Label:RHAPSIDO- remibrutinib tablet
remibrutinib
Quick Facts
Used For
RHAPSIDO is used to treat chronic spontaneous urticaria (CSU) in adults when antihistamines don’t work...
Common Side Effects
Side Effects from Clinical Studies Results from clinical studies may not match...
What You Should Know
Read the Patient Information sheet that comes with RHAPSIDO. How to Take RHAPSIDO: Take RHAPSIDO...
Prescription
Not Required
Generic Available
No
Indications and Usage
RHAPSIDO is used to treat chronic spontaneous urticaria (CSU) in adults when antihistamines don’t work well enough.
Limitations of Use:
RHAPSIDO is not for other types of urticaria.
RHAPSIDO®is indicated for the treatment of chronic spontaneous urticaria (CSU) in adult patients who remain symptomatic despite H1 antihistamine treatment.
Limitations of Use:
RHAPSIDO is not indicated for other forms of urticaria.
Dosage and Administration
How Much to Take
Take 25 mg by mouth two times each day with or without food.
Swallow RHAPSIDO tablet whole with water. Do not split, crush, or chew RHAPSIDO.
If You Miss a Dose
If you miss one or more doses of RHAPSIDO, skip the missed dose and take the next dose at the regular time. Do not take extra doses to make up for missed doses.
Stopping RHAPSIDO for Surgery
Stop taking RHAPSIDO for 3 to 7 days before and after surgery. The exact time depends on the type of surgery and your risk of bleeding.
Recommended Dosage
The recommended dosage is 25 mg taken orally twice daily with or without food.
Swallow RHAPSIDO tablet whole with water. Do not split, crush, or chew RHAPSIDO.
Missed Dose(s)
If a dose or doses of RHAPSIDO is missed, skip the missed dose, and take the next dose at its regularly scheduled time. Do not take an extra dose(s) of RHAPSIDO to make up for a missed dose(s).
Temporary Interruption of RHAPSIDO for Surgery
Interrupt treatment with RHAPSIDO for 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding[see Warnings and Precautions (5.1), Adverse Reactions (6.1) and Drug Interactions (7.2)].
Dosage Forms and Strengths
Tablets: 25 mg, light yellow, round, curved, smooth (no score line), film-coated tablet with “LV” on one side and Novartis logo on the other side. The tablet is 7 mm across.
Tablets: 25 mg, light yellow, round, curved, unscored, film-coated tablet, debossed with “LV” on one side and Novartis logo on the other side. The tablet diameter is 7 mm.
Contraindications
None.
None.
Warnings and Precautions
Risk of Bleeding
In studies, 9% of patients who took RHAPSIDO had bleeding problems in their skin or mucous membranes. Stop taking RHAPSIDO if you have bleeding. Your doctor will decide if you can start taking it again.
Stop taking RHAPSIDO 3 to 7 days before and after any surgery or medical procedure.
Taking blood thinners with RHAPSIDO may increase your risk of bleeding. Your doctor will decide if the benefits are worth the risks. Watch for any signs of bleeding.
Live Vaccines
There is no information about using live vaccines while taking RHAPSIDO. You should not get live vaccines while taking RHAPSIDO.
Risk of Bleeding
In placebo-controlled studies in patients with CSU, mucocutaneous-related bleeding occurred in 9% of patients who received RHAPSIDO[see Adverse Reactions (6.1)]. Interrupt treatment with RHAPSIDO if bleeding is observed and resume if the benefit is expected to outweigh the risk.
Interrupt treatment with RHAPSIDO for 3 to 7 days pre- and post-surgery or invasive procedures[see Dosage and Administration (2.2)].
Use of antithrombotic agents concomitantly with RHAPSIDO may further increase the risk of bleeding[see Drug Interactions (7.2)]. Consider the benefits and risks of antithrombotic agents when used concomitantly with RHAPSIDO. Monitor for signs and symptoms of bleeding.
Live Attenuated Vaccines
No data are available on the effects of live or live-attenuated vaccines in patients receiving RHAPSIDO. The use of live and live-attenuated vaccines should be avoided in patients receiving RHAPSIDO.
Adverse Reactions
Side Effects from Clinical Studies
Results from clinical studies may not match what happens in real-world use. Also, side effects from one drug’s studies can’t be directly compared to another drug’s studies.
RHAPSIDO’s safety was studied in two 52-week studies called REMIX-1 and REMIX-2. The studies included 912 adults with chronic hives (CSU) who still had symptoms even while taking antihistamines. 606 patients took RHAPSIDO 25 mg twice daily and 306 took placebo (a pill with no medicine) for 24 weeks.
Side effects that happened in 3% or more of patients and were more common with RHAPSIDO than placebo during the 24-week period are shown in Table 1.
Table 1: Side Effects with RHAPSIDO (3% or More) and More Common than Placebo in Adults with Chronic Hives (REMIX-1 and REMIX-2)
Side Effect | RHAPSIDO (606 patients) | Placebo (306 patients)
—|—|—
Nose and throat infectionsa | 67 (11%) | 27 (9%)
Bleedingb | 55 (9%) | 6 (2%)
Headachec | 41 (7%) | 19 (6%)
Nausea | 18 (3%) | 5 (2%)
Stomach paind | 18 (3%) | 6 (2%)
a includes sinus infections, stuffy nose, sore throat, strep throat, and upper respiratory infections
b includes bleeding in the eye, bruising, nosebleeds, bleeding gums, blood in urine, bleeding between periods, and small red spots on skin
c includes headache and migraine
d includes stomach discomfort, bloating, and upper stomach pain
Bleeding
In the REMIX-1 and REMIX-2 studies, bleeding happened in 9% of patients taking RHAPSIDO compared to 2% taking placebo during the 24-week period. Small red spots on the skin (4%) and bruising (2%) were the most common bleeding problems in patients taking RHAPSIDO. No serious bleeding happened. Bleeding was not linked to low platelet counts. 0.5% of patients stopped taking RHAPSIDO because of bleeding, while no one in the placebo group stopped for this reason. Similar results were seen through Week 52.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse drug reaction (ADR) 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 RHAPSIDO was based on a pooled safety population from two identical clinical trials of 52 weeks duration, REMIX-1 and REMIX-2[see Clinical Studies (14)]. The pooled safety population consisted of 912 adult patients with CSU who remain symptomatic despite H1 antihistamine treatment and who received RHAPSIDO 25 mg orally twice daily (N=606) or placebo (N=306) for 24 weeks during the double-blind, controlled treatment period of the trial.
Specific Adverse Reactions
Bleeding
In the pooled safety population (REMIX-1 and REMIX-2), bleeding occurred in 9% of patients treated with RHAPSIDO compared to 2% in the placebo group during the 24-week controlled treatment period[see Dosage and Administration (2.2), Warnings and Precautions (5.1), and Drug Interactions (7.2)]. Petechiae (4%) and contusion (2%) were the most commonly reported reactions in patients treated with RHAPSIDO. No severe bleeding reactions occurred. No association between bleeding reactions and low platelet counts was observed. In patients treated with RHAPSIDO, 0.5% experienced bleeding reactions that led to RHAPSIDO discontinuation, while none of these reactions occurred in the placebo group. Similar safety findings were observed through Week 52[see Clinical Studies (14)].
Drug Interactions
How Other Medicines Affect RHAPSIDO
Strong or Moderate CYP3A4 Inhibitors
Do not take RHAPSIDO with strong or moderate CYP3A4 inhibitors.
RHAPSIDO is broken down by an enzyme called CYP3A4. Taking it with medicines that block this enzyme increases the amount of RHAPSIDO in your body, which may cause more side effects.
Strong or Moderate CYP3A4 Inducers
Do not take RHAPSIDO with strong or moderate CYP3A4 inducers.
RHAPSIDO is broken down by an enzyme called CYP3A4. Taking it with medicines that speed up this enzyme decreases the amount of RHAPSIDO in your body, which may make RHAPSIDO work less well.
How RHAPSIDO Affects Other Medicines
P-gp Substrates
Your doctor should check you more often for side effects when taking RHAPSIDO with P-gp substrate medicines where small changes can cause serious problems (like digoxin).
RHAPSIDO blocks a protein called P-gp. This increases the amount of P-gp substrate medicines in your body, which may cause more side effects from those medicines.
Blood Thinners
Your doctor will consider the risks and benefits of taking blood thinners with RHAPSIDO.
There is no information about taking RHAPSIDO with anticoagulants (blood thinners). These medicines were not allowed in RHAPSIDO studies. Low-dose aspirin (up to 100 mg daily) or clopidogrel (up to 75 mg daily) were allowed in the studies.
Effect of Other Drugs on RHAPSIDO
Strong or Moderate CYP3A4 Inhibitors
Avoid use of RHAPSIDO with strong or moderate CYP3A4 inhibitors.
Remibrutinib is a CYP3A4 substrate. Concomitant use with a strong or moderate CYP3A4 inhibitor increases remibrutinib exposure[see Clinical Pharmacology (12.3)], which may increase the risk of RHAPSIDO adverse reactions.
Strong or Moderate CYP3A4 Inducers
Avoid use of RHAPSIDO with strong or moderate CYP3A4 inducers.
Remibrutinib is a CYP3A4 substrate. Concomitant use with a strong or moderate CYP3A4 inducer decreases remibrutinib exposure[see Clinical Pharmacology (12.3)], which may decrease the efficacy of RHAPSIDO.
Effect of RHAPSIDO on Other Drugs
P-gp Substrates
Monitor more frequently for adverse reactions when using RHAPSIDO with P-glycoprotein (P-gp) substrates where minimal concentration changes may lead to serious adverse reactions (e.g., digoxin).
Remibrutinib is a P-gp inhibitor. Remibrutinib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to P-gp substrates[see Clinical Pharmacology (12.3)].
Antithrombotic Agents
Consider the risks and benefits of concomitant administration of antithrombotic agents with RHAPSIDO[see Dosage and Administration (2.2), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
No data are available on concomitant use of RHAPSIDO with anticoagulants. The concomitant use of RHAPSIDO and anticoagulants was not allowed in clinical studies. Use of the antiplatelet agents, acetyl salicylic acid at doses up to 100 mg daily or clopidogrel up to 75 mg daily, was allowed in the RHAPSIDO clinical studies.
Pregnancy
Pregnancy
Pregnancy Registry
There is a pregnancy registry that tracks pregnancy outcomes in women who take RHAPSIDO during pregnancy. If you are pregnant and taking RHAPSIDO, you and your doctor can call Novartis at 1-888-669-6682.
Risk Summary
We don’t have enough information about using RHAPSIDO during pregnancy to know if it causes birth defects, miscarriage, or other problems for the mother or baby.
In animal studies, pregnant rabbits given remibrutinib at doses 141 times higher than the recommended human dose had babies with birth defects including eye problems, small jaws, and bent front legs. Pregnant rats given remibrutinib at doses up to 126 times higher than the recommended human dose did not have babies with birth defects.
We don’t know the background risk of birth defects and miscarriage for people who need this medicine. All pregnancies have some risk of birth defects, loss, or other problems. In the U.S. general population, about 2% to 4% of babies are born with major birth defects and about 15% to 20% of known pregnancies end in miscarriage.
Data
Animal Data
In pregnant rabbits, remibrutinib was given at doses of 100, 300, and 450 mg/kg/day during the time when organs form. At 300 mg/kg/day (141 times the recommended human dose), baby rabbits had birth defects like open or cloudy eyes, small jaws, and bent front legs. Mother rabbits ate less food and had other side effects. The problems in baby rabbits were not thought to be caused by the mother’s side effects. The dose of 450 mg/kg/day was too high for pregnant rabbits.
In pregnant rats, remibrutinib was given at doses of 100, 300, and 1000 mg/kg/day during the time when organs form. Remibrutinib did not cause problems in baby rats at doses up to 126 times the recommended human dose.
In another study, pregnant rats were given remibrutinib at doses of 100, 300, and 1000 mg/kg/day from day 6 of pregnancy through day 21 of nursing. At 1000 mg/kg/day (about 194 times the recommended human dose), mother rats had serious side effects and longer pregnancies. More baby rats were stillborn, dead, or missing, and litters were smaller. Baby rats that survived and grew into adults had no problems. No problems were seen at 300 mg/kg/day (about 58 times the recommended human dose).
Breastfeeding
Risk Summary
We don’t know if remibrutinib passes into breast milk or if it affects a breastfed baby or milk production. Talk with your doctor about the benefits of breastfeeding and your need for RHAPSIDO. Consider any possible effects on your baby from RHAPSIDO or from your health condition.
Children
The safety and effectiveness of RHAPSIDO have not been studied in children.
Older Adults
Of all patients treated with RHAPSIDO in studies, 53 patients (8.7%) were 65 to 85 years old. No patients were over 85 years old. Older adults had similar safety and effectiveness as younger adults.
Liver Problems
RHAPSIDO levels are higher in patients with mild, moderate, or severe liver problems (Child-Pugh Class A, B, and C) compared to patients with normal liver function. Do not use RHAPSIDO if you have mild, moderate, or severe liver problems (Child-Pugh Class A, B, and C).
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RHAPSIDO during pregnancy. Pregnant women exposed to RHAPSIDO and healthcare providers are encouraged to contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.
Risk Summary
Available data on the use of RHAPSIDO during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of remibrutinib to pregnant rabbits during organogenesis at exposures 141-times the human exposure at the maximum recommended human dose (MRHD) of 25 mg twice daily based on area under the curve (AUC) resulted in adverse developmental outcomes including external malformations. No adverse developmental effects were observed with oral administration of remibrutinib to pregnant rats during organogenesis at exposures up to 126-times the human exposure at the MRHD(see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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
In an embryo-fetal development (EFD) study in pregnant rabbits, remibrutinib was administered orally at doses of 100, 300, and 450 mg/kg/day during the period of organogenesis. Increased fetal external malformations (e.g. open/opaque eyes, small jaws, hyperflexion of forelimbs) and maternal toxicity (transiently reduced food consumption and adverse clinical signs) occurred at 300 mg/kg/day (141-times the MRHD based on AUC). The fetal findings were considered unlikely to be secondary to the maternal toxicity. The dose of 450 mg/kg/day was not tolerated by the pregnant rabbits.
In an EFD study in pregnant rats, remibrutinib was administered orally at doses of 100, 300, and 1000 mg/kg/day during the period of organogenesis. Remibrutinib did not cause adverse effects to the fetus at exposures up to 126 times that at the MRHD based on AUC.
In a pre- and postnatal development (PPND) study, remibrutinib was administered orally to pregnant rats at doses of 100, 300, and 1000 mg/kg/day from gestation day 6 to lactation day (LD) 21. Remibrutinib induced adverse effects at 1000 mg/kg/day (approximately 194 times the MRHD based on body surface area [BSA]), affected maternal animals (moribundity and clinical signs of toxicity, slightly longer gestation lengths) and offspring up to LD1 (slightly higher mean number of stillborn, dead, or missing pups, and smaller mean litter size). No adverse effects at doses up to 1000 mg/kg/day were noted in the surviving offspring developing into adulthood. No effects were observed at 300 mg/kg/day (approximately 58 times the MRHD based on BSA).
Lactation
Risk Summary
No data are available regarding the presence of remibrutinib in either human or animal milk, its effects on the breastfed child, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RHAPSIDO and any potential adverse effects on the breastfed child from RHAPSIDO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of RHAPSIDO have not been established in pediatric patients.
Geriatric Use
Of the total number of patients treated with RHAPSIDO in clinical studies for CSU, 53 (8.7%) were 65 to 85 years of age, with no patients over 85 years of age[see Clinical Studies (14)]. There were no observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.
Hepatic Impairment
RHAPSIDO exposure is increased in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C) relative to patients with normal hepatic function. Avoid use of RHAPSIDO in patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B, and C)[see Clinical Pharmacology (12.3)].
Lactation
Breastfeeding
What You Need to Know
We don’t know if RHAPSIDO passes into breast milk or if it affects breastfed babies. We also don’t know if it affects milk production.
Talk to your doctor about whether to breastfeed while taking RHAPSIDO. Think about:
– The benefits of breastfeeding for your baby
– How much you need this medicine
– Possible effects on your baby from RHAPSIDO or your health condition
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RHAPSIDO during pregnancy. Pregnant women exposed to RHAPSIDO and healthcare providers are encouraged to contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.
Risk Summary
Available data on the use of RHAPSIDO during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of remibrutinib to pregnant rabbits during organogenesis at exposures 141-times the human exposure at the maximum recommended human dose (MRHD) of 25 mg twice daily based on area under the curve (AUC) resulted in adverse developmental outcomes including external malformations. No adverse developmental effects were observed with oral administration of remibrutinib to pregnant rats during organogenesis at exposures up to 126-times the human exposure at the MRHD(see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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
In an embryo-fetal development (EFD) study in pregnant rabbits, remibrutinib was administered orally at doses of 100, 300, and 450 mg/kg/day during the period of organogenesis. Increased fetal external malformations (e.g. open/opaque eyes, small jaws, hyperflexion of forelimbs) and maternal toxicity (transiently reduced food consumption and adverse clinical signs) occurred at 300 mg/kg/day (141-times the MRHD based on AUC). The fetal findings were considered unlikely to be secondary to the maternal toxicity. The dose of 450 mg/kg/day was not tolerated by the pregnant rabbits.
In an EFD study in pregnant rats, remibrutinib was administered orally at doses of 100, 300, and 1000 mg/kg/day during the period of organogenesis. Remibrutinib did not cause adverse effects to the fetus at exposures up to 126 times that at the MRHD based on AUC.
In a pre- and postnatal development (PPND) study, remibrutinib was administered orally to pregnant rats at doses of 100, 300, and 1000 mg/kg/day from gestation day 6 to lactation day (LD) 21. Remibrutinib induced adverse effects at 1000 mg/kg/day (approximately 194 times the MRHD based on body surface area [BSA]), affected maternal animals (moribundity and clinical signs of toxicity, slightly longer gestation lengths) and offspring up to LD1 (slightly higher mean number of stillborn, dead, or missing pups, and smaller mean litter size). No adverse effects at doses up to 1000 mg/kg/day were noted in the surviving offspring developing into adulthood. No effects were observed at 300 mg/kg/day (approximately 58 times the MRHD based on BSA).
Lactation
Risk Summary
No data are available regarding the presence of remibrutinib in either human or animal milk, its effects on the breastfed child, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RHAPSIDO and any potential adverse effects on the breastfed child from RHAPSIDO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of RHAPSIDO have not been established in pediatric patients.
Geriatric Use
Of the total number of patients treated with RHAPSIDO in clinical studies for CSU, 53 (8.7%) were 65 to 85 years of age, with no patients over 85 years of age[see Clinical Studies (14)]. There were no observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.
Hepatic Impairment
RHAPSIDO exposure is increased in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C) relative to patients with normal hepatic function. Avoid use of RHAPSIDO in patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B, and C)[see Clinical Pharmacology (12.3)].
Pediatric Use
Pregnancy
Pregnancy Exposure Registry
There is a registry that tracks pregnancy outcomes in women who take RHAPSIDO during pregnancy. If you are pregnant and taking RHAPSIDO, you and your doctor can call Novartis at 1-888-669-6682.
Risk Summary
We don’t have enough information about using RHAPSIDO during pregnancy to know if it causes birth defects, miscarriage, or other problems for the mother or baby.
In animal studies, pregnant rabbits given remibrutinib at doses 141 times higher than the recommended human dose had babies with birth defects like eye problems, small jaws, and bent front legs. Pregnant rats given remibrutinib at doses up to 126 times the recommended human dose did not have these problems.
We don’t know the risk of birth defects and miscarriage for people who need this medicine. All pregnancies have some risk. In the U.S., about 2% to 4% of babies are born with major birth defects and about 15% to 20% of known pregnancies end in miscarriage.
Data
Animal Data
In pregnant rabbits, remibrutinib caused birth defects (open/cloudy eyes, small jaws, bent front legs) at 141 times the recommended human dose. The mother rabbits also had some side effects like eating less. The highest dose tested was too strong for the rabbits.
In pregnant rats, remibrutinib at doses up to 126 times the recommended human dose did not cause problems for the babies.
In another rat study, remibrutinib was given from pregnancy through nursing. At very high doses (194 times the recommended human dose), some mother rats got sick and had longer pregnancies. Some babies were stillborn or died, and litters were smaller. The babies that survived grew up normally. At lower doses (58 times the recommended human dose), there were no problems.
Lactation
Risk Summary
We don’t know if remibrutinib gets into breast milk or if it affects a breastfed baby or milk production. Talk with your doctor about the benefits of breastfeeding and your need for RHAPSIDO, along with any possible risks to your baby.
Pediatric Use
RHAPSIDO has not been studied in children. We don’t know if it is safe or works in children.
Geriatric Use
In studies, 53 patients (8.7%) were 65 to 85 years old. No patients were over 85 years old. Older patients had similar safety and results as younger adults.
Hepatic Impairment
People with mild, moderate, or severe liver problems have higher levels of RHAPSIDO in their body than people with normal liver function. Do not use RHAPSIDO if you have any level of liver problems.
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RHAPSIDO during pregnancy. Pregnant women exposed to RHAPSIDO and healthcare providers are encouraged to contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.
Risk Summary
Available data on the use of RHAPSIDO during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of remibrutinib to pregnant rabbits during organogenesis at exposures 141-times the human exposure at the maximum recommended human dose (MRHD) of 25 mg twice daily based on area under the curve (AUC) resulted in adverse developmental outcomes including external malformations. No adverse developmental effects were observed with oral administration of remibrutinib to pregnant rats during organogenesis at exposures up to 126-times the human exposure at the MRHD(see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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
In an embryo-fetal development (EFD) study in pregnant rabbits, remibrutinib was administered orally at doses of 100, 300, and 450 mg/kg/day during the period of organogenesis. Increased fetal external malformations (e.g. open/opaque eyes, small jaws, hyperflexion of forelimbs) and maternal toxicity (transiently reduced food consumption and adverse clinical signs) occurred at 300 mg/kg/day (141-times the MRHD based on AUC). The fetal findings were considered unlikely to be secondary to the maternal toxicity. The dose of 450 mg/kg/day was not tolerated by the pregnant rabbits.
In an EFD study in pregnant rats, remibrutinib was administered orally at doses of 100, 300, and 1000 mg/kg/day during the period of organogenesis. Remibrutinib did not cause adverse effects to the fetus at exposures up to 126 times that at the MRHD based on AUC.
In a pre- and postnatal development (PPND) study, remibrutinib was administered orally to pregnant rats at doses of 100, 300, and 1000 mg/kg/day from gestation day 6 to lactation day (LD) 21. Remibrutinib induced adverse effects at 1000 mg/kg/day (approximately 194 times the MRHD based on body surface area [BSA]), affected maternal animals (moribundity and clinical signs of toxicity, slightly longer gestation lengths) and offspring up to LD1 (slightly higher mean number of stillborn, dead, or missing pups, and smaller mean litter size). No adverse effects at doses up to 1000 mg/kg/day were noted in the surviving offspring developing into adulthood. No effects were observed at 300 mg/kg/day (approximately 58 times the MRHD based on BSA).
Lactation
Risk Summary
No data are available regarding the presence of remibrutinib in either human or animal milk, its effects on the breastfed child, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RHAPSIDO and any potential adverse effects on the breastfed child from RHAPSIDO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of RHAPSIDO have not been established in pediatric patients.
Geriatric Use
Of the total number of patients treated with RHAPSIDO in clinical studies for CSU, 53 (8.7%) were 65 to 85 years of age, with no patients over 85 years of age[see Clinical Studies (14)]. There were no observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.
Hepatic Impairment
RHAPSIDO exposure is increased in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C) relative to patients with normal hepatic function. Avoid use of RHAPSIDO in patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B, and C)[see Clinical Pharmacology (12.3)].
Geriatric Use
Pregnancy
Pregnancy Exposure Registry
There is a registry that tracks pregnancy outcomes in women who take RHAPSIDO during pregnancy. If you are pregnant and taking RHAPSIDO, you and your doctor can call Novartis at 1-888-669-6682.
Risk Summary
There is not enough information about using RHAPSIDO during pregnancy to know if it causes birth defects, miscarriage, or other problems for the mother or baby.
In animal studies, pregnant rabbits given remibrutinib at doses 141 times higher than the recommended human dose had babies with birth defects like open eyes, small jaws, and bent front legs. Pregnant rats given remibrutinib at doses up to 126 times higher than the recommended human dose did not have babies with birth defects.
We don’t know the background risk of birth defects and miscarriage for people who need this medicine. All pregnancies have some risk. In the U.S. general population, about 2% to 4% of babies are born with major birth defects and about 15% to 20% of known pregnancies end in miscarriage.
Data
Animal Data
In pregnant rabbits, remibrutinib caused birth defects at 141 times the recommended human dose. The mother rabbits also had some side effects like eating less food.
In pregnant rats, remibrutinib did not cause birth defects at doses up to 126 times the recommended human dose.
In another rat study, pregnant rats were given remibrutinib from pregnancy through nursing. At very high doses (194 times the recommended human dose), some mother rats had problems and some babies were stillborn or died. The babies that survived grew normally into adulthood. At lower doses (58 times the recommended human dose), no problems were seen.
Breastfeeding
Risk Summary
We don’t know if RHAPSIDO gets into breast milk or if it affects a breastfed baby. Talk with your doctor about the benefits of breastfeeding and your need for RHAPSIDO. Consider any possible effects on your baby.
Children
The safety and effectiveness of RHAPSIDO have not been studied in children.
Older Adults
In clinical studies, 53 patients (8.7%) were 65 to 85 years old. No patients were over 85 years old. Older patients did not have different side effects or results compared to younger adults.
Liver Problems
RHAPSIDO levels in the body are higher in patients with mild, moderate, or severe liver problems. Do not use RHAPSIDO if you have any level of liver problems.
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RHAPSIDO during pregnancy. Pregnant women exposed to RHAPSIDO and healthcare providers are encouraged to contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.
Risk Summary
Available data on the use of RHAPSIDO during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of remibrutinib to pregnant rabbits during organogenesis at exposures 141-times the human exposure at the maximum recommended human dose (MRHD) of 25 mg twice daily based on area under the curve (AUC) resulted in adverse developmental outcomes including external malformations. No adverse developmental effects were observed with oral administration of remibrutinib to pregnant rats during organogenesis at exposures up to 126-times the human exposure at the MRHD(see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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
In an embryo-fetal development (EFD) study in pregnant rabbits, remibrutinib was administered orally at doses of 100, 300, and 450 mg/kg/day during the period of organogenesis. Increased fetal external malformations (e.g. open/opaque eyes, small jaws, hyperflexion of forelimbs) and maternal toxicity (transiently reduced food consumption and adverse clinical signs) occurred at 300 mg/kg/day (141-times the MRHD based on AUC). The fetal findings were considered unlikely to be secondary to the maternal toxicity. The dose of 450 mg/kg/day was not tolerated by the pregnant rabbits.
In an EFD study in pregnant rats, remibrutinib was administered orally at doses of 100, 300, and 1000 mg/kg/day during the period of organogenesis. Remibrutinib did not cause adverse effects to the fetus at exposures up to 126 times that at the MRHD based on AUC.
In a pre- and postnatal development (PPND) study, remibrutinib was administered orally to pregnant rats at doses of 100, 300, and 1000 mg/kg/day from gestation day 6 to lactation day (LD) 21. Remibrutinib induced adverse effects at 1000 mg/kg/day (approximately 194 times the MRHD based on body surface area [BSA]), affected maternal animals (moribundity and clinical signs of toxicity, slightly longer gestation lengths) and offspring up to LD1 (slightly higher mean number of stillborn, dead, or missing pups, and smaller mean litter size). No adverse effects at doses up to 1000 mg/kg/day were noted in the surviving offspring developing into adulthood. No effects were observed at 300 mg/kg/day (approximately 58 times the MRHD based on BSA).
Lactation
Risk Summary
No data are available regarding the presence of remibrutinib in either human or animal milk, its effects on the breastfed child, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RHAPSIDO and any potential adverse effects on the breastfed child from RHAPSIDO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of RHAPSIDO have not been established in pediatric patients.
Geriatric Use
Of the total number of patients treated with RHAPSIDO in clinical studies for CSU, 53 (8.7%) were 65 to 85 years of age, with no patients over 85 years of age[see Clinical Studies (14)]. There were no observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.
Hepatic Impairment
RHAPSIDO exposure is increased in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C) relative to patients with normal hepatic function. Avoid use of RHAPSIDO in patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B, and C)[see Clinical Pharmacology (12.3)].
Hepatic Impairment
Pregnancy
Pregnancy Registry
There is a registry that tracks pregnancy outcomes in women who take RHAPSIDO during pregnancy. If you are pregnant and taking RHAPSIDO, you and your doctor can call Novartis at 1-888-669-6682.
What You Should Know
There is not enough information about using RHAPSIDO during pregnancy to know if it causes birth defects, miscarriage, or other problems for the mother or baby.
In animal studies, pregnant rabbits given remibrutinib at doses 141 times higher than the recommended human dose had babies with birth defects including eye problems, small jaws, and bent front legs. Pregnant rats given remibrutinib at doses up to 126 times the recommended human dose did not have babies with birth defects.
We don’t know the background risk of birth defects and miscarriage for people who need this medicine. All pregnancies have some risk. In the U.S. general population, about 2% to 4% of babies are born with major birth defects and about 15% to 20% of known pregnancies end in miscarriage.
Animal Study Details
In pregnant rabbits, remibrutinib was given at doses of 100, 300, and 450 mg/kg/day during the time when organs form. At 300 mg/kg/day (141 times the recommended human dose), baby rabbits had birth defects like open or cloudy eyes, small jaws, and bent front legs. Mother rabbits also had side effects like eating less and other health problems. The birth defects were likely not caused by the mother’s health problems. The 450 mg/kg/day dose was too high for pregnant rabbits to handle.
In pregnant rats, remibrutinib was given at doses of 100, 300, and 1000 mg/kg/day during the time when organs form. Remibrutinib did not cause problems for baby rats at doses up to 126 times the recommended human dose.
In another study, pregnant rats were given remibrutinib at doses of 100, 300, and 1000 mg/kg/day from day 6 of pregnancy through day 21 after birth. At 1000 mg/kg/day (about 194 times the recommended human dose), mother rats had serious side effects and took longer to give birth. Some baby rats were stillborn, died, or went missing, and litter sizes were smaller. Baby rats that survived grew normally into adulthood. At 300 mg/kg/day (about 58 times the recommended human dose), there were no problems.
Breastfeeding
What You Should Know
We don’t know if remibrutinib passes into breast milk or if it affects a breastfed baby or milk production. Talk with your doctor about the benefits of breastfeeding and your need for RHAPSIDO. Consider any possible effects on your baby from RHAPSIDO or from your health condition.
Children
The safety and effectiveness of RHAPSIDO have not been studied in children.
Older Adults
Of all patients treated with RHAPSIDO in studies, 53 patients (8.7%) were 65 to 85 years old. No patients were over 85 years old. Older patients did not have different side effects or results compared to younger adults.
Liver Problems
RHAPSIDO levels in the body are higher in patients with mild, moderate, or severe liver problems (Child-Pugh Class A, B, and C) compared to patients with normal liver function. Do not use RHAPSIDO if you have any level of liver problems (Child-Pugh Class A, B, or C).
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RHAPSIDO during pregnancy. Pregnant women exposed to RHAPSIDO and healthcare providers are encouraged to contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.
Risk Summary
Available data on the use of RHAPSIDO during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of remibrutinib to pregnant rabbits during organogenesis at exposures 141-times the human exposure at the maximum recommended human dose (MRHD) of 25 mg twice daily based on area under the curve (AUC) resulted in adverse developmental outcomes including external malformations. No adverse developmental effects were observed with oral administration of remibrutinib to pregnant rats during organogenesis at exposures up to 126-times the human exposure at the MRHD(see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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
In an embryo-fetal development (EFD) study in pregnant rabbits, remibrutinib was administered orally at doses of 100, 300, and 450 mg/kg/day during the period of organogenesis. Increased fetal external malformations (e.g. open/opaque eyes, small jaws, hyperflexion of forelimbs) and maternal toxicity (transiently reduced food consumption and adverse clinical signs) occurred at 300 mg/kg/day (141-times the MRHD based on AUC). The fetal findings were considered unlikely to be secondary to the maternal toxicity. The dose of 450 mg/kg/day was not tolerated by the pregnant rabbits.
In an EFD study in pregnant rats, remibrutinib was administered orally at doses of 100, 300, and 1000 mg/kg/day during the period of organogenesis. Remibrutinib did not cause adverse effects to the fetus at exposures up to 126 times that at the MRHD based on AUC.
In a pre- and postnatal development (PPND) study, remibrutinib was administered orally to pregnant rats at doses of 100, 300, and 1000 mg/kg/day from gestation day 6 to lactation day (LD) 21. Remibrutinib induced adverse effects at 1000 mg/kg/day (approximately 194 times the MRHD based on body surface area [BSA]), affected maternal animals (moribundity and clinical signs of toxicity, slightly longer gestation lengths) and offspring up to LD1 (slightly higher mean number of stillborn, dead, or missing pups, and smaller mean litter size). No adverse effects at doses up to 1000 mg/kg/day were noted in the surviving offspring developing into adulthood. No effects were observed at 300 mg/kg/day (approximately 58 times the MRHD based on BSA).
Lactation
Risk Summary
No data are available regarding the presence of remibrutinib in either human or animal milk, its effects on the breastfed child, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RHAPSIDO and any potential adverse effects on the breastfed child from RHAPSIDO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of RHAPSIDO have not been established in pediatric patients.
Geriatric Use
Of the total number of patients treated with RHAPSIDO in clinical studies for CSU, 53 (8.7%) were 65 to 85 years of age, with no patients over 85 years of age[see Clinical Studies (14)]. There were no observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.
Hepatic Impairment
RHAPSIDO exposure is increased in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C) relative to patients with normal hepatic function. Avoid use of RHAPSIDO in patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B, and C)[see Clinical Pharmacology (12.3)].
Renal Impairment
Pregnancy
Pregnancy Registry
There is a registry that tracks pregnancy outcomes in women who take RHAPSIDO during pregnancy. If you are pregnant and taking RHAPSIDO, you and your doctor can call Novartis at 1-888-669-6682.
Risk Summary
There is not enough information about using RHAPSIDO during pregnancy to know if it causes birth defects, miscarriage, or other problems for the mother or baby.
In animal studies, pregnant rabbits given remibrutinib during pregnancy at doses 141 times higher than the recommended human dose had babies with birth defects including eye problems, small jaws, and bent front legs. Pregnant rats given remibrutinib at doses up to 126 times higher than the recommended human dose did not have babies with birth defects.
We don’t know the background risk of birth defects and miscarriage for people who need this medicine. All pregnancies have some risk of birth defects, loss, or other problems. In the U.S. general population, about 2% to 4% of babies are born with major birth defects and about 15% to 20% of known pregnancies end in miscarriage.
Data
Animal Data
In a study with pregnant rabbits, remibrutinib was given by mouth at doses of 100, 300, and 450 mg/kg/day during early pregnancy. At 300 mg/kg/day (141 times the recommended human dose), baby rabbits had birth defects like open/cloudy eyes, small jaws, and bent front legs. Mother rabbits also had problems like eating less food and other side effects. The problems in baby rabbits were not thought to be caused by the mother’s side effects. The dose of 450 mg/kg/day was too high for the pregnant rabbits.
In a study with pregnant rats, remibrutinib was given by mouth at doses of 100, 300, and 1000 mg/kg/day during early pregnancy. Remibrutinib did not cause problems in baby rats at doses up to 126 times the recommended human dose.
In another study, remibrutinib was given by mouth to pregnant rats at doses of 100, 300, and 1000 mg/kg/day from day 6 of pregnancy through day 21 after birth. At 1000 mg/kg/day (about 194 times the recommended human dose), there were problems in mother rats (severe illness and side effects, slightly longer pregnancies) and baby rats up to day 1 after birth (more stillborn, dead, or missing pups, and smaller litters). The surviving baby rats that grew into adults had no problems. No problems were seen at 300 mg/kg/day (about 58 times the recommended human dose).
Breastfeeding
Risk Summary
We don’t know if remibrutinib passes into breast milk or if it affects a breastfed baby or milk production. Talk with your doctor about the benefits of breastfeeding and your need for RHAPSIDO. Also consider any possible effects on your baby from RHAPSIDO or from your condition.
Children
The safety and effectiveness of RHAPSIDO have not been studied in children.
Older Adults
Of all patients treated with RHAPSIDO in studies, 53 patients (8.7%) were 65 to 85 years old. No patients were over 85 years old. There were no differences in safety or how well it worked in older patients compared to younger adults.
Liver Problems
RHAPSIDO levels in the body are higher in patients with mild, moderate, or severe liver problems (Child-Pugh Class A, B, and C) compared to patients with normal liver function. Do not use RHAPSIDO if you have mild, moderate, or severe liver problems (Child-Pugh Class A, B, and C).
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RHAPSIDO during pregnancy. Pregnant women exposed to RHAPSIDO and healthcare providers are encouraged to contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.
Risk Summary
Available data on the use of RHAPSIDO during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of remibrutinib to pregnant rabbits during organogenesis at exposures 141-times the human exposure at the maximum recommended human dose (MRHD) of 25 mg twice daily based on area under the curve (AUC) resulted in adverse developmental outcomes including external malformations. No adverse developmental effects were observed with oral administration of remibrutinib to pregnant rats during organogenesis at exposures up to 126-times the human exposure at the MRHD(see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or 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
In an embryo-fetal development (EFD) study in pregnant rabbits, remibrutinib was administered orally at doses of 100, 300, and 450 mg/kg/day during the period of organogenesis. Increased fetal external malformations (e.g. open/opaque eyes, small jaws, hyperflexion of forelimbs) and maternal toxicity (transiently reduced food consumption and adverse clinical signs) occurred at 300 mg/kg/day (141-times the MRHD based on AUC). The fetal findings were considered unlikely to be secondary to the maternal toxicity. The dose of 450 mg/kg/day was not tolerated by the pregnant rabbits.
In an EFD study in pregnant rats, remibrutinib was administered orally at doses of 100, 300, and 1000 mg/kg/day during the period of organogenesis. Remibrutinib did not cause adverse effects to the fetus at exposures up to 126 times that at the MRHD based on AUC.
In a pre- and postnatal development (PPND) study, remibrutinib was administered orally to pregnant rats at doses of 100, 300, and 1000 mg/kg/day from gestation day 6 to lactation day (LD) 21. Remibrutinib induced adverse effects at 1000 mg/kg/day (approximately 194 times the MRHD based on body surface area [BSA]), affected maternal animals (moribundity and clinical signs of toxicity, slightly longer gestation lengths) and offspring up to LD1 (slightly higher mean number of stillborn, dead, or missing pups, and smaller mean litter size). No adverse effects at doses up to 1000 mg/kg/day were noted in the surviving offspring developing into adulthood. No effects were observed at 300 mg/kg/day (approximately 58 times the MRHD based on BSA).
Lactation
Risk Summary
No data are available regarding the presence of remibrutinib in either human or animal milk, its effects on the breastfed child, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RHAPSIDO and any potential adverse effects on the breastfed child from RHAPSIDO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of RHAPSIDO have not been established in pediatric patients.
Geriatric Use
Of the total number of patients treated with RHAPSIDO in clinical studies for CSU, 53 (8.7%) were 65 to 85 years of age, with no patients over 85 years of age[see Clinical Studies (14)]. There were no observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.
Hepatic Impairment
RHAPSIDO exposure is increased in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C) relative to patients with normal hepatic function. Avoid use of RHAPSIDO in patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B, and C)[see Clinical Pharmacology (12.3)].
Description
RHAPSIDO (remibrutinib) is a type of medicine called a kinase inhibitor.
Remibrutinib is a white to pale yellow powder that does not dissolve in water.
RHAPSIDO comes as coated tablets that you swallow. Each tablet contains 25 mg of remibrutinib. The tablets also contain other ingredients that help form the tablet and its coating.
RHAPSIDO (remibrutinib) is a kinase inhibitor.
Its empirical formula (remibrutinib) is C27H27F2N5O3. The chemical name for remibrutinib is N-(3-{6-Amino-5-[2-(N-methylprop-2-enamido)ethoxy]pyrimidin-4-yl}-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide. Its molecular weight is approximately 507.54 g/mol. The chemical structure of remibrutinib is:
Remibrutinib is white to pale yellow powder, and it is practically insoluble in water.
RHAPSIDO is supplied as film-coated tablets for oral administration, with each film-coated tablet containing 25 mg of remibrutinib. The tablet core inactive ingredients are copovidone, croscarmellose sodium, mannitol, microcrystalline cellulose, sodium lauryl sulfate, and sodium stearyl fumarate. The tablet coating inactive ingredients are polyethylene glycol 4000, polyvinyl alcohol, red iron oxide (E172), talc, titanium dioxide (E171), and yellow iron oxide (E172).
Mechanism of Action
How This Medicine Works
Remibrutinib is a pill that blocks a protein called BTK. BTK is found in certain immune cells in your body. These cells can cause allergic reactions and release substances like histamine that make you itch and break out in hives. By blocking BTK, remibrutinib helps stop these allergic reactions.
How Well It Works
Studies showed that remibrutinib worked about the same at different doses (from 0.2 to 4 times the recommended dose) when measuring hive symptoms after 4 weeks.
Effects on Heart Rhythm
At levels much higher than the recommended dose (about 9 times higher), remibrutinib did not cause dangerous changes in heart rhythm.
Effects on Blood Pressure
A study measured blood pressure in 144 people with chronic hives taking remibrutinib 25 mg twice daily. The medicine did not cause significant changes in blood pressure.
How the Body Processes This Medicine
When you take remibrutinib 25 mg twice daily, the average highest level in your blood is 57 ng/mL. The medicine reaches its highest level in your blood about 1 hour after you take it.
Food Effects
Taking remibrutinib with a high-fat meal does not significantly change how the medicine works.
How the Medicine Spreads in Your Body
About 95% of remibrutinib attaches to proteins in your blood. The medicine spreads throughout your body.
How the Body Removes the Medicine
Remibrutinib stays in your body for 1 to 2 hours before being removed. Your liver breaks down the medicine using an enzyme called CYP3A4. After that, 70% leaves your body in stool and 30% in urine.
Different Groups of People
The medicine works similarly in people of different ages (18 to 80 years), sex, race, and body weight (39 to 162 kg). It also works similarly in people with mild, moderate, or severe kidney problems.
People with Liver Problems
In people with liver problems, remibrutinib levels in the blood are higher:
– Mild liver problems: 2.3 times higher
– Moderate liver problems: 2.3 times higher
– Severe liver problems: 3.5 times higher
Interactions with Other Medicines
Strong CYP3A4 Blockers: Taking remibrutinib with ritonavir (a strong blocker) increased remibrutinib levels by 4.3 times. Grapefruit juice increased levels by 1.3 times.
Moderate CYP3A4 Blockers: Taking remibrutinib with erythromycin is expected to increase remibrutinib levels by about 2.3 times.
Strong CYP3A4 Reducers: Taking remibrutinib with carbamazepine decreased remibrutinib levels by 77%.
Moderate CYP3A4 Reducers: Taking remibrutinib with efavirenz is expected to decrease remibrutinib levels by about 64%.
Other Medicines: Remibrutinib can increase levels of digoxin (by 1.4 times) and rosuvastatin (by 1.7 times).
Remibrutinib did not significantly change levels of midazolam, birth control pills (ethinyl estradiol and levonorgestrel), tolbutamide, or caffeine.
Mechanism of Action
Remibrutinib is an oral, small molecule kinase inhibitor that inhibits Bruton’s tyrosine kinase (BTK). BTK is an intracellular protein expressed in mast cells, basophils, B cells, macrophages, and thrombocytes. BTK is involved in intracellular signaling via Fc epsilon receptor-1 (FcεR1), Fc gamma receptors (FcγR), and the B cell antigen receptor (BCR). Remibrutinib also inhibits the BTK-related kinases tec protein tyrosine kinase (TEC) and BMX non-receptor tyrosine kinase (BMX).
Remibrutinib inhibits mast cell and basophil degranulation, including release of histamine and other proinflammatory mediators, mediated by pathogenic IgE or IgG directed against the FcεR1 or IgE.
Pharmacodynamics
Exposure-Response
Within the range from 0.2 to 4 times the daily recommended dose, a flat dose-response relationship was observed for the weekly urticaria activity score (UAS7) at Week 4.
Cardiac Electrophysiology
At concentrations approximately 9 times the mean steady state peak plasma concentrations provided by the recommended dose, clinically significant QTc prolongation was not observed.
Effects on Blood Pressure
The effect of remibrutinib treatment on blood pressure was assessed in CSU patients using a 24-hour blood pressure measurement by ambulatory blood pressure monitoring (ABPM) at steady state (Week 4) compared to baseline in a multi-center, open-label study (A2305). The study enrolled 144 patients with CSU inadequately controlled by H1 antihistamines, who were administered remibrutinib 25 mg twice daily. Remibrutinib 25 mg twice daily was not associated with clinically significant changes in blood pressure.
Pharmacokinetics
No clinically significant differences in remibrutinib pharmacokinetics were observed between healthy subjects and patients with CSU.
Absorption
Remibrutinib median (min, max) time to maximum plasma concentration (Tmax) is 1 hour (0, 4 hours) at steady state.
Effect of food
No clinically significant differences in remibrutinib pharmacokinetics were observed following administration of a high-fat meal (1000 calories, 50% fat).
Distribution
Remibrutinib blood-to-plasma ratio is 0.813 in vitro. Plasma protein binding is 95.4% and is not concentration-dependent in vitro. The estimated remibrutinib steady state apparent (oral) volume of distribution is 1238 L.
Elimination
Remibrutinib estimated elimination half-life is 1 to 2 hours with an apparent (oral) clearance of 160 L/hr.
Metabolism
Remibrutinib is primarily metabolized by CYP3A4.
Excretion
Following IV administration of14C remibrutinib to healthy subjects, 70% of the total radioactivity was recovered in feces (0% as unchanged remibrutinib), and 30% was recovered in urine (2.9% as unchanged remibrutinib).
Specific Populations
No clinically significant differences in the pharmacokinetics of remibrutinib were observed based on age (range: 18 to 80 years), sex (63.5% females and 36.5% males), race/ethnicity (59.3% Non-Asian [White, Black, and Others], 8.8% Mainland Chinese, 12.2% Japanese, and 19.7% other Asian), body weight (range: 39 to 162 kg), and mild (eGFR 60-89 mL/min/1.73 m2, estimated by Cockcroft-Gault), moderate (eGFR 30-59 mL/min/1.73 m2) or severe (eGFR 15-29 mL/min/1.73 m2) renal impairment.
Patients with Hepatic Impairment
The pharmacokinetics of remibrutinib were evaluated in subjects with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), and severe (Child-Pugh Class C) hepatic impairment following administration of 25 mg twice daily. Relative to patients with normal hepatic function, remibrutinib AUC increased 2.33-fold and Cmaxincreased 1.85-fold in patients with mild hepatic impairment, AUC increased 2.3-fold and Cmaxincreased 1.65-fold in patients with moderate hepatic impairment, and AUC increased 3.49-fold and Cmaxincreased 1.99-fold in patients with severe hepatic impairment[see Use in Special Populations (8.6)].
Drug Interaction Studies
Clinical Studies and Model-Informed Approaches
Strong CYP3A4 Inhibitors:Remibrutinib Cmaxincreased by 3.3-fold and AUC increased by 4.3-fold following concomitant administration with ritonavir (a strong CYP3A4 inhibitor) 100 mg twice daily for 4 days[see Drug Interactions (7.1)].
Remibrutinib Cmaxincreased by 1.24-fold and AUC increased by 1.3-fold when co-administered with grapefruit juice.
Moderate CYP3A4 Inhibitors:Remibrutinib Cmaxis predicted to increase by approximately 1.9-fold and AUC is predicted to increase by approximately 2.3-fold following concomitant administration with erythromycin (a moderate CYP3A4 inhibitor) 500 mg four times a day for 7 days[see Drug Interactions (7.1)].
Strong CYP3A4 Inducers:Remibrutinib Cmaxdecreased by 74% and AUC decreased by approximately 77% following concomitant administration with carbamazepine (a strong CYP3A4 inducer) 300 mg twice daily for 14 days[see Drug Interactions (7.1)].
Moderate CYP3A4 Inducers:Remibrutinib Cmaxis predicted to decrease by approximately 60% and AUC is predicted to decrease by approximately 64% following concomitant administration with efavirenz (a moderate CYP3A4 inducer) 600 mg once daily for 14 days[see Drug Interactions (7.1)].
P-gp Substrates:Co-administration of remibrutinib at four times the recommended dosage with a single dose of 0.25 mg digoxin (a P-gp substrate) increased digoxin Cmaxby 2.1-fold and AUC by 1.4-fold[see Drug Interactions (7.1)].
BCRP Substrates:Co-administration of remibrutinib at four times the recommended dosage with a single dose of 10 mg rosuvastatin (a BCRP and OATP1B substrate) increased rosuvastatin Cmaxby 1.6-fold and AUC by 1.7-fold.
Other Drugs:No clinically significant differences in the pharmacokinetics of the following drugs were observed when used concomitantly with remibrutinib: oral midazolam (CYP3A4 substrate), oral contraceptives containing ethinyl estradiol and levonorgestrel (CYP3A4 substrate), tolbutamide (CYP2C9 substrate), caffeine (CYP1A2 substrate), and coproporphyrin I (an endogenous OATP1B substrate).
In Vitro Studies
CYP450 Enzymes:Remibrutinib is a CYP3A4 substrate. Remibrutinib inhibits CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5. Remibrutinib induces CYP1A2, CYP2B6, CYP2C9 and CYP3A4/5.
Transporter Systems:In vitro, remibrutinib is a P-gp substrate. Remibrutinib inhibits P-gp, BCRP, BSEP, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2 and MATE1.
Patient Counseling Information
Read the Patient Information sheet that comes with RHAPSIDO.
How to Take RHAPSIDO:
Take RHAPSIDO with or without food. Swallow the tablet whole with water. Do not split, crush, or chew the tablet.
Bleeding Risk:
RHAPSIDO can cause bleeding. Tell your doctor if you notice any signs of bleeding. Stop taking RHAPSIDO 3 to 7 days before any surgery. Tell your doctor if you take blood thinners because this can increase your risk of bleeding.
Vaccines:
Tell your doctor you are taking RHAPSIDO before getting any vaccines. Do not get live vaccines while taking RHAPSIDO.
Pregnancy:
There is a pregnancy registry for women who take RHAPSIDO during pregnancy.
Distributed by: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, New Jersey 07936
© Novartis
T2025-55
Advise patients to read the FDA-approved patient labeling (Patient Information).
Administration Instructions:
Inform patients to take RHAPSIDO with or without food. Advise patients not to split, crush, or chew the tablet and to swallow the tablet whole with water[see Dosage and Administration (2.1)].
Risk of Bleeding:
Inform patients that bleeding can occur with the use of RHAPSIDO, and to report any signs and symptoms to their healthcare practitioner. Inform patients that RHAPSIDO should be interrupted for 3 to 7 days for any surgical procedures. Instruct patients to inform their healthcare practitioner if they use RHAPSIDO with antithrombotic agents due to the potential increased risk of bleeding[see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
Live Attenuated Vaccines:
Instruct patients to inform the healthcare practitioner that they are taking RHAPSIDO prior to any potential vaccinations. Advise patients that the vaccines containing live virus (live and live-attenuated) should not be given during treatment with RHAPSIDO[see Warnings and Precautions (5.2)].
Pregnancy:
Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to RHAPSIDO during pregnancy[see Use in Specific Populations (8.1)].
© Novartis
T2025-55
Related Medications
Treats These Conditions
References
Label:RHAPSIDO- remibrutinib tablet (remibrutinib) [prescribing information]. March 2026. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e5e89bff-6ced-4165-acc5-fb13136b3a3d
Accessed: March 27, 2026