Avmapki (avutometinib potassium)

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Agents That Increase Cpk/Aumolertinib

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Aumolertinib may increase blood CPK levels leading to myopathy and rhabdomyolysis. Other agents that also increase CPK may contribute to additive effects on CPK levels.(1) In addition, aumolertinib may prolong the QTc interval. Concurrent use with other agents that prolong the QTc interval may result in additive effects on the QTc interval.(1) Taletrectinib and zidesamtinib may prolong the QTc interval.

CLINICAL EFFECTS: Concurrent use of aumolertinib and other agents that also increase CPK levels may increase the risk of myopathy or rhabdomyolysis, which is characterized by progressive muscle weakness and pain in the presence of a normal neurological exam.(1) In addition, the concurrent use of aumolertinib with other agents that prolong the QTc interval may result in potentially life-threatening cardiac arrhythmias, including torsades de pointes.(1) Taletrectinib and zidesamtinib may prolong the QTc interval.

PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may also be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. Patients on fluvastatin who are CYP2C9 intermediate or poor metabolizers may have increased fluvastatin concentrations and risk of myopathy. Patients on rosuvastatin with ABCG2 polymorphisms leading to decreased or poor BCRP transporter function may have increased rosuvastatin concentrations and risk of myopathy. The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, and advanced age.(1,2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2)

PATIENT MANAGEMENT: Concurrent use of aumolertinib and other agents that increase CPK levels should be avoided. Prior to initiation of aumolertinib, blood CPK levels should be obtained and periodically monitored during treatment and as clinically indicated.(1) If the patient develops elevated CPK levels or rhabdomyolysis, the following is recommended: For Grade 3 with muscular symptoms: - Withhold aumolertinib for up to 2 weeks. - If muscular symptoms resolve and CPK increase is <= Grade 3, resume at 110 mg dose for the first occurrence; resume at 55 mg for the second occurrence. - Permanently discontinue aumolertinib if symptoms/signs recur at anytime while on the reduced dose. - If muscular symptoms do not resolve and CPK increase does not improve to <= Grade 2, permanently discontinue aumolertinib. For Grade 4 with or without muscular symptoms: - Withhold aumolertinib for up to 2 weeks. - If muscular symptoms resolve and CPK increase is <= Grade 3, resume at 55 mg for the first occurrence. - Permanently discontinue aumolertinib if symptoms/signs recur at anytime while on the reduced dose. - If muscular symptoms do not resolve and CPK remains >= Grade 3, permanently discontinue aumolertinib. If rhabdomyolysis occurs, hold aumolertinib and initiate treatment for rhabdomyolysis.(1) In concurrent use is warranted, carefully monitor for myopathy or rhabdomyolysis. Patients should be instructed to report any symptoms of myopathy such as unexplained muscle aches, tenderness, weakness, or the onset of tingling/numbness in the fingers or toes.(1) The manufacturer of aumolertinib states that concurrent use of other drugs that are known to prolong the QTc interval should be avoided. Taletrectinib and zidesamtinib may also prolong the QTc interval. If a suitable alternative is not available, consider increasing the frequency of ECG and electrolyte monitoring.(1) Consider obtaining serum calcium, magnesium, and potassium levels and correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. If QTc prolongation occurs, follow recommended dose modifications: - Grade 2 (QTc interval >480 to 500 ms): Withhold aumolertinib for up to 2 weeks. If QTc interval has not recovered to <= 480 ms, permanently discontinue aumolertinib. If QTc interval recovers to <= 480 ms or within 30 ms of baseline, resume aumolertinib treatment at 110 mg. Monitor ECGs at least weekly for 2 weeks following return to <= 480 ms. Monitor and correct electrolytes and/or change concomitant medications. - Grade 3 (QTc interval > 500 ms or QTc interval increase of > 60 ms from baseline): Withhold aumolertinib for up to 2 weeks. If QTc interval has not recovered to <= 480 ms or within 30 ms of baseline, permanently discontinue aumolertinib. If QTc interval recovers to <= 480 ms and it is the first occurrence, resume treatment at 110 mg dose. If QTc interval recovers to <= 480 ms and it is the second occurrence or the first occurrence in patients with risk factors, resume treatment at 55 mg dose. Permanently discontinue aumolertinib if signs or symptoms recur at any time on the 55 mg dose. Monitor ECGs at least weekly for 2 weeks following return to <= 480 ms. Monitor and correct electrolytes and/or change concomitant medications. - QT interval prolongation associated with torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of other serious arrhythmia: permanently discontinue aumolertinib.(1)

DISCUSSION: Aumolertinib increased blood CPK levels in 31.7% of patients in clinical studies at recommended doses. Patients developed Grade 3 CPK elevations with muscular symptoms (7.5% of patients) and Grade 4 CPK elevations with or without muscular symptoms. Elevated CPK levels led to interruption or dose reduction in 6.1% and 2.0% of patients, respectively. Rhabdomyolysis occurred in 2.6% of patients.(1) A concentration-QT analysis predicted a QTc interval prolongation at 110 mg aumolertinib of 9.06 ms (upper confidence interval = 11.01 ms) in 49 subjects.(1) In clinical studies (n=545), QT prolongation was reported in 51 patients (9.4%) treated with aumolertinib 110 mg. Seven patients (1.3%) had symptomatic events, including cardiac arrest, syncope, and ventricular arrhythmia. One patient with cardio-respiratory arrest and one patient with sudden cardiac death died. QTcF increase >60 ms occurred in 4.2% of patients, and increase in QTcF to >500 ms occurred in 0.9% of patients.(1) Agents that are linked to this monograph may have varying degrees of potential to prolong the QTc interval. Agents linked to this monograph have been shown to prolong the QTc interval either through their mechanism of action, through studies on their effects on the QTc interval, or through reports of QTc prolongation and/or torsades de pointes in clinical trials and/or postmarketing reports.(3)

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

• Lactation

• Pregnancy

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

Less Frequent

• Hydronephrosis
• Intestinal obstruction
• Pyelonephritis
• Sepsis

More Frequent

• Abnormal hepatic function tests
• Acute abdominal pain
• Anemia
• Constipation
• Cough
• Diarrhea
• Dry skin
• Dyspepsia
• Dyspnea
• Edema
• Fatigue
• Hyperbilirubinemia
• Hypertriglyceridemia
• Increased creatine kinase level
• Lymphopenia
• Musculoskeletal pain
• Nausea
• Neutropenic disorder
• Pruritus of skin
• Skin rash
• Stomatitis
• Thrombocytopenic disorder
• Urinary tract infection
• Visual changes
• Vomiting

Less Frequent

• Alopecia
• Anorexia
• Dizziness
• Dry eye
• Dysgeusia
• Headache disorder
• Hemorrhage
• Hypertension
• Hypoalbuminemia
• Hypokalemia
• Paronychia
• Periorbital edema
• Peripheral neuropathy
• Proteinuria
• Retinal detachment
• Skin photosensitivity
• Upper respiratory infection
• Venous thrombosis
• Vitreous floater
• Weight loss
• Xerostomia

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.