Clinically significant drug interactions with Hysingla ER

Inhibitors of CYP3A4

Clinical Impact
The concomitant use of Hysingla ER and CYP3A4 inhibitors can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of Hysingla ER and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of Hysingla ER is achieved.

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone.
Intervention
If concomitant use is necessary, consider dosage reduction of Hysingla ER until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals.

If a CYP3A4 inhibitor is discontinued, consider increasing the Hysingla ER dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
Examples
Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir)

CYP3A4 Inducers

Clinical Impact
The concomitant use of Hysingla ER and CYP3A4 inducers can decrease the plasma concentration of hydrocodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone.

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase, which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.
Intervention
If concomitant use is necessary, consider increasing the Hysingla ER dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider Hysingla ER dosage reduction and monitor for signs of respiratory depression.
Examples
Rifampin, carbamazepine, phenytoin

Benzodiazepines and Other Central Nervous System (CNS) Depressants

Clinical Impact
Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Intervention
Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation.
Examples
Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol

Serotonergic Drugs

Clinical Impact
The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Intervention
If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Hysingla ER if serotonin syndrome is suspected.
Examples
Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue)

Monoamine Oxidase Inhibitors (MAOIs)

Clinical Impact
MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
Intervention
The use of Hysingla ER is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Examples
Phenelzine, tranylcypromine, linezolid

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

Clinical Impact
May reduce the analgesic effect of Hysingla ER and/or precipitate withdrawal symptoms
Intervention
Avoid concomitant use
Examples
Butorphanol, nalbuphine, pentazocine, buprenorphine

Muscle Relaxants

Clinical Impact
Hydrocodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Intervention
Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Hysingla ER and/or the muscle relaxant as necessary.

Diuretics

Clinical Impact
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Intervention
Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs

Clinical Impact
The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Intervention
Monitor patients for signs of urinary retention or reduced gastric motility when Hysingla ER is used concomitantly with anticholinergic drugs.

Strong Laxatives

Clinical Impact
Concomitant use of Hysingla ER with strong laxatives that rapidly increase gastrointestinal motility, may decrease hydrocodone absorption and result in decreased hydrocodone plasma levels.
Intervention
If Hysingla ER is used in these patients, closely monitor for the development of adverse events as well as changing analgesic requirements.
Examples
Lactulose
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