AFAXIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AFAXIN (AFAXIN).
Selective inhibitor of the sodium-dependent serotonin reuptake transporter (SERT), increasing serotonin levels in the synaptic cleft.
| Metabolism | Primarily hepatic via CYP2D6, CYP3A4, and CYP2C19. Active metabolite is paroxetine. |
| Excretion | Renal excretion accounts for approximately 60-70% of the administered dose as unchanged drug; biliary/fecal elimination accounts for 20-25% with the remainder as metabolites. |
| Half-life | Terminal elimination half-life is 12-15 hours in healthy adults, allowing twice-daily dosing; prolonged in renal impairment (up to 30 hours). |
| Protein binding | Approximately 95% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 1.5-2.0 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is 75-85% due to first-pass metabolism; intravenous bioavailability is 100%. |
| Onset of Action | Oral: 1-2 hours; intravenous: 5-10 minutes for peak effect. |
| Duration of Action | Oral: 8-12 hours; intravenous: 6-8 hours. Clinical effect persists for the dosing interval. |
500 mg orally twice daily
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-89 mL/min: no adjustment. GFR 15-29 mL/min: 250 mg twice daily. GFR <15 mL/min or dialysis: 250 mg once daily |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 250 mg twice daily. Child-Pugh C: not recommended |
| Pediatric use | Children ≥12 years: same as adult. <12 years: not established |
| Geriatric use | No specific adjustment; monitor renal function and consider reduced starting dose (250 mg twice daily) due to age-related decline in renal function |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AFAXIN (AFAXIN).
| Breastfeeding | No data on presence in human milk; however, due to molecular weight and high protein binding, excretion is likely. M/P ratio unknown. Potential for serious adverse reactions in nursing infants. Discontinue breastfeeding during therapy and for at least 2 weeks after last dose. |
| Teratogenic Risk | AFAXIN (afatinib) is an EGFR tyrosine kinase inhibitor. Animal studies show teratogenicity including embryolethality and fetal malformations at exposures below human therapeutic levels. First trimester exposure carries highest risk for structural anomalies; second and third trimester may cause fetal growth restriction and oligohydramnios. Avoid in pregnancy unless no alternative. |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor closely for worsening and emergence of suicidal thoughts and behaviors.
| Common Effects | Headache Nausea Stomach pain |
| Serious Effects |
Concurrent use with MAOIs or within 14 days of MAOI discontinuation; concomitant use with pimozide; hypersensitivity to paroxetine; use with linezolid or methylene blue; pregnancy (especially third trimester) due to risk of persistent pulmonary hypertension in newborns.
| Precautions | Increased risk of suicidal thoughts/behaviors in young adults; serotonin syndrome; activation of mania/hypomania; hyponatremia; increased bleeding risk; angle-closure glaucoma; sexual dysfunction; weight gain; QT prolongation (dose-dependent). |
| Food/Dietary |
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| Fetal Monitoring | Monitor pregnancy status before initiation in women of childbearing potential. Perform pregnancy test prior to treatment. If exposure occurs during pregnancy, monitor fetal growth and amniotic fluid volume via ultrasound. Assess for signs of renal impairment in neonate if exposure late in pregnancy. |
| Fertility Effects | Afatinib may impair female fertility based on animal studies showing decreased implantation and increased post-implantation loss. Reversible upon discontinuation. No data on male fertility, but EGFR inhibitors may affect spermatogenesis. Counsel on fertility preservation if desired. |
| Take afatinib on an empty stomach, at least 1 hour before or 2 hours after a meal. High-fat meals increase absorption; avoid food around dosing. Avoid grapefruit, grapefruit juice, and Seville oranges as they may alter drug metabolism. Avoid alcohol due to potential for increased liver toxicity and diarrhea aggravation. |
| Clinical Pearls | AFAXIN (afatinib) is an irreversible ErbB family blocker indicated for EGFR mutation-positive non-small cell lung cancer. Monitor for diarrhea, which can lead to dehydration and renal impairment; prophylactic loperamide is recommended. Consider dose reduction for intolerable grade 2 or grade 3 adverse reactions. Interstitial lung disease (ILD) has been reported; withhold afatinib if ILD is suspected. Strong CYP3A4 inducers may increase metabolism; avoid concurrent use. |
| Patient Advice | Take AFAXIN on an empty stomach at least 1 hour before or 2 hours after a meal. · Do not crush or split tablets. Swallow whole with water. · If you miss a dose, skip it and take your next dose at the usual time. Do not double up. · Common side effects: diarrhea, skin rash, mouth sores, and nail changes. Report severe or persistent diarrhea immediately. · Use effective contraception during treatment and for at least 2 weeks after last dose. · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment. · Notify your doctor if you develop new or worsening shortness of breath, cough, or fever. · Limit sun exposure and use sunscreen; photosensitivity may occur. |