PIFELTRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PIFELTRO (PIFELTRO).
Selective allosteric inhibitor of HIV-1 capsid protein, interfering with multiple steps of the viral life cycle including capsid assembly, nuclear import, and virion maturation.
| Metabolism | Primarily metabolized by CYP3A4 and UGT1A1. |
| Excretion | Primarily hepatic metabolism with subsequent biliary/fecal elimination. 86% of a single oral dose recovered in feces (mostly as metabolites) and <1% unchanged in urine. |
| Half-life | 12-13 hours in healthy subjects; clinically, supports once-daily dosing. |
| Protein binding | Approximately 76% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Mean Vd/F = 13.2 L (approx. 0.19 L/kg assuming 70 kg), suggesting distribution in total body water. |
| Bioavailability | Absolute bioavailability not directly determined; absorption is high (Tmax 4 hours) with food increasing exposure (37% higher AUC). |
| Onset of Action | Not applicable; used for chronic HIV-1 infection; steady-state achieved in 7 days. |
| Duration of Action | Effective over 24-hour dosing interval due to half-life; clinical efficacy maintained with once-daily administration. |
| Molecular Weight | 463.4 |
200 mg orally once daily, taken with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. Not recommended in end-stage renal disease (GFR <15 mL/min) or in patients on dialysis. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for patients aged ≥12 years and weighing ≥35 kg: 200 mg orally once daily. Safety and efficacy not established in pediatric patients <12 years or <35 kg. |
| Geriatric use | No specific dose adjustments necessary based on age. Clinical trials included limited number of patients ≥65 years; no overall differences in safety or efficacy observed. Use with caution due to potential comorbidities and concomitant medications. |
| 1st trimester | Insufficient human data; animal studies show no teratogenicity at exposures up to 12x human dose. Use only if benefit outweighs risk. |
| 2nd trimester | Insufficient human data; animal studies show no fetal harm. Use only if clearly needed. |
| 3rd trimester | Insufficient human data; consider risk of HIV transmission to infant. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for PIFELTRO (PIFELTRO).
| Placental transfer | Limited human data; in rats, drug crosses placenta with fetal concentrations up to 40% of maternal. Human transfer likely. |
| Breastfeeding | Pifeltro is not recommended during breastfeeding due to potential for HIV transmission via breast milk and unknown effects on infant. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to pifeltro or any componentConcurrent use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort)
| Precautions | Hepatotoxicity: monitor liver enzymes; discontinue if signs/symptoms of hepatitis develop., Immune reconstitution syndrome., Risk of drug interactions with strong CYP3A inducers or inhibitors., Not recommended for use with certain antiretrovirals due to potential loss of virologic response. |
| Food/Dietary | Take PIFELTRO with food to increase absorption. No specific food restrictions; avoid grapefruit products as they may affect drug levels. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating |
| L5 |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of fetal harm at exposures up to 12 times the human therapeutic exposure. However, because animal studies are not always predictive of human response, PIFELTRO should be used during pregnancy only if clearly needed. There is no known risk of teratogenicity in any trimester based on current data. |
| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) and renal function (serum creatinine) periodically. In pregnant women, monitor for signs of hepatotoxicity and perform routine prenatal monitoring including fetal growth assessments via ultrasound. Additionally, monitor for development of immune reconstitution syndrome. |
| Fertility Effects | In animal studies, no adverse effects on fertility or reproductive performance were observed at exposures up to 12 times the human therapeutic dose. There are no human data on the effect of PIFELTRO on fertility. Based on the mechanism of action, no significant impact on fertility is anticipated. |
| PIFELTRO (fostemsavir) is an HIV-1 attachment inhibitor indicated for heavily treatment-experienced adults with multidrug-resistant HIV-1. It must be used in combination with other antiretrovirals. Administer with food to enhance absorption. Monitor for immune reconstitution syndrome. Do not use in patients with severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take PIFELTRO exactly as prescribed, with food. · Do not miss doses; if you miss a dose, take it as soon as you remember unless it is almost time for the next dose. · PIFELTRO does not cure HIV; it is used in combination with other medicines to reduce viral load. · Tell your doctor about all medications you take, including over-the-counter drugs and supplements. · Common side effects include nausea, diarrhea, headache, and fatigue. |