Olanzapineinteractions

Strong CYP3A4 Inducers: Not recommended.

Strong CYP1A2 Inhibitors: Consider dosage reduction of olanzapine component of LYBALVI.

CYP1A2 Inducer: Consider dosage increase of the olanzapine component of LYBALVI.

CNS Acting Drugs: May potentiate orthostatic hypotension.

Anticholinergic Drugs: Can increase risk for severe gastrointestinal adverse reactions.

Antihypertensive Agents: Monitor blood pressure.

Levodopa and Dopamine Agonists: Not recommended.

7.1 Effects of

Other Drugs on LYBALVI Table 4 describes clinically significant drug interactions where the concomitant use of other drugs affects LYBALVI.

Table 4: Effects of Other Drugs on LYBALVI Strong CYP3A4 Inducer Clinical Implication: Coadministration of LYBALVI with a strong CYP3A4 inducer decreases AUC inf of olanzapine and samidorphan, which may reduce LYBALVI efficacy.

Prevention or Management: Concomitant use of LYBALVI with strong CYP3A4 inducers is not recommended. Strong CYP1A2 Inhibitor Clinical Implication: Concomitant use of LYBALVI with a strong CYP1A2 inhibitor increases olanzapine AUC and C max, which may increase the risk of LYBALVI adverse reactions.

Prevention or Management: Consider reducing the dosage of the olanzapine component in LYBALVI when used concomitantly with strong CYP1A2 inhibitors.

CYP1A2 Inducer Clinical Implication: Concomitant use of LYBALVI with CYP1A2 inducers decreases olanzapine exposure, which may reduce LYBALVI efficacy.

Prevention or Management: Consider increasing the dosage of the olanzapine component in LYBALVI when used concomitantly with CYP1A2 inducers. Diazepam, Alcohol, and Other CNS Acting Drugs Clinical Implication: Concomitant use of diazepam, alcohol, or other CNS acting drugs with LYBALVI may potentiate the orthostatic hypotension observed with olanzapine.

Prevention or Management: LYBALVI should be used with caution in patients receiving concomitantly diazepam or other CNS acting drugs, or using alcohol.

Anticholinergic Drugs Clinical Implication: Concomitant treatment with olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility.

Prevention or Management: LYBALVI should be used with caution in patients receiving medications having anticholinergic (antimuscarinic) effects.

7.2 Effects of LYBALVI on

Other Drugs Table 5 describes clinically significant drug interactions where concomitant use of LYBALVI affects other drugs.

Table 5: Effects of LYBALVI on Other Drugs Antihypertensive Agents Clinical Implication: LYBALVI may enhance the effects of certain antihypertensive agents.

Prevention or Management: Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling. Levodopa and Dopamine Agonists Clinical Implication: LYBALVI may antagonize the effects of levodopa and dopamine agonists.

Prevention or Management: Concomitant use of LYBALVI is not recommended with levodopa and dopamine agonists. 7.3 Opioids LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. LYBALVI increases the risk of precipitating acute opioid withdrawal in patients who are dependent on opioids. Prior to initiating LYBALVI, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. In emergency situations, if a LYBALVI-treated patient requires opioid treatment for anesthesia or analgesia, discontinue LYBALVI. The opioid should be administered by properly trained individual(s), and the patient should be properly monitored in a setting equipped and staffed for cardiopulmonary resuscitation. In non-emergency situations, if a LYBALVI-treated patient is expected to require opioid treatment (e.g., for analgesia during or after an elective surgical procedure) discontinue LYBALVI at least 5 days before opioid treatment and start olanzapine or another antipsychotic, if needed. Given that LYBALVI contains samidorphan, an opioid antagonist, opioid treatment may be less effective or ineffective shortly after LYBALVI discontinuation because of the presence of samidorphan.

7.4 Interference with

Laboratory Tests Interference with Laboratory Tests for Opioid Detection Because LYBALVI contains samidorphan, an opioid antagonist, LYBALVI may be cross-reactive with urinary immunoassay methods used for detecting opioids, resulting in false positive results. Use an alternative analytical technique (e.g., chromatographic methods) to confirm positive opioid urine drug screen results.