Allopurinol Sodium (allopurinol sodium)

Dosage of allopurinol varies with the severity of the disease and should be adjusted according to the response and tolerance of the patient. Dosage of allopurinol also may be adjusted according to results of serum uric acid concentrations, which should be maintained within the normal range.

Various approaches to dosing allopurinol in patients with renal impairment have been recommended in an attempt to minimize the risk of allopurinol-induced hypersensitivity reactions. Use of a low initial dosage has been recommended to reduce the risk of such reactions; the relationship between hypersensitivity reactions and the maintenance dosage used in renal impairment is more controversial. This uncertainty is reflected in the lack of consensus on allopurinol dosage in patients with renal impairment. (See Cautions: Dermatologic and Sensitivity Reactions.)

In patients with impaired renal function, allopurinol and particularly its metabolite oxypurinol may accumulate and, thus, dosage should be reduced. Initial dosages in these patients should be lower than those used in patients with normal renal function.

The manufacturers and some experts recommend that maximum dosages of allopurinol be adjusted according to creatinine clearance. For oral dosing, the manufacturers recommend 200 mg of allopurinol daily when creatinine clearance is 10-20 mL/minute and state that dosage should not exceed 100 mg daily in patients with creatinine clearances less than 10 mL/minute. In patients with severely impaired renal function (i.e., creatinine clearance less than 3 mL/minute), the manufacturers state that use of longer dosing intervals also may be required.

Some clinicians have recommended alternative maintenance dosages of allopurinol based on the patient's creatinine clearance (see Table 1). Although such creatinine clearance-based dosing was widely adopted, this dosing strategy frequently fails to reduce serum urate concentrations to target levels, and evidence that this strategy reduces the risk of allopurinol-induced hypersensitivity reactions in patients who tolerate low initial dosages of the drug is lacking. More recent data suggest that dosage can be increased safely beyond these creatinine clearance-based maintenance dosages, with greater reduction of serum urate concentrations.

Table 1. Creatinine Clearance-based Maintenance Dosages of Allopurinol in Renal Impairment

Creatinine Clearance (mL/minute) Maintenance Dosage 0 100 mg every 3 days 10 100 mg every 2 days 20 100 mg daily 40 150 mg daily 60 200 mg daily 80 250 mg daily

Based on data suggesting that initial dosage is a risk factor for allopurinol-induced hypersensitivity reactions, the American College of Rheumatology (ACR) and some clinicians recommend that allopurinol therapy be initiated at a reduced dosage of 50 mg daily in patients with stage 4 or worse chronic kidney disease (creatinine clearance less than 30 mL/minute). Dosage may be adjusted in increments of 50-100 mg every 2-5 weeks to achieve target serum urate concentrations. The ACR and some other clinicians state that dosage may be increased to levels exceeding 300 mg daily, even in patients with renal impairment, provided patients receive appropriate education and are monitored regularly for evidence of hypersensitivity reactions or other adverse effects.

Other experts and clinicians recommend use of even lower initial dosages (based on estimated glomerular filtration rate (eGFR)) in patients with renal impairment (see Table 2), followed by a gradual increase in dosage (e.g., in 50-mg increments at intervals of approximately every 4 weeks); although these experts state that maximum dosage in patients with renal impairment should be lower than in patients without renal impairment, target serum urate concentrations should be the same.

Table 2. GFR-based Dosages for Initiation of Allopurinol Therapy in Renal Impairment

Estimated GFR (mL/minute per 1.73 Initial Dosage m2) Less than 5 50 mg weekly 5-15 50 mg twice weekly 16-30 50 mg every 2 days 31-45 50 mg daily 46-60 50 and 100 mg on alternating days 61-90 100 mg daily

For IV dosing, the manufacturer states that patients with creatinine clearances of 10-20 mL/minute can receive 200 mg daily, those with creatinine clearances of 3-10 mL/minute can receive 100 mg daily, and those with creatinine clearances less than 3 mL/minute may receive 100 mg daily at extended intervals.

Allopurinol is administered orally. Allopurinol also has been administered rectally+. Allopurinol sodium is administered by IV infusion. IV therapy with the drug generally is used in patients who do not tolerate oral therapy.

In all patients receiving allopurinol, fluid intake should be sufficient to yield a daily urine output of at least 2 L and maintenance of a neutral or, preferably, alkaline urine is desirable.

The following drug interactions were observed in patients receiving oral allopurinol therapy. Although many patients received long-term oral administration of allopurinol (e.g., those with gout or renal calculi), these interactions may be relevant to allopurinol sodium for injection therapy as well.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Allopurinol/Didanosine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Didanosine is broken down to hypoxanthine by purine nucleoside phosphorylase (PNP) and uric acid by xanthene oxidase. Allopurinol is a xanthene oxidase inhibitor and therefore inhibits the metabolism of didanosine.(1,2)

CLINICAL EFFECTS: The concurrent administration of allopurinol and didanosine may result in elevated levels of and toxicity from didanosine.(3,4)

PREDISPOSING FACTORS: This interaction may be more severe in patients with renal insufficiency. Renal impairment may significantly increase the plasma half-life of oxypurinol, the main and active metabolite of allopurinol.

PATIENT MANAGEMENT: The manufacturer of didanosine states that the concurrent use of allopurinol is contraindicated.(3,4)

DISCUSSION: In two patients with renal impairment, the administration of didanosine (200 mg single dose) with allopurinol (300 mg daily) increased the area-under-curve (AUC) and maximum concentration (Cmax) of didanosine by 312% and 232%, respectively. In 14 healthy subjects, the administration of didanosine (400 mg single dose) with allopurinol (300 mg daily for 7 days) increased the AUC and Cmax of didanosine by 113% and 69%, respectively.(3,4) In a small study in four treatment-naive patients, the addition of allopurinol (300 mg daily) allowed the dose of didanosine to be decreased 50%. Didanosine plasma levels and HIV-1-RNA levels were unchanged after 4 and 17-20 months.(5)

Allopurinol/Fluorouracil & Fluorouracil Prodrugs

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Allopurinol may decrease conversion of fluorouracil to its active metabolites, FdUMP and FUTP.(1-4) Capecitabine and tegafur are prodrugs of fluorouracil.

CLINICAL EFFECTS: Concurrent use of allopurinol with fluorouracil or fluorouracil prodrugs (e.g., capecitabine, tegafur) may result in decreased levels of the active metabolites of fluorouracil and loss of efficacy.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The concurrent use of fluorouracil or fluorouracil prodrugs with allopurinol should be avoided.(1-4)

DISCUSSION: This is a theoretical interaction based on non-clinical data. Allopurinol may decrease the levels of the active metabolites of fluorouracil, FdUMP and FUTP. Capecitabine and tegafur are prodrugs of fluorouracil.(1-4)

Cyp1a2 Inhibitors/Fezolinetant

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Inhibitors of CYP1A2 may inhibit the metabolism of fezolinetant.(1-4)

CLINICAL EFFECTS: Concurrent use of a CYP1A2 inhibitor may increase levels of and adverse effects from fezolinetant.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Recommendations for concurrent use of fezolinetant with CYP1A2 inhibitors differ in different regions. The US manufacturer of fezolinetant states that concurrent use with strong, moderate, and weak CYP1A2 inhibitors is contraindicated.(1) The Australian, Canadian, and UK manufacturers of fezolinetant state that concurrent use with strong and moderate CYP1A2 inhibitors is contraindicated, while weak CYP1A2 inhibitors are not predicted to cause clinically relevant changes in fezolinetant exposure.(2-4)

DISCUSSION: In a study, fluvoxamine, a strong CYP1A2 inhibitor, increased fezolinetant maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 840%, respectively. Mexiletine (400 mg every 8 hours), a moderate CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 40% and 360%, respectively. Cimetidine (300 mg every 6 hours), a weak CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 30% and 100%, respectively.(1) Strong CYP1A2 inhibitors linked to this monograph include angelica root, ciprofloxacin, enasidenib, enoxacin, fluvoxamine, and rofecoxib. Moderate CYP1A2 inhibitors linked to this monograph include capmatinib, centanafadine, dipyrone, fexinidazole, genistein, hormonal contraceptives, methoxsalen, mexiletine, osilodrostat, phenylpropanolamine, pipemidic acid, rucaparib, troleandomycin, vemurafenib, and viloxazine. Weak CYP1A2 inhibitors linked to this monograph include acyclovir, allopurinol, artemisinin, belumosudil, caffeine, cannabidiol, cimetidine, curcumin, dan-shen, deferasirox, disulfiram, Echinacea, famotidine, ginseng, norfloxacin, obeticholic acid, parsley, piperine, propafenone, propranolol, ribociclib, simeprevir, thiabendazole, ticlopidine, triclabendazole, valacyclovir, verapamil, and zileuton.(5-7)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Allopurinol/Selected Anticoagulants (Vitamin K Antagonists)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Possible inhibition of anticoagulant metabolism by allopurinol.

CLINICAL EFFECTS: Concurrent use of anticoagulants and allopurinol may increase the risk for bleeding.

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: Documentation is lacking; however, if an interaction occurs, the consequences could be severe.

Allopurinol/Theophyllines

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Allopurinol may inhibit the metabolism of theophylline.

CLINICAL EFFECTS: Increased levels of theophylline may result in theophylline toxicity.

PREDISPOSING FACTORS: Larger doses of allopurinol given for greater than two weeks.

PATIENT MANAGEMENT: Monitor theophylline levels in patients receiving concurrent therapy with theophylline and allopurinol. The dosage of theophylline may need to be decreased during concurrent therapy.

DISCUSSION: Decreased metabolism of theophylline has been reported during concurrent administration with large doses of allopurinol (600 mg daily) given over two weeks. There is one case report of a 38% increase in theophylline levels following the addition of allopurinol (100 mg daily) to therapy. Other authors have reported no effect on theophylline clearance by allopurinol when allopurinol was administered in smaller doses for shorter courses of therapy.

Allopurinol; Oxypurinol/Thiopurines

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Inhibition of xanthine oxidase leads to decreased thiopurine metabolism.

CLINICAL EFFECTS: Potentiation of thiopurine effects, with increased bone marrow suppression. Fatalities have been reported.

PREDISPOSING FACTORS: Higher doses of the thiopurine would increase the risk for severe toxicity. Patients with reduced or absent thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) activity are at higher risk of accumulating thiopurine metabolites and severe myelosuppression, since two thiopurine metabolism pathways would be blocked. Approximately 0.3 % of patients of European, Latino, or African descent have mutations of the TPMT gene resulting in little to no TPMT activity (homozygous deficiency), and approximately 10 % have intermediate TPMT activity (heterozygous deficiency). NUDT15 deficiency is not seen in patients of African descent and is seen in less than 1 % of patients of European descent. Approximately 1 % of patients of East Asian descent, 0.5 % of patients of central/south Asian descent, and 2 % of patients of Latino descent have homozygous NUDT15 deficiency. About 17 % of patients of East Asian descent, 13 % of patients of central/south Asian descent, and 8 % of patients of Latino descent have heterozygous NUDT15 deficiency.

PATIENT MANAGEMENT: Due to the magnitude and severity of this interaction, avoid the concurrent use of allopurinol and thiopurines without a dosage adjustment of the thiopurine, especially in patients with thiopurine S-methyltransferase (TPMT) deficiency. Consult the thiopurine prescriber prior to initiation of a xanthine oxidase inhibitor. Reduce the dose of azathioprine or mercaptopurine to one third to one quarter of the usual dose (a 66% to 75% reduction) in patients receiving allopurinol to decrease the risk for toxicity. A further dose reduction or alternative therapy is recommended in patients with low or absent TPMT activity. It would be prudent to reduce the dose of other thiopurines in patients receiving allopurinol, as well as decreasing the dose of these agents in patients taking oxypurinol. Patients should be closely monitored during concurrent therapy.

DISCUSSION: The concurrent administration of either mercaptopurine or azathioprine with allopurinol has been shown to result in increases in the pharmacologic and toxic effects of the thiopurines. In one study in five patients, pretreatment with allopurinol increased the peak plasma concentration of mercaptopurine by 500%. The combination of dose-adjusted thiopurines and allopurinol has been used effectively in the treatment of auto-immune diseases such as inflammatory bowel disease. Oxypurinol is the major metabolite of allopurinol and is a non-competitive inhibitor of xanthine oxidase.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Selected Moderate And Weak Cyp1a2 Inhibitors/Tizanidine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Moderate and weak CYP1A2 inhibitors may inhibit the metabolism of tizanidine by CYP1A2.(1)

CLINICAL EFFECTS: Concurrent use of moderate and weak CYP1A2 inhibitors may result in elevated levels of and effects from tizanidine, including hypotension, bradycardia, drowsiness, sedation, and decreased psychomotor function.

PREDISPOSING FACTORS: The risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2)

PATIENT MANAGEMENT: The US manufacturer of tizanidine states that concurrent use of tizanidine with inhibitors of CYP1A2 should be avoided.(3) If adverse reactions such as hypotension, bradycardia or excessive drowsiness occur, reduce tizanidine dosage or discontinue tizanidine therapy.(3)

DISCUSSION: In a study, cannabidiol 750 mg twice daily (a weak CYP1A2 inhibitor) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a 200 mg single dose of caffeine (a sensitive CYP1A2 substrate) by 15% and 95%, respectively.(1) In a study in 10 healthy subjects, concurrent fluvoxamine, a strong inhibitor of CYP1A2, increased tizanidine Cmax, AUC, and half-life (T1/2) by 12-fold, 33-fold, and 3-fold, respectively. Significant decreases in blood pressure and increases in drowsiness and psychomotor impairment occurred.(3) In a study in 10 healthy subjects, concurrent ciprofloxacin, a strong inhibitor of CYP1A2, increased tizanidine Cmax and AUC by 7-fold and 10-fold, respectively. Significant decreases in blood pressure and increases in drowsiness and psychomotor impairment occurred.(3) Moderate CYP1A2 inhibitors linked to this monograph include: centanafadine, dipyrone, fexinidazole, genistein, methoxsalen, phenylpropanolamine, pipemidic acid, propranolol, rucaparib, and troleandomycin. Weak CYP1A2 inhibitors linked to this monograph include: allopurinol, artemisinin, belumosudil, caffeine, cannabidiol, curcumin, dan-shen, disulfiram, Echinacea, ginseng, parsley, piperine, ribociclib, simeprevir, thiabendazole, and triclabendazole.(4)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Allopurinol/Amoxicillin, Ampicillin, Bendamustine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown. Allopurinol, amoxicillin, ampicillin, and bendamustine have been documented to cause cases of Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), and Drug reaction with eosinophilia and systemic symptoms (DRESS).(1)

CLINICAL EFFECTS: Concurrent administration of allopurinol with amoxicillin, ampicillin or bendamustine may result in an increased incidence of rash which may be severe.

PREDISPOSING FACTORS: Patients who are HLA-B*58:01 positive may be at increased risk.

PATIENT MANAGEMENT: Consider an alternative to amoxicillin, ampicillin, or bendamustine in patients with a history of serious skin rashes, such as SJS, TEN, or DRESS. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when used with amoxicillin or ampicillin or bendamustine. Instruct patients to seek medical attention for any peeling skin rash or blisters.(1)

DISCUSSION: In the Boston Collaborative Drug Surveillance Program, drug rash was seen in 22.4% of 67 hospitalized patients (relative risk 3.0) receiving concurrent allopurinol and ampicillin compared to 7.5% of 1257 patients receiving only ampicillin and 2.1% of 283 patients rceiving only allopurinol.(4) A hospital drug monitoring program found the observed risk of developing an exanthema with concurrent use is as follows: aminopenicillin without allopurinol 10.1%, aminopenicillin combined with allopurinol 7.2%, allopurinol without aminopenicillin 3.0%, or neither of the two drugs 1.5%.(6) A case-control study did not find a statistically significant increased risk of SJS with concurrent use of allopurinol and amoxicillin or ampicillin (allopurinol alone 4.4% vs. with amoxicillin 6.8%; allopurinol alone 0.1% vs. with ampicillin 2.7% at 1 month)(allopurinol alone 4.4% vs. with amoxicillin 5.7% or allopurinol alone 0.2% vs. with ampicillin 2.9% at 3 months).(8) In a retrospective study looking at mortality data, records were screened for administration of high risk drugs associated with SJS. Allopurinol and ampicillin was one of the drug combinations listed as contributing to mortality in patients (p = 0.049).(9)

Allopurinol/Thiazide Diuretics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown. Allopurinol has been documented to cause Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), and Drug reaction with eosinophilia and systemic symptoms (DRESS).(1)

CLINICAL EFFECTS: Concurrent administration of allopurinol with thiazides may result in an increased incidence of rash which may be severe.

PREDISPOSING FACTORS: Patients who are HLA-B*58:01 positive or have impaired renal function may be at increased risk.

PATIENT MANAGEMENT: The manufacturer of allopurinol recommends monitoring renal function and reducing the dose of allopurinol in patients with concomitant thiazide diuretic use and impaired renal function. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when used with thiazide diuretics. Instruct patients to seek medical attention for any peeling skin rash or blisters.(1)

DISCUSSION: There are case reports of patients on concurrent thiazide diuretics and allopurinol developing SJS, TEN, or DRESS.(1,2)

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• HLa-B *58:01 positive
• Lactation

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min

• Anemia
• Dehydration
• Disease of liver
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Leukopenia
• Thrombocytopenic disorder

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More Frequent

• Abnormal hepatic function tests
• Allergic dermatitis
• Pruritus of skin
• Urticaria

Less Frequent

• Skin rash

Rare or Very Rare

• Acute gouty arthritis
• Acute pancreatitis
• Acute respiratory failure
• Agranulocytosis
• Anemia
• Aplastic anemia
• Apnea
• Bone marrow depression
• Bradycardia
• Bronchospastic pulmonary disease
• Cataracts
• DRESS syndrome
• Drug-induced hepatitis
• Epistaxis
• Erythema multiforme
• Exfoliative dermatitis
• Gastrointestinal hemorrhage
• Hemolytic anemia
• Hepatic necrosis
• Hypercalcemia
• Hypersensitivity drug reaction
• Jaundice
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Kidney stone
• Lymphadenopathy
• Lymphocytosis
• Nephritis
• Obstructive hyperbilirubinemia
• Onycholysis
• Optic neuritis
• Pancytopenia
• Pericarditis
• Peripheral neuropathy
• Purpura
• Renal failure
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Toxic epidermal necrolysis
• Vasculitis

More Frequent

• Diarrhea
• Nausea

Less Frequent

• Vomiting

Rare or Very Rare

• Abdominal pain with cramps
• Acute cognitive impairment
• Alopecia
• Anorexia
• Arthralgia
• Asthma
• Conjunctivitis
• Depression
• Dizziness
• Drowsy
• Dysgeusia
• Dyspepsia
• Ecchymosis
• Edema
• Eosinophilia
• Erectile dysfunction
• Facial edema
• Fever
• Furunculosis
• Gastritis
• General weakness
• Gynecomastia
• Headache disorder
• Hematuria
• Hyperhidrosis
• Hypotonia
• Insomnia
• Iritis
• Leukocytosis
• Leukopenia
• Libido changes
• Lichen planus
• Male infertility
• Memory impairment
• Myalgia
• Myopathy
• Paresthesia
• Pharyngitis
• Proteinuria
• Rhinitis
• Sialoadenitis
• Stomatitis
• Tachypnea
• Thrombophlebitis
• Tinnitus
• Toxic amblyopia
• Vasodilation of blood vessels
• Vertigo

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No enhanced messaging available.

Although there are no adequate and controlled studies to date using allopurinol in pregnant women, the drug has been shown to be teratogenic in mice using intraperitoneal allopurinol doses of 50 or 100 mg/kg (0.3 or 0.75 times the recommended human dose on a mg/m2 basis) on gestation days 10 or 13. Allopurinol should be used during pregnancy only when clearly needed.

Since allopurinol and oxypurinol are distributed into milk, allopurinol should be used with caution in nursing women.

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