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Drug Interactions between bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride and dolutegravir / rilpivirine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

sodium bicarbonate dolutegravir

Applies to: bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride and dolutegravir / rilpivirine

ADJUST DOSING INTERVAL: Coadministration with medications containing polyvalent cations such as aluminum, calcium, iron, or magnesium may decrease the oral bioavailability of dolutegravir. The mechanism of interaction has not been established. In 16 study subjects, administration of a single 50 mg dose of dolutegravir simultaneously with an antacid (Maalox) decreased dolutegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin; 24 hours post-dose) by 72%, 74% and 74%, respectively, compared to administration without the antacid. When the antacid was administered 2 hours after dolutegravir, the Cmax, AUC and Cmin of dolutegravir decreased by just 18%, 26% and 30%, respectively. Administration of single-dose dolutegravir simultaneously with a multivitamin (One-A-Day) decreased the Cmax, AUC and Cmin of dolutegravir by 35%, 33% and 32%, respectively.

MANAGEMENT: Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations such as antacids, laxatives, or mineral supplements.

References

  1. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):

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Moderate

sodium bicarbonate bisacodyl

Applies to: bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride and bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride

ADJUST DOSING INTERVAL: By increasing gastric pH, antacids may reduce the resistance of the enteric coating of bisacodyl tablets, resulting in earlier release of bisacodyl and gastric irritation and dyspepsia.

MANAGEMENT: The administration of antacids and bisacodyl should be separated by at least one hour.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

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Moderate

sodium bicarbonate rilpivirine

Applies to: bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride and dolutegravir / rilpivirine

ADJUST DOSING INTERVAL: Coadministration with antacids may decrease the oral bioavailability of rilpivirine. The proposed mechanism involves a pH-dependent reduction in dissolution and absorption of rilpivirine, which is poorly soluble over a wide pH range. The interaction has not been studied specifically with antacids, but has been reported for H2-receptor antagonists and proton pump inhibitors.

MANAGEMENT: To minimize the risk of reduced viral susceptibility and resistance development associated with subtherapeutic levels of rilpivirine, antacids or other medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) should be administered at least 2 hours before or 4 hours after the rilpivirine dose.

References

  1. "Product Information. Edurant (rilpivirine)." Tibotec Pharmaceuticals (2011):

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Moderate

bisacodyl polyethylene glycol 3350

Applies to: bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride and bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride

GENERALLY AVOID: Concomitant use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) may increase the risk of serious gastrointestinal adverse effects associated with certain osmotic laxatives (e.g., polyethylene glycol (PEG), oral sulfate solution), such as colonic mucosal ulcerations or ischemic colitis. There have been isolated case reports of ischemic colitis occurring with the use of PEG-based bowel cleansing products in combination with higher dosages of bisacodyl (usually greater than 10 mg). Bisacodyl can cause colonic ischemia due to transient reduction in splanchnic blood flow. When administered in conjunction with an osmotic laxative such as PEG, increased intramural pressure secondary to increased peristalsis may lead to ischemic colitis and perforation.

MANAGEMENT: The manufacturers for some osmotic bowel cleansing products recommend avoiding the concurrent use of stimulant laxatives. However, stimulant laxatives, in particular bisacodyl and sodium picosulfate, are sometimes used with PEG in certain bowel cleansing regimens to help reduce dose volume and improve patient tolerability and acceptance. Please consult individual product labeling for specific recommendations and guidance. Patients using osmotic bowel cleansing products and stimulant laxatives who present with sudden abdominal pain, rectal bleeding, or other symptoms of ischemic colitis should be evaluated promptly.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. Baudet JS, Castro V, Redondo I "Recurrent ischemic colitis induced by colonoscopy bowel lavage." Am J Gastroenterol 105 (2010): 700-1
  4. "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories (2010):
  5. Ajani S, Hurt RT, Teeters DA, Bellmore LR "Ischaemic colitis associated with oral contraceptive and bisacodyl use." BMJ Case Rep 2012 (2012):
  6. "Product Information. MoviPrep (polyethylene glycol 3350 with electrolytes)." Physicians Total Care (2016):
  7. "Product Information. Plenvu (polyethylene glycol 3350 with electrolytes)." Bausch Health US (formerly Valeant Pharmaceuticals) (2020):
  8. "Product Information. GaviLyte-H and Bisacodyl with Flavor Packs (bisacodyl-PEG 3350 with electrolytes)." Gavis Pharmaceuticals (2022):
  9. "Product Information. Bi-Peglyte (bisacodyl-PEG 3350 with electrolytes)." Pendopharm PROD
  10. Vaizman K, Li J, Iswara K, Tenner S "Ischemic colitis induced by the combination of Bisacodyl and polyethylene glycol in preparation for colonoscopy." Am J Gastroenterol 102 (2007): S267
  11. Belsey J, Epstein O, heresbach D "Systematic review: adverse event reports for oral sodium phosphate and polyethylene glycol." Aliment Pharmacol Ther 29 (2009): 15-28
  12. Hung SY, Chen HC, Chen WT "A randomized trial comparing the bowel cleansing efficacy of sodium picosulfate/magnesium citrate and polyethylene glycol/Bisacodyl (The Bowklean Study)" Sci Rep 10 (2020): 5604
  13. Adamcewicz M, Bearelly D, Porat G, Friedenberg FK "Mechanism of action and toxicities of purgatives used for colonoscopy preparation." Expert Opin Drug Metab Toxicol 7 (2011): 89-101
  14. Anastassopoulos K, Farraye FA, Knight T, Colman S, Cleveland MvB, Pelham RW "A comparative study of treatment-emergent adverse events following use of common bowel preparations among a colonoscopy screening population: results from a post-marketing observational study." Dig Dis Sci 61 (2016): 2993-3006
  15. Barbeau P, Wolfe D, Yazdi F, et al. "Comparative safety of bowel cleansers: protocol for a systematic review and network meta-analysis." BMJ Open 8 (2018): e021892
View all 15 references

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Moderate

bisacodyl rilpivirine

Applies to: bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride and dolutegravir / rilpivirine

MONITOR: Bowel cleansing as well as overuse of certain laxatives may cause electrolyte loss and increase the risk of torsade de pointes ventricular arrhythmia in patients treated with drugs that prolong the QT interval. Electrolyte disturbances including hypokalemia and hypomagnesemia have been reported with laxative abuse and are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Patients treated with drugs that prolong the QT interval should exercise caution when self-medicating with laxatives. The recommended dosage and duration of use should not be exceeded. Patients treated with lactulose for more than six months should be monitored periodically for electrolyte imbalance. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Chin RL "Laxative-induced hypokalemia." Ann Emerg Med 32 (1998): 517-8
  2. Muller-Lissner SA "Adverse effects of laxatives: fact and fiction." Pharmacology 47 (1993): 138-45
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Schaefer DC, Cheskin LJ "Constipation in the elderly." Am Fam Physician 58 (1998): 907-14
View all 6 references

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Moderate

polyethylene glycol 3350 rilpivirine

Applies to: bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride and dolutegravir / rilpivirine

MONITOR: Bowel cleansing as well as overuse of certain laxatives may cause electrolyte loss and increase the risk of torsade de pointes ventricular arrhythmia in patients treated with drugs that prolong the QT interval. Electrolyte disturbances including hypokalemia and hypomagnesemia have been reported with laxative abuse and are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Patients treated with drugs that prolong the QT interval should exercise caution when self-medicating with laxatives. The recommended dosage and duration of use should not be exceeded. Patients treated with lactulose for more than six months should be monitored periodically for electrolyte imbalance. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Chin RL "Laxative-induced hypokalemia." Ann Emerg Med 32 (1998): 517-8
  2. Muller-Lissner SA "Adverse effects of laxatives: fact and fiction." Pharmacology 47 (1993): 138-45
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Schaefer DC, Cheskin LJ "Constipation in the elderly." Am Fam Physician 58 (1998): 907-14
View all 6 references

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Drug and food interactions

Moderate

rilpivirine food

Applies to: dolutegravir / rilpivirine

GENERALLY AVOID: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of rilpivirine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. In 15 study subjects given rilpivirine (150 mg once daily) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), mean rilpivirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) were increased by 30%, 49% and 76%, respectively. In 16 study subjects given a single 500 mg dose of a less potent CYP450 3A4 inhibitor chlorzoxazone two hours after rilpivirine (150 mg once daily), mean rilpivirine Cmax, AUC, and Cmin were increased by 17%, 25%, and 18%, respectively. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

ADJUST DOSING INTERVAL: The administration of rilpivirine in a fasting state may decrease its oral absorption. Under fasted conditions, the systemic exposure to rilpivirine was 40% lower compared to normal or high-fat caloric meals (533 to 928 Kcal). The systemic exposure was 50% lower when rilpivirine was taken with a protein-rich nutritional beverage.

MANAGEMENT: Coadministration of grapefruit or grapefruit juice with rilpivirine should preferably be avoided. For optimal absorption, it is recommended to take rilpivirine on a regular schedule with a meal.

References

  1. "Product Information. Edurant (rilpivirine)." Tibotec Pharmaceuticals (2011):
  2. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):

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Minor

dolutegravir food

Applies to: dolutegravir / rilpivirine

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.

References

  1. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.