Macrogol

A06A - Drugs for constipation ATC A06AD15 Small molecule

JFDA label: Forlax Powder

Mechanism of Action

— Osmotic laxative; — Laxative

Indications

Approved

Constipation, occasional

Off-label

Bowel preparation before colonoscopy
Occasional constipation (infants, children, adolescents

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Relaxa: Use in children Absolute
Hypersensitivity to polyethylene glycol or any component of the formulation Absolute
known or suspected bowel obstruction OTC labeling: When used for self-medication, do not use if you have renal disease unless advised by a health care provider Absolute

Adverse Reactions

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

Gastrointestinal disorders (5)

Not Known Abdominal cramps · bloating of the stomach · diarrhea · flatulence · nausea

Skin and subcutaneous tissue disorders (1)

Not Known Urticaria

Dosing

Source: Lexicomp

Bowel preparation before colonoscopy (off-label use): Oral: 17 g (~1 heaping tablespoon) in 240 mL (8 ounces) of clear liquid every 10 minutes until 2,000 mL of volume are consumed (start within 6 hours after administering bisacodyl delayed-release tablets or magnesium citrate) (ASCRS/ASGE/SAGES [Wexner 2006]) Constipation, occasional: Oral: 17 g (~1 heaping tablespoon) dissolved in 120 to 240 mL (4 to 8 ounces) of beverage, once daily; do not use for >1 to 2 weeks (product specific) unless directed by health care provider. In a clinical trial, 34 g once daily was shown to be effective, but with increased adverse effects (DiPalma 1999).

(For additional information see "Polyethylene glycol 3350: Pediatric drug information") Bowel preparation before colonoscopy (off-label): Children >2 years of age and Adolescents: Limited data available: Oral: 1.5 g/kg/day for 4 days; maximum dose: 100 g/day (Pashankar 2004) Constipation, occasional (off-label use): Infants, Children, and Adolescents Note: Dosage should be individualized to achieved desired effect, infants and young children may require higher doses than school-aged children (Loening-Buck 2004; Pashankar 2001) Adolescents ≥17 years of age: Refer to adult dosing. Fecal impaction, slow disimpaction (off-label use): Limited data available: Children and Adolescents: Oral: 1 to 1.5 g/kg daily for 3 to 6 consecutive days (NASPGHAN [Tabbers] 2014; Youssef 2002); maximum daily dose: 100 g/day (Youssef 2002); following disimpaction maintenance dose of 0.4 g/kg daily should be continued for ≥2 months (NASPGHAN [Tabbers] 2014)

Refer to adult dosing.

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

Warnings & Precautions

Source: Lexicomp

Electrolyte imbalance

Prolonged, frequent, or excessive use may lead to electrolyte imbalance.

Hypersensitivity

Do not use if you are hypersensitive to polyethylene glycol. If an allergic reaction develops (eg, rash, swelling, difficulty breathing), discontinue use immediately and seek medical care. Disease-related concern:

Bowel obstruction

Evaluate patients with symptoms of bowel obstruction, appendicitis, or inflamed bowel (nausea, vomiting, abdominal pain or distension) prior to use; use is contraindicated in patients with known or suspected bowel obstruction.

Renal impairment

Use with caution in patients with renal impairment. Do not use in renal impairment unless under supervision of a health care professional. Other warnings/precautions:

Administration

If severe diarrhea occurs, discontinue use. When used for bowel preparation for colonoscopy (off-label use), oral medications should not be administered within 1 hour of start of therapy.

Duration of therapy

Do not use for longer than 1 to 2 weeks (product specific); 2 to 4 days may be required to produce bowel movement.

OTC labeling

When used for self-medication, patients should consult health care provider prior to use if they have nausea, vomiting, or abdominal pain, irritable bowel syndrome, or a sudden change in bowel habits for >2 weeks. Patients should be instructed to discontinue use and consult health care provider if they have severe diarrhea, rectal bleeding, if abdominal pain, bloating, cramping, or nausea gets worse, or if need to use for >1 week.

Pregnancy & Lactation

Pregnancy

Polyethylene glycol (PEG) has minimal systemic absorption and would be unlikely to cause fetal malformations. However, until additional information is available, use to treat constipation in pregnancy should be avoided unless other preferred methods are inadequate (Mahadevan 2006). Use as a bowel preparation prior to colonoscopy in pregnant women may be considered (Wexner 2006).

Chemistry & Properties

Formula	C2H6O2
Molecular weight	62.07 g/mol
IUPAC name	ethane-1,2-diol
CAS	107-21-1
PubChem CID	174
InChIKey	`LYCAIKOWRPUZTN-UHFFFAOYSA-N`
logP	-1.4 (XLogP -1.4)
Polar surface area	40.5 Å²
H-bond acceptors / donors	2 / 2

SMILES

C(CO)O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	2.132 h
Volume of distribution	0.453 L/kg
Protein binding	19.3%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—

Transporters

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

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Forlax Powder	Powder 10 g	20 vial	Abu Sharef Medical Stores	3.020