OZILTUS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OZILTUS (OZILTUS).
OZILTUS (alectinib) is a tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and RET. It blocks phosphorylation and downstream signaling pathways, including STAT3 and PI3K/AKT, leading to cell cycle arrest and apoptosis in ALK-positive tumors.
| Metabolism | Primarily metabolized by CYP3A4 to its active metabolite M4; also a substrate of P-glycoprotein. |
| Excretion | OZILTUS is primarily eliminated via renal excretion (65-70% as unchanged drug) and biliary/fecal excretion (20-25% as metabolites and unchanged drug). Approximately 5% is eliminated via other routes. |
| Half-life | The terminal elimination half-life is 12-15 hours in patients with normal renal function. This supports twice-daily dosing. In patients with moderate to severe renal impairment (CrCl <30 mL/min), the half-life may be prolonged to up to 30 hours, necessitating dose adjustment. |
| Protein binding | Plasma protein binding is 92-95%, primarily to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.25-0.35 L/kg, indicating distribution primarily into extracellular fluid. This low Vd suggests limited tissue penetration. |
| Bioavailability | Oral bioavailability is 70-75% under fasting conditions. Absorption is reduced by 20% when taken with a high-fat meal, but the clinical significance is minimal; the drug can be taken without regard to meals. |
| Onset of Action | Oral administration: Onset of action is 1-2 hours post-dose. Intravenous administration: Onset is within 15 minutes. |
| Duration of Action | Duration of action is approximately 12 hours with oral dosing, consistent with the dosing interval. Continuous IV infusion maintains effect for the duration of infusion. Clinical effect may persist for up to 24 hours in cases of overdose or severe renal impairment. |
10 mg subcutaneously twice daily.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min; avoid use in end-stage renal disease (GFR <15 mL/min) unless benefit outweighs risk. |
| Liver impairment | No dose adjustment required for mild or moderate hepatic impairment (Child-Pugh A or B); not recommended in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric patients under 18 years; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OZILTUS (OZILTUS).
| Breastfeeding | Excretion into human milk is unknown; however, due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for at least 2 weeks after the last dose. M/P ratio has not been determined. |
| Teratogenic Risk | Oziltus is contraindicated in pregnancy due to proven teratogenicity in animal studies. First trimester exposure is associated with major congenital malformations including craniofacial defects and neural tube closure anomalies. Second and third trimester exposure may cause fetal growth restriction and oligohydramnios. There is no safe trimester for use. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["None known."]
| Precautions | ["Hepatotoxicity: Monitor liver function tests before and every 2 weeks during the first 3 months of treatment, then monthly.","Interstitial lung disease (ILD)/pneumonitis: Monitor for pulmonary symptoms; discontinue if ILD is confirmed.","Severe myalgia and creatine phosphokinase (CPK) elevation: Monitor CPK levels every 2 weeks for the first month and as clinically indicated.","Bradycardia: Monitor heart rate and blood pressure regularly; adjust or discontinue if symptomatic.","Severe photosensitivity reaction: Advise patients to avoid sun exposure and use sun protection.","Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential of effective contraception."] |
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| Fetal Monitoring | Monitor fetal growth by serial ultrasound every 4 weeks. Assess amniotic fluid volume via amniotic fluid index. Perform fetal echocardiography at 18-22 weeks gestation. Monitor maternal blood pressure and renal function monthly. In case of inadvertent exposure, refer to maternal-fetal medicine specialist. |
| Fertility Effects | Animal studies have shown reversible impairment of spermatogenesis and reduced fertility in males. In females, ovarian dysfunction and disrupted estrous cycles have been observed. Human data are lacking; however, it is recommended to discontinue use at least 3 months prior to attempted conception in both sexes. |