Opioid Constipation- Ochs

What is the most expected ADR with opioids? (happens 40-80% of the time)

constipation

What receptor is primarily responsible for opioid-induced constipation?

activation of μ receptors

Is treating opioid-induced constipation the same as other forms?

no, warrants individualized management

What are the 4 different types of tx for opioid-induced constipation? (in order of 1st line—> last line)

1. traditional laxatives

2. peripherally acting μ-opioid receptor antagonists (PAMORAs)

3. intestinal secretagogues

4. selective 5-HT agonists

How is opioid-induced constipation diagnosed?

• ROME IV criteria

  • must have 2+ of the listed symptoms

What are the classes and medications of traditional laxatives? (not Och’s focus)

• osmotic- PEG, lactulose, Mg Citrate, Mg hydroxide

• stimulant- senna, bisacodyl

• stool softeners- docusate

• lubricant- mineral oil

What is 1st line for opioid-induced constipation? What do we use if that doesn’t work?

traditional laxatives 1st line, use PAMORAs as 2nd line

Before using a 2nd line therapy, what is an adequate trial for 1st line tx/traditional laxatives?

• know

SCHEDULED bowel regimen (not PRN) of 2 or more class types for at least 2-3 weeks

(basically means, before switching to PAMORA, must take 2+ traditional laxative for 2-3 weeks. also, must have a scheduled regimen for taking the laxatives)

What are the names of the PAMORAs or peripherally acting μ-opioid receptor antagonists that are approved for OIC? (brand/generic)

• Naldemedine (Symproic)

• Naloxegol (Movantik)

• Methylnaltrexone (Relistor)

If I start a PAMORA, do I continue or discontinue traditional laxatives?

discontinue

All PAMORAs are contraindicated in _____________________.

GI obstruction

Which PAMORAs have a strong recommendation and which have conditional?

• Naldemedine- strong

• Naloxegol- strong

• Methylnaltrexone- conditional

(we are gonna use a strong rec before a conditional)

What are the ADRs of PAMORAs?

• abdominal pain

• n/v

• diarrhea

How should each PAMORA be administered orally?

• Naldemedine- with or without food

• Naloxegol- ON AN EMPTY stomach (1-2 hrs after 1st meal)

• Methylnaltrexone- with water on empty stomach (30 min before 1st meal)

What should be monitored for the PAMORAs?

monitor for GI perforation

What PAMORA is available SQ?

Methylnaltrexone

Methylnaltrexone (Relistor) should not be confused with what drug with a similar name?

Temazepam (Restoril)

What is the name of a PAMORA is NOT approved for opioid-induced constipation?

Alvimopan (Entereg)

What is the indication for Alvimopan?

postoperative ileus in short-term hospital use

What is the BBW of Alvimopan?

increased incidence of MI, REMS program

What are some non-pharm recommendation for managing opioid-induced constipation?

1. increase fluids

2. exercise

3. toileting practices

4. change to less-constipating opioid

Why is a non-pharm recommendation for opioid induced constipation NOT FIBER?

bc the problem here is not with the diet, the receptors in our intestine are effected by opioids… increasing fiber intake will do nothing to the receptors

PRACTICE:

What medications are used 1st line for management of opioid-induced constipation?

• traditional laxatives

  • stimulants

  • Osmotics

  • stool softeners

  • mineral oil

PRACTICE:

What are the components of an adequate 1st-line agent trial prior to escalating therapy?

• scheduled regimen

• laxatives from 2+ classes for ≥2-3 weeks

PRACTICE:

What med class is considered 2nd-line for the management of opioid-induced constipation?

PAMORAs

PRACTICE:

What contraindication do all the PAMORAs share?

suspected/confirmed GI obstruction

PRACTICE:

Which PAMORA can be taken with or without food?

Naldemedine (Symproic)

What are 2 medications that do NOT have an AGA recommendation for use due to evidence gaps?

• Lubiprostone (Amitiza)

• Prucalopride (Motegrity)

Describe the entire tx approach towards opioid induced constipation:

1. lifestyle changes

2. traditional laxatives

3. PAMORAs