Allopurinol Sodium

FDA Drug Information • Also known as: Allopurinol Sodium

Brand Names: Allopurinol Sodium
Route: INTRAVENOUS
Dosage Form: INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Allopurinol Sodium for Injection, a xanthine oxidase inhibitor, is a sterile, white, lyophilized powder or cake, in a single-dose vial for reconstitution. Each vial contains 500 mg of allopurinol equivalent to 580.7 mg of allopurinol sodium and 162.5 mg of sodium hydroxide as a solubilizer. Sodium hydroxide is also used as a pH adjuster. Allopurinol Sodium for Injection contains no preservatives. Allopurinol is a xanthine oxidase inhibitor. The chemical name for allopurinol sodium is 1,5-dihydro-4 H -pyrazolo[3,4- d ]pyrimidin-4-one monosodium salt. It is a white amorphous mass with a molecular weight of 158.09 and molecular formula C 5 H 3 N 4 NaO. The structural formula is: The pKa of allopurinol sodium is 9.31. Allopurinol Structural Formula

What Is Allopurinol Sodium Used For?

1 INDICATIONS AND USAGE Allopurinol Sodium for Injection is indicated for the management of adult and pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels and who cannot tolerate oral therapy. Allopurinol Sodium for Injection is a xanthine oxidase inhibitor indicated for the management of adult and pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels and who cannot tolerate oral therapy. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Recommended Dosage ( 2.2 ) Adult Patients 200 mg/m 2 /day to 400 mg/m 2 /day Maximum 600 mg/day Pediatric Patients Starting Dose 200 mg/m 2 /day Maximum 400 mg/day Recommended Dosage in Adult Patients with Renal Impairment ( 2.2 , 5.2 , 8.6 ) Creatinine Clearance Recommended Daily Dose 10 to 20 mL/min 200 mg/day Less than 10 mL/min 100 mg/day On dialysis 50 mg every 12 hours, or 100 mg every 24 hours 2.1 Recommended Dosage Initiate therapy with Allopurinol Sodium for Injection 24 to 48 hours before the start of chemotherapy known to cause tumor cell lysis. Additionally, administer fluids sufficient to yield a daily urinary output of at least two liters in adults with a neutral or, preferably, slightly alkaline urine. The recommended daily dose of Allopurinol Sodium for Injection is shown in Table 1. Administer the daily dose as single infusion or in equally divided infusions at 6-, 8-, or 12-hour intervals at a rate appropriate for the volume of infusate. Table 1: Recommended Daily Dose of Allopurinol Sodium for Injection Adult Patients 200 mg/m 2 /day to 400 mg/m 2 /day intravenously Maximum 600 mg/day Pediatric Patients Starting Dose 200 mg/m 2 /day intravenously Maximum 400 mg/day The dosage of Allopurinol Sodium for Injection to lower serum uric acid to normal or near-normal varies with the severity of the disease. Monitor serum uric acid levels at least daily and administer Allopurinol Sodium for Injection at a dose and frequency to maintain the serum uric acid within the normal range. Discontinue Allopurinol Sodium for Injection when the patient is able to take oral therapy or when the risk of tumor lysis has abated. 2.2 Dosage Modifications in Patients with Renal Impairment Reduce the dose of Allopurinol Sodium for Injection in patients with impaired renal function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . The recommended dosage reductions of Allopurinol Sodium for Injection in adult patients with renal impairment are shown in Table 2. Table 2: Recommended Daily Dose of Allopurinol Sodium for Injection in Adult Patients with Renal Impairment Creatinine Clearance Recommended Daily Dose 10 to 20 mL/min 200 mg/day Less than 10 mL/min 100 mg/day On dialysis 50 mg every 12 hours, or 100 mg every 24 hours Treatment with Allopurinol Sodium for Injection has not been studied in pediatric patients with severe renal impairment or on dialysis. For pediatric patients with severe renal impairment or on dialysis, consider the risks and potential benefits before initiating treatment with Allopurinol Sodium for Injection [see Warnings and Precautions (5.2) and Use In Specific Populations (8.6) ] . 2.3 Preparation Instructions Reconstitute and further dilute Allopurinol Sodium for Injection prior to intravenous infusion. Reconstitution Reconstitute each vial of Allopurinol Sodium for Injection with 25 mL of Sterile Water for Injection, USP to obtain a concentration of 20 mg/mL of allopurinol....

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Skin Rash and Hypersensitivity [see Warnings and Precautions (5.1) ] Renal Function Impairment [see Warnings and Precautions (5.2) ] Hepatoxicity [see Warnings and Precautions (5.3) ] Myelosuppression [see Warnings and Precautions (5.4) ] Drowsiness [see Warnings and Precautions (5.5) ] Most common adverse reactions (incidence > 1%) are skin rash, nausea, vomiting, and renal failure/insufficiency. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 Allopurinol Sodium for Injection was evaluated in an uncontrolled compassionate use study of 1,378 patients with advanced malignancies requiring treatment with cytotoxic chemotherapy and in patients with other serious conditions. Adverse reactions were reported in 9% (125/1378) of the patients treated with Allopurinol Sodium for Injection. The most common adverse reaction was skin rash. Two patients experience serious adverse reactions (decreased renal function and generalized seizure) and one patient experienced severe diarrhea. Approximately 1.1% of patients experienced allergic adverse reactions (including rash, eosinophilia, local injection site reaction). A listing of the adverse reactions reported from clinical trials follows: Incidence Greater Than 1%: Cutaneous/Dermatologic: rash (1.5%) Genitourinary: renal failure/insufficiency (1.2%) Gastrointestinal: nausea (1.3%), vomiting (1.2%) Incidence Less Than 1%: Body as a Whole: fever, pain, chills, alopecia, infection, sepsis, enlarged abdomen, mucositis/pharyngitis, blast crisis, cellulitis, hypervolemia Cardiovascular: heart failure, cardiorespiratory arrest, hypertension, pulmonary embolus, hypotension, decreased venous pressure, flushing, headache, stroke, septic shock, cardiovascular disorder, ECG abnormality, hemorrhage, bradycardia, thrombophlebitis, ventricular fibrillation Cutaneous/Dermatologic: urticaria, pruritus, local injection site reaction Gastrointestinal: diarrhea, gastrointestinal bleeding, hyperbilirubinemia, splenomegaly, hepatomegaly, intestinal obstruction, jaundice, flatulence, constipation, liver failure, proctitis Genitourinary: hematuria, increased creatinine, oliguria, kidney function abnormality, urinary tract infection Hematologic: leukopenia, marrow aplasia, thrombocytopenia, eosinophilia, neutropenia, anemia, pancytopenia, ecchymosis, bone marrow suppression, disseminated intravascular coagulation Metabolic: hypocalcemia, hyperphosphatemia, hypokalemia, hyperuricemia, electrolyte abnormality, hypercalcemia, hyperglycemia, hypernatremia, hyponatremia, metabolic acidosis, edema, glycosuria, hyperkalemia, lactic acidosis, water intoxication, hypomagnesemia Neurologic: seizure, status epilepticus, myoclonus, twitching, agitation, mental status changes, cerebral infarction, coma, dystonia, paralysis, tremor Pulmonary: respiratory failure/insufficiency, ARDS, increased respiration rate, apnea Musculoskeletal: arthralgia Other: hypotonia, diaphoresis, tumor lysis syndrome

Drug Interactions

7 DRUG INTERACTIONS Clinically important interactions with the drugs listed below were observed in patients undergoing treatment with an oral allopurinol formulation. Capecitabine: Avoid the concomitant use of allopurinol ( 7.2 ). Pegloticase: Discontinue and do not institute allopurinol therapy during treatment with pegloticase ( 7.2 ). Mercaptopurine or Azathioprine: Reduce mercaptopurine or azathioprine dose as recommended in the respective prescribing information ( 7.2 ). See full prescribing information for complete list of significant drug interactions ( 7 ). 7.1 Drugs Known to Affect the Occurrence of Skin Rash and Hypersensitivity Concomitant use of the following drugs may increase the risk of skin rash, which may be severe: bendamustine, thiazide diuretics, ampicillin and amoxicillin. Renal impairment may further increase risk with concomitant use of thiazide diuretics [see Warnings and Precautions (5.1) (5.2) and Clinical Pharmacology (12.2) ] . Monitor renal function and reduce the dose of Allopurinol Sodium for Injection in patients with concomitant thiazide diuretic use and impaired renal function [see Dosage and Administration (2.2) ]. Discontinue Allopurinol Sodium for Injection at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when use concomitantly with these drugs. 7.2 Other Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Sodium for Injection Table 4: Interventions for Clinically Important Drug Interactions with Allopurinol Sodium for Injection Capecitabine Clinical Impact Concomitant use with allopurinol may decrease concentration of capecitabine’s active metabolites, which may decrease capecitabine efficacy. Intervention Avoid the use of Allopurinol Sodium for Injection during treatment with capecitabine. Cyclosporine Clinical Impact Concomitant use of allopurinol increases cyclosporine concentrations which may increase the risk of adverse reactions. Intervention Increase frequency of monitoring cyclosporine concentrations as reflected in the prescribing information when used concomitantly with Allopurinol Sodium for Injection. Cytotoxic Agents Clinical Impact Concomitant use of allopurinol with cytotoxic agents increases bone marrow suppression among patients with neoplastic disease, except leukemia [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.2) ] . Intervention Blood count monitoring and regular physician follow-up recommended. Fluorouracil Clinical Impact Based on non-clinical data, allopurinol may decrease anti-tumor activity due to suppression of phosphorylation of 5-fluorouracil. Intervention Concomitant administration with fluorouracil should be avoided. Mercaptopurine or Azathioprine Clinical Impact Allopurinol inhibits xanthine oxidase mediated metabolism of mercaptopurine and azathioprine. Concomitant use of allopurinol increases the exposure of either mercaptopurine or azathioprine which may increase the risk of their...

Contraindications

4 CONTRAINDICATIONS Allopurinol Sodium for Injection is contraindicated in patients with a history of severe reaction to any formulation of allopurinol. Known hypersensitivity to allopurinol. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on findings in animals, Allopurinol Sodium for Injection may cause fetal harm when administered to a pregnant woman. Adverse developmental outcomes have been described in exposed animals (see Data ) . Allopurinol and its metabolite oxypurinol have been shown to cross the placenta following administration of maternal allopurinol. Available limited published data on allopurinol use in pregnant women do not demonstrate a clear pattern or increase in frequency of adverse developmental outcomes. Among approximately 50 pregnancies described in published literature, 2 infants with major congenital malformations have been reported with following maternal allopurinol exposure. Advise pregnant women of the potential risk to a fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 There was no evidence of fetotoxicity or teratogenicity in rats or rabbits treated during the period of organogenesis with oral allopurinol at doses up to 200 mg/kg/day and up to 100 mg/kg/day, respectively (about three times the human dose on a mg/m 2 basis). However, there is a published report in pregnant mice that single intraperitoneal doses of 50 or 100 mg/kg (about 1/3 or 3/4 the human dose on a mg/m 2 basis) of allopurinol on gestation days 10 or 13 produced significant increases in fetal deaths and teratogenic effects (cleft palate, harelip, and digital defects). It is uncertain whether these findings represented a fetal effect or an effect secondary to maternal toxicity. In another published study with no reported maternal toxicity, allopurinol administered orally at 15 or 45 mg/kg to pregnant rats during...

Overdosage

10 OVERDOSAGE In the management of overdosage, there is no specific antidote for Allopurinol Sodium for Injection. Both allopurinol and oxypurinol are dialyzable; however, the usefulness of hemodialysis or peritoneal dialysis in the management of an overdose of Allopurinol Sodium for Injection is unknown.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING STERILE SINGLE DOSE VIAL FOR INTRAVENOUS INFUSION. Allopurinol Sodium for Injection, 50 mL flint glass vials with rubber stoppers each containing allopurinol sodium equivalent to 500 mg of allopurinol (white lyophilized powder), individually boxed, ( NDC 0143-9533-01 ). Store unreconstituted powder at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.