Is there safety and/or efficacy data in using docusate for constipation in pediatric patients less than 2 years of age?

Comment by InpharmD Researcher

Despite its historical use, there does not appear to be robust evidence evaluating the use of docusate in pediatric patients at any age group, including those below two years of age. While the use of docusate as a stool softener is mentioned in systematic reviews, these papers do not place a heavy emphasis on its use. One retrospective study (Table 1) found a docusate enema solution (combined with other agents) to not significantly differ compared with sodium phosphate or soap sud enemas. A landmark 1957 study of docusate (Table 2) provided some efficacy data, reporting successful stools as early as 2 days after administration with 10-40 mg/day; however, due to the age of this study and lack of a control group, clinical trial standards may not fully meet modern-day expectations. The majority of literature on the use of docusate in pediatrics is qualitative, reporting docusate utilization, instead of evaluating efficacy or establishing optimal dosing in this population.

docusate pediatric dose "less than 2" "<2 years"

Background

A 2020 systematic review on treating constipation in pediatric patients mentions docusate 5 mg/kg/day (max 400 mg) as a potential agent for maintenance therapy, but no evidence is presented for its use. In general, most experts prefer non-stimulant laxatives, such as polyethylene glycol (PEG) 3350, lactulose, and milk of magnesia, since they tend to be gentle when used at an appropriate dose. Of note, the review does not provide dosing recommendations for docusate in children <2 years of age. However, it does provide dosing recommendations for other laxatives in this age group, including senna (1-2 years: 2.2-4.4 mg/day in 1-2 divided doses) and magnesium hydroxide (<2 years: 0.5 mL/kg/day). [1]

Another systematic review on treating constipation in children states there is no evidence that docusate is effective in pediatric patients with functional constipation. Docusate is mainly administered rectally, even though oral formulations exist. One randomized, controlled trial found high-dose PEG to be as equally effective as docusate enemas for bowel disimpaction. Similarly, dosing recommendations for docusate in children <2 years of age were not provided. [2]

The efficacy of docusate, as a component of a combined enema solution, was compared to sodium phosphate and soap sud enemas in a 2020 retrospective review (Table 1). Children (N= 768) treated in a pediatric emergency department over a period of 5 years (mean age 6.2 years) were given enema solutions for constipation, including sodium phosphate (n= 396), “pink lady” (a compounded combination of docusate, magnesium citrate, mineral oil, and sodium phosphate; n= 198), soap suds (n= 160), or other (n= 14). No significant difference in stool output was reported between sodium phosphate, pink lady, and soap suds solutions (p= 0.88). A higher incidence of adverse events, including abdominal pain, was reported with soap suds (10.6%, p= 0.0003). Initial recording of stool output outcomes was subjective (e.g., “minimal,” “good,” or “very good”), potentially preventing an accurate comparison of outcomes. As docusate was combined in a solution with additional agents, its true efficacy as an individual drug cannot be concluded based on these results. No control group was included in this study. The authors mentioned the lack of available literature to guide the selection of enemas for acute pediatric constipation, stating that the current selection is generally based on preference of the ordering physician. [3]

A landmark 1957 study (Table 2) evaluated the use of docusate sodium (dioctyl sodium sulfosuccinate) in 50 children, aged between 5 weeks and 14 years, who had persistent chronic constipation or acute/subacute constipation. Docusate was given as 10 mg/day in infants and 120 mg/day in older children for up to 15 days (or used PRN after 15 days). The docusate was reported to be very effective, with the effects noted as early as 2 days after initiating therapy. This study did not report the baseline characteristics of enrolled patients and did not include a control group. Of note, several children had migraine headaches that the author suspected to be associated with “faulty elimination”; these headaches disappeared when the constipation resolved. While docusate offers a relatively safe way to draw water into the colon and soften stool, its use can be limited by the medicine’s bitter taste. Newer medications, such as PEG, can accomplish the same goal without a bitter taste. [4], [5]

Background References: [1] LeLeiko NS, Mayer-Brown S, Cerezo C, Plante W. Constipation. Pediatrics In Review. 2020;41(8):379-392. doi:10.1542/pir.2018-0334
[2] Koppen IJ, Lammers LA, Benninga MA, Tabbers MM. Management of Functional Constipation in Children: Therapy in Practice. Paediatr Drugs. 2015;17(5):349-360. doi:10.1007/s40272-015-0142-4
[3] Anderson J, Furnival RA, Zhang L, et al. A Comparison of the Efficacy of Enema Solutions in Pediatric Emergency Department Patients. J Emerg Med. 2019;57(4):461-468. doi:10.1016/j.jemermed.2019.07.009
[4] Tevetoglu F. Pediatric use of dioctyl sodium sulfosuccinate. J Pediatr. 1957;50(3):304-307. doi:10.1016/s0022-3476(57)80027-4
[5] Focht DR. 50 years ago in the journal of pediatrics. The Journal of Pediatrics. 2007;150(4):417. doi:10.1016/j.jpeds.2006.10.016
Literature Review

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

Is there safety and/or efficacy data in using docusate for constipation in pediatric patients less than 2 years of age?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-2 for your response.


 

A COMPARISON OF THE EFFICACY OF ENEMA SOLUTIONS IN PEDIATRIC EMERGENCY DEPARTMENT PATIENTS
Design

Retrospective study

N= 768

Objective To assess and compare the efficacy of the various enema solutions used in a pediatric ED, including the "pink lady," a previously unreported compounded combination of docusate, magnesium citrate, mineral oil, and sodium phosphate
Study Groups

Sodium phosphate (n= 396)

Pink lady (n= 198)

Soap suds (n= 160)

Other (n= 14)

Inclusion Criteria Children who received any enema over a 5-year period in an urban, quaternary care pediatric ED
Exclusion Criteria Patients receiving air enemas for intussusception were not sampled
Methods

The pink lady enema was locally compounded using 100 mL docusate liquid, 60 mL magnesium citrate, 60 mL mineral oil, and 66 mL sodium phosphate enema solution (total 286 mL).

Physician investigators reviewed visit documentation to confirm enema type and dosage, assess co-morbidities, indications, efficacy, and side effects. Stool output was classified as none, small, medium, or large by reviewer consensus.

Duration January 2011 to January 2016
Outcome Measures

Primary: Stool output after enema administration

Secondary: Side effects, hospital admission rate

Baseline Characteristics   All patients (n= 768) Sodium Phosphate (n= 396) Pink Lady (n= 198) Soap Suds (n= 160) Other (n= 14)
Age, median years (IQR) 6.2 (3.3-10.3) 4.7 (2.6-8.5) 7.3 (4.6-12.0) 7.9 (4.7-11.9) 4.7 (3.8-16.3)
Female 418 (54.6%) 200 (50.6%) 109 (55.1%) 103 (64.8%) 6 (42.9%)
Weight, kg, median (IQR) 22.1 (14.8-35.8) 18.5 (12.9-29.8) 26.4 (18.0-44.2) 30.1 (18.4-47.0) 21.0 (10.1-41.6)
Results   All (N= 768) Sodium Phosphate (n= 396) Pink Lady (n= 198) Soap Suds (n= 160) Other (n= 14)
None 52 (7.5%) 20 (5.5%) 11 (6.3%) 17 (11.3%) 4 (36.4%)
Small 144 (20.6%) 81 (22.38%) 31 (17.7%) 29 (19.3%) 3 (27.3%)
Medium 243 (34.8%) 128 (35.4%) 63 (36.0%) 49 (32.7%) 3 (27.3%)
Large 253 (36.3%) 133 (36.7%) 66 (37.7%) 53 (35.3%) 1 (9.0%)
Adverse Events Abdominal pain was the most frequent side effect, significantly more common in patients receiving soap suds (10.6%, p=0.0003)
Study Author Conclusions There was no significant difference in reported stool output produced by sodium phosphate, soap suds, and pink lady enemas in children treated in an ED. Further study via randomized controlled trials would be beneficial in guiding selection of enema solution.
Critique The study's retrospective design limits the ability to control for confounding variables and introduces potential biases in data collection. The subjective nature of stool output assessment and the lack of randomization are significant limitations. However, the large sample size provides valuable insights into current practices and highlights the need for further research through randomized controlled trials.

 

Table 1 References:
[6] Anderson J, Furnival RA, Zhang L, et al. A Comparison of the Efficacy of Enema Solutions in Pediatric Emergency Department Patients. J Emerg Med. 2019;57(4):461-468. doi:10.1016/j.jemermed.2019.07.009

 

Pediatric Use of Dioctyl Sodium Sulfosuccinate
Design

Prospective observational study

N= 50

Objective To evaluate the effectiveness of dioctyl sodium sulfosuccinate as a fecal softener in treating constipation in infants and children
Study Groups

Infants under 1 year (n= 9)

Infants 1 to 3 years (n= 16)

Older children 4 to 14 years (n= 25)

Inclusion Criteria Constipated infants and children aged 5 weeks to 14 years, followed in outpatient clinics or pediatric wards
Exclusion Criteria Not specified
Methods Dioctyl sodium sulfosuccinate was administered in soft gelatin capsules or as an aqueous solution. Dosages varied by age and severity of constipation: 10-40 mg for infants under 1 year, 25-100 mg for older children. Medication was given in the evening or both morning and evening, mixed with milk or juice to mask taste. Treatment lasted for at least 15 days.
Duration Not explicitly stated, but treatment lasted for at least 15 days
Outcome Measures

Primary: Relief of constipation and production of soft normal stools

Secondary: Healing of anal fissures, reduction in associated symptoms like headache

Baseline Characteristics   Infants under 1 year (n= 9) Infants 1 to 3 years (n= 16) Older children 4 to 14 years (n= 25)
Effective dose, mg/day 10-40 25-50 40-120
Results   Effective Dose, mg/day Outcome
Infants under 1 year 10-40 Soft normal stools, healing of anal fissures
Infants 1 to 3 years 25-50 Soft normal stools
Older children 4 to 14 years 40-120 Soft normal stools, improvement in headaches
Adverse Events Watery stools in three patients; no other side effects observed
Study Author Conclusions Dioctyl sodium sulfosuccinate is an effective fecal softener for treating constipation in infants and children, with minimal side effects. It offers a physiological approach to breaking the pattern of constipation without causing bowel irritation or nutritional interference.
Critique The study demonstrates the effectiveness of dioctyl sodium sulfosuccinate in pediatric constipation with a clear methodology and positive outcomes. However, the lack of a control group and potential bias due to the non-randomized design may limit the generalizability of the results. Additionally, the study does not address long-term effects or compare with other treatments.

 

Table 2 References:
[7] Tevetoglu F. Pediatric use of dioctyl sodium sulfosuccinate. J Pediatr. 1957;50(3):304-307. doi:10.1016/s0022-3476(57)80027-4