FDA Drug Safety Communication: FDA warns of possible harm from exceeding recommended dose of over-the-counter sodium phosphate products to treat constipation
- Safety Announcement
- Facts about over-the-counter (OTC) sodium phosphate drug products
- Additional Information for Patients
- Additional Information for Health Care Professionals
- Data Summary
[1-8-2014] The U.S. Food and Drug Administration (FDA) is warning that using more than one dose in 24 hours of over-the-counter (OTC) sodium phosphate drugs to treat constipation can cause rare but serious harm to the kidneys and heart, and even death. OTC sodium phosphate drug products include oral solutions taken by mouth and enemas used rectally. Consumers and health care professionals should always read the Drug Facts label for OTC sodium phosphate drugs and use these products as recommended on the label, and not exceed the labeled dose. Caregivers should not give the oral products to children 5 years and younger without first discussing with a health care professional. Health care professionals should use caution when recommending an oral dose of these products for children 5 years and younger. The rectal form of these products should never be given to children younger than 2 years.
FDA has become aware of reports of severe dehydration and changes in the levels of serum electrolytes from taking more than the recommended dose of OTC sodium phosphate products, resulting in serious adverse effects on organs, such as the kidneys and heart, and in some cases resulting in death. These serum electrolytes include calcium, sodium, and phosphate. According to the reports, most cases of serious harm occurred with a single dose of sodium phosphate that was larger than recommended or with more than one dose in a day.
Some individuals may be at higher risk for potential adverse events when the recommended dose of OTC sodium phosphate is exceeded. These individuals include young children; individuals older than 55 years; patients who are dehydrated; patients with kidney disease, bowel obstruction, or inflammation of the bowel; and patients who are using medications that may affect kidney function. These medications include diuretics or water pills; angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) used to treat high blood pressure; and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen.
Facts about over-the-counter (OTC) sodium phosphate drug products
- Used for the relief of occasional constipation.
- Available as a solution for oral or rectal (enema) use.
- Available as single-ingredient drug products, containing either sodium biphosphate or sodium phosphate, and as combination drug products containing both ingredients.
- The recommended dose is a single dose given once a day for not more than 3 days.
- Marketed under the brand-name Fleet, and as store brands and generic products.
Additional Information for Patients
- Always read and follow the directions on the Drug Facts labels included on over-the-counter sodium phosphate oral solutions and rectal enemas to find out the correct dose and dosing frequency. Changes in blood electrolyte levels, resulting in serious harm to the kidneys and heart and, more rarely, death, have occurred in adults and children who used more than the recommended dose of OTC sodium phosphate products to treat constipation.
- Do not use more than one dose of these products in 24 hours. Even if you or your children do not have a bowel movement after taking a single oral or rectal dose, do not use another dose within 24 hours. Contact a health care professional for advice.
- Serious harm can occur with use of either the oral or rectal forms of OTC sodium phosphate.
- Do not give these products rectally to children younger than 2 years.
- Do not give these products by mouth to children 5 years and younger without first talking with a health care professional.
- Talk with a health care professional before using these products if you are older than 55 years; have kidney disease, bowel inflammation or bowel obstruction; have heart or kidney failure; are dehydrated; or take certain medications. These medications include diuretics or water pills; angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) to treat high blood pressure; and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen.
- If you or your child experiences symptoms of kidney injury, seek medical attention immediately and do not take another dose of the product. Symptoms of kidney injury include drowsiness, sluggishness, decreased amount of urine, or swelling of the ankles, feet, and legs.
- Report side effects from OTC sodium phosphate drug products to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of this page.
Additional Information for Health Care Professionals
- Severe dehydration and electrolyte abnormalities associated with serious complications such as acute kidney injury, arrhythmias, and death have occurred in adults and children who overdosed using oral or rectal over-the-counter (OTC) sodium phosphate solutions to treat constipation.
- The severity of adverse events is similar regardless of the route of sodium phosphate administration. Rectal forms of sodium phosphate drug products should not be considered safer than the oral forms.
- Rectal sodium phosphate drug products should not be used at all in children younger than 2 years.
- Use caution if recommending use of an oral OTC sodium phosphate drug product in children 5 years and younger.
- Avoid exceeding the maximum recommended rectal or oral dose of sodium phosphate products for both children and adults.
- Additional doses are not recommended within 24 hours for patients who do not have a bowel movement after taking an oral or rectal dose.
- Avoid concomitant treatment with laxatives containing sodium phosphate.
- Use caution when recommending these products to patients at potentially higher risk for product-related adverse events. These include those older than 55 years; patients with hypovolemia; or decreased intravascular volume; those who have baseline kidney disease, decreased bowel transit time, bowel obstruction, or active colitis; and those who are using medications that affect renal perfusion or function, such as diuretics, ACEIs, ARBs, or NSAIDs.
- Advise patients to ensure they are adequately hydrated during product use. Assess serum electrolytes and renal function in patients who may be at higher risk for product-related adverse events, which includes those who have retained a rectal dose for more than 30 minutes, who are vomiting, or who may have signs of dehydration.
- Report adverse events involving OTC sodium phosphate drug products to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of this page.
FDA reviewed the FDA Adverse Event Reporting System (FAERS) database from 1969 through 2012 and the medical literature from 1957 through August 2013 for cases describing serious adverse events associated with the oral or rectal use of over-the-counter (OTC) sodium phosphate drug products used to treat constipation. We identified 54 cases describing serious adverse events in 25 adults and in 29 children. Ten cases were reported to the FAERS database and 44 were published in the medical literature. 1-39 The age of the consumers ranged widely from 8 days to 97 years, but most cases involved older adults and children younger than 5 years. Nearly two-thirds of the adults and nearly half of the children in whom adverse events were reported had one or more of the following:.
- Dehydration, kidney disease, acute colitis, or delayed bowel emptying
- Concomitant use of drugs that act on renal function, including diuretics, ACEIs, ARBs, and NSAIDs
- Moseley PK, Segar WE. Fluid and serum electrolyte disturbances as a complication of enemas in Hirschsprung's disease. Am J Dis Child 1968;115:714-8.
- Young JF, Brooke BN. Enema shock in Hirschsprung's disease. Dis Colon Rectum 1968;11:391-5.
- Chesney RW, Haughton PB. Tetany following phosphate enemas in chronic renal disease. Am J Dis Child 1974;127:584-6.
- Oxnard SC, O'Bell J, Grupe WE. Severe tetany in an azotemic child related to a sodium phosphate enema. Pediatrics 1974;53:105-6.
- Swerdlow DB, Labow S, D'Anna J. Tetany and enemas: report of a case. Dis Colon Rectum 1974;17:786-7.
- Zipser RD, Bischel MD, Abrams DE. Hypocalcemic tetany due to sodium phosphate ingestion in acute renal failure. Nephron 1975;14:378-81.
- Davis RF, Eichner JM, Bleyer WA, Okamoto G. Hypocalcemia, hyperphosphatemia, and dehydration following a single hypertonic phosphate enema. J Pediatr 1977;90:484-5.
- Loughnan P, Mullins GC. Brain damage following a hypertonic phosphate enema. Am J Dis Child 1977;131:1032.
- Forman J, Baluarte HJ, Gruskin AB. Hypokalemia after hypertonic phosphate enemas. J Pediatr 1979;94:149-51.
- Biberstein M, Parker BA. Enema-induced hyperphosphatemia. Am J Med 1985;79:645-6.
- Haskell LP. Hypocalcaemic tetany induced by hypertonic-phosphate enema. Lancet 1985;2:1433.
- Spinrad S, Sztern M, Grosskopf Y, Graff E, Blum I. Treating constipation with phosphate enema: an unnecessary risk. Isr J Med Sci 1989;25:237-8.
- Wason S, Tiller T, Cunha C. Severe hyperphosphatemia, hypocalcemia, acidosis, and shock in a 5-month-old child following the administration of an adult Fleet enema. Ann Emerg Med 1989;18:696-700.
- Edmondson S, Almquist TD. Iatrogenic hypocalcemic tetany. Ann Emerg Med 1990;19:938-40.
- McCabe M, Sibert JR, Routledge PA. Phosphate enemas in childhood: cause for concern. BMJ 1991;302:1074.
- Korzets A, Dicker D, Chaimoff C, Zevin D. Life-threatening hyperphosphatemia and hypocalcemic tetany following the use of fleet enemas. J Am Geriatr Soc 1992;40:620-1.
- .Hunter MF, Ashton MR, Griffiths DM, Ilangovan P, Roberts JP, Walker V. Hyperphosphataemia after enemas in childhood: prevention and treatment. Arch Dis Child 1993;68:233-4.
- Craig JC, Hodson EM, Martin HC. Phosphate enema poisoning in children. Med J Aust 1994;160:347-51.
- Selva O'Callaghan A, San Jose A, Simeon CP, Arruche M, Galicia M, Benavente V, et al. Fatal hypocalcemia from sodium phosphate enemas. J Am Geriatr Soc 1995;43:1447-8.
- Knobel B, Petchenko P. Hyperphosphatemic hypocalcemic coma caused by hypertonic sodium phosphate (fleet) enema intoxication. J Clin Gastroenterol 1996;23:217-9.
- Helikson MA, Parham WA, Tobias JD. Hypocalcemia and hyperphosphatemia after phosphate enema use in a child. J Pediatr Surg 1997;32:1244-6.
- Szabo A, Eitan A, Zveibil F, Weiss M, Waksman I, Makhoul N. Life-threatening electrolyte abnormalities induced by hypertonic phosphate enema intoxication. Clinical Intensive Care 1999;10:21-3.
- Nir-Paz R, Cohen R, Haviv YS. Acute hyperphosphatemia caused by sodium phosphate enema in a patient with liver dysfunction and chronic renal failure. Ren Fail 1999;21:541-4.
- Ismail EA, Al-Mutairi G, Al-Anzy H. A fatal small dose of phosphate enema in a young child with no renal or gastrointestinal abnormality. J Pediatr Gastroenterol Nutr 2000;30:220-1.
- Walton DM, Thomas DC, Aly HZ, Short BL. Morbid hypocalcemia associated with phosphate enema in a six-week-old infant. Pediatrics 2000;106:E37.
- Melvin JD, Watts RG. Severe hypophosphatemia: a rare cause of intravascular hemolysis. Am J Hematol 2002;69:223-4.
- Marraffa JM, Hui A, Stork CM. Severe hyperphosphatemia and hypocalcemia following the rectal administration of a phosphate-containing Fleet pediatric enema. Pediatr Emerg Care 2004;20:453-6.
- Butani L. Life-threatening hyperphosphatemia and hypocalcemia from inappropriate use of Fleet enemas. Clin Pediatr (Phila) 2005;44:93.
- Farah R. Fatal acute sodium phosphate enemas intoxication. Acta Gastroenterol Belg 2005;68:392-3.
- Domico MB, Huynh V, Anand SK, Mink R. Severe hyperphosphatemia and hypocalcemic tetany after oral laxative administration in a 3-month-old infant. Pediatrics 2006;118:e1580-3.
- Eckstein J, Savic S, Eugster T, Pargger H, Gürke L, Pechula M, et al. Extensive calcifications induced by hyperphosphataemia caused by phosphate-based enema in a patient after kidney transplantation. Nephrol Dial Transplant 2006;21:2013-6.
- Hay E, Boksenbojm P, Esther P. Case report: Fleet enema in the renal patient. Israeli Journal of Emergency Medicine 2006;6:49-51.
- Hebbar K, Fortenberry JD, Parks JS. Severe hypocalcemic tetany and respiratory failure in an infant given oral phosphate soda. Pediatr Emerg Care 2006;22:118-20.
- Hsu HJ, Wu MS. Extreme hyperphosphatemia and hypocalcemic coma associated with phosphate enema. Intern Med 2008;47:643-6.
- Biebl A, Grillenberger A, Schmitt K. Enema-induced severe hyperphosphatemia in children. Eur J Pediatr 2009;168:111-2.
- Viel G, Cecchetto G, Fabbri LD, Furlan C, Ferrara SD, Montisci M. Forensic application of ESEM and XRF-EDS techniques to a fatal case of sodium phosphate enema intoxication. Int J Legal Med 2009;123:345-50.
- Kostic D, Rodrigues AB, Leal A, Metran C, Nagaiassu M, Watanabe A, et al. Flow-through peritoneal dialysis in neonatal enema-induced hyperphosphatemia. Pediatr Nephrol 2010;25:2183-6.
- Ladenhauf HN, Stundner O, Spreitzhofer F, Deluggi S. Severe hyperphosphatemia after administration of sodium-phosphate containing laxatives in children: case series and systematic review of literature. Pediatr Surg Int 2012;28:805-14.
- Szoke D, Dolci A, Genderini A, Panteghini M. Fatal electrolyte abnormalities following enema administration. Clin Chem 2012;58:1515-8.