PIFELTRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PIFELTRO (PIFELTRO).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PIFELTRO (PIFELTRO).

Breastfeeding	It is not known whether PIFELTRO is excreted in human breast milk. The M/P ratio has not been determined. Because of the potential for adverse reactions in nursing infants, breastfeeding should be discontinued during therapy, or alternatively, the drug should not be used in nursing mothers.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort).","Concomitant use with carbamazepine, phenytoin, or other potent enzyme inducers."]

Clinical Precautions

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."]

Clinical Tips & Counseling

Drug interactions

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PIFELTRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PIFELTRO (PIFELTRO).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PIFELTRO (PIFELTRO).

Breastfeeding	It is not known whether PIFELTRO is excreted in human breast milk. The M/P ratio has not been determined. Because of the potential for adverse reactions in nursing infants, breastfeeding should be discontinued during therapy, or alternatively, the drug should not be used in nursing mothers.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort).","Concomitant use with carbamazepine, phenytoin, or other potent enzyme inducers."]