Evicenter
P&T meetings

Hovilpri (pritelivir)

Refractory mucocutaneous herpes simplex virus infection in immunocompromised adults

Also known as AIC316
Last updated
239 sources

Product information and disease descriptionProduct descriptionProduct informationDrug/Drug, drug/disease interactions

Effects of other drugs on pritelivir

13 evidence topics · 7 sources

Gastric pH and pritelivir bioavailability

“Elevation of gastric pH may decrease the systemic bioavailability of HOVILPRI” (opens the prescribing information at this quote)

“which may reduce its effectiveness or cause drug resistance to HOVILPRI” (opens the prescribing information at this quote)

Clinically significant drug interactions: proton pump inhibitors, H2-receptor antagonists, and antacids
Drug classPrevention or management
Proton pump inhibitors: agents and doses to avoid“Avoid concomitant use of esomeprazole or rabeprazole with HOVILPRI. Avoid concomitant use of omeprazole or lansoprazole at daily doses above 20 mg with HOVILPRI. Avoid concomitant use of pantoprazole at daily doses above 40 mg with HOVILPRI”
Proton pump inhibitors: acceptable doses“Concomitant use of omeprazole, lansoprazole, or pantoprazole below the doses listed above is acceptable, as these lower doses do not reduce pritelivir exposure to a clinically relevant extent.”
H2-receptor antagonists“Take HOVILPRI at least 2 hours before or 12 hours after H2- receptor antagonist intake”
Antacids“Take HOVILPRI at least 2 hours before or 2 hours after antacid intake”
Acid-reducing agents as summarized in the label highlights

“Avoid concomitant use with esomeprazole or rabeprazole. Avoid concomitant use with omeprazole or lansoprazole at daily doses above 20 mg, or with pantoprazole at daily doses above 40 mg.” (opens the prescribing information at this quote)

“Stagger concomitant use with H2-receptor antagonists or antacids.” (opens the prescribing information at this quote)

Esomeprazole interaction study: prescribing information

“Co-administration of a single oral dose of 100 mg pritelivir (on Day 1) with esomeprazole 40 mg once daily (from Day -3 to Day 1; 4 days total) decreased Cmax by approximately 76% and AUC by approximately 59% compared to pritelivir administered alone” (opens the prescribing information at this quote)

Changes in pritelivir pharmacokinetics with esomeprazole: geometric mean ratio (90% CI), with and without the co-administered drug
Co-administered drug and regimenPritelivir regimenNAUC0-infAUC0-lastCmax
Esomeprazole 40 mg once daily“100 mg single dose”“15”“0.41 (0.36, 0.48)”“0.41 (0.35, 0.47)”“0.24 (0.20-0.30)”
Lower-dose proton pump inhibitors and H2-receptor antagonists in PRIOH-1 Parts C to F

“In the Phase 3 trial (PRIOH-1, Parts C-F), pritelivir exposures were evaluated for participants who received concomitant omeprazole or lansoprazole (≤20 mg daily), pantoprazole (≤40 mg daily), or an H2-receptor antagonist (with pritelivir administered at least 2 hours before or 12 hours after the H2-receptor antagonist).” (opens the prescribing information at this quote)

“Pritelivir exposures in participants receiving these acid-reducing agents were not clinically meaningfully different from those in participants who did not receive any acid-reducing agents” (opens the prescribing information at this quote)

Esomeprazole interaction trial: design

“This was a single-center, open-label, 2-period, fixed-sequence Phase 1 trial in 16 healthy adult male and female subjects (at least 7 subjects per sex).” (opens the source at this quote in a new tab)

“In the first period, subjects received treatment 1 (T1; single dose of 100 mg PTV on Day 1). In the second period, subjects received treatment 2 (T2: 40 mg qd ESO from Day -3 to Day 1 followed by a single dose of 100 mg PTV on Day 1).” (opens the source at this quote in a new tab)

“The wash-out period between PTV administrations in T1 and T2 was at least 4 weeks.” (opens the source at this quote in a new tab)

“Point estimates (GMR) and 90% confidence intervals (90% CIs) will be computed for the ratio T2 (test) /T1 (reference) to evaluate the effect of esomeprazole on pritelivir PK under fasted conditions.” (opens the source at this quote in a new tab)

Esomeprazole interaction trial: pritelivir pharmacokinetic parameters as posted on the registry
ParameterPritelivir 100 mg aloneEsomeprazole 40 mg once daily with pritelivir 100 mg
Participants analyzed for Cmax“16”“15”
Cmax (ng/mL), mean (standard deviation)“1102(421)”“282(141)”
AUC(0-last) (ng*h/mL), mean (standard deviation)“67599(22012)”“28325(11071)”
AUC(0-infinity) (ng*h/mL), mean (standard deviation)“69140(22147)”“29404(11447)”
tmax (hours), median (full range)“3.00 (0.50 to 10.00)”“8.00 (0.75 to 48.00)”
t1/2z (hours), mean (standard deviation)“67.7(12)”“73.7(13)”
CL/F (L/h), mean (standard deviation)“1.58(0.46)”“3.93(1.6)”
Vd/F (L), mean (standard deviation)“157(63)”“432(231)”
Esomeprazole interaction trial: participant flow as posted on the registry

“16 subjects enrolled in PTV 100 mg (T1), 15 completed. The 15 completed were enrolled into ESO 40 mg/PTV 100 mg (T2)” (opens the source at this quote in a new tab)

Esomeprazole interaction trial: adverse events as posted on the registry
Category, affected / at risk (%)Pritelivir 100 mg aloneEsomeprazole 40 mg once daily with pritelivir 100 mg
All-cause mortality“0/16 (0.00%)”“0/15 (0.00%)”
Serious adverse events“0/16 (0.00%)”“0/15 (0.00%)”
Other (not including serious) adverse events“2/16 (12.50%)”“4/15 (26.67%)”
Solubility of pritelivir at acidic and higher pH

“Pritelivir mesylate monohydrate is a BCS class 2 drug substance.” (opens the source at this quote in a new tab)

“it is well soluble below pH 2–3. With increasing pH value, the solubility decreases substantially” (opens the source at this quote in a new tab)

“Results from dissolution studies (data on file) showed that the HPMC capsule used in Trial 2 had a much lower dissolution rate compared to the clinical tablet formulation used in Trial 1.” (opens the source at this quote in a new tab)

“This likely delayed the time of drug release until the capsule had passed beyond the low pH environment of the stomach required for adequate drug solubility of pritelivir.” (opens the source at this quote in a new tab)

Pritelivir as a substrate of cytochrome P450 enzymes

“As pritelivir is primarily metabolized by non-enzymatic hydrolysis, leading to the formation of AIC090015 and AIC090105, clinically relevant drug-drug interactions with pritelivir as a CYP enzyme substrate are not expected.” (opens the prescribing information at this quote)

“Therefore, pritelivir is not expected to be a sensitive substrate for drug-drug interactions (DDIs) through CYP enzymes.” (opens the source at this quote in a new tab)

Pritelivir as a substrate of drug transporters

“Pritelivir is a substrate of both P-glycoprotein (P-gp) and BCRP efflux transporters in vitro, but is not a substrate of OATP1B1, OATP1B3, OATP2B1, organic cation transporter (OCT)1, or organic anion transporter (OAT)1.” (opens the prescribing information at this quote)

“Because pritelivir has a high absolute oral bioavailability of 72%, co-administration of P- gp or BCRP inhibitors is not expected to impact the oral absorption of HOVILPRI to a clinically relevant extent.” (opens the prescribing information at this quote)

“Furthermore, pritelivir was considered to be a substrate for P-glycoprotein (P-gp) and BCRP.” (opens the source at this quote in a new tab)

“interactions of pritelivir as the substrate for P-gp and BCRP are not expected to impact the oral permeability to a clinically relevant extent.” (opens the source at this quote in a new tab)