Docusate

A06A - Drugs for constipation ATC A06AA02 Small molecule Natural product

JFDA label: Mulin 10 solution

Mechanism of Action

— Surfactant laxative

Indications

Approved

Stool softener

Off-label

Ceruminolytic

Contraindications

Source: Lexicomp

OTC labeling: When used for self-medication, do not use for longer than 7 days Absolute
or concomitantly with mineral oil (oral products only) Absolute
when abdominal pain, nausea, or vomiting is present Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Other (1)

Common Respiratory: Throat irritation (liquid)

Dosing

Source: Lexicomp

Note: The following are general dosing guidelines; refer to specific product labeling for dosing instructions. Stool softener: Oral: Docusate calcium: 240 mg once daily Docusate sodium: 50 to 360 mg once daily or in divided doses Rectal: 283 mg per 5 mL: 283 mg (1 enema) 1 to 3 times daily Ceruminolytic (off-label use): Intra-aural: Administer 1 mL of docusate sodium in 2 mL syringes; if no clearance in 15 minutes, irrigate with 50 or 100 mL lukewarm normal saline (Singer 2000)

(For additional information see "Docusate: Pediatric drug information") Note: The following are general dosing guidelines; refer to specific product labeling for dosing instructions. Stool softener: Oral: Docusate calcium: Children ≥12 years and Adolescents: Refer to adult dosing. Docusate sodium: Children 2 to Children ≥12 years and Adolescents: Refer to adult dosing. Alternate dosing (off-label dose): Docusate sodium: Constipation (occasional): Infants ≥6 months and Children Children ≥2 to Rectal: Children 2 to 100 mg per 5 mL: 100 mg (1 enema) once daily 283 mg per 5 mL: 283 mg (1 enema) once daily Children ≥12 years and Adolescents: 283 mg per 5 mL: Refer to adult dosing. Ceruminolytic (off-label use): Children and Adolescents: Intra-aural: Administer 1 mL of docusate sodium in 2 mL syringes; if no clearance in 15 minutes, irrigate with 50 or 100 mL lukewarm normal saline (Singer 2000)

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Benzyl alcohol and derivatives

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin.

Enema

For rectal use only; lubricate tip prior to insertion. Discontinue use and notify health care provider if rash around the anus/rectal irritation occurs or if resistance is encountered with insertion; forcing the tube may result in injury or damage to the rectum. Other warnings/precautions:

Self-medication (OTC use)

When used for self-medication (OTC), patients should be instructed to contact healthcare provider prior to use if nausea, stomach pain, or vomiting are present, or if a sudden change in bowel habits occurs and persists over 14 days. Patients should discontinue use and notify healthcare provider if rectal bleeding occurs, if a bowel movement fails to occur after use, or if use is needed >7 days.

Pregnancy & Lactation

Pregnancy

Hypomagnesemia was reported in a newborn following chronic maternal overuse of docusate sodium throughout pregnancy (Schindler 1984). Treatment of constipation in pregnant women is similar to that of nonpregnant patients and medications may be used when diet and lifestyle modifications are not effective. Agents other than docusate are preferred for initial treatment. Docusate sodium may be used if needed, but may not be as effective as other agents (ACG [Christie 2007]).

Lactation

It is not known if docusate is present in breast milk; because there is some systemic absorption, use of other agents may be preferred in breastfeeding women (Lewis 1985). Diarrhea was noted in a breastfeeding infant following maternal use of danthron and docusate sodium (Greenhalf 1973).

Monitoring

Clinical pearl	Rectal: Periodic rectal exams are recommended in patients with impaired rectal function, especially loss of sensation.

Chemistry & Properties

Formula	C20H38O7S
Molecular weight	422.58 g/mol
IUPAC name	1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonic acid
CAS	10041-19-7
PubChem CID	11339
InChIKey	`HNSDLXPSAYFUHK-UHFFFAOYSA-N`
logP	4.15 (XLogP 5.1)
Polar surface area	106.97 Å²
H-bond acceptors / donors	6 / 1
Drug-likeness (QED)	0.29
Lipinski violations	0

SMILES

CCCCC(CC)COC(=O)CC(C(=O)OCC(CC)CCCC)S(=O)(=O)O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.459 h
Volume of distribution	0.851 L/kg
Protein binding	97.3%
BBB penetrant	No

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (4, DDInter)

Interacting drug	Severity	Management
Lactulose	moderate
Mineral oil	moderate
Phenolphthalein	moderate
Linaclotide	minor

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Dewax ear drops	Eye/Ear Drops 0.5 %	10 ml	Amman Pharmaceutical Indusries	0.890
Mulin 10 solution	Solution 10 mg/ml	50 ml	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	1.200
Waxsol	Solution 0.5 %	10 ml	Khoury Drug Store	1.330