Wayrilz Drug Information
Generic name: RILZABRUTINIB
Kinase Inhibitor [EPC]
Uses of Wayrilz
is indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. WAYRILZ is a kinase inhibitor indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Dosage & Administration of Wayrilz
Recommended Testing
Before Initiating WAYRILZ Verify pregnancy status of females of reproductive potential prior to initiating WAYRILZ treatment .
Recommended Dosage
The recommended dosage of WAYRILZ is 400 mg taken orally twice daily. WAYRILZ can be taken at approximately the same time each day with or without food. In patients who experience gastrointestinal symptoms, taking WAYRILZ with food may improve tolerability.
Advise patients to swallow tablets whole with a glass of water. Advise patients not to cut, crush or chew the tablets. If a dose is missed, patients should take the missed dose of WAYRILZ as soon as possible on the same day and at least 2 hours apart from the next regular scheduled dose.
If taking antacid or histamine H2 receptor antagonist, administer the dose of WAYRILZ at least 2 hours before the antacid or histamine H2 receptor antagonist.
Monitoring and Dose Modifications for Hepatotoxicity Evaluate bilirubin and transaminases at baseline
and as clinically indicated during treatment with WAYRILZ. For patients who develop abnormal liver tests after WAYRILZ, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If Drug-Induced Liver Injury (DILI) is suspected, withhold WAYRILZ. Upon confirmation of DILI, discontinue WAYRILZ.
Side Effects of Wayrilz
Clinical Trials Experience
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. The safety of WAYRILZ was evaluated in a randomized, double-blind (DB), placebo-controlled, parallel-group study (LUNA-3), in which 202 adult patients with persistent or chronic ITP received either WAYRILZ (n=133) or placebo (n=69) . During the 24-week DB period, the median duration of WAYRILZ exposure was 98 days (range: 22 to 182). The most common adverse reactions (≥10%) were diarrhea, nausea, headache, abdominal pain, and COVID-19. Adverse reactions resulting in discontinuation of WAYRILZ included erythema nodosum, neutropenia, arthralgia, dyspepsia, headache, pain in extremity, abdominal discomfort, diarrhea, nausea, and pneumonia and occurred in 4.5% of patients. Table 1 presents common adverse reactions from the LUNA-3 Study.
Table 1: Common Adverse Reactions Adverse reactions that occurred in at least 5% of WAYRILZ treated patients and at least 3% higher than placebo-treated patients. in Patients with ITP During Double-Blind Period of the LUNA-3 Study Adverse Reactions WAYRILZ (N=133) Placebo (N=69) All Grades % Grade 3 or Higher % All Grades % Grade 3 or Higher % Diarrhea 32 0 10 0 Nausea 20 0 6 0 Headache 18 0 7 0 Abdominal Pain Grouped term 14 0 1 0 COVID-19 14 0.8 4 0 Arthralgia 9 0 4 0 Dizziness 8 0 1 0 Nasopharyngitis 7 0 3 0 Vomiting 7 0 1 0 Dyspepsia 5 0 0 0 Cough 5 0 0 0 Specific Adverse Reactions Gastrointestinal Events In the LUNA-3 Study DB period, the most common gastrointestinal (GI) adverse reactions were diarrhea (32%), nausea (20%), and abdominal pain (14%) in the WAYRILZ group. These events were Grade 1 or 2. Of those who experienced GI adverse reactions, 2 patients discontinued due to GI adverse reactions. Recovery or resolution with supportive treatment allowing continuation of WAYRILZ treatment occurred in 91% of patients with diarrhea, 85% with nausea and 79% with abdominal pain.
Neutropenia In the LUNA-3 Study DB period, Grade 1 or 2 neutropenia occurred in 11% of patients in the WAYRILZ group.
Warnings & Cautions for Wayrilz
Serious Infections
An increased risk of serious infections (including bacterial, viral, or fungal) can occur in patients treated with Bruton's tyrosine kinase (BTK) inhibitors, including WAYRILZ. In the LUNA-3 trial, fatal pneumonia occurred in one participant in the WAYRILZ group. Other serious infections included COVID-19 infection, wound infection, and one patient experienced urinary tract infection and kidney abscess. Monitor patients for signs and symptoms of infection and treat appropriately.
Hepatotoxicity, Including Drug-Induced Liver Injury Hepatotoxicity, including severe, life-threatening, and potentially fatal
cases of DILI, can occur in patients treated with BTK inhibitors. In the clinical trials of WAYRILZ in patients with ITP, elevations of liver transaminases occurred and were generally mild to moderate in severity. Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment with WAYRILZ. For patients who develop abnormal liver tests after WAYRILZ, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity.
If DILI is suspected, withhold WAYRILZ. Upon confirmation of DILI, discontinue WAYRILZ.
Embryo-Fetal Toxicity
Based on findings from preliminary animal reproduction studies, WAYRILZ may cause fetal harm when administered to a pregnant woman. Adverse visceral and skeletal findings occurred in rat fetuses at a maternally toxic dose at exposures 22-times the human exposure at the maximum recommended human dose (MRHD), and renal visceral malformations occurred in a single rabbit fetus at 5.6-times the human exposure (based on AUC) at the MRHD. Verify pregnancy status of females of reproductive potential prior to initiating WAYRILZ treatment. Advise females of reproductive potential to use an effective method of contraception during treatment with WAYRILZ and for 1 week after the final dose .
Drug Interactions with Wayrilz
Effect of Other Drugs on
WAYRILZ Strong and Moderate CYP3A Inhibitors Avoid concomitant use of WAYRILZ with strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor cannot be avoided, and these inhibitors will be used short term (such as anti-infectives for seven days or less), interrupt treatment with WAYRILZ. Avoid concomitant use of grapefruit, starfruit and products containing these fruits, and Seville oranges with WAYRILZ, as these are moderate and strong inhibitors of CYP3A. Rilzabrutinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor increases rilzabrutinib C max and AUC , which increases the risk of WAYRILZ adverse reactions.
Strong and Moderate CYP3A Inducers Avoid concomitant use of WAYRILZ with strong or moderate CYP3A inducers. Rilzabrutinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inducer decreases rilzabrutinib C max and AUC , which may reduce WAYRILZ efficacy.
Gastric Acid Reducing Agents Administer the dose of WAYRILZ at least 2 hours before administration of an antacid or histamine H2 receptor antagonist. Avoid concomitant use of proton pump inhibitors with WAYRILZ. Rilzabrutinib exhibits pH-dependent solubility. Acid reducing agents decrease rilzabrutinib exposure , which may reduce WAYRILZ efficacy.
Effect of
WAYRILZ on Other Drugs CYP3A Substrates Monitor for adverse reactions of the concurrently administered CYP3A substrate more frequently and consider dosage adjustment in accordance with the Prescribing Information of the CYP3A substrate. Rilzabrutinib is a moderate inhibitor of CYP3A and increases exposure of these substrates , which increases the risk of adverse reactions related to these substrates. P-gp, BCRP, and OATP1B Substrates Monitor for adverse reactions of the concurrently administered P-gp, BCRP, or OATP1B substrate more frequently, unless otherwise recommended in the substrate Prescribing Information, when WAYRILZ is used concomitantly with P-gp, BCRP, or OATP1B substrates where minimal substrate concentration changes may lead to serious adverse reactions.
Rilzabrutinib is an inhibitor of P-gp, BCRP and OATP1B in vitro. The effect of concomitant use of WAYRILZ with OATP1B and BCRP substrates has not been established in clinical studies. However, based on in vitro inhibitory potential , concomitant use of WAYRILZ may increase the risk of adverse reactions related to these substrates.
Pregnancy Safety for Wayrilz
Pregnancy Risk Summary Based on animal data, WAYRILZ may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of rilzabrutinib to pregnant rats and rabbits during organogenesis at exposures 4- to 10-times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 400 mg twice daily did not cause adverse developmental effects. However, adverse visceral and skeletal findings occurred in rat fetuses at a maternally toxic dose at exposures 22-times the human exposure (based on AUC) at the MRHD ( see Data ). There are no available clinical data on the use of WAYRILZ during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, and other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Rilzabrutinib given to pregnant rats by oral gavage at 50, 150 or 300 mg/kg/day during the period of organogenesis (gestation day 7 to 17) did not cause adverse effects on embryo-fetal development at exposures approximately 10-times the clinical exposure at the maximum recommended human dose (MRHD), based on AUC. Increased incidence of post-implantation loss (25%), delayed ossification associated with a markedly lower (24%) mean fetal weight, and increased skeletal (scoliosis) and visceral malformations (abnormalities of major vessels, urogenital tract, and kidney) occurred in a preliminary study in rats at a maternally toxic dose of 500 mg/kg/day that resulted in exposures 22-times the clinical exposure at the MRHD, based on AUC. Rilzabrutinib given to pregnant rabbits by oral gavage at 10, 30 or 100 mg/kg/day during the period of organogenesis (gestation day 7 to 19) did not cause adverse effects on embryo-fetal development at exposures approximately 4-times the clinical exposures at the MRHD, based on AUC. Renal visceral malformations occurred in a single fetus in a preliminary study in rabbits at 150 mg/kg/day that resulted in exposures 5.6-times the clinical exposure at the MRHD, based on AUC. In a pre- and postnatal developmental toxicity study, pregnant rats were given rilzabrutinib by oral gavage at doses of 50, 150 or 300 mg/kg/day during the periods of gestation, parturition, and lactation (gestation day 7 to lactation day 21). Decreased body weight was observed in pups in the presence of maternal toxicity at 300 mg/kg/day, at exposures approximately 18-times the MRHD based on AUC. There were no effects of rilzabrutinib on the ability of F1 offspring to reproduce or on subsequent F2 development at any dose.
Pediatric Use of Wayrilz
Pediatric Use Safety and effectiveness of WAYRILZ have not been established in pediatric patients.
Overdosage Information for Wayrilz
In the event of overdosage, closely monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Clinical Studies of Wayrilz
Immune Thrombocytopenia (ITP) The safety and efficacy of WAYRILZ in adult patients with primary persistent or chronic ITP was evaluated in a randomized, double-blind (DB), placebo-controlled, parallel-group study consisting of 24 weeks of blinded treatment followed by an open-label (OL) period. Patients received an initial 12 weeks of DB period treatment. Those who achieved platelet count response at 12 weeks were eligible to continue the full 24-week DB period.
The patients enrolled in this study had an unsustained response to either intravenous immunoglobulin (IVIg/anti-D) or corticosteroid (CS) or had a documented intolerance or insufficient response to any appropriate course of standard-of-care ITP therapy. Patients were randomized 2:1 to receive WAYRILZ 400 mg or placebo twice daily and randomization was stratified based on prior splenectomy (yes/no) and severity of thrombocytopenia (platelet count <15 ×10 9 /L or ≥15 ×10 9 /L). Concomitant ITP medicines were allowed at stable doses at least 2 weeks before the start of the study and throughout the DB period. In the LUNA-3 Study, 202 patients were randomized and treated, 133 to the WAYRILZ group and 69 to the placebo group.
At baseline, the median age was 47 years (range: 18 to 80 years), 63% were female, 62% were Caucasian, 32% Asian, 1% were Black or African American, 2% were American Indian or Alaska native, 20% were Hispanic or Latino/a, and 77% were not Hispanic or Latino/a. Baseline demographics were generally similar across groups with the exception of sex which was 59% female in the WAYRILZ group and 71% in the placebo group. At baseline 93% of patients had chronic ITP (i.e., for 1 year or longer), with a median time since ITP diagnosis of 7.69 years (range: 0.3, 52.2), and 28% had undergone splenectomy.
The median platelet count was 15.3 × 10 9 /L, with almost half (48%) less than 15 × 10 9 /L. The median number of prior therapies, including splenectomy, was 4 (range: 1, 15). Prior ITP treatments varied, with the most common prior therapies being CS (96%), TPO-RAs (69%), IVIg or anti-D immunoglobulins (55%), and anti-CD20 monoclonal antibody/rituximab (35%). In addition, at baseline 66% of patients received both CS and TPO-RAs. Baseline disease characteristics were generally similar across both groups. During the DB period, the median duration of exposure was 98 days (range: 22 to 182) and 84 days (range: 17 to 173) for the WAYRILZ group and placebo group, respectively.
The cumulative duration of treatment exposure was 44 participant-years and 18 participant-years for the WAYRILZ and placebo groups, respectively. Concomitant use of CS and/or TPO-RA with study drug occurred in 60% and 67% of patients in the WAYRILZ and placebo arms, respectively. During the first 12 weeks of the DB period, 85 (63.9%) patients and 22 (31.9%) patients in the WAYRILZ group and placebo group, respectively, achieved platelet count response (≥50 × 10 9 /L or between 30 × 10 9 /L and <50 × 10 9 /L and doubled from baseline). Those who achieved platelet count response were eligible to continue the DB period.
The efficacy of WAYRILZ was based on durable platelet response. A durable platelet response was defined as a weekly platelet count ≥50 × 10 9 /L for ≥ two-thirds of at least 8 non-missing weekly scheduled platelet measurements during the last 12 weeks of the 24-week DB period in the absence of rescue therapy, provided that at least 2 non-missing weekly scheduled platelet measurements were ≥50 × 10 9 /L during the last 6 weeks of the DB period. The results of the major efficacy endpoints during the DB period are summarized in Table 2. Table 2: LUNA-3 Study Outcomes During the 24-week DB Period – Adult Population Study Outcomes Statistic WAYRILZ 400 mg BID (N=133) Placebo (N=69) Abbreviations: LS=Least Square; NR=Not Reached; CI=Confidence Interval; SE=Standard Error.
Durable Platelet Response p-value was derived by Cochran-Mantel-Haenszel (CMH) test adjusted by stratification factors. n (%) 31 0 95% CI 16.12, 30.49 0.00, 0.00 Risk difference (95% CI) vs placebo 23.1 p-value <0.0001 Number of Weeks with Platelet Response Numbers of weeks with platelet response was based on 24-week blinded treatment period. Platelet counts assessed within 4 weeks of rescue medication intake are considered as no response; missing weekly platelet counts due to any reasons are considered as no response. p-value was derived by a mixed-effect model with repeated measures on longitudinal binary data with treatment, stratification factors, week (Weeks 2 to 25), treatment-by-week interaction as categorical fix effects. ≥50 × 10 9 /L or between 30 × 10 9 /L and <50 × 10 9 /L and doubled from baseline LS Mean (SE) 7.18 0.72 LS Mean difference (SE) vs placebo 6.46 95% CI 4.92, 7.99 p-value <0.0001 ≥30 × 10 9 /L and doubled from baseline LS Mean (SE) 6.95 0.64 LS Mean difference (SE) vs placebo 6.31 95% CI 4.79, 7.83 p-value <0.0001 Time to First Platelet Response Platelet count ≥50 × 10 9 /L or between 30 × 10 9 /L and <50 × 10 9 /L and at least doubled from baseline in absence of rescue therapy; p-value was derived by log-rank test adjusted by stratification factors. Median number of days to first platelet count (95% CI) 36 NR Hazard ratio (95% CI) vs placebo 3.10 p-value <0.0001 Rescue medication was required by 33% and 58% of patients receiving WAYRILZ and placebo, respectively.
The median time to first use of rescue therapy was not reached in the WAYRILZ group and 56 days in the placebo group. During the OL period, 7/73 (10%) patients who received WAYRILZ during the DB period achieved a durable response for the first time.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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