Careful Patient Management Essential for Mitigating Opioid Side Effects

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By Annette M. Boyle

Rollin M. “Mac” Gallagher, MD, MPH

PHILADELPHIA – More than 50% of all VHA patients and more than 90% of those with polytrauma report experiencing chronic pain and, for many, only opioids provide significant relief. Unfortunately, gastrointestinal side effects, principally constipation and nausea, can make the drugs almost as intolerable as the pain.

“Nausea frequently abates over time, or a patient can switch to another opioid, if nausea remains an issue. Constipation is an issue for almost anyone on opioids,” said Rollin M. “Mac” Gallagher, MD, MPH, national program director for pain management, VHA.

The VA and DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain notes that constipation is one of the adverse effects of opioid therapy that does not diminish over time. Consequently, discussing lifestyle changes and symptom management with patients is essential.

“The guidelines are very clear about this,” Gallagher said. “They specifically recommend taking a proactive approach about diet, use of stool softeners and having a laxative available. These three form the core for preventing problems long-term. Regular follow-up keeps problems from getting out of hand.”

One of the biggest challenges is getting patients on opioids to change their diets. “The good ol’ American diet is not ideal for someone likely to experience constipation. They need to increase consumption of fruits and vegetables. While that seems simple, changes in day-to-day habits are very challenging,” Gallagher said.

Increased consumption of fluids and regular exercise also help prevent constipation but, like dietary changes, require focus and support.

“You can get people to do it, if you spend the time counseling them and have a good clinical team who will follow up on protocols,” Gallagher noted.

Increased fluid consumption may partially offset the reduction in intestinal fluids caused by absorption of electrolytes when opioids bind to the peripheral opioid receptors in the gastrointestinal tract. Increased fiber from fruits and vegetables can combat abnormal GI motility associated with activation of enteric opioid receptors.

For many patients, the VA’s approach to treatment offers advantages not available in more traditional structures.

“The patient-aligned care team permits fine tuning of the treatment and individualized therapy,” Gallagher pointed out. “Patients may need a good nurse who will work with them and can provide one-on-one counseling” to affect dietary changes and manage constipation.

First-Line Treatments

Lifestyle measures can mitigate constipation but are rarely sufficient to prevent the problem for patients on long-term opioid therapy. Typically, patients require a stimulant-based bowel regimen that starts simultaneously with opioid therapy.

“If the initial regimen is inadequate, mild hyperosmotic, saline and emollient laxatives may be added,” according to the VA/DoD guidelines. Bulking laxatives such as psyllium and polycarbophil should be avoided to prevent bowel obstructions, particularly in older patients, Gallagher noted.

Regardless, about half of patients on opioids fail to respond sufficiently to laxatives. Opioid-induced constipation (OIC) accounts for termination of opioid therapy in about one-third of patients, according to Heather Payton, PharmD, South Texas Veterans Health Care System, San Antonio.

Pharmacotherapeutic Options

For some of those patients, two pharmacotherapies might be helpful.

The FDA recently approved the use of lubiprostone, an oral medication, for constipation caused by opioids. The drug had gained approval for use in treatment of chronic idiopathic constipation in adults and constipation associated with irritable bowel syndrome in women.

“While I haven’t used it, it sounds like it [lubiprostone] will have a role in constipation management. The VA and DoD will be evaluating where it fits into our algorithm for managing opioid therapy and will probably make it available,” Gallagher told U.S. Medicine. “Usually where there is a new drug, we see where it fits into the systematic approach of management.”

Lubiprostone, already approved  for the treatment of chronic idiopathic constipation i in adults and irritable bowel syndrome with constipation in women 18 years of age and older, has been used in very specific situations in the VA for the past several years. The drug works by activating CIC-2 chloride channels in the intestinal epithelium, increasing fluid secretion, softening the stool and enhancing motility.

VHA Pharmacy Benefits Management-Strategic Healthcare Group and Medical Advisory Panel’s Nonformulary Criteria for Use currently establishes high hurdles for lubiprostone usage. Patients must have a documented lack of response to or intolerance of at least three agents from the VA National Formulary, which includes bulk-forming laxatives, osmotic laxatives, stimulant laxatives and nonpharmacologic measures. In addition, they must meet the American Gastroenterological Association’s criteria for chronic functional constipation for the three months prior to treatment with symptoms beginning at least six months before diagnosis.

Another drug, methylnaltrexone bromide (MNTX), was approved by the FDA in 2009. It is a subcutaneous injectable for short-term treatment of OIC in patients receiving palliative care for advanced stage diseases such as cancer, end-stage COPD and HIV/AIDS who have insufficient response to laxative therapy. MNTX reverses opioid effects on the GI tract without diminishing the analgesic effects on the central nervous system.

In 2012, the FDA declined to approve MNTX for treatment of OIC in patients with chronic noncancer pain. Use of MNTX for more than four months has not been studied and is not recommended for patients with known or suspected bowel obstructions because of case reports of intestinal perforations.

MNTX may be useful in short term situations, however. The drug “is being studied for use in noncancer patients, post-surgery, who are not taking oral fluids or oral laxatives and need pain control with opioids,” Gallagher noted.

The circumstances under which patients may use medications to manage OIC may expand in the near future, he said.

“When new drugs come along, you add those to the opportunities for better management and to the treatment algorithms,” Gallagher said. “They give more options for the provider and the patient to work with.”

But in the end, he added, “there’s no substitute for good patient management. You simply can’t substitute some new drug for good patient counseling and behavioral change and common sense management of side effects.”

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