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

OPIOID-INDUCED CONSTIPATION IN PALLIATIVE CARE AND NEW TREATMENT OPTIONS

Causes of opioid-induced constipationCauses 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

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

Opioid-induced constipation– Opioid-induced constipation– few considerationsfew considerations

Ideal new treatment option?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

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, double-blind, 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 – main clinical studiesRELISTOR – main clinical studies

RELISTOR – clinical studies resultsRELISTOR – clinical studies resultsThomas, 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 RELISTOR – indicated – indicated for the treatment of opioid-inducedfor the treatment of opioid-induced constipation in patients with advanced illness who are constipation in patients with advanced illness who are

receivingreceiving palliative care, when response to laxative therapy palliative care, when response to laxative therapy has not beenhas not been sufficient 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).

PRECAUTIONSPRECAUTIONS(1) RELISTOR is effective ONLY if opioids are the reason of constipation!(1) RELISTOR is effective ONLY if opioids are the reason of constipation!

(2) RELISTOR is contraindicated in patients with known or suspected (2) RELISTOR is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction or acute abdomen!mechanical gastrointestinal obstruction or acute abdomen!

(3) (3) RRELISTORELISTOR may work within a few minutes to a few hours may work within a few minutes to a few hours of the of the injection. Therefore, it is important to be near toiletinjection. Therefore, it is important to be near toilet facilities soon after facilities soon after

receiving your dose with assistancereceiving your dose with assistanceavailable if necessary.available if necessary.

Probing for suspected constipationProbing for suspected constipation

Clinical practice Clinical practice recommendations recommendations for prophylaxis, for prophylaxis,

ongoing ongoing assessment and assessment and

treatment of treatment of constipation in constipation in palliative carepalliative care

Clinical practice recommendations for Clinical practice recommendations for management of opioid-induced management of opioid-induced constipation in palliative careconstipation 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.