Naltrexone - Warnings and Precautions

WARNINGS Vulnerability to Opioid Overdose After opioid detoxification, patients are likely to have reduced tolerance to opioids.

As the blockade of exogenous opioids provided by naltrexone hydrochloride wanes and eventually dissipates completely, patients who have been treated with naltrexone hydrochloride may respond to lower doses of opioids than previously used, just as they would shortly after completing detoxification.

This could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids.

Cases of opioid overdose with fatal outcomes have been reported in patients after discontinuing treatment.

Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after naltrexone hydrochloride treatment is discontinued.

It is important that patients inform family members, and the people closest to the patient of this increased sensitivity ot opioids and the risk of overdose (see PRECATIONS, Information for Patients ).

There is also the possibility that a patient who is treated with naltrexone hydrochloride could overcome the opioid blockade effect of naltrexone hydrochloride.

Although naltrexone hydrochloride is a potent antagonist, the blockade produced by naltrexone hydrochloride is surmountable.

The plasma concentration of exogenous opioids attained immediately following their acute administration may be sufficient to overcome the competitive receptor blockade.

This poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids.

Any attempt by a patient to overcome the antagonism by taking opioids is especially dangerous and may lead to life-threatening opioid intoxication or fatal overdose.

Patients should be told of the serious consequences of trying to overcome the opioid blockade (see PRECAUTIONS, Information for Patients ).

Precipitated Opioid Withdrawal The symptoms of spontaneous opioid withdrawal (which are associated with the discontinuation of opioid in a dependent individual) are uncomfortable, but they are not generally believed to be severe or necessitate hospitalization.

However, when withdrawal is precipitated abruptly by the administration of an opioid antagonist to an opioid-dependent patient, the resulting withdrawal syndrome can be severe enough to require hospitalization.

Symptoms of withdrawal have usually appeared within five minutes of ingestion of naltrexone hydrochloride and have lasted for up to 48 hours.

Mental status changes including confusion, somnolence and visual hallucinations have occurred.

Significant fluid losses from vomiting and diarrhea have required intravenous fluid administration.

Review of postmarketing cases of precipitated opioid withdrawal in association with naltrexone treatment has identified cases with symptoms of withdrawal severe enough to require hospital admission, and in some cases, management in the intensive care unit.

To prevent occurrence of precipitated withdrawal in patients dependent on opioids, or exacerbation of a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride treatment.

An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids.

Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks.

If a more rapid transition from agonist to antagonist therapy is deemed necessary and appropriate by the healthcare provider, monitor the patient closely in an appropriate medical setting where precipitated withdrawal can be managed.

In every case, healthcare providers should always be prepared to manage withdrawal symptomatically with non-opioid medications because there is no completely reliable method for determining whether a patient has had an adequate opioid-free period.

A naloxone challenge test may be helpful; however, a few case reports have indicated that patients may experience precipitated withdrawal despite having a negative urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of transitioning from buprenorphine treatment).

Patients should be made aware of the risks associated with precipitated withdrawal and encouraged to give an accurate account of last opioid use.