IMFINZI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IMFINZI (IMFINZI).
Programmed cell death ligand 1 (PD-L1) inhibitor; binds to PD-L1 on tumor cells and immune cells, blocking interaction with PD-1 and B7.1 receptors on T cells, thereby restoring anti-tumor immune response.
| Metabolism | Metabolized by catabolism into small peptides and amino acids via general protein degradation pathways; no CYP450 involvement. |
| Excretion | Durvalumab is eliminated primarily through catabolism into small peptides and amino acids. No significant renal or biliary excretion of intact drug occurs. Based on population pharmacokinetic analysis, the mean clearance (CL) is 0.235 L/day in patients with typical body weight (70 kg). |
| Half-life | The terminal elimination half-life (t1/2) is approximately 21 days (range: 14–27 days) in patients with advanced solid tumors. This long half-life supports a fixed dosing interval of every 2 or 4 weeks. |
| Protein binding | Durvalumab is a human IgG1 monoclonal antibody; it does not bind to plasma proteins in a specific manner. Nonspecific binding is minimal, and no dedicated protein binding data are available. Typically, monoclonal antibodies have negligible protein binding. |
| Volume of Distribution | The central volume of distribution (Vc) is approximately 3.29 L (0.047 L/kg for a 70 kg patient), and the peripheral volume (Vp) is about 1.89 L (0.027 L/kg), resulting in a total Vd of 5.18 L (0.074 L/kg). This low Vd indicates limited extravascular distribution, consistent with a large antibody primarily in the vascular space. |
| Bioavailability | Durvalumab is administered only intravenously; bioavailability is 100% by IV route. No other routes of administration are approved. |
| Onset of Action | Clinical onset of action (e.g., tumor response) is variable and typically observed after 2–3 cycles (6–9 weeks) of treatment, but earlier responses can occur. |
| Duration of Action | The pharmacodynamic effect (e.g., immune activation) persists for several months after discontinuation due to the long half-life; clinical responses may be sustained for months to years. |
| Action Class | Monoclonal antibodies |
10 mg/kg intravenously every 2 weeks for up to 12 months or until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate or severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; clinical studies included patients ≥65 years with no overall differences in safety or efficacy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IMFINZI (IMFINZI).
| Breastfeeding | There is no information regarding the presence of IMFINZI (durvalumab) in human milk, its effects on the breastfed infant, or its effects on milk production. Durvalumab is a monoclonal antibody of the IgG1 subclass, and human IgG is excreted in breast milk, but it is unknown if durvalumab transfers into breast milk. Because of the potential for adverse reactions in the breastfed infant, advise women not to breastfeed during treatment with IMFINZI and for at least 3 months after the last dose. No M/P ratio is available. |
| Teratogenic Risk | Based on its mechanism of action (programmed cell death ligand-1 [PD-L1] blockade) and animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Human IgG immunoglobulins cross the placental barrier; thus, IMFINZI may be transmitted from the mother to the developing fetus. In animal reproduction studies, administration of IMFINZI during organogenesis resulted in embryo-fetal toxicity including increased abortion and premature delivery. There are no adequate and well-controlled studies in pregnant women. The risk is present throughout pregnancy, but the highest risk is during the second and third trimesters when IgG transport is most active. Advise pregnant women of the potential risk to the fetus. |
■ FDA Black Box Warning
Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis; severe or fatal immune-mediated adverse reactions can occur.
| Serious Effects |
No absolute contraindications; relative contraindications: history of severe or life-threatening immune-mediated adverse reactions to other immune checkpoint inhibitors, active autoimmune disease requiring systemic immunosuppression, active infections (e.g., tuberculosis), prior allogeneic HSCT within 2 years.
| Precautions | ["Immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatitis, myocarditis)","Infusion-related reactions","Complications of allogeneic hematopoietic stem cell transplantation (HSCT)","Embryo-fetal toxicity","Increased mortality in multiple myeloma when combined with thalidomide analogue and dexamethasone"] |
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| Fetal Monitoring | Monitor pregnant women for potential fetal harm, including growth restriction and preterm delivery. No specific fetal monitoring is mandated, but consider serial ultrasound assessments for fetal growth and amniotic fluid volume if exposure occurs during pregnancy. In women of reproductive potential, verify pregnancy status prior to initiation of IMFINZI. Additionally, monitor for immune-related adverse events in the mother that may affect pregnancy outcome. |
| Fertility Effects | Based on animal studies, IMFINZI may impair fertility in females of reproductive potential. In a 26-week toxicology study in cynomolgus monkeys, durvalumab was associated with decreased menstrual cyclicity and an increased incidence of corpora lutea atrophy, suggesting potential impairment of female fertility. No data are available on male fertility. |