RILPIVIRINE HYDROCHLORIDE

Clinical safety rating: safe

Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.

How it works

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. It binds to HIV-1 reverse transcriptase, causing a conformational change that inhibits enzyme activity and prevents viral RNA conversion to DNA.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contributions from CYP2C8 and CYP2C19.
Excretion	Primarily hepatic metabolism (CYP3A4), with 85% of dose excreted in feces (unchanged drug and metabolites) and 6.1% in urine (unchanged drug). Renal elimination of unchanged drug is <1%.
Half-life	Terminal elimination half-life is approximately 34.6 hours (range 25–56 hours), supporting once-daily dosing. Steady-state reached in ~2 weeks.
Protein binding	Approximately 99.7% bound to albumin.
Volume of Distribution	Apparent volume of distribution (Vd/F) is 0.95 L/kg (mean; ~72 L), indicating extensive tissue distribution into extravascular spaces.
Bioavailability	Oral bioavailability is approximately 35% (range 25–50%) under fed conditions; reduced by 40% when taken fasting. Absorption is pH-dependent with increased gastric pH reducing absorption.
Onset of Action	Oral: Time to maximum plasma concentration (Tmax) is 3–4 hours post-dose. Antiviral activity begins within days, but clinical efficacy is assessed after 4–8 weeks.
Duration of Action	Duration of antiviral effect is 24 hours with once-daily dosing due to sustained plasma levels above IC95 for wild-type HIV-1. Missed doses >24 hours may lead to virologic failure.

Classification & Brands

Dosing & administration

25 mg orally once daily with a meal.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease.
Liver impairment	Child-Pugh Class A and B: No dose adjustment. Child-Pugh Class C: Not recommended.
Pediatric use	For patients weighing ≥35 kg and aged ≥12 years: 25 mg orally once daily with a meal. Not approved for children <12 years or <35 kg.
Geriatric use	No specific dose adjustment; monitor renal function and consider potential for increased adverse effects due to age-related changes.

Use during pregnancy

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

Clinical note

Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.

FDA category	Animal
Breastfeeding	Unknown if excreted in human milk; M/P ratio not established. Theoretical risk of adverse effects in infant. Use with caution; alternatives preferred.
Teratogenic Risk	Insufficient human data; animal studies show no teratogenic effects at exposures up to 15 times human exposure. No increased risk of major birth defects observed in limited case series. Avoid in first trimester unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Depression
Serious Effects

Absolute Contraindications

["Concomitant use with potent CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's wort)","Concomitant use with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole)","History of hypersensitivity to rilpivirine or any component of the formulation"]

Clinical Precautions

Precautions

["Hepatotoxicity, including severe cases and hepatic failure","Risk of QT interval prolongation; avoid use with drugs that prolong QT or in patients with hypokalemia, hypomagnesemia, or congenital long QT syndrome","Severe skin and hypersensitivity reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)","Depressive disorders, including suicidal ideation","Lipodystrophy and metabolic changes","Immune reconstitution syndrome","Decreased efficacy with high baseline viral load (>100,000 copies/mL) or low CD4 count (<200 cells/mm^3)"]

Clinical Tips & Counseling

Drug interactions

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RILPIVIRINE HYDROCHLORIDE

Clinical safety rating: safe

Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contributions from CYP2C8 and CYP2C19.
Excretion	Primarily hepatic metabolism (CYP3A4), with 85% of dose excreted in feces (unchanged drug and metabolites) and 6.1% in urine (unchanged drug). Renal elimination of unchanged drug is <1%.
Half-life	Terminal elimination half-life is approximately 34.6 hours (range 25–56 hours), supporting once-daily dosing. Steady-state reached in ~2 weeks.
Protein binding	Approximately 99.7% bound to albumin.
Volume of Distribution	Apparent volume of distribution (Vd/F) is 0.95 L/kg (mean; ~72 L), indicating extensive tissue distribution into extravascular spaces.
Bioavailability	Oral bioavailability is approximately 35% (range 25–50%) under fed conditions; reduced by 40% when taken fasting. Absorption is pH-dependent with increased gastric pH reducing absorption.
Onset of Action	Oral: Time to maximum plasma concentration (Tmax) is 3–4 hours post-dose. Antiviral activity begins within days, but clinical efficacy is assessed after 4–8 weeks.
Duration of Action	Duration of antiviral effect is 24 hours with once-daily dosing due to sustained plasma levels above IC95 for wild-type HIV-1. Missed doses >24 hours may lead to virologic failure.

Classification & Brands

Dosing & administration

25 mg orally once daily with a meal.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease.
Liver impairment	Child-Pugh Class A and B: No dose adjustment. Child-Pugh Class C: Not recommended.
Pediatric use	For patients weighing ≥35 kg and aged ≥12 years: 25 mg orally once daily with a meal. Not approved for children <12 years or <35 kg.
Geriatric use	No specific dose adjustment; monitor renal function and consider potential for increased adverse effects due to age-related changes.

Use during pregnancy

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

Clinical note

Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.

FDA category	Animal
Breastfeeding	Unknown if excreted in human milk; M/P ratio not established. Theoretical risk of adverse effects in infant. Use with caution; alternatives preferred.
Teratogenic Risk	Insufficient human data; animal studies show no teratogenic effects at exposures up to 15 times human exposure. No increased risk of major birth defects observed in limited case series. Avoid in first trimester unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Depression
Serious Effects