Laxatives

Constipation (Adult)
a) 5-15 mg orally once daily up to 30 mg/day [Onset of action: 6 to 10 hours]
b) 10 mg suppository rectally once daily  [Onset of action: 15 to 60 minutes]

Preparation of bowel for procedure
a) 10-15 mg orally once daily up to 30 mg/day
b) 10 mg suppository rectally once daily
Onset: bowel movement within 15 to 60 min .

Supplied:
Rectal suppository: 10 mg.
Tablet [enteric coated]: 5 mg.

Dosing (Adults)
Stool softener:
Oral: 50-500 mg/day in 1-4 divided doses  [Onset of action:  12 - 72 hours]
Rectal: Add 50-100 mg of docusate liquid to enema fluid (saline or water); give as retention or flushing enema.

MECHANISM OF ACTION — Reduces surface tension of the oil-water interface of the stool resulting in enhanced incorporation of water and fat allowing for stool softening.

Adults and children 12 years and older
1) Laxative: 15 to 45 mL. Dilute recommended dose with at least one-half glass (4 fl. oz.) of cold water or other clear liquid. Drink, then follow with at least one additional glass (8 fl. oz.) of water or other clear liquid.

2) Standard bowel cleansing dosage is two 30- to 45-mL doses separated by 10-12 hours (in at-risk patients, - below - consider using the lower end of the dosing range.
AT RISK Patients: Debilitated or elderly; Pregnant or nursing; Increased risk for underlying renal impairment; Colostomy or ileostomy; Heart disease/acute myocardial infarction/unstable angina; Pre-existing electrolyte disturbance. In at-risk patients consider obtaining baseline and posttreatment electrolytes and using the lower end of the dosing range of Fleet® Phospho-soda® (two 30-mL doses given 10-12 hours apart).

Supplied: 748 mOsmol/45mL. The process is associated with transient serum electrolyte changes. Each Tablespoon (15 mL) of FLEET® Phospho-soda® oral saline laxative contains 7.2 g monobasic sodium phosphate monohydrate and 2.7 g dibasic sodium phosphate heptahydrate in a stable, buffered aqueous solution.

ELEMENTAL AND ELECTROLYTIC CONTENT
mEq Phosphate (PO4 )/mL: 12.45
mEq Sodium (Na)/mL: 4.82
mg Sodium (Na)/mL: 111
mmole Phosphorus (P)/mL: 4.15

Dosage: Children >6 years and Adults: 1 adult suppository 1-2 times/day as needed.
[Onset of action: 15 - 30 minutes]

Acute Hepatic encephalopathy or portosystemic encephalopathy (PSE):
Adults: Oral: 20-30 g (30-45 ml) every 1-2 hours to induce rapid laxation. Adjust dosage daily to produce 2-3 soft stools. Doses of 30-45 ml may be given hourly to cause rapid laxation, then reduce to recommended dose.
Usual daily dose: 60-100 g (90-150 mL) daily. Rectal administration: 200 g (300 ml) diluted with 700 ml of H20 or NS - administer rectally via rectal balloon catheter and retain 30-60 minutes every 4-6 hours

CONTRAINDICATIONS:
Pediatric patients up to 6 years of age.
Patients with known or suspected mechanical gastrointestinal obstruction.

WARNINGS AND PRECAUTIONS
Diarrhea: Patients may experience severe diarrhea. Hold or stop LINZESS.
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Mechanism of Action: Linaclotide is a guanylate cyclase-C (GC-C) agonist. Both linaclotide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevation in intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, linaclotide has been shown to both accelerate GI transit and reduce intestinal pain. The linaclotide-induced reduction in visceral pain in animals is thought to be mediated by increased extracellular cGMP, which was shown to decrease the activity of pain-sensing nerves.

INDICATIONS AND USAGE:
1.1 Irritable Bowel Syndrome with Constipation (IBS-C)
LINZESS (linaclotide) is indicated in adults for the treatment of irritable bowel syndrome with constipation (IBS-C).

1.2 Chronic Idiopathic Constipation (CIC)
LINZESS is indicated in adults for the treatment of chronic idiopathic constipation (CIC).

DOSAGE AND ADMINISTRATION

HOW SUPPLIED:

145 mcg capsules are white to off-white opaque with gray imprint “FL 145”
290 mcg capsules are white to off-white opaque with gray imprint “FL 290”

1] Treatment of chronic idiopathic constipation in adults
Dose: 24 mcg taken twice daily orally with food and water. Physicians and patients should periodically assess the need for continued therapy.

2] Treatment of irritable bowel syndrome with constipation in women  ≥ 18 years old
Dose: 8 mcg taken twice daily orally with food and water
 
Renal Impairment: Amitiza has not been studied in patients who have renal impairment.
Hepatic Impairment: Amitiza has not been studied in patients who have hepatic impairment.

Supplied: Gelatin capsules: 8 mcg and 24 mcg

WARNINGS AND PRECAUTIONS

• Women who could become pregnant should have a negative pregnancy test prior to beginning therapy and should be capable of complying with effective contraceptive measures.
• Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Patients may experience nausea; concomitant administration of food may reduce this symptom.
• Do not prescribe for patients that have severe diarrhea.
• Patients taking Amitiza may experience dyspnea within an hour of first dose. This symptom generally resolves within 3 hours, but may recur with repeat dosing.
• Evaluate patients with symptoms suggestive of mechanical gastrointestinal obstruction prior to initiating treatment with Amitiza.

ADVERSE REACTIONS

• Most common adverse reactions (incidence > 4%) in chronic idiopathic constipation are nausea, diarrhea, headache, abdominal pain, abdominal distension, and flatulence.
• Most common adverse reactions (incidence > 4%) in irritable bowel syndrome with constipation are nausea, diarrhea, and abdominal pain.

Mechanism of Action:
Lubiprostone is a locally acting chloride channel activator that enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium concentrations in the serum.

Dosing (Adults): Cathartic: Oral: Adults: 1/2 to 1 full bottle (150-300 mL). May be taken as a single daily dose or divided doses. Maximum 300ml in a 24 hour period (manufacturer).
Dave's note: (MAXIMUM DOSE) Some sources list the daily maximum as 25 grams which is equivalent to ~425 ml.  [See renal impairment below - may not be indicated]

Supplied: Solution, oral: 290 mg/5 mL (300 mL).
Absorption: Oral: 15% to 30%. Excretion: Urine.

MECHANISM OF ACTION - Promotes bowel evacuation by causing osmotic retention of fluid which distends the colon with increased peristaltic activity

RENAL IMPAIRMENT - Patients in severe renal failure should not receive magnesium due to toxicity from accumulation. Patients with a Clcr <25 mL/minute should be monitored by serum magnesium levels.

Dosing in renal impairment: Patients in severe renal failure should not receive magnesium due to toxicity from accumulation. Patients with a Clcr<25 mL/minute receiving magnesium should be monitored by serum magnesium levels.

Administration
Liquid doses may be diluted with a small amount of water prior to administration. All doses should be followed by 8 ounces of water.

Adult Dose: dissolve one leveled scoop (one heaping tablespoon - 19g) in 8 ounces of cold water up to three times daily at the first sign of constipation. Children age 6 to 12 years of age: one-half the adult dose stirred briskly in 8 ounces of cold water, once daily at the first sign of constipation. The mixture should be administered promptly and drinking another glass of water is highly recommended

Bowel clearance: 118 ml rectally once daily as an enema.

Protect clothing - may have oil leakage from rectum.

Initial U.S. Approval:  2017

Mechanism of Action:
Naldemedine is an opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid receptors. Naldemedine functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids.

Naldemedine is a derivative of naltrexone to which a side chain has been added that increases the molecular weight and the polar surface area, thereby reducing its ability to cross the blood-brain barrier (BBB).

Naldemedine is also a substrate of the P-glycoprotein (P-gp) efflux transporter. Based on these properties, the CNS penetration of naldemedine is expected to be negligible at the recommended dose levels, limiting the potential for interference with centrally-mediated opioid analgesia.

INDICATIONS AND USAGE:
SYMPROIC is an opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain

DOSAGE AND ADMINISTRATION: PDF
2.1 Administration
Alteration of analgesic dosing regimen prior to initiating SYMPROIC is not required.
Patients receiving opioids for less than 4 weeks may be less responsive to SYMPROIC.
Discontinue SYMPROIC if treatment with the opioid pain medication is also discontinued.

2.2 Adult Dosage
The recommended dosage of SYMPROIC is 0.2 mg orally once daily with or without food.

HOW SUPPLIED:
Tablets: 0.2 mg naldemedine

Initial U.S. Approval:  2014

Mechanism of Action:  Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids.

Naloxegol is a PEGylated derivative of naloxone, and is a substrate for the P-glycoprotein transporter (P-gp). Also, the presence of the PEG moiety in naloxegol reduces its passive permeability as compared with naloxone. Due to the reduced permeability and increased efflux of naloxegol across the blood-brain barrier, related to P-gp substrate properties, the CNS penetration of naloxegol is expected to be negligible at the recommended dose levels limiting the potential for interference with centrally mediated opioid analgesia.

INDICATIONS AND USAGE:  MOVANTIK (naloxegol) is an opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain

HOW SUPPLIED:  Tablets: 12.5 mg and 25 mg

Avoid use of TRULANCE in patients 6 years to less than 18 years of age [see WARNINGS AND PRECAUTIONS (5.1), USE IN SPECIFIC POPULATIONS (8.4)].
The safety and effectiveness of TRULANCE have not been established in patients less than 18 years of age [see USE IN SPECIFIC POPULATIONS (8.4)].

Initial U.S. Approval:  2017

Mechanism of Action:
Plecanatide is structurally related to human uroguanylin, and similar to uroguanylin, plecanatide functions as a guanylate cyclase-C (GC-C) agonist. Both plecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevation of intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, plecanatide has been shown to increase fluid secretion into the gastrointestinal (GI) tract, accelerate intestinal transit, and cause changes in stool consistency.

In an animal model of visceral pain, plecanatide reduced abdominal muscle contractions, a measure of intestinal pain. The mechanism has not been studied.

INDICATIONS AND USAGE:
TRULANCE is indicated in adults for the treatment of chronic idiopathic constipation (CIC).

DOSAGE AND ADMINISTRATION:
2.1 Recommended Dosage
The recommended dosage of TRULANCE is 3 mg taken orally once daily.

2.2 Preparation and Administration Instructions
Take TRULANCE with or without food.
If a dose is missed, skip the missed dose and take the next dose at the regular time. Do not take two doses at the same time.
Swallow a tablet whole for each dose.
For adult patients with swallowing difficulties, TRULANCE tablets can be crushed and administered orally either in applesauce or with water or administered with water via a nasogastric or gastric feeding tube. Mixing TRULANCE crushed tablets in other soft foods or in other liquids has not been tested.
Oral Administration in Applesauce:

In a clean container, crush the TRULANCE tablet to a powder and mix with 1 teaspoonful of room temperature applesauce.
Consume the entire tablet-applesauce mixture immediately. Do not store the mixture for later use.

Oral Administration in Water:
Place the TRULANCE tablet in a clean cup.
Pour approximately 30 mL of room temperature water into the cup.
Mix by gently swirling the tablet and water mixture for at least 10 seconds. The TRULANCE tablet will fall apart in the water.
Swallow the entire contents of the tablet water mixture immediately.
If any portion of the tablet is left in the cup, add another 30 mL of water to the cup, swirl for at least 10 seconds, and swallow immediately.
Do not store the tablet-water mixture for later use.

Administration with Water via a Nasogastric or Gastric Feeding Tube:
Place the TRULANCE tablet in a clean cup with 30 mL of room temperature water.
Mix by gently swirling the tablet and water mixture for at least 15 seconds. The TRULANCE tablet will fall apart in the water.
Flush the nasogastric or gastric feeding tube with 30 mL of water using an appropriate syringe.
Draw up the mixture using the syringe and immediately administer via the nasogastric or gastric feeding tube. Do not reserve for future use.
If any portion of the tablet is left in the cup, add another 30 mL of water to the cup, swirl for at least 15 seconds, and using the same syringe, administer via the nasogastric or gastric feeding tube.
Using the same or a fresh syringe, flush the nasogastric or gastric feeding tube with at least 10 mL of water.

HOW SUPPLIED:
TRULANCE Tablets: 3 mg: white to off-white, plain, round tablet debossed with "SP" on one side and "3" for 3 mg on the other side.

Packets:
Active ingredient (in each dose)
Polyethylene Glycol 3350, 17 grams / packet

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Purpose
Osmotic Laxative

Use
-relieves occasional constipation (irregularity)
-generally produces a bowel movement in 1 to 3 days
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Directions (Bottle Only):

• do not take more than directed unless advised by your doctor
• the bottle top is a measuring cap marked to contain 17 grams of powder when filled to the indicated line (white section in cap)
• adults and children 17 years of age and older:
  • fill to top of white section in cap which is marked to indicate the correct dose (17 g)
  • stir and dissolve in any 4 to 8 ounces of beverage (cold, hot or room temperature) then drink
  • use once a day
  • use no more than 7 days
• children 16 years of age or under: ask a doctor

Directions (Packet Only):

• do not take more than directed unless advised by your doctor
• adults and children 17 years of age and older:
  • stir and dissolve one packet of powder (17 g) in any 4 to 8 ounces of beverage (cold, hot or room temperature) then drink
  • use once a day
  • use no more than 7 days
• children 16 years of age or under: ask a doctor

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Unlabeled use:
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Bowel prep - colonoscopy:
Mix 17grams of powder in 8 ounces of water of clear liquid and give q10min until 2 liters consumed (start within 6 hrs after ingesting 20mg bisacodyl delayed-release tabs).

Mechanism of Action: Sodium picosulfate is hydrolyzed by colonic bacteria to form an active metabolite: bis-(p-hydroxy-phenyl)-pyridyl-2-methane, BHPM, which acts directly on the colonic mucosa to stimulate colonic peristalsis.

Magnesium oxide and citric acid react to create magnesium citrate in solution, which is an osmotic agent that causes water to be retained within the gastrointestinal tract

INDICATIONS AND USAGE
Prepopik® is a combination of sodium picosulfate, a stimulant laxative, and magnesium oxide and anhydrous citric acid which form magnesium citrate, an osmotic laxative, indicated for cleansing of the colon as a preparation for colonoscopy in adults

DOSAGE AND ADMINISTRATION
Prepopik®, supplied as a powder, must be reconstituted with cold water right before its use (2.1, 2.2)
Two dosing regimens, each requires two separate dosing times (2.1)

"Split-Dose" method is preferred method (2.3)
First dose: during evening before the colonoscopy
Second dose: next day, during the morning prior to the colonoscopy

"Day-Before" method is alternative method if "Split-Dose" is not appropriate (2.4)
First dose: during afternoon or early evening before the colonoscopy
Second dose: 6 hours later during evening before colonoscopy

Additional clear liquids (no solid food or milk) must be consumed after every dose in both dosing regimens (2.3, 2.4)

DOSAGE FORMS AND STRENGTHS
For oral solution: Each of 2 packets contains 16.1 g of powder for orange flavor or 16.2 grams of powder for cranberry flavor: 10 mg sodium picosulfate, 3.5 g magnesium oxide, and 12 g anhydrous citric acid

CONTRAINDICATIONS
Patients with severely reduced renal function (creatinine clearance less than 30 mL/minute).
Gastrointestinal (GI) obstruction or ileus
Bowel perforation
Toxic colitis or toxic megacolon
Gastric retention

WARNINGS AND PRECAUTIONS
Risk of fluid and electrolyte abnormalities, arrhythmia, seizures, and renal impairment: Encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after use (5.1, 5.2, 5.3, 5.4)
Risks in patients with renal insufficiency or patients taking concomitant medications that affect renal function: Use caution, ensure adequate hydration and consider testing (5.3)
Mucosal ulcerations: Consider potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease (5.5)
Suspected GI obstruction or perforation: Rule out diagnosis before administration (4, 5.6)
Patients at risk for aspiration: Observe during administration (5.7)
Not for direct ingestion: Dissolve and take with additional water (5.8)

Onset of action: 12-24 hours
Peak effect: 2-3 days

Each tablet contains 8.6 mg sennosides.

[Onset of action: 6 to 12 hours]

 [Supplied: Senokot tablets: Each tablet contains 8.6 mg sennosides. Senokot Granules: Each teaspoonful contains 15 mg sennosides. Senokot-S Tablets: Each tablet contains 8.6 mg sennosides and 50 mg of docusate sodium]

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Adjunct to sodium polystyrene sulfonate: 15 mL as 70% solution orally until diarrhea occurs (10-20 mL/2 hours) or 20-100 mL as an oral vehicle for the sodium polystyrene sulfonate resin

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Poisoning:
When administered with charcoal: 
Oral:
Adults:  (Sorbitol 70% w/w solution = 0.9 grams/ml):  1 g/kg (range: 1-2 grams/kg) may be given with the initial dose of activated charcoal.   Note: NOT recommended in young children-  may develop diarrhea ==> potentially dangerous fluid shifts and/or electrolyte imbalances.

Supplied
Solution, oral: 70% w/w (480 mL).   Contains 0.9 grams/ml or 13.5 grams/tablespoonful.

Initial U.S. Approval:  2013

Mechanism of Action: The primary mode of action of Suclear is the osmotic effect of the unabsorbed polyethylene glycol (PEG) and sulfate salts. Sulfate salts provide sulfate anions, which are poorly absorbed. The osmotic effect of unabsorbed sulfate anions and the associated cations causes water to be retained within the gastrointestinal tract.

PEG is also a largely unabsorbed osmotic agent which causes water to be retained within the gastrointestinal tract.

INDICATIONS AND USAGE:   Suclear is a combination of osmotic laxatives and indicated for cleansing of the colon in preparation for colonoscopy in adults.
DOSAGE AND ADMINISTRATION
Suclear, supplied as oral solution (Dose 1) and for oral solution (Dose 2), must be reconstituted with cool water before use.
Do not consume solid food/milk (clear liquids only); avoid alcohol.
Two dosing regimens, each requires two separate dosing times.
“Split-Dose (2-Day)” regimen is the preferred method:
       Dose 1 (oral solution): during evening before colonoscopy
       Dose 2 (for oral solution): during morning of colonoscopy
“Day-Before (1-Day)” regimen is an alternative method:
       Dose 1 (oral solution): during early evening before colonoscopy
       Dose 2 (for oral solution): 2 hours after starting Dose 1 during evening before colonoscopy
Consume additional water after every dose in dosing regimens

HOW SUPPLIED:  Oral solution: one 6 -oz bottle contains 17.5 g sodium sulfate, 3.13 g potassium sulfate, and 1.6 g magnesium sulfate.
For oral solution: one 2-L jug with powder contains 210 g PEG-3350, 5.6 g sodium chloride, 2.86 sodium bicarbonate, and 0.74 g potassium chloride