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Urinary Tract and Kidney Warnings on Nonprescription Products

W. Steven Pray, PhD, DPh
Bernhardt Professor, Nonprescription Products and Devices

College of Pharmacy

Southwestern Oklahoma State University

Weatherford, Oklahoma

Gabriel E. Pray, PharmD
Walmart Pharmacy

Edmond, Oklahoma



8/20/2014

US Pharm. 2014;39(8):12-15. 

Pharmacists are in a unique position with regard to counseling about OTC products. They can explore the various warnings and precautions on a product’s label to help patients decide when a product is inappropriate and a physician should be consulted, a process called pharmacist-assisted self-care triage. Many nonprescription products carry warnings related to the urinary tract, and knowledge of those products and the rationale for the warnings can help pharmacists provide the highest level of care.

Prostate Warnings

An enlarged prostate is a fact of life for males, especially as they reach the age of 40 years and beyond; by the age of 80 years, at least 90% of men suffer from benign prostatic hyperplasia (BPH).1 Because of its location surrounding the urethra, an enlarged prostate usually inhibits urine flow.2 Several classes of nonprescription products are contraindicated in men with BPH, because they contain alpha-adrenergic agonists and/or anticholinergics.

Alpha-adrenergic agents such as pseudoephedrine, phenylephrine, and ephedrine all act to increase sphincter strength at the neck of the bladder, inhibiting a patient’s ability to urinate.3 For this reason, most nonprescription medications with these ingredients warn against use if the patient has decreased urination due to an enlarged prostate. If the patient were to ignore the warnings and use the product anyway, it is possible that acute urinary retention could result, requiring emergency catheterization to relieve the distended bladder.4

Alpha-adrenergic agonists (i.e., sympathomimetics) are found in numerous products marketed for the common cold, flu symptoms, and sinus problems, as well as in single-entity oral nasal decongestant products (e.g., Sudafed, Sudafed PE), topical nasal decongestants (e.g., Afrin, Neo-Synephrine), asthma products (e.g., Primatene), hemorrhoid products (e.g., several Preparation H products), and some ophthalmic drops (e.g., Opcon-A, Naphcon-A, Visine-A).5

Nonprescription medications with anticholinergic effects could also inhibit bladder flow.6 The target group for this labeling includes the large number of products containing first-generation antihistamines, such as chlorpheniramine, clemastine, cyclizine, dimenhydrinate, diphenhydramine, doxylamine, meclizine, pheniramine, and pyrilamine. Some products containing them are safe and effective for treating allergic rhinitis and/or the common cold, such as Chlor-Trimeton, Tavist, and Benadryl. Others help relieve occasional insomnia (e.g., Nytol, Unisom). They are also the single ingredient in products for preventing and treating motion sickness (e.g., Dramamine, Bonine, Marezine) and are a component of ophthalmic vasoconstrictor/antihistamine drops (e.g., Opcon-A, Naphcon-A, Visine-A). They are also found in numerous combination products marketed for the common cold and related conditions. All of these products will carry the required prostate warning.5

Kidney Disease

A number of nonprescription products carry a vague warning against use if the patient has “kidney disease.” The spectrum of kidney disease is exceedingly broad, but the label was apparently kept nonspecific so that all patients with any type of kidney disease would be alerted to seek professional advice before using them.

Antacid product labels must display the kidney disease warning if they contain >50 mEq of magnesium or >25 mEq of potassium per maximum recommended daily dose. The warning is intended to prevent hypermagnesemia and hyperkalemia in patients with a reduced ability to eliminate these ions through urination. Such products include Maalox Advanced Regular Strength Liquid and Alka-Seltzer Gold.5

Certain histamine2 (H2)-blockers carry the kidney disease precaution, as they are primarily eliminated renally.7 These include Pepcid AC Maximum Strength and Zantac 150.5 The lower-dose formulations of both of these products are not required to carry a kidney disease precaution.

Laxatives containing magnesium also carry a warning against use in patients with kidney disease. Like antacids, laxatives must carry a kidney disease warning if they contain >50 mEq of magnesium per maximum recommended daily dose. This would apply to Phillips’ Milk of Magnesia and magnesium citrate products such as Citroma. Another laxative with a kidney disease warning is polyethylene glycol (PEG) 3350 (e.g., MiraLAX). The concern is apparently that PEG might cause volume depletion.8

Oral analgesics may carry a warning against use with kidney disease. For the same reasons mentioned above (i.e., avoiding hypermagnesemia), the precaution is found on magnesium salicylate-containing analgesics, such as Doan’s Pain Reliever.5

One of the more inclusive labeling changes in regard to kidney disease was proposed by the FDA in a 2006 issue of the Federal Register and finalized in 2009.9,10 The FDA stated that it had received serious adverse event reports regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and renal toxicity. The agency affirmed that most healthy people who ingest NSAIDs for a limited time tolerate them well.9 However, the FDA went on to list a group of patients who are predisposed to adverse renal effects when taking NSAIDs. The possible sequelae are life-threatening nephro-toxicity, such as acute renal failure and serious fluid and electrolyte disorders. Patients more prone to this adverse effect include those with volume depletion, underlying kidney disease, congestive heart failure, liver dysfunction with ascites, and the elderly. Furthermore, use during the last trimester of pregnancy can induce significant neonatal nephrotoxicity.

In further discussion, the FDA explored the link between NSAIDs and nephrotoxicity.9,10 For instance, a decrease in renal production of vasodilatory prostaglandins would lead to acute reduction in blood flow and glomerular filtration. These changes would be expected to cause fluid retention, edema, and elevated serum creatinine. Thus, a pronounced decrease in renal perfusion could cause renal failure.

As a result of its exhaustive investigation of this issue, the FDA now requires the kidney disease warning on all products containing aspirin, magnesium salicylate, ibuprofen, naproxen, and ketoprofen.10

Second-generation antihistamines carry a warning against self-use with kidney disease. The products include loratadine (e.g., Claritin), cetirizine (e.g., Zyrtec), and fexofenadine (e.g., Allegra 24HR).5

Kidney Stones

As of this writing, the only non-prescription products to carry a specific warning against use with kidney stones are oxybutynin transdermal patches (Oxytrol for Women) and orlistat (alli). Orlistat can induce oxalate nephropathy
and resultant renal stone disease.11 Oxalate nephropathy is characterized as a “rare but serious adverse effect” of orlistat directly due to an increase in fat malabsorption, which is the mechanism by which orlistat helps with weight loss.12

Limited Fluid Intake Due to Renal Disease

Patients with renal failure or any other condition that requires them to limit fluid intake should be cautious in the use of fiber-replacement products such as psyllium (e.g., Metamucil) and methylcellulose (e.g., Citrucel).5

Oxybutynin Transdermal System

The most extensive set of warnings related to the urinary tract on any nonprescription product label is found on oxybutynin transdermal system (Oxytrol for Women).13 The product is indicated only for overactive bladder in women, characterized by two or more of the following (lasting for 3 months or more): urinary frequency more than 8 times in 24 hours, urinary urgency, and/or urge incontinence. The label warns prospective purchasers that frequent urination may also be caused by a urinary tract infection (UTI), diabetes, early pregnancy, and other more serious conditions, all of which require a physician appointment. The label also points out various symptoms of UTI, any of which would require an immediate physician appointment, including pain or burning when urinating (perhaps accompanied by fever or chills), blood in the urine, unexplained pain in the lower back or side, and/or urine that is cloudy or foul-smelling.13

Women are advised not to use Oxytrol if they only experience accidental urine loss when they cough, sneeze, or laugh, as those are characteristic of stress incontinence, which will not be alleviated by the product. Patients who have urinary retention are cautioned not to use the product. The patch is not to be used if the patient has kidney stones. Patients are advised to stop use and make a physician appointment if they are not able to empty the bladder.13

Suggesting Alternative Approaches

The pharmacist can suggest alternative therapeutic approaches for patients with urinary tract contraindications in some cases. Nasal congestion may be relieved by nasal strips such as Breathe Right, as they are safe for those with urinary compromise. Redness of the eye may be treated with single-entity ophthalmic drops (e.g., Visine), which do not carry prostate warnings. Allergic conjunctivitis may be treated with a single-entity ophthalmic antihistamine, such as Zaditor, as it is also free of urinary tract precautions.5

Nonprescription antihistamines all carry urinary tract warnings: against use in patients with prostatic enlargement in the case of first-generation products, and against use in kidney disease in the case of second-generation products. Patients with allergic rhinitis can be advised to try cromolyn nasal spray (NasalCrom) or triamcinolone acetonide nasal spray (Nasacort Allergy 24HR). Neither carries a warning concerning the urinary tract.5

In regard to gastric products, patients may try such antacid ingredients as calcium carbonate (e.g., Tums) or bismuth subsalicylate (e.g., Pepto-Bismol). They may also try the lower dose versions of Pepcid and Zantac, neither of which carries a urinary tract warning. Further, none of the four currently available proton pump inhibitors (e.g., Prilosec OTC, Prevacid 24HR, Zegerid OTC, Nexium 24HR) carries a urinary tract-related label precaution, and may be recommended for the patient with frequent heartburn, as defined on the label of those products.5

Acetaminophen is free of urinary tract warnings, and may be preferable for the patient with kidney disease. However, as with all nonprescription product counseling sessions, pharmacists should point out the numerous additional warnings and situations in which acetaminophen is contraindicated, such as with liver disease.5

PATIENT INFORMATION

Prostate Problems

The prostate is a male organ that circles the urinary outflow channel leading from the bladder. As men age, a large percentage of them develop a condition known as benign prostatic hyperplasia, or enlargement of the prostate. An enlarged prostate slowly restricts bladder outflow, making it difficult to urinate. Some nonprescription products can make it even harder to urinate, and the patient who takes them without reading and following the label may need to visit an emergency room to be catheterized so the bladder can be emptied.

These patients should first speak to their physician so the doctor can judge whether they might be able to use such a product in their particular situation. Products of concern include nasal decongestants (e.g., pseudoephedrine, phenylephrine, naphazoline), as found in such dosage forms as tablets, oral liquids, nasal sprays, and nasal drops. Nasal decongestants are also popular ingredients in combination products for the common cold, allergic rhinitis, sinus problems, and flu symptoms.

Some antihistamines are also hard on the prostate. They are found in products for the common cold and allergic rhinitis, motion sickness products, sleep aids, and some eye drops. Ingredients of concern include doxylamine, clemastine, cyclizine, meclizine, chlorpheniramine, diphenhydramine, dimenhydrinate, and pheniramine.

If you do not have a physician who can be consulted, you should ask your pharmacist. Pharmacists can often suggest therapeutic alternatives that would be risk-free for those with prostate enlargement.

Kidney Disease

Some nonprescription products are eliminated from your body via your urine. They include some antacids (products containing magnesium and/or potassium), other stomach medications (some products containing ranitidine or famotidine), some laxatives (those containing magnesium), and certain antihistamines (loratadine, cetirizine, and fexofenadine). If your body’s ability to eliminate these medications is compromised by kidney disease, the drug levels in your blood can endanger your health. Your physician should be consulted to make a decision about possibly lowering the dose on the label so you will be safe. Once again, your pharmacist can help you with therapeutic alternatives that do not present problems with kidney disease, when they are available.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a type of pain medication that can cause kidney damage, especially if you already have kidney disease. Examples include aspirin, magnesium salicylate, ibuprofen, naproxen, and ketoprofen. It is best to avoid NSAIDs completely and speak to your physician or pharmacist about safer alternatives.

Kidney Stones

If you have kidney stones, you should avoid taking the OTC weight-loss product alli (due to an increase in fat malabsorption). You should also not use Oxytrol for Women, a patch product for overactive bladder in women, because it might possibly cause urinary retention.

Limited Fluid Intake Due to Renal Disease

Some patients have kidney damage that forces them to limit their fluid intake to prevent fluid overload. If you have this problem, you should avoid nonprescription products that must be taken with a lot of fluid so you can get them down. This includes bowel regulation products containing psyllium and methylcellulose. 

REFERENCES

1. Enlarged prostate. MedlinePlus. www.nlm.nih.gov/medlineplus/ency/article/000381.htm. Accessed June 20, 2014.
2. Prostate enlargement: benign prostatic hyperplasia. National Kidney and Urologic Diseases Information Clearinghouse. http://kidney.niddk.nih.gov/kudiseases/pubs/prostateenlargement/. Accessed June 20, 2014.
3. Stress incontinence. MedlinePlus. www.nlm.nih.gov/medlineplus/ency/article/000891.htm. Accessed June 20, 2014.
4. Soyer T, Göl IH, Eroglu F, Cetin A. Acute urinary retention due to pseudoephedrine hydrochloride in a 3-year-old child. Turk J Pediatr. 2008;50(1):98-100.
5. Various products. www.drugstore.com. Accessed June 20, 2014.
6. Roehrborn CG. Acute urinary retention: risks and management. Rev Urol. 2005;7(suppl 4):S31-S41.
7. Ranitidine 150 mg. National Institutes of Health. http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=41453. Accessed June 20, 2014.8. Cohen LB, Kastenberg DM, Safdi AV. Current issues in clinical bowel preparation. Gastroenterol Hepatol. 2009;5(11 suppl 19):3-11.
9. FDA. Internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; proposed amendment of the tentative final monograph; required warnings and other labeling. Fed Regist. 2006;71(247):77314-77353.
10. FDA. Organ-specific warnings; internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; final monograph. Fed Regist. 2009;74(81):19385-19409.
11. Ahmed MH. Orlistat and calcium oxalate crystalluria: an association that needs consideration. Ren Fail. 2010;32(8):1019-1021.
12. Chaudhari D, Crisostomo C, Youngberg G. Acute oxalate nephropathy associated with orlistat: a case report with a review of the literature. Case Rep Nephrol. 2013;2013:124604. www.ncbi.nlm.nih.gov/pmc/articles/PMC3914170/. Accessed June 20, 2014.
13. Oxytrol for Women (oxybutynin transdermal system) package insert. Whitehouse Station, NJ: MSD Consumer Care, Inc; 2014.14. CDC. Prostate cancer. What are the symptoms? www.cdc.gov/cancer/prostate/basic_info/symptoms.htm. Accessed June 20, 2014.
15. Prostatitis—bacterial. MedlinePlus. www.nlm.nih.gov/medlineplus/ency/article/000519.htm. Accessed June 20, 2014.

To comment on this article, contact rdavidson@uspharmacist.com.

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