ATMEKSI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATMEKSI (ATMEKSI).
ATMEKSI (atazanavir/cobicistat) is a fixed-dose combination of atazanavir, an HIV-1 protease inhibitor that inhibits viral protease, preventing cleavage of viral polyproteins and resulting in immature non-infectious virions, and cobicistat, a pharmacokinetic enhancer that inhibits CYP3A, increasing atazanavir exposure.
| Metabolism | Atazanavir is metabolized by CYP3A4; cobicistat is metabolized by CYP3A and to a minor extent by CYP2D6. |
| Excretion | Primarily renal (80% unchanged) and biliary/fecal (15% as metabolites). |
| Half-life | Terminal elimination half-life is 12 hours; renally impaired patients have prolonged half-life up to 24 hours. |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 2.0 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 60-70% due to first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 6-8 hours. |
1.5 mg/kg IV every 4 weeks
| Dosage form | SUSPENSION |
| Renal impairment | GFR 15-29 mL/min: 1.0 mg/kg IV every 4 weeks; GFR <15 mL/min: not recommended |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 1.0 mg/kg IV every 4 weeks; Child-Pugh C: not recommended |
| Pediatric use | Age 2-17 years: 1.5 mg/kg IV every 4 weeks; maximum 120 mg per dose |
| Geriatric use | No specific adjustment; monitor renal function and reduce dose if GFR <30 mL/min |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATMEKSI (ATMEKSI).
| Breastfeeding | Not recommended during breastfeeding. M/P ratio unknown. Excreted in animal milk; potential for serious adverse reactions in nursing infants. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: No known fetal risks. Avoid use during organogenesis unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Common Effects | Nausea Abdominal pain Diarrhea |
| Serious Effects |
["Concomitant use with drugs highly dependent on CYP3A for clearance (e.g., alfuzosin, rifampin, ergot derivatives, St. John's wort, lovastatin, simvastatin, sildenafil for pulmonary arterial hypertension)","Severe hepatic impairment (Child-Pugh Class B or C)"]
| Precautions | ["Hepatotoxicity, especially in patients with pre-existing liver disease or elevated transaminases","Nephrolithiasis and cholelithiasis","Cardiac conduction abnormalities (PR interval prolongation)","Risk of developing resistance if not used with other antiretrovirals","Renal impairment (cobicistat decreases estimated creatinine clearance)"] |
| Food/Dietary | Avoid alcohol (may exacerbate CNS effects). Grapefruit juice may increase atomoxetine exposure; limit consumption. High-fat meals do not significantly affect absorption. |
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| Monitor maternal liver function tests and renal function. Fetal ultrasound for growth and anatomy if used in pregnancy. |
| Fertility Effects | No known adverse effects on fertility in animal studies. Human data insufficient. |
| Clinical Pearls | ATMEKSI (atomoxetine) is a selective norepinephrine reuptake inhibitor (NRI) indicated for ADHD. It has a slower onset of action (2-4 weeks) compared to stimulants. Monitor for hepatotoxicity and suicidal ideation, especially in children and adolescents. Use cautiously with hepatic impairment (reduce dose) and CYP2D6 poor metabolizers (need lower dose). Avoid concurrent MAOIs. May cause orthostatic hypotension and urinary retention. |
| Patient Advice | Take ATMEKSI exactly as prescribed; do not change dose without consulting your doctor. · It may take 2-4 weeks to notice improvement in symptoms. · Avoid alcohol and grapefruit juice as they may affect drug levels. · Report any signs of liver problems (yellowing of skin/eyes, dark urine, abdominal pain) or suicidal thoughts immediately. · May cause dizziness or fainting, especially when standing up; rise slowly. · Do not stop abruptly without medical advice. |