Does taking Colace (docusate) with narcotics prevent constipation? Or is there another medication recommended to decrease constipation associated with narcotics?

Comment by InpharmD Researcher

Evidence from various reviews suggests a lack of strong evidence to support the efficacy of docusate in OIC prophylaxis, despite its widespread use due to the high incidence of OIC, impact on quality of life, accessibility, and relatively low risk. It is noted that the inclusion of docusate in major guidelines and consensus recommendations for OIC management is weakly evidence-based. Even though the use of laxatives has been most commonly demonstrated in different patient populations, including palliative care and oncological patients, there were no conclusions in regards to using docusate (or stool softeners) versus other laxatives in the prevention of OIC. Other agents mentioned in the available literature without strong evidence include magnesium oxide/citrate and senna.

Background

Per the American Gastroenterological Association guidelines on the medical management of opioid-induced constipation (OIC), traditional laxatives, including docusate, are recommended as the first-line agents in treating OIC; however, the role of docusate or other laxatives in OIC prophylaxis is not explicitly discussed. [1]

A 2021 review evaluating the clinical evidence for docusate use in OIC management identified 13 guidelines or consensus recommendations (CR) and four primary literature studies. The authors noted consistent design limitations in the primary literature and a lack of primary evidence cited in the guidelines or CR to support their recommendations of using docusate for OIC prophylaxis or treatment. Even though docusate is widely prescribed for OIC, the evidence behind this recommendation is collectively weak across most of the guidelines and CR. Therefore, a close assessment of OIC protocols and/or algorithms among institutions and health care providers are warranted to incorporate evidence-based therapy and reduce unnecessary docusate use and associated costs. [2]

A 2020 expert opinion of a multidisciplinary panel of physician experts who treat OIC suggested that prescribers do not limit interventions for OIC to lifestyle changes or dietary/hydration recommendations. Instead, it was suggested to prescribe a laxative for OIC prevention, even though the efficacy of laxatives in OIC was controversial with low patient satisfaction. However, the panel discussion did not cover a standard preventative approach for the clinical management of OIC. [3]

A 2002 nursing-based protocol suggests a prophylactic daily laxative regimen, senna with docusate sodium 2 tablets PO QHS, in patients who receive daily doses of opioids for the first 2 or 3 days. On the other hand, a 2016 British review highlighted that despite the routine prophylactic laxatives at the time of, or before, opioid prescription to prevent OIC, there was little evidence to support this practice. Although in one single-center study, patients who received laxatives (mainly magnesium oxide 62.1%; magnesium oxide + pantethine 14.3%; magnesium oxide + senna 9.9%; senna alone 7.9%) before opioids had a lower incidence of developing constipation, the use of laxatives was not standardized in the trial. Similarly, the American Academy of Pain Medicine stated in its consensus recommendations that prophylactic and first-line over-the-counter (OTC) therapies for OIC did not usually lead to consistent and predictable therapeutic responses based on inadequate literature in such treatments. Regardless, both review articles concluded that the high incidence of OIC, its impact on quality of life, accessibility, and relatively low risk of OTC laxatives may still justify their prophylactic and first-line use for OIC in practice. [4], [5], [6], [7]

A 2014 Canadian review including studies (systematic reviews, randomized controlled trials [RCTs], and non-randomized studies) of adult patients with constipation for whom prevention of constipation is desired (Table 1) concluded that there is a lack of data on supporting the use of docusate for prevention or management of constipation. While the studies were limited based on the small sample size and confounding factors (using additional bowel medications), the authors stated that the study results are more generalizable to patients with opioid-induced constipation. [8]

A 2019 review on OIC in cancer patients stated that anticipating and preventing OIC or treating it when it is mild is always more practical as the management could be more challenging in developed constipation. The authors stated that while the European Society of Medical Oncology (ESMO) has recommended the routine prescription of laxatives for both prophylaxis and treatment of OIC, more supporting evidence is needed to indicate the prophylactic effects of laxatives for OIC prevention. There were no conclusions in regards to using docusate (or stool softeners) versus other laxatives in the prevention of OIC. [9]

A 2021 article reviewing the management of OIC discussed the options for OIC prophylaxis. The authors stated that while increasing dietary fiber, fluid intake, and physical exercise are the backbone of prevention therapy, stool softeners (like docusate) are also ideal for preventing constipation. Another laxative agent mentioned by the author is saline laxative, such as magnesium citrate, which has a delayed onset of action from 30 to 180 mins. The authors also noted that bulk-forming laxatives should be avoided since opioids prevent peristalsis of the increased bulk, leading to bowel obstruction. [10]

Finally, a review article on the management of OIC in palliative care patients does not discuss docusate salts as a laxative option in this population. It states that osmotic agents or stimulant laxatives (if no response in two days) can be considered in clinical practice; however, it notes there is a lack of evidence to guide safe and effective treatment of OIC in this group of patients. [11]

References:

[1] Crockett SD, Greer KB, Heidelbaugh JJ, Falck-Ytter Y, Hanson BJ, Sultan S; American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019 Jan;156(1):218-226. doi: 10.1053/j.gastro.2018.07.016. Epub 2018 Oct 16. PMID: 30340754.
[2] Engle AL, Winans ARM. Rethinking Docusate's Role in Opioid-Induced Constipation: A Critical Analysis of the Evidence. J Pain Palliat Care Pharmacother. 2021 Mar;35(1):63-72. doi: 10.1080/15360288.2020.1828529. Epub 2021 Feb 17. PMID: 33596159.
[3] Alvaro, D., Caraceni, A., Coluzzi, F. et al. What to Do and What Not to Do in the Management of Opioid-Induced Constipation: A Choosing Wisely Report. Pain Ther 9, 657–667 (2020).
[4] Plaisance L, Ellis JA. Opioid-induced constipation. Management is necessary but prevention is better. Am J Nurs. 2002;102(3):72-73. doi:10.1097/00000446-200203000-00027
[5] Prichard D, Norton C, Bharucha AE. Management of opioid-induced constipation. Br J Nurs. 2016;25(10):S4-S11. doi:10.12968/bjon.2016.25.10.S4
[6] Ishihara M, Ikesue H, Matsunaga H, Suemaru K, Kitaichi K, Suetsugu K, Oishi R, Sendo T, Araki H, Itoh Y; Japanese Study Group for the Relief of Opioid-induced Gastrointestinal Dysfunction. A multi-institutional study analyzing effect of prophylactic medication for prevention of opioid-induced gastrointestinal dysfunction. Clin J Pain. 2012 Jun;28(5):373-81. doi: 10.1097/AJP.0b013e318237d626. PMID: 22156893.
[7] Argoff CE, Brennan MJ, Camilleri M, Davies A, Fudin J, Galluzzi KE, Gudin J, Lembo A, Stanos SP, Webster LR. Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation. Pain Med. 2015 Dec;16(12):2324-37. doi: 10.1111/pme.12937. Epub 2015 Nov 19. PMID: 26582720; PMCID: PMC4738423.
[8] Dioctyl Sulfosuccinate or Docusate (Calcium or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; June 26, 2014.
[9] Mesía R, Virizuela Echaburu JA, Gómez J, Sauri T, Serrano G, Pujol E. Opioid-Induced Constipation in Oncological Patients: New Strategies of Management. Curr Treat Options Oncol. 2019;20(12):91. Published 2019 Dec 19. doi:10.1007/s11864-019-0686-6
[10] Sizar O, Genova R, Gupta M. Opioid Induced Constipation. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 January. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493184/. Accessed February 7, 2022.
[11] Prichard D, Bharucha A. Management of opioid-induced constipation for people in palliative care. Int J Palliat Nurs. 2015;21(6):272, 274-80.

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Does taking Colace (docusate) with narcotics prevent constipation? Or is there another medication recommended to decrease constipation associated with narcotics?

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Tables 1-2 for your response.


 

Summary of Clinical Review and Trial Characteristics

Citation/design

Population

Intervention

Results

 Limitations

Ahmedzai et al.

2010

Systematic review

 

N=22

People prescribed opioids

 

Patients received Docusate 240 mg BID x 3 weeks compared to PL in a cross-over design.

  • No significant difference between docusate vs. placebo in stool frequency or consistency at 8 weeks after cross-over in 15/22 (68%) in those who completed the trial

  • Mean numbers of BM/week:  4.25 vs. 4.12 (not significant; p values not reported)

  • Percentage of soft and normal stools: 97% vs. 93% (not significant; p values not reported)
  • The opioid dose was unclear, sample size with even less completing the trial; results were presented without p values.

  • Open-label studies were included.

  • List of excluded studies not provided.

 

Ruston et al.

2013

Systematic review

Aged ≥18 years, constipation associated with chronic opioid use (for cancer and non-cancer pain or substance withdrawal), in- or out-patients, or palliative care

RCTs compared PEG to one of the following: lactulose, docusate, or sennosides

  • Management of constipation.
  • No studies met the inclusion criteria; hence, no conclusion can be drawn.

  • Insufficient evidence exists to determine the efficacy and side effect profiles of lactulose, docusate sodium, sennosides, and PEG in the treatment of OIC.

  • Inclusion criteria may have been too stringent.

  • Lack of clear definition for opioid-induced constipation.

  • List of excluded studies not provided but PRISMA diagram provided.

 

Tarumi et al.

2013

Prospective, multicentre, double-blind, placebo-controlled RCT (10-day trial)

N= 74

Aged ≥ 18 years; with cancer, newly admitted hospice residents, able to take oral meds, no gastrointestinal stoma, PPS score of ≥ 20%, Folstein MMSE score of > 23; expanded criteria to include patients with non-malignant disease and those not taking opioids

DS Group (n= 35): 2 x 100mg DS BID capsules plus, 1 to 3 S 8.6 mg tablets QD to TID

PL Group (n= 39): 2 x PL BID plus, 1 to 3 S 8.6 mg tablets QD to TID

  • Management of constipation.
  • BM mean difference: 0.05 (95% CI: -0.09 to 0.19)

    Responder Analysis:

  • BM on 50% or more days: DS 56% vs. PL71%

  • 1 BM every 3 consecutive days: DS 70.8% vs. PL 80.6%

  • Mean stool frequency: DS 1.0 ± 0.5 vs. PL 0.88 ± 0.30

  • No significant differences between stool volume in DS vs PL

  • Difficult BM: DS 32.5% vs. PL 25.0% (p= 0.57)

  • Sense of complete evacuation: DS 73.5% vs. PL 78.6 (p= 0.77)

  • Bowel care interventions: DS 68.6% vs. PL 74.4% (p= 0.77)

  • Allocation concealment and ITT not specified; (10 [40%] and 8 [21%] patients did not complete study in DS and PL groups, respectively).

 

  • Inclusion criteria expanded ~5 months after the start of the trial to include patients with non-malignant disease and those not taking opioids.

 

  • Randomization code could be broken at the request of the physician or patient; the occurrence of this is not specified.
 

Fosnes et al.

2011

Cross-sectional study

N= 197

Aged ≥ 60 years; nursing home residents; some mobile, some bedridden; using laxatives regularly or on-demand

Laxative Interventions:

  • Osmotic (lactulose, macrogol combinations)

  • Contact (bisacodyl, senna glycosides, sodium pico sulphate)

  • Bulk (ispaghula [psylla seeds])

  • Enemas (docusate sodium, laurilsulfate)

  • Softeners/Emollients (liquid paraffin)

Dosing Schedules:

 

  • On-demand
  • Regular use (standard dose) was the dosing schedule for docusate 

  • Regular use (high dose)

  • Management of constipation.
  • No results were explicitly provided for docusate sodium.

  • No conclusion could be reached as only five patients were reported to have used this treatment.

 
  • Inclusion of frail and mentally reduced participants; may reduce data quality for patients self-reported symptoms.

  • Differing sites may have alternate reporting methods, and the use of laxatives may have been imprecisely registered as they may not have been handled as accurately as other drugs.

  • Only a small number of patients used DS (n=5), and it was only one of many treatment regimens examined.

 

Hawley et al.

2008

Non-randomized, non-blinded, sequential cohort study

(total of 488 days of observation)

N= 60

Hospitalized cancer patients (80% taking
opioids); 8.4 ± 2.5 days vs. 7.8 ± 2.7 days on bowel protocol in the
DS + S vs. S protocol, respectively

 

DS + S Protocol (n= 30)

Step 1: DS 200 mg po BID

Step 2: DS 200 mg po BID + S 17.2 mg po qhs

Step 3: DS 200 mg po TID + S 17.2 mg po BID (if no BM in past 48 hrs)

Step 4: DS 200 mg po TID + S 17.2 mg po TID (if no BM in next 24 hrs)

Step 5: DS 200mg po TID + S 25.8 mg po TID (if no BM after a further 24 hrs)

S-only Protocol (n=30)

Step 1: S 17.2 mg po qhs

Step 2: S 17.2 mg po BID (if no BM in past 48 hrs)

Step 3: S 17.2 mg po TID (if no BM in next 24 hrs)

Step 4: S 25.8 mg po TID (if no BM after a further 24 hrs)

Prevention and management of constipation.
 
Percent of days with at least 1 BM:
  • DS + S 49%
  • S 50% (p= 0.86)
 
BM at least 50% of days:
  • DS + S 43.3%
  • S 19 63.3% (p= 0.12)

BM at least 40% of days:

  • DS + S 60%
  • S 24 80% (p= 0.09)

Use of rescue medications:

  • DS + S 56.7%
  • S 40% (p= 0.19)

Subanalysis of patients admitted for symptom control or supportive care, DS+S (n= 19) and S (n= 24):

BM at least 50% of days:

  • DS + S 31.6%
  • S 62.5% (p= 0.04)

BM at least 40% of days:

  • DS + S 47.4%
  • S 79.2% (p= 0.09)

Subanalysis of patients admitted for symptom control or supportive care and on opioids, DS+S (n= 19) and S (n= 24):

BM at least 50% of days:

  • DS + S 31.3%
  • S 57.1% (p= 0.12)

BM at least 40% of days:

  • DS + S 50.0%
  • S 76.2% (p= 0.1)
  • No matching or adjustments for co-founders.

  • Many different healthcare providers were involved in patient care and were not all aware of their patient’s participation in the study.

  • Patients could take an enema, lactulose, or a suppository as required, therefore potentially confounding results.

  • More patients with GU cancer were enrolled in the second (S only) cohort, while GU was the least common cancer diagnosis in the first (DS + S) cohort.

 

SR, systematic review; RCT, randomized controlled trial; BM, bowel movement; D, docusate; OIC = opioid-induced constipation; PEG = polyethylene glycol; PL, placebo; MMSE, Mini-Mental Status Examination; PPS, Palliative Performance Scale, DS, docusate sodium; PL, placebo; S, sennosides; CI, confidence interval

 

 

References:

Adapted from:
Dioctyl Sulfosuccinate or Docusate (Calcium or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; June 26, 2014.

 

Rates of appropriate laxative prophylaxis for opioid-induced constipation in veterans with lung cancer: a retrospective cohort study

Design

Retrospective, observational, cross-sectional cohort study

N= 130,990

Objective

To evaluate the prescription of laxatives for opioid-induced constipation (OIC) to adult patients with incident lung cancer seen in the Veteran’s Affairs (VA) system

Study Groups

No OIC prophylaxis (n= 98,206)

Docusate monotherapy (n= 16,129)

Laxative monotherapy (n= 9,990)

Docusate + laxative (n= 6,665)

Inclusion Criteria

Patients with information in Corporate Data Warehouse (CDW) were included if they had an International Classification of Diseases (ICD) 9 or 10 code for lung cancer

Exclusion Criteria

Patients on a laxative or docusate regimen prior to the diagnosis of lung cancer and initiation of opioids

Methods

Eligible patients were analyzed to assess the prevalence of OIC prophylaxis and regimens according to the agent used (none, docusate monotherapy, laxative, or docusate + laxative). The proportion of patients receiving OIC prophylaxis was calculated as the lung cancer patients in each of the exposure categories divided by all patients receiving opioid therapy. Laxative use was considered prophylactic if the treatment was prescribed within one week of the initiation of the first opioid prescription. 

Duration

From January 1, 2003, through December 31, 2016

Outcome Measures

Primary: prevalence of appropriate OIC prophylaxis (defined as non-docusate laxative prescription)

Secondary: subsequent rates of constipation at 3 and 6 months necessitating an emergency room visit, urgent care visit, or inpatient admission from diagnostic codes

Baseline Characteristics

 

No OIC prophylaxis
(n= 98,206)

Docusate monotherapy
(n= 16,129)

Laxative monotherapy
(n= 9,990) 
Docusate + laxative
(n= 6,665)

Age, years

67.3± 9.5 66.8 ± 9.3 67.6 ± 9.5 66.7± 9.4

Male

95,696 (97.4%)

15,717 (97.4%)

9,780 (97.9%)

6,506 (97.6%)

White

72,185 (73.5%)

11,694 (72.5%)

7,217 (72.2%)

4,819 (72.3%)

Metastatic Disease

11,922 (12.1%)

2,208 (13.6%)

1,565 (15.7%)

1,189 (17.8%)

Results

Endpoint

No OIC prophylaxis
(n= 98,206)

Docusate monotherapy
(n= 16,129)

Laxative monotherapy
(n= 9,990)

Docusate + laxative
(n= 6,665)

Rate of constipation

At 3 months 

At 6 months 

 

986 (1.0%)

1,576 (1.6%)

 

361 (2.2%)

499 (3.1%)

 

396 (4.0%)

498 (5.0%)

 

491 (7.4%)

556 (8.3%)

In total, 87.3% of patients received inadequate prevention (75% no prophylaxis and 12% docusate alone), while 5.1% received OIC prophylaxis with the unnecessary addition of docusate to another laxative.

In the study period, rates of no OIC prophylaxis, docusate monotherapy, or docusate + laxative prescription were not significantly changed over time by linear regression analysis (p= 0.0899, p= 0.8451, p= 0.598, respectively). Rates of laxative prescription for OIC prophylaxis decreased through the study period (95% confidence interval for slope = − 0.001195 to − 0.0001452, p= 0.0170). 

Adverse Events

N/A

Study Author Conclusions

In this study of veterans with lung cancer, almost 90% received inadequate or inappropriate OIC prophylaxis. Efforts to educate physicians and patients to promote appropriate OIC prophylaxis in combination with systems-level changes are warranted.

InpharmD Researcher Critique

In this cohort, docusate was prescribed as part of an OIC regimen in more than 70% of patients receiving OIC prophylaxis; instead, patients should have received a regimen containing a stimulant laxative (such as senna) or polyethylene glycol. The study was limited due to the retrospective and observational design, and drawing a definite conclusion may be challenging due to potential confounding factors. Additionally, the adherence of patients to laxatives was not clear in the study. 



References:

Brown TJ, Keshvani N, Gupta A, Yang H, Agrawal D, Le TC, Gerber DE, Alvarez CA. Rates of appropriate laxative prophylaxis for opioid-induced constipation in veterans with lung cancer: a retrospective cohort study. Support Care Cancer. 2020 Nov;28(11):5315-5321. doi: 10.1007/s00520-020-05364-6. Epub 2020 Mar 2. PMID: 32124025.