INDICATION
XROMI® is indicated to reduce the frequency of painful crises and reduce the need for blood transfusions in pediatric patients 6 months of age and older with sickle cell anemia with recurrent moderate to severe painful crises.
CLINICAL/SAFETY
XROMI is effective and easy to take1,2
PK similarities
- Using a PK model, systemic hydroxyurea exposure seen with XROMI is comparable to values of capsules, tablets, and compounded liquids seen in a published study1,a
- The PK of hydroxyurea is similar between children (6 months to 18 years) and adults2
aValues used in Dong M, et al. Br J Clin Pharmacol. 2016;81:742–752.
Secondary end point outcomes1
|
|
6 months to |
2 to <6 years |
6 to <18 years |
Overall |
|
Number of hospitalizations (mean [SD]) |
||||
|
Prior to treatment |
0.3 (0.82) |
2.0 (1.59) |
1.9 (1.45) |
1.7 (1.54) |
|
After treatment |
0.3 (0.82) |
0.3 (0.45) |
0.5 (0.85) |
0.3 (0.65) |
|
Number of hospitalizations for vaso-occlusive crisis (mean [SD]) |
||||
|
Prior to treatment |
0.0 (0.00) |
0.7 (1.08) |
0.6 (0.84) |
0.5 (0.92) |
|
After treatment |
0.3 (0.82) |
0.0 (0.00) |
0.3 (0.67) |
0.2 (0.51) |
|
Number of other SCA-related hospitalizations (mean [SD]) |
||||
|
Prior to treatment |
0.3 (0.82) |
0.4 (0.63) |
0.4 (0.70) |
0.4 (0.67) |
|
After treatment |
0.0 (0.00) |
0.0 (0.00) |
0.1 (0.32) |
0.0 (0.18) |
PK study design: Open-label, single-arm, multicenter study of 32 pediatric patients aged 6 months to 18 years with SCA on the maximum tolerated dose (15 mg/kg/day to 35 mg/kg/day) followed for a maximum of 12 to 15 months.
Palatability1
In a palatability assessment study in children <6 years old, 22 participants completed the questionnaire:
Dosing per weight and age2,3
|
Age (yrs) |
Weight (kg)b |
15 mg/kg dose |
20 mg/kg dose |
35 mg/kg dose |
|
6 months |
7.9 |
119 |
158 |
277 |
| 1 |
9.6 |
144 |
192 |
336 |
| 2 |
12.2 |
183 |
244 |
427 |
| 3 |
14.3 |
215 |
286 |
501 |
| 4 |
16.3 |
245 |
326 |
571 |
| 5 |
18.3 |
275 |
366 |
641 |
| 6 |
20.5 |
308 |
410 |
718 |
bCalculations based on 50th percentile weight for a boy (World Health Organization (WHO) child growth standards)3
Safety profile2
XROMI can cause serious side effects, including:
- Myelosuppression: XROMI may cause severe myelosuppression. Do not give if bone marrow function is markedly depressed. Monitor blood counts at baseline and throughout treatment. Interrupt treatment and reduce dose as necessary.
- Malignancies: Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies.
Most common adverse reactions (incidence >5%):
REFERENCES
- Data on file. Rare Disease Therapeutics, Inc.
- Xromi (hydroxyurea) 100 mg/mL oral solution [package insert]. Franklin, TN: Rare Disease Therapeutics, Inc.; December 2024.
- National Center for Health Statistics. WHO Growth Charts Data Files: weight-for-age charts, birth to 24 months, LMS parameters and selected smoothed weight percentiles in kilograms, by age; boys dataset. Accessed November 14, 2024. https://ftp.cdc.gov/pub/Health_Statistics/NCHS/growthcharts/WHO-Boys-Weight-for-age-Percentiles.xlsx.
ABBREVIATIONS
PK, pharmacokinetics; SCA, sickle cell anemia.
IMPORTANT SAFETY INFORMATION
|
WARNING: MYELOSUPPRESSION and MALIGNANCIES
|
CONTRAINDICATIONS
XROMI is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.
WARNINGS AND PRECAUTIONS
Myelosuppression
Hydroxyurea causes severe myelosuppression. Do not initiate treatment with hydroxyurea in patients if bone marrow function is markedly depressed. Bone marrow suppression may occur, and leukopenia is generally its first and most common manifestation. Thrombocytopenia and anemia occur less often and are seldom seen without a preceding leukopenia.
Some patients, treated at the recommended initial dose of 15 mg/kg/day, have experienced severe or life-threatening myelosuppression.
Evaluate hematologic status prior to and during treatment with XROMI. Provide supportive care and modify dose or discontinue XROMI as needed. Recovery from myelosuppression is usually rapid when therapy is interrupted.
Hemolytic Anemia
Cases of hemolytic anemia in patients treated with hydroxyurea for myeloproliferative diseases have been reported. In the setting of confirmed diagnosis of hemolytic anemia and in the absence of other causes, discontinue XROMI.
Malignancies
Hydroxyurea is a human carcinogen. In patients receiving long-term hydroxyurea for myeloproliferative disorders (a condition for which XROMI is not approved), secondary leukemia has been reported.
Secondary leukemia has also been reported in patients treated with long-term hydroxyurea for sickle cell anemia. Leukemia has also been reported in patients with sickle cell anemia and no prior history of treatment with hydroxyurea.
All patients using XROMI should be followed up on a long-term basis with regular blood counts to detect development of leukemia.
Skin cancer has also been reported in patients receiving long-term hydroxyurea. Advise protection from sun exposure and monitor for the development of secondary malignancies.
Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals, XROMI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus and to avoid becoming pregnant while being treated with XROMI.
Advise females of reproductive potential to use effective contraception during and after treatment with XROMI for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with XROMI for at least 1 year after therapy.
Vasculitic Toxicities
Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. If cutaneous vasculitic ulcers occur, institute treatment and discontinue XROMI.
Live Vaccines
Avoid use of live vaccines in patients taking XROMI as it may potentiate the replication of the virus and/or may increase the adverse reaction of the vaccine because normal defense mechanisms may be suppressed by XROMI. Vaccination with live vaccines in a patient receiving XROMI may result in severe infection. Patient’s antibody response to vaccines may be decreased. Consider consultation with a specialist.
Risks with Concomitant Use of Antiretroviral Drugs
Pancreatitis, hepatotoxicity, and peripheral neuropathy have occurred when hydroxyurea was administered concomitantly with antiretroviral drugs, including didanosine and stavudine.
Macrocytosis
XROMI may cause macrocytosis, which is self-limiting, and is often seen early in the course of treatment. The morphologic change resembles pernicious anemia, but is not related to vitamin B12 or folic acid deficiency. This may mask the diagnosis of pernicious anemia. Prophylactic administration of folic acid is recommended.
Laboratory Test Interference
Interference with uric acid, urea, or lactic acid assays is possible, rendering falsely elevated results of these in patients treated with hydroxyurea.
Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin.
ADVERSE REACTIONS
Most common adverse reactions (incidence >5%) are neutropenia, thrombocytopenia, and papular rash.
USE IN SPECIFIC POPULATIONS
- Females and Males of Reproductive PotentialXROMI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating XROMI therapy. Advise females to immediately report pregnancy.XROMI may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Based on findings in animals and humans, male fertility may be compromised by treatment with XROMI.
- Pediatric Use: Continuous follow-up of the growth of treated children is recommended.
- Renal Impairment: Reduce dosage and closely monitor the hematologic parameters when XROMI is administered to patients with renal impairment who have a creatinine clearance of less than 60 mL/min.
- Hepatic Impairment: Close monitoring of hematologic parameters is advised in these patients receiving XROMI.
OVERDOSAGE
Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at doses several times above the therapeutic dose. Soreness, violet erythema, oedema on palms and soles followed by scaling of hand and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed.
Please see complete Prescribing Information including BOXED WARNING and Patient Information or at www.xromi.com/pi.
To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics, Inc., at 1-844-472-7389 or by email at safety@raretx.com or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
XRO-ISIF-004
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Franklin, TN 37067
©2025 Rare Disease Therapeutics, Inc. All Rights Reserved. Intended for US Healthcare Professionals Only. XROweb005E April 2025
IMPORTANT SAFETY INFORMATION
|
WARNING: MYELOSUPPRESSION and MALIGNANCIES
|
IMPORTANT SAFETY INFORMATION
|
WARNING: MYELOSUPPRESSION and MALIGNANCIES
|
CONTRAINDICATIONS
XROMI is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.
WARNINGS AND PRECAUTIONS
Myelosuppression
Hydroxyurea causes severe myelosuppression. Do not initiate treatment with hydroxyurea in patients if bone marrow function is markedly depressed. Bone marrow suppression may occur, and leukopenia is generally its first and most common manifestation. Thrombocytopenia and anemia occur less often and are seldom seen without a preceding leukopenia.
Some patients, treated at the recommended initial dose of 15 mg/kg/day, have experienced severe or life-threatening myelosuppression.
Evaluate hematologic status prior to and during treatment with XROMI. Provide supportive care and modify dose or discontinue XROMI as needed. Recovery from myelosuppression is usually rapid when therapy is interrupted.
Hemolytic Anemia
Cases of hemolytic anemia in patients treated with hydroxyurea for myeloproliferative diseases have been reported. In the setting of confirmed diagnosis of hemolytic anemia and in the absence of other causes, discontinue XROMI.
Malignancies
Hydroxyurea is a human carcinogen. In patients receiving long-term hydroxyurea for myeloproliferative disorders (a condition for which XROMI is not approved), secondary leukemia has been reported.
Secondary leukemia has also been reported in patients treated with long-term hydroxyurea for sickle cell anemia. Leukemia has also been reported in patients with sickle cell anemia and no prior history of treatment with hydroxyurea.
All patients using XROMI should be followed up on a long-term basis with regular blood counts to detect development of leukemia.
Skin cancer has also been reported in patients receiving long-term hydroxyurea. Advise protection from sun exposure and monitor for the development of secondary malignancies.
Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals, XROMI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus and to avoid becoming pregnant while being treated with XROMI.
Advise females of reproductive potential to use effective contraception during and after treatment with XROMI for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with XROMI for at least 1 year after therapy.
Vasculitic Toxicities
Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. If cutaneous vasculitic ulcers occur, institute treatment and discontinue XROMI.
Live Vaccines
Avoid use of live vaccines in patients taking XROMI as it may potentiate the replication of the virus and/or may increase the adverse reaction of the vaccine because normal defense mechanisms may be suppressed by XROMI. Vaccination with live vaccines in a patient receiving XROMI may result in severe infection. Patient’s antibody response to vaccines may be decreased. Consider consultation with a specialist.
Risks with Concomitant Use of Antiretroviral Drugs
Pancreatitis, hepatotoxicity, and peripheral neuropathy have occurred when hydroxyurea was administered concomitantly with antiretroviral drugs, including didanosine and stavudine.
Macrocytosis
XROMI may cause macrocytosis, which is self-limiting, and is often seen early in the course of treatment. The morphologic change resembles pernicious anemia, but is not related to vitamin B12 or folic acid deficiency. This may mask the diagnosis of pernicious anemia. Prophylactic administration of folic acid is recommended.
Laboratory Test Interference
Interference with uric acid, urea, or lactic acid assays is possible, rendering falsely elevated results of these in patients treated with hydroxyurea.
Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin.
ADVERSE REACTIONS
Most common adverse reactions (incidence >5%) are neutropenia, thrombocytopenia, and papular rash.
USE IN SPECIFIC POPULATIONS
- Females and Males of Reproductive Potential
XROMI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating XROMI therapy. Advise females to immediately report pregnancy.
XROMI may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Based on findings in animals and humans, male fertility may be compromised by treatment with XROMI. - Pediatric Use: Continuous follow-up of the growth of treated children is recommended.
- Renal Impairment: Reduce dosage and closely monitor the hematologic parameters when XROMI is administered to patients with renal impairment who have a creatinine clearance of less than 60 mL/min.
- Hepatic Impairment: Close monitoring of hematologic parameters is advised in these patients receiving XROMI.
OVERDOSAGE
Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at doses several times above the therapeutic dose. Soreness, violet erythema, oedema on palms and soles followed by scaling of hand and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed.
Please see complete Prescribing Information including BOXED WARNING and Patient Information or at www.xromi.com/pi.
To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics, Inc., at 1-844-472-7389 or by email at safety@raretx.com or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.