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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 information

Contraindications/Warnings/Precautions/Adverse effects

15 evidence topics · 2 sources

Warnings and precautions
Contraindications

“None.” (opens the prescribing information at this quote)

Warning: drug interactions with acid-reducing agents

“Concomitant use of HOVILPRI with certain acid-reducing agents may reduce pritelivir exposure, potentially resulting in reduced therapeutic effect and development of resistance.” (opens the prescribing information at this quote)

“Avoid concomitant use with certain proton pump inhibitors, and stagger concomitant use with H2-receptor antagonists and antacids” (opens the prescribing information at this quote)

Interpretation of adverse reaction rates from clinical trials

“Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.” (opens the prescribing information at this quote)

Size of the clinical safety database

“The safety of HOVILPRI was evaluated in 206 adults treated with HOVILPRI and an additional 100 healthy adult participants exposed to HOVILPRI in clinical trials.” (opens the prescribing information at this quote)

Adverse reactions in PRIOH-1 Part C: safety population and exposure

“The safety of HOVILPRI was evaluated in a Phase 3, randomized, open-label, comparator-controlled trial, PRIOH-1 (Part C), in immunocompromised participants with mucocutaneous (mucosal and/or cutaneous lesions) HSV infection that was refractory (with or without documented resistance) to treatment with acyclovir, valacyclovir, or famciclovir” (opens the prescribing information at this quote)

“Participants received HOVILPRI (400 mg loading dose on Day 1 followed by 100 mg once daily) or Investigator’s Choice treatment (IV foscarnet, IV/topical cidofovir, or 5% topical imiquimod) for up to 28 days until all lesions healed, extended up to 42 days if lesions were improving.” (opens the prescribing information at this quote)

“A total of 101 participants were randomized 1:1 and treated with either HOVILPRI or the Investigator’s Choice.” (opens the prescribing information at this quote)

“Across the 51 participants treated with HOVILPRI, the mean duration of treatment was 27.1 days (range 6–43).” (opens the prescribing information at this quote)

Adverse reactions in PRIOH-1 Part C: headache, overall incidence, and discontinuations

“The most common adverse reaction (incidence >5%) was headache.” (opens the prescribing information at this quote)

“The adverse reaction (all grades) occurring in more than 5% of participants receiving HOVILPRI was headache, which occurred in 6% and 4% of the HOVILPRI and Investigator’s choice participants, respectively.” (opens the prescribing information at this quote)

“Adverse reactions were reported in 22% of HOVILPRI-treated participants, compared with 54% of participants in the Investigator’s Choice treatment arm.” (opens the prescribing information at this quote)

“Discontinuations due to adverse drug reactions occurred in 2% and 20% of participants, respectively.” (opens the prescribing information at this quote)

Adverse reactions and hepatic laboratory abnormalities in PRIOH-1 Part C by treatment arm
EventHOVILPRI, N=51Investigator's Choice, N=50
Headache, all grades“6%”“4%”
Any adverse reaction“22%”“54%”
Discontinuation due to adverse drug reactions“2%”“20%”
ALT elevation of 2.5 times the upper limit of normal or more“4/51 (8%)”“1/50 (2%)”
AST elevation of 2.5 times the upper limit of normal or more“3/51 (6%)”“2/50 (4%)”
Laboratory abnormalities: hepatic enzymes in PRIOH-1 Part C

“Hepatic laboratory abnormalities were observed in both treatment groups in PRIOH-1, Part C.” (opens the prescribing information at this quote)

“ALT elevations ≥2.5 × upper limit of normal (ULN) were reported in 4/51 (8%) participants receiving HOVILPRI and 1/50 (2%) receiving Investigator’s Choice, while AST elevations ≥2.5 × ULN were reported in 3/51 (6%) and 2/50 (4%) participants, respectively.” (opens the prescribing information at this quote)

“One participant discontinued HOVILPRI due to elevated liver enzymes.” (opens the prescribing information at this quote)

Safety in PRIOH-1 Parts D and F

“The safety of HOVILPRI was also evaluated in a non-randomized, open-label, multicenter, single-arm Phase 3 trial, PRIOH-1 (Parts D and F) in immunocompromised adults with acyclovir/foscarnet (ACV/FOS) refractory HSV infection or who were FOS intolerant (N=35).” (opens the prescribing information at this quote)

“The safety and tolerability profile observed in these” (opens the prescribing information at this quote)

“populations was consistent with that observed in Part C, with no new or unexpected adverse drug reactions identified.” (opens the prescribing information at this quote)

Overdosage

“There is no known specific antidote for HOVILPRI.” (opens the prescribing information at this quote)

“In the event of an overdose, patients should be monitored for adverse reactions and managed with supportive care, as appropriate.” (opens the prescribing information at this quote)

“Due to the high plasma protein binding of pritelivir, hemoperfusion or dialysis is unlikely to significantly reduce systemic exposure of pritelivir.” (opens the prescribing information at this quote)

“Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.” (opens the prescribing information at this quote)

Patient counseling

“Advise the patient to read the FDA-approved patient labeling (Patient Information).” (opens the prescribing information at this quote)

“Inform patients that HOVILPRI may interact with some drugs; therefore, advise patients to report the use of any other medications to their healthcare provider” (opens the prescribing information at this quote)

“Inform patients that it is important not to miss or skip doses and to take HOVILPRI for the duration that is recommended by the healthcare provider.” (opens the prescribing information at this quote)

“Inform patients that HOVILPRI is indicated to heal lesions caused by HSV but is not a cure for HSV infection.” (opens the prescribing information at this quote)

Side effects as stated in the patient information

“The most common side effect of HOVILPRI is headache.” (opens the prescribing information at this quote)

“Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.” (opens the prescribing information at this quote)

Nonclinical toxicology: carcinogenesis and mutagenesis

“Carcinogenicity studies with pritelivir are ongoing.” (opens the prescribing information at this quote)

“Pritelivir free base and pritelivir mesylate monohydrate were not mutagenic in in vitro and in vivo genotoxicity assays which included bacterial mutation assays in S. typhimurium, micronucleus tests with cultured mammalian cells, and in the rodent micronucleus assay.” (opens the prescribing information at this quote)

Nonclinical toxicology: ocular findings in repeat-dose rodent studies

“In a 26-week oral toxicity study in rats at 10, 50, 250 mg/kg/day, early stages of lenticular opacity (cataracts) and vitreous floaters in the eye were observed at 250 mg/kg/day.” (opens the prescribing information at this quote)

“In a 13-week mouse toxicity study at 100, 500, 1,500 mg/kg/day, lenticular opacity and compound depositions were noted at ≥500 mg/kg/day.” (opens the prescribing information at this quote)

“No ocular findings occurred in the rat and mouse at systemic exposures (AUC) approximately 28- (rats) and 14- (mice) times the human exposure at the therapeutic dose of 100 mg.” (opens the prescribing information at this quote)

“Further, no ocular findings were apparent in the monkey with up to 39 weeks of treatment at 1,000 mg/kg/day.” (opens the prescribing information at this quote)

Nonclinical safety pharmacology: hERG channel and carbonic anhydrase

“A 50% inhibitory concentration of approximately 160 μM was determined which is more than 100-fold higher than the maximum observed plasma concentration at therapeutic doses after correction for protein binding.” (opens the source at this quote in a new tab)

“Primary sulfonamides are well-known for their affinity to carbonic anhydrases (CAs).” (opens the source at this quote in a new tab)