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Alectinib: Drug information

Alectinib: Drug information
(For additional information see "Alectinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Alecensa
Brand Names: Canada
  • Alecensaro
Pharmacologic Category
  • Antineoplastic Agent, Anaplastic Lymphoma Kinase Inhibitor;
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
Dosing: Adult

Note: Select patients for treatment based on the presence of abnormal ALK positivity in tumor tissue or plasma specimens; if ALK rearrangements are not detected in plasma, test tumor tissue if feasible.

Non–small cell lung cancer, metastatic

Non–small cell lung cancer, metastatic (ALK-positive): Oral: 600 mg twice daily; continue until disease progression or unacceptable toxicity (Ref).

Missed doses: If a dose is missed or if vomiting occurs, administer the next dose at the regularly scheduled time.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Preexisting renal impairment:

CrCl ≥30 mL/minute: No dosage adjustment is necessary.

CrCl <30 mL/minute or ESRD: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Renal toxicity during treatment:

Grade 3 renal impairment: Withhold alectinib until serum creatinine recovers to ≤1.5 times ULN, then resume at reduced dose (see Dosage Adjustment for Toxicity for recommended alectinib dosage reduction levels).

Grade 4 renal impairment: Permanently discontinue alectinib.

Dosing: Hepatic Impairment: Adult

Preexisting hepatic impairment:

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment is necessary.

Severe impairment (Child-Pugh class C): 450 mg twice daily.

Hepatotoxicity during treatment:

ALT or AST >5 times ULN and total bilirubin ≤2 times ULN: Withhold alectinib; upon recovery to baseline or to ALT/AST ≤3 times ULN, then resume at a reduced dose (see Dosage Adjustment for Toxicity for recommended alectinib dosage reduction levels).

ALT or AST >3 times ULN and total bilirubin >2 times ULN (in the absence of cholestasis or hemolysis): Permanently discontinue alectinib.

Total bilirubin >3 times ULN: Withhold alectinib; upon recovery to baseline or to total bilirubin ≤1.5 times ULN, then resume at a reduced dose (see Dosage Adjustment for Toxicity for recommended alectinib dosage reduction levels).

Dosing: Adjustment for Toxicity: Adult

Recommended Alectinib Dose Reduction Levels

Dose reduction schedule

Dose level

a Discontinue alectinib if unable to tolerate 300 mg twice daily.

Starting (usual) dose

600 mg twice daily

First dose reduction

450 mg twice daily

Second dose reduction

300 mg twice dailya

Cardiac toxicity:

Symptomatic bradycardia: Withhold alectinib until recovery to asymptomatic bradycardia or until the heart rate is ≥60 beats per minute (bpm). If a contributing concomitant medication is identified and discontinued (or dose adjusted), resume alectinib at the previous dose upon recovery (to asymptomatic bradycardia or heart rate ≥60 bpm). If no contributing concomitant medication is identified (or cannot be discontinued or dose adjusted), resume alectinib at a reduced dose upon recovery (to asymptomatic bradycardia or heart rate ≥60 bpm).

Life-threatening bradycardia/heart rate <60 bpm (urgent intervention required): Permanently discontinue alectinib if no contributing concomitant medication is identified. If a contributing concomitant medication is identified and discontinued (or dose adjusted), resume alectinib (with frequent monitoring) at a reduced dose upon recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm. Permanently discontinue for recurrent life-threatening bradycardia.

CPK elevation:

CPK >5 times ULN: Withhold alectinib; upon recovery to baseline or to ≤2.5 times ULN, then resume alectinib at the same dose.

CPK >10 times ULN or 2nd occurrence of CPK >5 times ULN: Withhold alectinib; upon recovery to baseline or to ≤2.5 times ULN, then resume alectinib at a reduced dose.

Hemolytic anemia: Withhold alectinib if hemolytic anemia suspected; upon recovery, resume alectinib at a reduced dose or permanently discontinue.

Pulmonary toxicity: Interstitial lung disease (ILD)/pneumonitis, any grade (treatment-related): Permanently discontinue alectinib.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reaction reported in adults.

>10%:

Cardiovascular: Bradycardia (8% to 18%), edema (22% to 30%)

Dermatologic: Skin rash (15% to 18%)

Endocrine & metabolic: Hyperglycemia (22% to 36%), hyperkalemia (12%), hypoalbuminemia (14%), hypocalcemia (29% to 32%), hypokalemia (17% to 29%), hyponatremia (18% to 20%), hypophosphatemia (9% to 21%), weight gain (10% to 11%)

Gastrointestinal: Constipation (34%), diarrhea (12% to 16%; grades 3/4: 1%), nausea (14% to 18%; grades 3/4: <1%), vomiting (7% to 12%)

Hematologic & oncologic: Anemia (56% to 62%; grades 3/4: 2% to 7%), lymphocytopenia (14% to 22%; grades 3/4: 1% to 5%), neutropenia (14%)

Hepatic: Hyperbilirubinemia (39% to 54%), increased serum alanine aminotransferase (34% to 40%), increased serum alkaline phosphatase (47% to 50%), increased serum aspartate aminotransferase (50% to 51%)

Nervous system: Fatigue (≤41%), headache (17%)

Neuromuscular & skeletal: Asthenia (≤41%), back pain (12%), increased creatine phosphokinase in blood specimen (37% to 43%), musculoskeletal pain (≤29%), myalgia (≤29%)

Renal: Increased serum creatinine (28% to 38%), renal insufficiency (8% to 12%)

Respiratory: Cough (19%), dyspnea (16%)

1% to 10%:

Cardiovascular: Pulmonary embolism (1%)

Dermatologic: Skin photosensitivity (5% to 10%)

Endocrine & metabolic: Increased gamma glutamyl transferase (7%)

Gastrointestinal: Dysgeusia (3%), stomatitis (3%)

Hepatic: Hepatic injury (1%)

Ophthalmic: Visual disturbances (5% to 10%)

Respiratory: Interstitial pulmonary disease (1%), pneumonia (5%)

<1%: Respiratory: Pneumonitis

Postmarketing: Hematologic & oncologic: Hemolytic anemia

Contraindications

There are no contraindications listed in the manufacturer’s US labeling.

Canadian labeling: Known hypersensitivity to alectinib or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bradycardia: Symptomatic bradycardia may occur with alectinib; heart rate <50 beats per minute has been reported in nearly 20% of patients. If symptomatic bradycardia (non–life-threatening) occurs, withhold treatment until recovery to asymptomatic bradycardia or to a heart rate of ≥60 beats per minute, evaluate concurrent medications, and potentially reduce alectinib dose. Permanently discontinue for life-threatening bradycardia due to alectinib if no contributing concomitant medication is identified and for recurrent bradycardia. If life-threatening bradycardia occurs and concurrent medications associated with bradycardia can be discontinued or dose adjusted, restart alectinib at a reduced dose (with frequent monitoring).

• Hemolytic anemia: Hemolytic anemia, including cases associated with a negative direct antiglobulin test, has been reported.

• Hepatotoxicity: LFT abnormalities have been reported, including elevations of AST/ALT >5 times ULN and bilirubin >3 times ULN; most abnormalities occurred during the first 3 months of therapy. Concurrent ALT/AST elevations ≥3 times ULN and total bilirubin ≥2 times ULN with normal alkaline phosphatase occurred rarely. Liver biopsy demonstrated drug-induced liver injury in some patients with grade 3 to 4 AST or ALT elevations. May require therapy interruption, dose reduction, or permanent discontinuation.

• Myalgia: Myalgia or musculoskeletal pain occurred in over one-quarter of patients treated with alectinib (including grade 3 toxicity). Elevations of creatine phosphokinase (CPK) were commonly reported in clinical trials. The median time to grade 3 CPK elevations was 14 days. Advise patients to report unexplained muscle pain, tenderness, or weakness. May require therapy interruption and/or dose reduction.

• Pulmonary toxicity: Severe interstitial lung disease (ILD) has been reported rarely. Evaluate promptly for ILD/pneumonitis in patients who present with worsening of respiratory symptoms or who have signs/symptoms suggestive of ILD/pneumonitis (eg, cough, dyspnea, fever). Immediately interrupt therapy for confirmed ILD/pneumonitis; permanently discontinue if alectinib is determined to be the causative factor.

• Renal toxicity: Renal impairment has been reported, including grade 3 and rare fatal events. The median time to ≥ grade 3 renal impairment was 3.7 months (range: 0.5 to 14.7 months). Renal toxicity may require therapy interruption, dose reduction, or permanent discontinuation.

Other warnings/precautions:

• Anaplastic lymphoma kinase testing: Select patients for treatment based on the presence of abnormal ALK positivity in tumor tissue or plasma specimens. If ALK rearrangements are not detected in plasma, test tumor tissue (if feasible). Information on tests approved for detection of ALK rearrangements in non–small cell lung cancer is available at http://www.fda.gov/CompanionDiagnostics.

• Photosensitivity: Patients should avoid sun exposure (during treatment and for 7 days after the final alectinib dose) and use a broad-spectrum sunscreen and lip balm (SPF ≥50).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Alecensa: 150 mg [contains corn starch]

Generic Equivalent Available: US

No

Pricing: US

Capsules (Alecensa Oral)

150 mg (per each): $92.69

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Alecensaro: 150 mg [contains corn starch]

Prescribing and Access Restrictions

Available through specialty pharmacies and distributors. Further information may be obtained from the manufacturer, Genentech, at 1-888-249-4918 or at https://www.alecensa.com/.

Administration: Adult

Oral: Administer with food. Swallow capsule whole; do not open or dissolve the contents of the capsule. If vomiting occurs after taking the dose, do not administer an extra dose; administer the next dose at the regularly scheduled time.

Use: Labeled Indications

Non–small cell lung cancer, metastatic (ALK-positive): Treatment of anaplastic lymphoma kinase (ALK)-positive, metastatic non–small cell lung cancer (NSCLC) as detected by an approved test.

Medication Safety Issues
Sound-alike/look-alike issues:

Alectinib may be confused with abemaciclib, acalabrutinib, afatinib, alpelisib, avapritinib, axitinib, binimetinib, brigatinib, ceritinib, crizotinib, entrectinib, larotrectinib, lorlatinib.

Alecensa may be confused with Alesse.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination

Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Reproductive Considerations

Females of reproductive potential should use effective contraception during therapy and for 1 week after the final dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 3 months after the last dose.

Pregnancy Considerations

Based on data from animal reproduction studies and its mechanism of action, alectinib may be expected to cause fetal harm if administered during pregnancy.

Breastfeeding Considerations

It is not known if alectinib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy or for 1 week after the final alectinib dose.

Monitoring Parameters

Test for ALK positivity in tumor tissue or plasma specimens; if ALK rearrangements are not detected in plasma, test tumor tissue if feasible. LFTs (ALT, AST, total bilirubin) every 2 weeks during the first 3 months of therapy, then monthly and as clinically necessary (monitor more frequently in patients who develop transaminase and bilirubin elevations; CPK levels every 2 weeks for the first month of therapy, then as clinically necessary. Monitor heart rate and blood pressure regularly. Monitor for signs/symptoms of hemolytic anemia, interstitial lung disease/pneumonitis, and myalgia. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]).

Mechanism of Action

Alectinib is a tyrosine kinase receptor inhibitor which inhibits anaplastic lymphoma kinase (ALK) and RET (with similar potency to ALK; Ou 2016). ALK gene abnormalities due to mutations or translocations may result in expression of oncogenic fusion proteins (eg, ALK fusion protein) which alter signaling and expression and result in increased cellular proliferation and survival in tumors which express these fusion proteins. Inhibition of ALK phosphorylation and ALK-mediated activation of downstream signaling results in decreased tumor cell viability. Alectinib is more potent than crizotinib against ALK, and can inhibit most of the clinically observed acquired ALK resistance mutations to crizotinib (Ou 2016).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: A high-fat, high-calorie meal increased the combined exposure of alectinib plus its active metabolite M4 by 3.1-fold

Distribution: Parent drug: 4,016 L; M4 (active metabolite): 10,093 L; distributes in the CSF at approximately the free concentrations in plasma

Protein binding: >99% to plasma proteins

Metabolism: Hepatic via CYP3A4 to major active metabolite M4; M4 is also metabolized by CYP3A4

Bioavailability: 37% (under fed conditions)

Half-life elimination: Parent drug: 33 hours; M4: 31 hours

Time to peak: 4 hours

Excretion: Feces (98%; 84% as unchanged parent drug and 6% as M4); urine (<0.5%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Following administration of a single 300 mg oral dose, the mean ratio for the combined AUC (parent drug and M4) was 1.36 in moderate impairment (Child-Pugh class B) and 1.76 in severe impairment (Child-Pugh class C) compared to subjects with normal hepatic impairment.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Alecensa;
  • (AR) Argentina: Alecensa;
  • (AT) Austria: Alecensa;
  • (AU) Australia: Alecensa;
  • (BD) Bangladesh: Alecinix;
  • (BE) Belgium: Alecensa;
  • (BG) Bulgaria: Alecensa;
  • (BR) Brazil: Alecensa;
  • (CH) Switzerland: Alecensa;
  • (CL) Chile: Alecensa;
  • (CO) Colombia: Alecensa;
  • (CZ) Czech Republic: Alecensa;
  • (DE) Germany: Alecensa;
  • (EC) Ecuador: Alecensa;
  • (EE) Estonia: Alecensa;
  • (EG) Egypt: Alecensa;
  • (ES) Spain: Alecensa;
  • (FI) Finland: Alecensa;
  • (FR) France: Alecensa;
  • (GB) United Kingdom: Alecensa;
  • (GR) Greece: Alecensa;
  • (HK) Hong Kong: Alecensa;
  • (HR) Croatia: Alecensa;
  • (HU) Hungary: Alecensa;
  • (ID) Indonesia: Alecensa;
  • (IE) Ireland: Alecensa;
  • (IT) Italy: Alecensa;
  • (JP) Japan: Alecensa;
  • (KR) Korea, Republic of: Alecensa;
  • (KW) Kuwait: Alecensa;
  • (LB) Lebanon: Alecensa;
  • (LT) Lithuania: Alecensa;
  • (LV) Latvia: Alecensa;
  • (MX) Mexico: Alecensa;
  • (MY) Malaysia: Alecensa;
  • (NL) Netherlands: Alecensa;
  • (NO) Norway: Alecensa;
  • (NZ) New Zealand: Alecensa;
  • (PE) Peru: Alecensa;
  • (PH) Philippines: Alecensa;
  • (PL) Poland: Alecensa;
  • (PR) Puerto Rico: Alecensa;
  • (PT) Portugal: Alecensa;
  • (PY) Paraguay: Alecensa;
  • (QA) Qatar: Alecensa;
  • (RO) Romania: Alecensa;
  • (RU) Russian Federation: Alecensa;
  • (SA) Saudi Arabia: Alecensa;
  • (SE) Sweden: Alecensa;
  • (SG) Singapore: Alecensa;
  • (SI) Slovenia: Alecensa;
  • (SK) Slovakia: Alecensa;
  • (TH) Thailand: Alecensa;
  • (TN) Tunisia: Alecensa;
  • (TR) Turkey: Alecensa;
  • (TW) Taiwan: Alecensa;
  • (UA) Ukraine: Alecensa;
  • (UY) Uruguay: Alecensa;
  • (ZA) South Africa: Alecensa
  1. Alecensa (alectinib) [prescribing information]. South San Francisco, CA: Genentech USA Inc; September 2021.
  2. Alecensaro (alectinib) [product monograph]. Mississauga, Ontario, Canada: Hoffmann-La Roche Ltd; May 2022.
  3. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
  4. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  5. Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
  6. Ou SI, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. 2016;34(7):661-668. [PubMed 26598747]
  7. Peters S, Camidge DR, Shaw AT, et al; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795 [PubMed 28586279]
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