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December 13, 2021
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Combination products containing opioid antagonists: What prescribers need to know

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FDA recently approved Lybalvi for the treatment of schizophrenia and for use in manic and mixed (depressive and manic) episodes of bipolar I disorder as an acute treatment, a maintenance treatment, and for use with valproate or lithium.

Lybalvi contains a combination of olanzapine, an atypical antipsychotic medication, and samidorphan, a novel opioid antagonist that helps to mitigate weight gain that is commonly associated with olanzapine.

An infographic that describes what health care professionals should do in nonemergency (discontinue Lybalvi at least 5 days before opioid treatment and start olanzapine or another antipsychotic) and emergency situations (one option is to have appropriately trained personnel should continuously monitor the patient in a setting equipped and staffed for cardiopulmonary resuscitation) involving Lybalvi.
Reference: the FDA

Samidorphan is an orally bioavailable opioid antagonist that blocks opioid action by attaching to the opioid receptors without activating them, ultimately preventing opioids from working. This action can cause unintended consequences for patients dependent on opioids by precipitating opioid withdrawal. When precipitated abruptly by the administration of an opioid antagonist to an opioid-dependent patient, the withdrawal syndrome can be severe enough to require hospitalization.

Jana McAninch

In addition, products containing orally bioavailable opioid antagonists like samidorphan present challenges for patients who need opioid analgesics to manage pain. Samidorphan may reduce the effectiveness of pain control in patients who require opioids for unexpected severe pain (eg, trauma or emergency surgery). Patients may be at increased risk for opioid overdose if attempts are made to overcome the opioid blockade by using repeated or high doses of opioids. This is particularly the case following interruption or discontinuation of the opioid antagonist-containing drug because it may subject the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes.

Patients with a history of chronic opioid use prior to treatment with Lybalvi may also have decreased opioid tolerance if Lybalvi therapy is interrupted or discontinued. This decreased tolerance may increase the risk of opioid overdose if the patient resumes opioids at the previously tolerated dosage.

What actions health care providers should take

Lybalvi is contraindicated in patients using opioids or undergoing acute opioid withdrawal. Prior to starting Lybalvi, patients should not have taken short-acting opioids for at least 7 days, and not have taken long-acting opioids for at least 14 days. Health care providers should inquire about patients’ opioid use and inform patients about the risk of precipitated opioid withdrawal. Patients who used opioids chronically prior to Lybalvi treatment should be aware that they may have a lower tolerance to opioids than before if Lybalvi therapy is interrupted or discontinued and opioids are resumed.

CDR Mark A. Liberatore

Providers should also inform patients of the potential consequences of trying to overcome opioid blockade from the samidorphan in Lybalvi, and the serious risks of taking opioids concurrently with Lybalvi or while transitioning off Lybalvi. Providers should also emphasize the importance of the patient disclosing Lybalvi treatment to their other health care providers, particularly in emergency situations or if a need for opioids is anticipated, such as for a planned surgical procedure.

In emergency situations, if a patient treated with Lybalvi requires opioid treatment as part of anesthesia or analgesia:

  • Discontinue Lybalvi.
  • Opioids should be administered by individual(s) trained in the use of anesthetic drugs and the management of the respiratory effects of opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation.
  • Appropriately trained personnel should continuously monitor the patient in a setting equipped and staffed for cardiopulmonary resuscitation.

In nonemergency situations, if a patient treated with Lybalvi is expected to require opioid treatment (eg, after an elective surgery or for the treatment of opioid use disorder), discontinue Lybalvi at least 5 days before opioid treatment and start olanzapine or another antipsychotic, if needed.

Marc Stone

Contrave: Another FDA-approved product containing an opioid antagonist

Lybalvi is not the only combination product on the market today that contains an orally bioavailable opioid antagonist. FDA approved Contrave (naltrexone hydrochloride and bupropion hydrochloride) in 2014 for chronic weight management in conjunction with caloric reduction and exercise. Contrave is intended for adults who are overweight or obese with at least one weight-related condition, such as hypertension, type 2 diabetes or high cholesterol. The naltrexone component of Contrave is an opioid antagonist, and Contrave’s FDA-approved labeling includes similar contraindications and warnings regarding use of opioid analgesics to those for Lybalvi.