Allopurinol is often considered to be one of the top 100 most-prescribed medications in the U.S., so it will definitely be on your exams or something you’ll see in the clinical setting. Let’s go through all the things you need to know about allopurinol using the Straight A Nursing DRRUGS framework. 

D: Drug Class

Allopurinol is one of those medications classed both pharmacologically and therapeutically. It is in the pharmacologic class of xanthine oxidase inhibitors, and in the therapeutic class of antigout agents and antihyperuricemics. 

So let’s look at that pharmacologic class. Xanthine oxidase is the enzyme that synthesizes the formation of uric acid from the purine, hypoxanthine. Purines are organic compounds made up of nitrogen and carbon atoms, and can be differentiated as endogenous or exogenous. 

Endogenous purines make up the majority of the purines in the body. These are the purines the body produces and are found within cells. As cells dye or are damaged, the body must process the purines that are released. On the other hand, are exogenous purines. Exogenous purines are those that are obtained via nutrition. As the body processes purines, a byproduct called uric acid is formed. In normal physiology, most uric acid is reabsorbed and the rest is excreted via feces and urine.

When uric acid builds up (hyperuricemia), this can lead to the formation of kidney stones and the development of gout, which is a painful inflammation of the joints. This is why your patients with these conditions will be advised to avoid eating foods high in purines. Examples are meats (especially organ meats), sugary foods and sodas, seafood (especially mackerel, sardine, scallops, herring and anchovies), and alcohol.

R: Routes of Allopurinol Administration

Allopurinol is given PO and IV (we’ll talk about the different indications for each in just a moment!).

R: Regular Dose Range for Allopurinol

The regular dose range for PO allopurinol will vary a bit based on why it is being used and the patient’s level of uric acid. In general, you will see dose ranges for adults from 100 to 800 mg/day. For doses above 300 mg/day it is recommended that allopurinol be given in divided doses.

The adult IV dose of allopurinol ranges from 200 to 400 mg/m2/day with a max dose of 600 mg/day. This can be administered as one single dose or divided doses.

As with many medications, the dose will be adjusted in cases of renal impairment. Depending on the severity of impairment, the dose will be decreased by 30 up to 50%.

U: Uses of Allopurinol

PO allopurinol is used for patients with gout (sometimes referred to as gouty arthritis) and to prevent kidney stones secondary to hyperuricemia. Both PO and IV allopurinol are used to treat hyperuricemia in patients receiving treatment for tumors or leukemias.

There area few off-label uses of allopurinol, so you may see it prescribed for your patients for a variety of conditions not directly related to hyperuricemia:

  • Dermatology – Allopurinol may be used for psoriasis, sarcoidosis, and cutaneous leishmaniasis
  • Cardiology – Evidence shows a direct relationship between hyperuricemia and cardiovascular events. Allopurinol has been shown to improve exercise capacity and endothelial function in individuals with angina. It’s ability to decrease oxidative stress has shown to be beneficial in congestive heart failure, improving contractility and left ventricular ejection fraction.
  • Malaria – Studies show that allopurinol, when given with quinine, can be an effective and faster therapy for malaria than quinine alone.
  • Schizophrenia – Through its action as a xanthine oxidase inhibitor, allopurinol can lead to increased adenosine levels in the body (in fact, you may hear it referred to as an adenosine agonist for this reason). Adenosine is a neuromodulator that affects the glutamatergic and dopaminergic pathways, which are dysfunctional in individuals with schizophrenia. For this reason, allopurinol has been shown to be helpful when used as an adjunct in pharmacologic treatment of this disease.

G: Guidelines for Allopurinol Administration

Key factors in safe and effective allopurinol administration are: 

  • Teach patients that it may take a while for the medication to dissolve the uric acid crystals and they could still have gout attacks while initially taking the medication, especially if their levels are high or they’ve had gout for a long period of time.
  • Allopurinol is typically not prescribed to individuals of Korean, Han-Chinese or Thai origin due to the likelihood of the HLA-B*5801 allele which puts them at risk for a severe cutaneous adverse reaction called allopurinol hypersensitivity syndrome.
  • Further, all individuals who could have this allele are likely to get testing prior to allopurinol administration. This includes all individuals of Asian, African, and Native Hawaiian/Pacific Islander ancestry.
  • Allopurinol is used cautiously if a current attack of gout is occurring and will not stop the attack.
  • Allopurinol has several drug-drug interactions. It will increase the effects of warfarin as well as cyclosporine levels. Additionally, there is a higher risk of hypersensitivity reaction if used concurrently with ACE inhibitors or thiazide diuretics. (There are others, but these are the most common medications.)
  • Ensure the patient understands adequate hydration is a priority. Dehydration puts the patient at increased risk for the formation of renal calculi. Additionally, dehydration can worsen gout.
  • Monitor intake and output to ensure adequate hydration and to monitor for obstructive kidney stone formation.
  • For individuals with gout, monitor their pain and joint swelling.
  • Lab tests include: serum and urine uric acid levels (which should start to decrease after a few days of therapy), CBC (may cause anemia or thrombocytopenia due to bone marrow suppression), renal function (can cause increased BUN and creatinine), and hepatic function (can lead to elevated AST, ALT, alk phos and bilirubin levels). Blood glucose levels will be assessed in individuals taking an oral hypoglycemic as allopurinol can potentiate the hypoglycemic effect of these drugs. 
  • To minimize gastric irritation, allopurinol can be given with meals or milk.
  • If given to patients receiving chemotherapy, it is given 24-48 hours before the chemotherapeutic agent.
  • The patient may be advised to avoid alcohol and adopt a more alkaline diet rich in fruits and vegetables to improve uric acid levels in the body.
  • Teach the patient to report any skin rashes as this is a potential sign of hypersensitivity.

S: Side Effects of Allopurinol

The most serious side effects of allopurinol are dermatological in nature. These include Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS (drug reaction with eosinophilia and systemic symptoms).

Allopurinol hypersensitivity syndrome, though rare, is a severe (and even life-threatening) adverse reaction that is associated with the HLA-B*5801 allele, but can also occur in individuals without this allele in their genetic makeup. Other factors that put a patient at risk for AHS are a higher starting dose of allopurinol, renal impairment, and concurrent use of a thiazide diuretic. Signs of AHS include a severe rash, blisters, jaundice, fever, acute renal failure, eosinophilia and GI bleeding.

More common effects are rash, GI upset and drowsiness.

TL;DR 

Allopurinol is a medication mainly used to treat gout and prevent kidney stone formation, though you may also see it used in tumor lysis syndrome or in patients at risk for TLS who are receiving cancer treatment. Teach patients that they may still have gout attacks when initiating therapy, and that this does not mean the medication is not working. Allopurinol has several drug-drug interactions and can potentiate the effects of warfarin, cyclosporine and oral hypoglycemics. Teach patients to drink enough water to ensure proper hydration and to adopt a diet rich in fruits and vegetables. The most serious side effects are dermatologic in nature, and having the HLA-B*5801 allele puts the individual at higher risk for allopurinol hypersensitivity reaction.

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References:

Dean, L., & Kane, M. (n.d.). Allopurinol Therapy and HLA-B*58:01 Genotype—Medical Genetics Summaries—NCBI Bookshelf. Retrieved January 11, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK127547/

Drugs.com. (n.d.). Allopurinol Disease Interactions. Drugs.Com. Retrieved January 11, 2022, from https://www.drugs.com/disease-interactions/allopurinol.html

Esche, J., Krupp, D., Mensink, G. B., & Remer, T. (2018). Dietary Potential Renal Acid Load Is Positively Associated with Serum Uric Acid and Odds of Hyperuricemia in the German Adult Population. The Journal of Nutrition, 148(1), 49–55. https://doi.org/10.1093/jn/nxx003

Favus, M. J., & Coe, F. L. (1980). The effects of allopurinol treatment on stone formation on hyperuricosuric calcium oxalate stone-formers. Scandinavian Journal of Urology and Nephrology. Supplementum, 53, 265–271.

Halevy, S., Ghislain, P.-D., Mockenhaupt, M., Fagot, J.-P., Bouwes Bavinck, J. N., Sidoroff, A., Naldi, L., Dunant, A., Viboud, C., Roujeau, J.-C., & EuroSCAR Study Group. (2008). Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. Journal of the American Academy of Dermatology, 58(1), 25–32. https://doi.org/10.1016/j.jaad.2007.08.036

Hande, K. R. (1986). Evaluation of a thiazide-allopurinol drug interaction. The American Journal of the Medical Sciences, 292(4), 213–216. https://doi.org/10.1097/00000441-198610000-00006

Kelkar, A., Kuo, A., & Frishman, W. H. (2011). Allopurinol as a cardiovascular drug. Cardiology in Review, 19(6), 265–271. https://doi.org/10.1097/CRD.0b013e318229a908

Lee, H. Y., Pang, S. M., & Thamotharampillai, T. (2008). Allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis. Journal of the American Academy of Dermatology, 59(2), 352–353. https://doi.org/10.1016/j.jaad.2008.02.021

Lintunen, J., Lähteenvuo, M., Tiihonen, J., Tanskanen, A., & Taipale, H. (2021). Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia. Npj Schizophrenia, 7(1), 1–7. https://doi.org/10.1038/s41537-020-00135-y

Lupton, G. P., & Odom, R. B. (1979). The allopurinol hypersensitivity syndrome. Journal of the American Academy of Dermatology, 1(4), 365–374. https://doi.org/10.1016/s0190-9622(79)70031-4

Martinez, S., & Marr, J. J. (1992). Allopurinol in the Treatment of American Cutaneous Leishmaniasis. New England Journal of Medicine, 326(11), 741–744. https://doi.org/10.1056/NEJM199203123261105

MD, J. F. (n.d.). What Are Purines? Arthritis-Health. Retrieved January 11, 2022, from https://www.arthritis-health.com/types/gout/what-are-purines

Rothschild, B. (n.d.). Which medications in the drug class Xanthine Oxidase Inhibitors are used in the treatment of Gout and Pseudogout? Retrieved January 11, 2022, from https://www.medscape.com/answers/329958-13556/which-medications-in-the-drug-class-xanthine-oxidase-inhibitors-are-used-in-the-treatment-of-gout-and-pseudogout

Sarma, P. S., Mandal, A. K., & Khamis, H. J. (1998). Allopurinol as an additive to quinine in the treatment of acute complicated falciparum malaria. The American Journal of Tropical Medicine and Hygiene, 58(4), 454–457. https://doi.org/10.4269/ajtmh.1998.58.454

Slobodnick, A., Toprover, M., Greenberg, J., Crittenden, D. B., Pike, V. C., Qian, Y., Zhong, H., & Pillinger, M. H. (2020). Allopurinol use and type 2 diabetes incidence among patients with gout. Medicine, 99(35), e21675. https://doi.org/10.1097/MD.0000000000021675

Stamp, L. K., & Barclay, M. L. (2018). How to prevent allopurinol hypersensitivity reactions? Rheumatology, 57(suppl_1), i35–i41. https://doi.org/10.1093/rheumatology/kex422

Stamp, L. K., & Chapman, P. T. (2020). Allopurinol hypersensitivity: Pathogenesis and prevention. Best Practice & Research Clinical Rheumatology, 34(4), 101501. https://doi.org/10.1016/j.berh.2020.101501

Tsai, T.-F., & Yeh, T.-Y. (2010). Allopurinol in dermatology. American Journal of Clinical Dermatology, 11(4), 225–232. https://doi.org/10.2165/11533190-000000000-00000

Versus Arthritis. (n.d.). Allopurinol. Versus Arthritis. Retrieved January 11, 2022, from https://www.versusarthritis.org/about-arthritis/treatments/drugs/allopurinol/

WebMD. (n.d.). Allopurinol Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing. Retrieved January 11, 2022, from https://www.webmd.com/drugs/2/drug-8610/allopurinol-oral/details