Allopurinol: Uses, Indications, Dosages, Precautions, Contraindications, Side Effects & Interactions

Allopurinol

(al-oh-PYOUR-ih-nohl)

Classification and Category
Pharmacotherapeutic: Xanthine oxidase inhibitor
Clinical: Antigout drug, antihyperuricemic

Pregnancy category: C

Apo-Allopurinol (CAN), Lopurin, Purinol (CAN), Zyloprim

General Information

Allopurinol is used to prevent gout, which is caused by deposits of uric acid crystals in the joints. Allopurinol blocks an enzyme called xanthine oxidase which is involved in the formation of uric acid. It is also used to lower high uric acid levels (hyperuricaemia) caused by other drugs. Allopurinol should never be started until several weeks after an acute attack subsides because it could cause a new episode

Treatment with the drug should be continued indefinitely to prevent new attacks. An acute attack may occur at the start of treatment, and colchicine or an anti-inflammatory drug may also be given until uric acid levels are reduced. If an acute attack occurs while taking allopurinol, treatment should be continued along with an anti-inflammatory drug

Action

It inhibits the enzyme xanthine oxidase, reducing the synthesis of uric acid

Therapeutic Effect

Reduces uric acid concentrations in serum and urine

Availability (Rx)

Tablets (Zyloprim): 100 mg, 300 mg

Powder for Injection (Aloprim): 500 mg

Uses

• PO: Management of primary or secondary gout (e.g., acute attack, nephropathy)

Treatment of secondary hyperuricemia that may occur during cancer treatment.

Management of recurrent uric acid and calcium oxalate calculi

• Injection: Management of elevated uric acid in cancer treatment for leukemia, lymphoma, or solid tumor malignancies

• Unlabeled uses: Preservation of cadaveric kidneys for transplantation

Precautions

Pregnancy (C), breastfeeding, children, renal/hepatic disease

Make sure to tell your doctor if:

• You have long-term hepatic or kidney problems

• You have had a previous sensitivity reaction to allopurinol

• You have a current attack of gout

• You are taking other medicines

Indications and Dosages

 ‣ To increased uric acid levels in malignancies 

PO

• Adult: 600-800 mg/day in divided doses, for 2-3 days; start up to 1-2 days prior to chemotherapy

• Child 6-10 yr: 300 mg/day, adjust dose after 48 hr

Child ,6 yr: 150 mg/day, adjust dose after 48 hr

IV

• Adult: INF 200-400 mg/m2/day, max 600 mg/day 24-48 hr prior to chemotherapy, may be divided at 6-, 8-, 12-hr intervals

• Child: INF 200 mg/m2/day, initially as a single dose or divided q6-12hr

‣ To treat Gout (mild)

PO

• Adults, Elderly. 100 mg/day, increase qwk based on uric acid levels, max 800 mg/day, maintenance dose 100-200 mg bid-tid

‣ To treat Gout (moderate-severe)

PO

• Adults:400-600 mg/day in a single dose or divided bid-tid, max 800 mg/day, doses .300 mg should be given in divided doses

‣ To treat gout and hyperuricemia

PO

• Adults: 200 to 600 mg daily in divided doses, depending on disease severity. Usual: 200 to 300 mg daily. Maximum: 800 mg daily 

‣ To treat secondary hyperuricemia caused by neoplastic disease

PO

• Children ages 6 to 10. 300 mg daily, adjusted after 48 hr, depending on response to treatment

• Children under age 6. 150 mg daily, adjusted after 48 hr, depending on response to treatment

‣ To treat recurrent calcium oxalate calculi

PO

• Adults: 200 to 300 mg daily as a single dose or in divided doses; Elderly. Initially, 100 mg/day, adjusted based on 24-hr urine urate level

‣ To treat increased serum and urine uric acid levels in patients with leukemia, lymphoma, and solid tumors whose cancer chemotherapy has increased those levels and who can’t tolerate oral therapy

IV

• Adult: 200 to 400 mg/m2 daily as a single infusion or in equally divided infusions every 6, 8, or 12 hr. Maximum: 600 mg daily

• Children: 200 mg/m2 daily as a single infusion or in equally divided infusions every 6, 8, or 12 hr

‣ Dosage in renal impairment

PO/IV (Dosage is modified based on creatinine clearance)

• Adults: CCr 81-100 ml/min 300 mg/day; CCr 61-80 ml/min 250 mg/day; CCr 41-60 ml/min 200 mg/day; CCr 21-40 ml/min 150 mg/day; CCr 10-20 ml/min 100-200 mg/day; CCr 3-9 ml/min 100 mg/day or 100 mg every other day; CCr,3 ml/min 100 mg q24hr or longer or 100 mg every third day 

Pharmacokinetics

Well absorbed from the GI tract. Widely distributed. Metabolized in the liver to active metabolite. Excreted primarily in urine. Removed by hemodialysis. Half-life: 1-3 h; metabolite, 12-30 h

Implementation

PO route

• Give with meals to prevent GI symptoms; crush and mix with food or fluids for patients with swallowing difficulties

• Increase fluid intake to 2 L/day

• Give 1-2 days before antineoplastic therapy if using for hyperuricemia associated with malignancy

Intermittent IV infusion route

• Reconstitute 30-ml vial with 25 ml of sterile water for inj; dilute to desired conc (#6 mg/ml) with 0.9% NaCl for inj or D5 for inj, begin inf within 10 hr

IV Incompatibilities

Amikacin (Amikin), amphotericin B, carmustine (BiCNU), cefotaxime (Claforan), chlorpromazine (Thorazine), cimetidine (Tagamet), clindamycin (Cleocin), cytarabine (Ara-C), dacarbazine (DTIC), daunorubicin, diphenhydramine (Benadryl), doxorubicin (Adriamycin), doxycycline (Vibramycin), droperidol (Inapsine), floxuridine, fludarabine (Fludara), gentamicin (Garamycin), haloperidol (Haldol), hydroxyzine (Vistaril), idarubicin (Idamycin), imipenem-cilastatin (Primaxin), mechlorethamine, meperidine (Demerol), methylprednisolone (Solu-Medrol), metoclopramide (Reglan), minocycline, nalbuphine, netilmicin, ondansetron (Zofran), prochlorperazine (Compazine), promethazine (Phenergan), sodium bicarbonate, streptozocin (Zanosar), tobramycin (Nebcin), vinorelbine (Navelbine)

IV compatibilities

Acyclovir, aminophylline, amphotericin B lipid complex, anidulafungin, argatroban, atenolol, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, CARBOplatin, caspofungin, ceFAZolin, cefoperazone, cefoTEtan, cefTAZidime, ceftizoxime, cefTRIAXone, cefuroxime, CISplatin, cyclophosphamide, DACTINomycin, DAUNOrubicin liposome, dexamethasone, dexmedetomidine, DOCEtaxel, DOXOrubicin liposomal, enalaprilat, etoposide, famotidine, fenoldopam, filgrastim, fluconazole, fludarabine, fluorouracil, furosemide, gallium, ganciclovir, gatifloxacin, gemcitabine, gemtuzumab, granisetron, heparin, hydrocortisone phosphate, hydrocortisone succinate, HYDROmorphone, ifosfamide, linezolid, LORazepam, mannitol, mesna, methotrexate, metroNIDAZOLE, milrinone, mitoXANtrone, morphine, nesiritide, octreotide, oxytocin, PACLitaxel, pamidronate, pantoprazole, PEMEtrexed, piperacillin, piperacillin-tazobactam, plicamycin, potassium chloride, ranitidine, sodium, sulfamethoxazole-trimethoprim, teniposide, thiotepa, ticarcillin, ticarcillin clavulanate, tigecycline, tirofiban, vancomycin, vasopressin, vinBLAStine, vinCRIStine, voriconazole, zidovudine, zoledronic acid

Contraindications

Hypersensitivity to allopurinol

Interactions

Individual drugs

Ammonium chloride, potassium/sodium phosphate, vit C: increased kidney stone formation

Ampicillin, amoxicillin: increased risk of rash, avoid concurrent use

AzaTHIOprine: increased bone marrow depression

Mercaptopurine: increased bone marrow depression

Rasburicase: increased xanthine nephropathy, calculi

Theophylline: increased action of theophylline

Drug classifications

• ACE inhibitors: May increase risk of hypersensitivity reactions

• Anticoagulants (oral): increased action of oral anticoagulants

• Antidiabetics (oral): increased action of antidiabetics

• Antineoplastics: increased bone marrow suppression

• Azathioprine, mercaptopurine: May increase therapeutic effect and toxicity of azathioprine and mercaptopurine

• Cyclophosphamide: May increase cyclophosphamide myelosuppressive effect, increasing risk of bleeding and infection

• Warfarin: May increase anticoagulant effect of coumarins

• Thiazide diuretics: May decrease renal elimination of allopurinol. Monitor need for dose adjustment.

Drug/laboratory tests

• May increase serum BUN, alkaline phosphatase, ALT, AST, creatinine

Drugs/food

• None known

Side effects

• CNS: Chills, drowsiness, fever, headache,

neuritis, paresthesia, peripheral neuropathy,

somnolence

• CV: Vasculitis

• EENT: Epistaxis, loss of taste

• GI: Abdominal pain, diarrhea, dysphagia, elevated liver function test results, gastritis, granulomatous hepatitis, hepatic necrosis, hepatomegaly, nausea, vomiting

• GU: Exacerbated renal calculi, renal failure

• HEME: Agranulocytosis, aplastic anemia, bone marrow depression, eosinophilia,

leukocytosis, leukopenia, thrombocytopenia

• MS: Arthralgia, exacerbation of gout, myopathy

• SKIN: Alopecia; ecchymosis; jaundice; maculopapular, scaly, or exfoliative rash (sometimes fatal); pruritus; urticaria

Nursing considerations

Baseline assessment

• Obtain baseline BMP, LFT. 

• Instruct pt to drink minimum of 2,500–3,000 mL of fluid daily while taking medication

Intervention/evaluation

• Discontinue medication immediately if rash or other evidence of allergic

reaction occurs

• Monitor I&O (output should be at least 2,000 mL/day)

• Assess serum chemistries, uric acid, hepatic function. Assess urine for cloudiness, unusual color, odor

• Gout: Assess for therapeutic response: relief of pain, stiffness, swelling; increased joint mobility; reduced joint tenderness; improved grip strength

Equipment must be available for anaphylaxis

• Assess for pain including location, characteristics, onset/duration, frequency, quality, intensity or severity of pain, precipitating factors; gout: joint pain, swelling, may use with NSAIDs for acute gouty attacks

• Monitor uric acid levels q2wk; normal uric acid levels are 6 mg/dl or less; effect may take several wk; check I&O ratio, increase fluids to 2 L/day to prevent stone formation, toxicity

• Monitor CBC, AST, BUN, creatinine before starting treatment, monthly; check blood glucose in diabetic patients

Evaluation

Positive therapeutic result

• Decreased pain in joints

• Decreased stone formation in kidney

• Decreased uric acid level to 6 mg/dl

Patient/family teaching

• Tell patient To take as prescribed; if dose is missed, take as soon as remembered; do not double dose; tabs may be crushed

• Instruct patient to take with or immediately after meals or milk. Drink enough fluid daily to maintain a urine output of 2 L/day, if possible

• Tell patient to Maintain adequate hydration; drink 2,500–3,000 mL of fluid daily while taking medication

• Instruct patient to report unusual bleeding or bruising, fever, chills, gout attack, numbness, and tingling.

• Inform patient that acute gout attacks may occur more often early in allopurinol

treatment and that results may not be noticeable for 2 weeks or longer

• Instruct patient not to drive or perform hazardous tasks if drug causes drowsiness

• Tell patient to report skin rash, stomatitis, malaise, aching; product should be

discontinued

• Advise patient to avoid hazardous activities if drowsiness or dizziness occurs; response may take several days to determine

• Tell patient to avoid alcohol, caffeine; these substances increase uric acid levels and decrease allopurinol levels

• Teach patient to report side effects and adverse reactions to prescriber, including rash, itching, nausea, vomiting

• Instruct patient to administer dosages > 300 mg/day in divided doses. It may take 1 wk or longer for the full therapeutic effect of the drug to be evident.

• Inform patient that for IV use, reconstitute 500-mg vial with 25 mL sterile water for injection, which produces a clear, almost colorless solution (concentration of

20 mg/mL). Further dilute with 0.9% NaCl or D5W as desired, with a final maximum concentration of 6 mg/mL. Infuse over 30-60 min