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OPIOID-INDUCED CONSTIPATION
IN PALLIATIVE CARE AND
NEW TREATMENT OPTIONS
Prim. mag. Marija Cesar Komar dr.med.
1st Congress of the Slovenian Association for
Pain Therapy and Symposium on Clinical
Neurophysiology of Pain
Bled, 9-10 October 2009
Causes of opioid-induced constipation
 Opioids: agonists of mu-receptors, desired analgesic effect
 Mu-receptors: in CNS, on periphery and in GI tract
 Opioid binding on mu-receptors in GIT: decreased
propulsion, decreased peristalsis, decreased intestinal
secretions, increased water absorption...
 Constipation - dependent of opioid dose and opioid type:
very unpleasant, stressful adverse event
 Prevalence up to 90 % - in oncology patients and other
advanced chronic diseases which require palliative care and
opioid therapy
 A number of different causes: inactivity, unsufficient fluid
intake, bad nutrition-not enough fibres, metabolic and
endocrine changes, sedation, depression, neurological
dissorders...
 Constipation is often resistant to usual standard laxatives
Opioid-induced constipation–
few considerations
Persistent constipation:
 strongly worsens QoL
 interferes with efficient pain therapy (need for lowering
effective doses, rotation and change of opioids)
 hospitalizations
 increase of health care costs
 stress and troubles – for patient and families, as well as
for doctors and nurses
Ideal new treatment option?
 targeted effect
 mu-receptor antagonist
 effective only in GIT
 analgesic effect of opioids
must remain unaffected
 good profile of undesired
effects and drug
interactions
RELISTOR – main clinical studies
1)Thomas J. et al., 2008 – placebo controled, multicentric,
double-blind, randomized study; 133 patients –
methylnaltrexone for opioid-induced constipation in
advanced illness
Thomas, J. et al. 2008. Methylnaltrexone for Opioid-Induced Constipation in Advanced
Illness. The New England Journal of Medicine 358(22):2332-2343.
2)Slatkin N. et al., 2009 – single dose, multicentric, doubleblind, randomized study; Advanced illness and opioid
therapy, 154 patients
Slatkin, N. et al., 2009. Methylnaltrexone for Treatment of Opioid-Induced Constipation in
Advanced Illness Patients. The Journal of Supportive Oncology 7(1):39–46.
RELISTOR – clinical studies results
Thomas, J. et al. 2008. Methylnaltrexone for Opioid-Induced Constipation in Advanced Illness. NEJM
358(22):2332-2343. Slatkin, N. et al., 2009. Methylnaltrexone for Treatment of Opioid-Induced Constipation in
Advanced Illness Patients. J Support Oncol 7(1):39–46. RELISTOR – SmPC
RELISTOR – indicated for the treatment of opioid-induced
constipation in patients with advanced illness who are
receiving palliative care, when response to laxative therapy
has not been sufficient
 RELISTOR is available in single-use vials for subcutaneous injection (upper
arm, abdomen or thigh). It is added to usual laxatives therapy.
 The most common adverse reactions with RELISTOR in clinical trials were
abdominal pain, flatulence, and nausea (in placebo-controlled trials, the
discontinuation rate due to AE was 1.2% for RELISTOR and 2.4% for placebo).
 No dose adjustment required in elderly patients. No dose adjustment
required in patients with mild or moderate renal or hepatic impairment. Dose
lowering is recommended in patients with severe renal impairment (creatinine
clearance less than 30 ml/min).
PRECAUTIONS
(1) RELISTOR is effective ONLY if opioids are the reason of constipation!
(2) RELISTOR is contraindicated in patients with known or suspected
mechanical gastrointestinal obstruction or acute abdomen!
(3) RELISTOR may work within a few minutes to a few hours of the
injection. Therefore, it is important to be near toilet facilities soon after
receiving your dose with assistanceavailable if necessary.
Probing for suspected constipation
Clinical practice
recommendations
for prophylaxis,
ongoing
assessment and
treatment of
constipation in
palliative care
Clinical practice recommendations for
management of opioid-induced
constipation in palliative care
Larkin, P., 2009. Clinical practice recommendations for the management of constipation in palliative care: what do
they mean for opioid-induced constipation?European Journal of Palliative Care, Supplement: 1-8.