5 days after discontinuation of treatment. When outdoors, patients should be advised to wear a hat and protective clothing, and to use a broad-spectrum Ultraviolet A (UVA)/ Ultraviolet B (UVB) sunscreen and lip balm (SPF ≥30) to help protect against potential sunburn. For severe photosensitivity reactions (≥ Grade 3), Alunbrig should be withheld until recovery to baseline. The dose should be modified accordingly (see Dosage & Administration).
Lactose: Alunbrig contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.
Effects on Ability to Drive and Use Machines: Alunbrig has minor influence on the ability to drive and use machines. However, caution should be exercised when driving or operating machines as patients may experience visual disturbance, dizziness, or fatigue while taking Alunbrig.