November 2016 FAQs

What drugs can be used to manage floppy iris syndrome during cataract surgery?

Introduction

Intraoperative floppy iris syndrome (IFIS) occurs during cataract surgery procedures and is characterized by flopping or billowing of the iris, intraoperative miosis, and iris prolapse.^1,2 Miosis is a problem because adequate pupil dilation is an important requirement for safe and effective cataract surgeries.³ Undesirable complications of IFIS include posterior capsule rupture, vitreous loss, retained fragments, increased intraocular pressure, hyphema, and corneal tissue loss.¹ Some effects may not be reversible after surgery including pupil deformity, macular edema, retinal detachment, or endophthalmitis and subsequent visual loss. Although IFIS only occurs in about 2% of cataract surgeries in the U.S., the seriousness of its consequences warrant use of appropriate preventative measures and management strategies. This article will focus on pharmacologic prevention and management techniques. Surgical management strategies have also been described in the literature but are outside the scope of this article.

Drugs associated with causing floppy iris syndrome

The etiology of IFIS has been linked to hypertension, but the strongest association is with several alpha-1 receptor antagonists that are commonly used in the management of benign prostatic hypertrophy.^1,2 Multiple agents have been implicated including tamsulosin, silodosin, alfuzosin, doxazosin, terazosin, and prazosin. Tamsulosin may have the highest risk for IFIS because of its high affinity and selectivity for the alpha-1A receptor. Observational studies suggest that 50% to 90% of patients who undergo cataract surgery and have prior exposure to tamsulosin may develop IFIS.⁴ Due to this risk, the American Society of Cataract and Refractive Surgery and the American Academy of Ophthalmology (AAO) recommend that patients with cataracts should undergo cataract surgery before starting tamsulosin or should receive a nonselective alpha-1 antagonist instead.⁵ In addition to current use of tamsulosin, past use is a risk factor for IFIS even if tamsulosin was stopped months or years before the surgical procedure.^1,2 Hypotheses regarding the pathophysiology of the long association with tamsulosin include atrophy of the dilator muscles, dysfunctional vasculature during pupillary dilation, or alpha receptor downregulation.¹

Other medications that have been associated with IFIS in case reports and observational studies include antipsychotics that affect the alpha-1 receptor (specifically chlorpromazine, quetiapine, and haloperidol), benzodiazepines, duloxetine, donepezil, finasteride, labetalol and carvedilol. ^1,6,7

Prevention of floppy iris syndrome

The best method of preventing IFIS is a thorough presurgical medication history to identify use of alpha-1 antagonists or other causative medications.¹ A medication history should also be performed in women because alpha-1 antagonists are used in women for the management of urinary voiding dysfunction. Stopping a potentially causative medication is not necessary since IFIS can occur long after discontinuation. Atropine is the most common medication that is used for prevention of IFIS in susceptible patients.^1,8,9 One regimen that is commonly used is atropine 1% drops applied 2 to 3 times daily for 1 to 2 days before surgery, although a 10-day course before surgery has been reported in the literature.^1,3,9 Atropine may help the patient to achieve adequate pupillary dilation for the procedure but has not been shown to reduce iris prolapse and may have long-lasting side effects in elderly patients.^3,10

Treatment of floppy iris syndrome

The AAO recommends that IFIS management include a combination of surgical and pharmacologic techniques.² Pharmacologic management is limited to the use of intracameral injections of vasoconstrictors (alpha-1 agonists).¹ Intracameral phenylephrine and epinephrine decrease the floppiness of the iris and help the pupil to remain dilated so that the procedure can continue. The preferred agent in the U.S. is preservative-free and bisulfite-free epinephrine but there have been shortage issues with this formulation in recent years.^1,5 One author notes anecdotal reports of using bisulfite-containing epinephrine diluted 1:4 in standard or fortified balanced salt irrigation solutions (BSS or BSS Plus, respectively) but published reports to support the safety of this practice are lacking.¹¹

Numerous epinephrine dosing modalities have been reported, including an irrigation solution of 1 mL of epinephrine 1 mg/mL in 1000 mL of BSS.³ Authors have reported the intracameral administration of 0.3 to 0.5 mL of preservative-free epinephrine diluted to a concentration of 1:2500 with BSS.¹² Preservative-free epinephrine (0.1 mL of a 0.5 mg/mL solution) diluted with 2 mL of BSS to a final concentration of 1:4000, with 1 mL injected intracamerally has also been suggested. ¹³

Epinephrine has also been combined with lidocaine for intracameral injection. In 2006, Shugar described the preparation of an epinephrine intracameral injection that is now known as “Shugarcaine”.^14,15 The formula is 3 parts BSS Plus and one part preservative-free lidocaine 4%. Three parts of this solution is mixed with one part epinephrine 1 mg/mL. One milliliter of the final solution (epinephrine concentration of 1:4000) is injected into the anterior chamber of the eye. A variation of this formula involves the use of BSS rather than BSS Plus.¹⁶ A more recent intracameral combination is as follows: 1.5 mL of BSS, 1.5 mL of preservative-free lidocaine 4%, and 1 mL of epinephrine 1 mg/mL.¹⁷ One to 2 mL of this solution was injected by the investigators before surgery; however, this solution did not reduce the incidence of IFIS compared to no prophylaxis.

Intracameral phenylephrine is commonly used in Europe.⁷ Intracameral preservative-free phenylephrine 2.5% (0.25 mL mixed with 1 or 2 mL of BSS) has been reported.^18,19 However, a preservative-free phenylephrine product is not available in the U.S. so this therapeutic strategy is not readily available to most clinicians. There have been reports of toxicities after intracameral administration, including hypertension and cardiac arrhythmias, but not all studies have observed these effects.^7,20,21

A recent abstract reported the use of an intracameral phenylephrine/ketorolac injection (Omidria) in patients with poor pupil dilation or IFIS during cataract surgery.²² Further studies with this product in patients with IFIS are needed.

Conclusion

Intraoperative floppy iris syndrome is a serious complication of cataract surgery. It is most likely to occur in patients with a history (recent or remote) of alpha-1 receptor antagonist use, particularly tamsulosin. In the U.S., intracameral epinephrine plus lidocaine is the primary pharmacologic management strategy but evidence supporting the efficacy and safety of this therapy is limited to single-center case series and retrospective reviews.^14,15,17 Topical atropine has been used in the prevention of IFIS but evidence for its use is limited. Current recommendations for prevention include taking a thorough medication history in men and women before cataract surgery. If cataract surgery is needed and cannot be performed before starting a causative mediation, surgeons can adjust their technique and be prepared to use pharmacologic treatments if IFIS develops.

References

1.         Enright JM, Karacal H, Tsai LM. Floppy iris syndrome and cataract surgery. Curr Opin Ophthalmol. 2016. DOI 10.1097/icu.0000000000000322

2.         Cataract in the Adult Eye Preferred Practice Pattern. American Academy of Opthalmology website. http://www.aao.org/Assets/e14f2979-177b-4169-8e0c-33bdf267b137/636123049525130000/cataract-in-the-adult-eye-ppp-in-press-pdf. Published September 2016. Accessed October 19, 2016.

3.         Storr-Paulsen A, Norregaard JC, Borme KK, Larsen AB, Thulesen J. Intraoperative floppy iris syndrome (IFIS): a practical approach to medical and surgical considerations in cataract extractions. Acta Ophthalmol. 2009;87(7):704-708.

4.         Ramsey E, Ramsey BL, 3rd, Childers J. Floppy iris syndrome: a drug-related complication of cataract surgery. JAAPA. 2012;25(5):37-38, 41.

5.         Intraoperative Floppy Iris Syndrome (IFIS) Associated with Systemic Alpha‐1 Antagonists – 2014. American Academy of Ophthalmology website. http://www.aao.org/clinical-statement/intraoperative-floppy-iris-syndrome-ifis-associate-2. Published April 2014. Accessed October 19, 2016.

6.         Zaman F, Bach C, Junaid I, et al. The floppy iris syndrome – what urologists and ophthalmologists need to know. Curr Urol. 2012;6(1):1-7.

7.         Tint NL, Dhillon AS, Alexander P. Management of intraoperative iris prolapse: stepwise practical approach. J Cataract Refract Surg. 2012;38(10):1845-1852.

8.         Chang DF, Braga-Mele R, Mamalis N, et al. Clinical experience with intraoperative floppy-iris syndrome. Results of the 2008 ASCRS member survey. J Cataract Refract Surg. 2008;34(7):1201-1209.

9.         Bendel RE, Phillips MB. Preoperative use of atropine to prevent intraoperative floppy-iris syndrome in patients taking tamsulosin. J Cataract Refract Surg. 2006;32(10):1603-1605.

10.       Handzel DM, Briesen S, Rausch S, Kalble T. Cataract surgery in patients taking alpha-1 antagonists: know the risks, avoid the complications. Dtsch Arztebl Int. 2012;109(21):379-384.

11.       Myers WG, Edelhauser HF. Shortage of bisulfite-free preservative-free epinephrine for intracameral use. J Cataract Refract Surg. 2011;37(3):611.

12.       Masket S, Belani S. Combined preoperative topical atropine sulfate 1% and intracameral nonpreserved epinephrine hydrochloride 1:4000 [corrected] for management of intraoperative floppy-iris syndrome. J Cataract Refract Surg. 2007;33(4):580-582.

13.       Takmaz T, Can I. Clinical features, complications, and incidence of intraoperative floppy iris syndrome in patients taking tamsulosin. Eur J Ophthalmol. 2007;17(6):909-913.

14.       Shugar JK. Use of epinephrine for IFIS prophylaxis. J Cataract Refract Surg. 2006;32(7):1074-1075.

15.       Shugar JK. Prophylaxis for IFIS. J Cataract Refract Surg. 2007;33(6):942-943.

16.       Schulze R, Jr. Epi-Shugarcaine with plain balanced salt solution for prophylaxis of intraoperative floppy-iris syndrome. J Cataract Refract Surg. 2010;36(3):523.

17.       Chen AA, Kelly JP, Bhandari A, Wu MC. Pharmacologic prophylaxis and risk factors for intraoperative floppy-iris syndrome in phacoemulsification performed by resident physicians. J Cataract Refract Surg. 2010;36(6):898-905.

18.       Manvikar S, Allen D. Cataract surgery management in patients taking tamsulosin staged approach. J Cataract Refract Surg. 2006;32(10):1611-1614.

19.       Gurbaxani A, Packard R. Intracameral phenylephrine to prevent floppy iris syndrome during cataract surgery in patients on tamsulosin. Eye (Lond). 2007;21(3):331-332.

20.       Shams F, Jafari AA, Mansfield D. Cardiovascular hazard of intracameral phenylephrine. J Cataract Refract Surg. 2015;41(9):2021-2022.

21.       Bekir OA, Toufeeq S, Woods E, Jabir M. Effect of intracameral phenylephrine on systemic blood pressure. Eye (Lond). 2014;28(10):1267-1268.

22.       Myers WG. Safety of intracameral phenylephrine. J Cataract Refract Surg. 2016;42(6):944-945.

November 2016

The information presented is current as of October 21, 2016. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.

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What is the latest information on gadolinium-based contrast agents and brain deposits?

Background

Gadolinium-based contrast agents (GBCAs) including gadofosveset trisodium (Ablavar), gadoterate meglumine (Dotarem), gadoxetate disodium (Eovist), gadobutrol (Gadavist), gadopentetate dimeglumine (Magnevist), gadobenate dimeglumine (MultiHance), gadodiamide (Omniscan), gadoversetamide (OptiMARK), and gadoteridol (ProHance) have been used for years to enhance images made by magnetic resonance imaging (MRI).¹  During an MRI, protons of water molecules become excited when the tissues are hit with radiofrequency in the presence of a magnetic field.² The image is produced when protons relax and release energy as they go back to their ground state. Gadolinium-based contrast agents reduce protons’ relaxation times and thereby increase the signal intensity of the image. Most of the GBCAs are used for imaging of multiple organs including central nervous system (CNS), whole body, liver, kidney as well as for magnetic resonance angiography (MRA) and peripheral MRA (see Table 1).¹

The different agents can be separated into 2 main groups based on their structure, linear and macrocyclic.² Macrocyclic agents form a complex with the gadolinium ion that resembles a cage while linear agents have an open structure. Macrocyclic GBCAs tend to be more stable due to lower dissociation constants compared to linear agents. Gadolinium ion releases easier from the complex if dissociation constant is higher. Heavy metals such as gadolinium are highly toxic to humans and other mammals, which is why gadolinium is chelated to different agents.

If used at correct doses, GBCAs have been regarded as safe and generally well tolerated until a decade ago.³ In 2006, studies showed that deposits of free gadolinium in the skin of patients with renal insufficiency caused nephrogenic systemic fibrosis (NSF). Nephrogenic systemic fibrosis is marked by deposition of fibroblasts and collagen into tissues and is a debilitating disease that can be fatal.⁴ This condition mainly presents in patients with reduced renal function who have received a linear GBCA.³ In 2015, the Food and Drug Administration (FDA) issued a drug safety communication regarding brain deposits from GBCAs in patients that have undergone 4 or more contrast MRI scans.⁵ These brain deposits were found in patients with normal renal function.

Table. Gadolinium-based agents and indications.^1,6

Evidence Behind Brain Deposits

Imaging studies, examination of postmortem subjects, and studies within patients created growing evidence of brain deposits with GBCAs.⁴ Gadodiamide (Omniscan) and gadopentetate dimeglumine (Magnevist) are the agents commonly associated with the deposits. Smaller human studies and an animal study also found deposits with gadoteridol (ProHance) and gadoterate meglumine (Dotarem). Most deposits occur in the globus pallidus and the dentate nucleus, and some studies showed deposits in CNS regions and endothelial walls and neuronal interstitium of brain.⁷ One study found that GBCA deposition occurs more often in globus pallidus and dentate nucleus compared to other regions such as cerebellar white matter, frontal lobe cortex, frontal lobe white matter.⁸

Studies by Errante and colleagues and Kanda and colleagues found a relationship between gadolinium deposits within the globus pallidus and dentate nucleus and cumulative doses of GBCAs and type of GBCAs utilized.^9-11 Patients with multiple sclerosis or brain metastases and normal renal function undergoing 6 or more MRI scans enhanced by gadodiamide (Omniscan) had significantly more deposits in the dentate nucleus compared to patients who underwent only 1 gadodiamide-enhanced MRI.⁹ Another study showed that gadolinium deposits were associated with linear GBCAs and not with macrocyclic GBCAs after analyzing MRI images of the dentate nucleus in 360 patients with normal renal function.¹¹

Proposed Mechanism of Action

The accumulation of gadolinium may explain the deposits from these contrast agents.² Gadolinium dissociates from its chelate and then is able to chelate within tissues.  In vitro and in vivo studies propose that the dissociation of gadolinium from its ligand is due to the kinetic and thermodynamic stabilities.⁴ The kinetic stability relates to how fast the gadolinium ion is released from the gadolinium complex. Gadolinium ion dissociates at a slower speed from the complex when the kinetic stability is high. Thermodynamic stability is related to the energy required for the gadolinium complex to release the free metal ion. If thermodynamic stability is high, the gadolinium ion is less readily released from the contrast agent complex.

The amount of competitors in the body interacting with the ligand or gadolinium itself may also lead to release of free gadolinium.⁴ Different endogenous cations including calcium, iron, and magnesium compete with gadolinium for the ligand.  Endogenous anions such as phosphate compete with the ligand for the gadolinium ion.  These competitive interactions can destabilize the complex leading to the release of free gadolinium. Currently, it is unclear whether observed brain deposits with GBCAs involve chelated or unchelated gadolinium.

The most recent evidence reveals a relationship between the amount of deposition and the structure of the GBCA.^2,3,7 The linear agents are considered less stable and more prone to releasing free gadolinium compared to the macrocyclic structures. Linear agents such as gadopentetate dimeglumine (Magnevist), gadodiamide (Omniscan), and gadobenate (MultiHance) were associated with brain deposits.¹² Gadobenate (MultiHance) showed less brain deposits compared to gadodiamide (Omniscan).⁴ In human and animal studies, gadoterate meglumine (Dotarem) and gadoteridol (ProHance), more stable macrocytic GBCAs, were not associated with any brain deposition or MRI changes. Interestingly, a more stable macrocyclic agent, gadobuterol (Gadavist), showed brain deposits. Therefore, all GBCAs should be individually evaluated prior to use in MRIs.

Clinical Outcomes

Even though evidence regarding gadolinium deposits in brain exists, the clinical outcomes from these deposits are unknown.  It is still unclear if the deposits consist of toxic free gadolinium or nontoxic gadolinium chelates.⁷ Animal studies did not show any neurologic effects of intravenously administered gadolinium chelates.⁴ However, when chelated gadolinium was given via intraventricular route or intravenous route with presence of blood-brain barrier disruption, brain toxicity occurred in rats. Evidence on adverse effects in humans is lacking.¹²

Conclusion

As more evidence is released regarding brain deposits caused by GBCAs, providers must carefully weigh the benefits and the risks when using a GBCA for enhancing MRI images. Choosing a more stable macrocyclic agent may result in less brain deposits.  More research on the clinical consequences of the brain deposits is necessary to determine the safety of these agents.

References

1.         Runge VM, Ai T, Hao D, Hu X. The developmental history of the gadolinium chelates as intravenous contrast media for magnetic resonance. Invest Radiol. 2011;46(12):807-816.

2.         Rogosnitzky M, Branch S. Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms. Biometals. 2016;29(3):365-376.

3.         Lancelot E. Revisiting the pharmacokinetic profiles of gadolinium-based contrast agents: differences in long-term biodistribution and excretion. Invest Radiol. 2016; 51(11):691-700.

4.         Ramalho J, Semelka RC, Ramalho M, Nunes RH, AlObaidy M, Castillo M. Gadolinium-based contrast agent accumulation and toxicity: an update. AJNR Am J Neuroradiol. 2016;37(7):1192-1198.

5.         FDA drug safety communication: FDA evaluating the risk of brain deposits with repeated use of gadolinium-based contrast agents for magnetic resonance imaging (MRI). Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/ucm455386.htm. Published July 27, 2015. Accessed July 25, 2016.

6.         UpToDate [database online]. Alphen aan den Rijn, Netherlands: Wolters Kluwer; 2016. http://www.uptodate.com/. Accessed July 25, 2016.

7.         Montagne A, Toga AW, Zlokovic BV. Blood-brain barrier permeability and gadolinium: benefits and potential pitfalls in research. JAMA Neurol. 2016;73(1):13-14.

8.         Kanda T, Fukusato T, Matsuda M, et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology. 2015;276(1):228-232.

9.         Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC. Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation. Invest Radiol. 2014;49(10):685-690.

10.       Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology. 2014;270(3):834-841.

11.       Kanda T, Osawa M, Oba H, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology. 2015;275(3):803-809.

12.       Stojanov D, Aracki-Trenkic A, Benedeto-Stojanov D. Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents-current status. Neuroradiology. 2016;58(5):433-441.

Prepared by:
Ashley Loethen, PharmD
PGY1 Pharmacy Practice Resident
College of Pharmacy
University of Illinois at Chicago

Edited by:
Janna Afanasjeva, PharmD, BCPS

November 2016

The information presented is current as of August 15, 2016. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.

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Is there literature to support the adjunct use of simethicone prior to colonoscopy to improve visualization?

Introduction

The American Cancer Society recommends that most men and women over 50 years of age have a screening colonoscopy every 10 years.¹ Proper bowel cleansing before the procedure is an important step to achieving a safe and successful screening, and often includes temporary dietary modifications along with oral hydration and cathartic medications.² Polyethylene glycol electrolyte solutions (PEG-ELS) are the cornerstone of purgative regimens, although, there are various methods of administration based on patient specific factors. High volume PEG-ELS involve consumption of at least 4 L of medication. Low volume regimens requiring around 2 L of cathartic ingestion are also available, although, up to an additional 2 L of oral hydration may be needed for proper preparation. Cleansing efficacy is improved by splitting the total volume of preparation into two doses, such as giving 2 L the night before the procedure and 2 L within 3 to 8 hours of the procedure. This 4 L split-dose PEG-ELS regimen is considered the current standard colonoscopy preparation.

Adjunctive agents can be added to the purgative regimen for various purposes.² The addition of flavorings may mitigate the poor taste of PEG-ELS products. Bisacodyl and/or magnesium citrate may reduce the volume required by some of the cathartic regimens, therefore, alleviating some of the volume related symptoms such as abdominal bloating and cramping. Similarly, metoclopramide has been used to reduce nausea and bloating associated with PEG-ELS. Simethicone has also been used to reduce abdominal discomfort and bloating and has the added benefit of decreasing gas and adherent bubbles in the gastrointestinal tract, potentially leading to enhanced mucosal visualization.

Interestingly, there are inconsistencies between national and international guidelines concerning the use of simethicone before colonoscopy.^3,4 The United States Multi-Society Task Force on Colorectal Cancer provides a weak recommendation against the routine use of adjunct agents for colonoscopy.³ This group does, however, state that simethicone is the best-studied adjunctive therapy for colonoscopy preparation and bowel cleansing, with particular mention of reduction of colonic bubbles. On the other hand, the European Society of Gastrointestinal Endoscopy (ESGE) guidelines provide a weak recommendation to add simethicone to standard bowel preparation regimens.⁴ Per the ESGE, adjunct therapy with simethicone is a safe and inexpensive strategy to reduce the surface tension of air bubbles and enhance visualization. Literature cited by both organizations’ guidelines is similar and calls into question the true value of the adjunct use of simethicone.

Clinical Efficacy

Table 1 provides a summary of the recent literature describing the use of simethicone as an adjunctive agent for bowel preparation prior to colonoscopy; results presented focus specifically on simethicone’s effect on colonic visualization.^6-11 To summarize, several randomized controlled trials have demonstrated simethicone to be effective in enhancing visualization and/or decreasing colonic bubbles in patients undergoing colonoscopy who receive PEG-based regimens.^5-8,10,11 In most studies, simethicone was administered immediately following PEG administration. Limited data also suggest that simethicone increases visualization when sodium phosphate (NaP)-based bowel preparations are used.¹² In addition to enhanced visualization, patient satisfaction was also improved with simethicone-containing regimens in several studies.^8,9 Although there do not appear to be any differences in simethicone’s ability to enhance visualization when considering the purpose of colonoscopy (elective screening, diagnostic, etc.), the specific reasons for completing the procedure were not stated in all studies.

Table 1. Data for the use of simethicone to enhance visualization during colonoscopy (n≥200).^6-11

Conclusion

Several studies have shown that simethicone improves visualization during colonoscopy without increasing the incidence of adverse events.^5-8,10,11 However, only limited data have shown the agent to improve the efficacy of bowel cleansing.¹⁰ Although national guidelines do not recommend its use as an adjunct therapy during colonoscopy, international groups provide more liberal recommendations for its use.^3,4 When considering the available data, low cost, and relatively benign side effect profile, clinicians should consider the potential added benefits of simethicone prior to colonoscopy.

References

1.    American Cancer Society Guidelines for the Early Detection of Cancer. American Cancer Society website. www.cancer.org/healthy/findcancerearly/cancerscreeningguidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer. Updated July 26, 2016. Accessed September 30, 2016.

2.    ASGE Standards of Practice Committee. Bowel preparation before colonoscopy. Gastrointest Endosc. 2015;81(4):781-794. 

3.    U.S. Multi-Society Task Force on Colorectal Cancer. Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the U.S. multi-society task force on colorectal cancer. Gastroenterology. 2014;147(4):903-924.

4.    Hassan C, Bretthauer M, Kaminski MF, et al; European Society of Gastrointestinal Endoscopy. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2013;45(2):142-150. 

5.    Mathus-Vliegen E, Pellisé M, Heresbach D, et al. Consensus guidelines for the use of bowel preparation prior to colonic diagnostic procedures: colonoscopy and small bowel video capsule endoscopy. Curr Med Res Opin. 2013;29(8):931-945.

6.    Wu L, Cao Y, Liao C, Huang J, Gao F. Systematic review and meta-analysis of randomized controlled trials of simethicone for gastrointestinal endoscopic visibility. Scand J Gastroenterol. 2011;46(2):227-235. 

7.    Yoo IK, Jeen YT, Kang SH, et al. Improving of bowel cleansing effect for polyethylene glycol with ascorbic acid using simethicone: A randomized controlled trial. Medicine (Baltimore). 2016;95(28):e4163.

8.    Parente F, Vailati C, Bargiggia S, et al. 2-Litre polyethylene glycol-citrate-simethicone plus bisacodyl versus 4-litre polyethylene glycol as preparation for colonoscopy in chronic constipation. Dig Liver Dis. 2015;47(10):857-863

9.    Valiante F, Bellumat A, De Bona M, De Boni M. Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy. World J Gastroenterol. 2013;19(33):5493-5499.

10.   Repici A, Cestari R, Annese V, et al. Randomised clinical trial: low-volume bowel preparation for colonoscopy – a comparison between two different PEG-based formulations. Aliment Pharmacol Ther. 2012;36(8):717-724.

11.   Jansen SV, Goedhard JG, Winkens B, van Deursen CT. Preparation before colonoscopy: a randomized controlled trial comparing different regimes. Eur J Gastroenterol Hepatol. 2011;23(10):897-902.

12.   Tongprasert S, Sobhonslidsuk A, Rattanasiri S. Improving quality of colonoscopy by adding simethicone to sodium phosphate bowl preparation. World J  Gastroenterol. 2009;15(24):3032-3037.

Prepared by:
Anne Marie Guthrie, PharmD
PGY1 Pharmacy Practice Residen
College of Pharmacy
University of Illinois at Chicago

November 2016

The information presented is current as Thursday, September 22, 2016. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.