Antimetabolite

Xromi

Approved 4 Apr 2024OralSolution

Indications

XROMI is indicated to reduce the frequency of painful crises and reduce the need for blood transfusions in pediatric patients aged 6 months of age and older with sickle cell anemia with recurrent moderate to severe painful crises. XROMI is an antimetabolite indicated to reduce the frequency of painful crises and reduce the need for blood transfusions in pediatric patients aged 6 months of age and older with sickle cell anemia with recurrent moderate to severe painful crises.

(1)

Contraindications

XROMI is contraindicated in patients: who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation. [see Adverse Reactions (6) ] . In patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation. (4)

Warnings and precautions

Hemolytic anemia: Monitor blood counts throughout treatment. If hemolysis persists, discontinue XROMI. ( 5.2 ) Embryo-Fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3) Vasculitic toxicities: Institute treatment and discontinue XROMI if this occurs. (5.5) Live Vaccinations: Avoid live vaccine use in a patient taking XROMI. (5.6) Risks with concomitant use of antiretroviral drugs: Pancreatitis, hepatotoxicity, and neuropathy have occurred.

Monitor for signs and symptoms in patients with HIV infection using antiretroviral drugs; discontinue XROMI and implement treatment. (5.7)

5.1Myelosuppression

Hydroxyurea causes severe myelosuppression. Do not initiate treatment with XROMI 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 (CBC, reticulocyte count) prior to and every 2 weeks during dose-escalation period of XROMI treatment. Once a stable dose of XROMI is achieved, monitor every 4 weeks. Provide supportive care and modify dose or discontinue XROMI as needed. Recovery from myelosuppression is usually rapid when therapy is interrupted. [see Dosage and Administration (2.1) ] .

At a glance

Brand name: Xromi
Active substance: hydroxyurea
Pharmacologic class: Antimetabolite
Route: Oral
Dosage form: Solution
Applicant: Nova Labs LTD
Status: Prescription
FDA approval: 4 Apr 2024
Application: NDA216593-001

Indications

(1)

Contraindications

Warnings and precautions

Monitor for signs and symptoms in patients with HIV infection using antiretroviral drugs; discontinue XROMI and implement treatment. (5.7)

5.1Myelosuppression

Interactions

Antiretroviral drug. (7.1) Laboratory Test Interference. (7.2)

7.1Increased Toxicity with Concomitant Use of Antiretroviral Drugs Pancreatitis

In patients with HIV infection during therapy with hydroxyurea and didanosine, with or without stavudine, fatal and nonfatal cases of pancreatitis have occurred. Hydroxyurea is not indicated for the treatment of HIV infection; however, if patients with HIV infection are treated with hydroxyurea, and in particular, in combination with didanosine and/or stavudine, close monitoring for signs and symptoms of pancreatitis is recommended.

Permanently discontinue therapy with hydroxyurea in patients who develop signs and symptoms of pancreatitis. Hepatotoxicity Hepatotoxicity and hepatic failure resulting in death have been reported during postmarketing surveillance in patients with HIV infection treated with hydroxyurea and other antiretroviral drugs. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine.

Avoid this combination. Peripheral Neuropathy Peripheral neuropathy, which was severe in some cases, has been reported in patients with HIV infection receiving hydroxyurea in combination with antiretroviral drugs, including didanosine, with or without stavudine.

7.2Laboratory Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays

Studies have shown that there is an analytical interference of hydroxyurea with the enzymes (urease, uricase, and lactate dehydrogenase) used in the determination of urea, uric acid, and lactic acid, rendering falsely elevated results of these in patients treated with hydroxyurea. Interference with Continuous Glucose Monitoring Systems 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.

If a patient using a CGM is to be prescribed hydroxyurea, consult with the CGM prescriber about alternative glucose monitoring methods.

Adverse reactions

The following clinically significant adverse reactions are described in detail in other labeling sections: Myelosuppression [see Warnings and Precautions (5.1) ] Hemolytic anemia [see Warnings and Precautions (5.2) ] Malignancies [see Warnings and Precautions (5.3) ] Vasculitic toxicities [see Warnings and Precautions (5.5) ] Live vaccinations [see Warnings and Precautions (5.6) Risks with concomitant use of antiretroviral drugs [see Warnings and Precautions (5.7) ] Macrocytosis [see Warnings and Precautions (5.8) ] Pulmonary toxicity [see Warnings and Precautions (5.9) ] Most common adverse reactions (incidence > 5%) are neutropenia and thrombocytopenia, and popular rash.

(6) To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics, Inc. at 844-472-7389 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 XROMI was evaluated in 32 pediatric patients aged 10 months -16 years with sickle cell anemia in a single-arm, open-label, prospective, multi-center, pharmacokinetic, safety and efficacy study (HUPK study).

Only adverse reactions associated with the use of XROMI in pediatric patients aged 10 months to less than 2 years are presented. The most frequently reported adverse reactions in HUPK study (<33%) were neutropenia, and thrombocytopenia [see Table 3]. Table 3. Adverse Reactions Reported in Pediatric Patients Aged 10 Months and Older Enrolled in HUPK 10 Months–<2 Years 2 –<6 Years 6 –<18 Years Overall Body System Adverse Reactions (n=6)% (n=16)% (n=10)% (n=32)% Neutropenia 3 (50) 1 (6) 0 4 (13) Thrombocytopenia 2 (33) 1 (6) 0 3 (9) Diarrhea 1 (17) 0 0 1 (3) GGT Increased 0 0 1(10) 1 (3) Absolute Reticulocyte Count Decreased 1 (17) 0 0 1 (3) Alopecia 0 1 (6) 0 1 (3) Nail Discolouration 0 0 1 (10) 1 (3) Rash 0 0 1 (10) 1 (3) Rash Popular 0 1 (6) 1 (10) 2 (6)

6.2 Post marketing Experience The following adverse reactions have been identified during post-approval use of hydroxyurea. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency. Reproductive System and Breast disorders: azoospermia, and oligospermia Gastrointestinal disorders: stomatitis, nausea, vomiting, diarrhea, and constipation Metabolism and Nutrition disorders: anorexia Skin and subcutaneous tissue disorders: maculopapular rash, skin ulceration, cutaneous lupus erythematosus, dermatomyositis-like skin changes, peripheral and facial erythema, hyperpigmentation, nail hyperpigmentation, atrophy of skin and nails, scaling, violet papules, and alopecia Renal and urinary disorders: dysuria, elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels Nervous system disorders: headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions General disorders: fever, chills, malaise, edema, and asthenia Hepatobiliary disorders: elevation of hepatic enzymes, cholestasis, and hepatitis Respiratory disorders: diffuse pulmonary infiltrates, dyspnea, and pulmonary fibrosis, interstitial lung disease, pneumonitis, alveolitis, allergic alveolitis and cough Immune disorders: systemic lupus erythematosus Hypersensitivity: Drug-induced fever (pyrexia) (>39°C, >102°F) requiring hospitalization has been reported concurrently with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological or cardiovascular manifestations.

Onset typically occurred within 6 weeks of initiation and resolved upon discontinuation of hydroxyurea. Upon re-administration fever reoccurred typically within 24 hours. Blood and lymphatic system disorders: hemolytic anemia

Xromi

Indications

Contraindications

Warnings and precautions

5.1Myelosuppression

At a glance

Two medicines in one question?

Xromi

Indications

Contraindications

Warnings and precautions

5.1Myelosuppression

At a glance

Two medicines in one question?

5.2Hemolytic Anemia Cases

5.3Malignancies

5.5Vasculitic Toxicities

5.6Live Vaccinations

5.7Risks with Concomitant Use of Antiretroviral Drugs

5.8Macrocytosis

5.9Pulmonary Toxicity

5.10Laboratory Test Interference Interference

Interactions

7.1Increased Toxicity with Concomitant Use of Antiretroviral Drugs Pancreatitis

7.2Laboratory Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Official product information