Diclegis Drug Interactions: What to Avoid and What to Tell Your Doctor

Diclegis (doxylamine succinate/pyridoxine hydrochloride) is generally well-tolerated, but it has significant interactions with several medications and substances. Because Diclegis contains an antihistamine (doxylamine) with strong central nervous system (CNS) depressant effects, combining it with other sedating agents can be dangerous. Here's what every patient taking Diclegis needs to know.

Contraindicated: MAO Inhibitors (Never Combine)

The most serious interaction with Diclegis is with monoamine oxidase (MAO) inhibitors. These drugs intensify and prolong the adverse CNS effects of doxylamine in a dangerous way. Diclegis is absolutely contraindicated with MAO inhibitors, which include:

Phenelzine (Nardil)

Tranylcypromine (Parnate)

Isocarboxazid (Marplan)

Selegiline (Eldepryl, Zelapar) — also used for Parkinson's disease

If you are currently taking an MAO inhibitor or have stopped taking one within the past 2 weeks, tell your doctor before starting Diclegis. Do NOT take both medications.

Avoid or Use With Extreme Caution: Other CNS Depressants

The sedating effect of Diclegis is significantly amplified when combined with other CNS depressants. This combination increases the risk of severe sedation, respiratory depression, falls, and accidents. Avoid or use with extreme caution:

Alcohol: Alcohol dramatically increases doxylamine's sedating effect. Avoid completely while taking Diclegis.

Benzodiazepines (diazepam, lorazepam, alprazolam, clonazepam): Increased sedation and respiratory depression risk.

Opioid pain medications (oxycodone, hydrocodone, morphine, codeine): Risk of severe respiratory depression, particularly buprenorphine products.

Sodium oxybate (Xyrem/Lumryz): Profound sedation, respiratory depression, coma, and death may result. Absolutely avoid.

Muscle relaxers (cyclobenzaprine, carisoprodol): Additive CNS depression; increases fall risk.

Sleep aids (zolpidem, eszopiclone, diphenhydramine): Excessive sedation. Do not double up on sleep aids with Diclegis.

Olopatadine intranasal (Patanase): FDA label specifically calls out this combination; avoid or use an alternate drug.

Clobazam (Onfi): Potential for increased CNS effects. Monitor closely.

Avoid: Selinexor (Xpovio)

Selinexor (used in multiple myeloma) can cause neurological toxicities including dizziness and confusion. Combining it with doxylamine (a component of Diclegis) is not recommended due to additive neurological risk.

Interactions Involving the Pyridoxine (Vitamin B6) Component

The pyridoxine (vitamin B6) component of Diclegis has its own interactions:

Cisplatin: Pyridoxine may decrease cisplatin's effectiveness. Use caution and monitor closely.

Clarithromycin and Azithromycin: These antibiotics may decrease pyridoxine levels by altering intestinal flora. Monitor for reduced Diclegis efficacy if taking antibiotics.

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The Anticholinergic Effect: Caution in Certain Conditions

Doxylamine has anticholinergic properties, which means it can worsen certain pre-existing conditions. Tell your doctor if you have:

Narrow-angle glaucoma — anticholinergics can increase intraocular pressure

Urinary retention or bladder obstruction

Peptic ulcer disease or pyloroduodenal obstruction

Asthma — use with caution, as anticholinergics can thicken respiratory secretions

Drug Screen Warning

Diclegis can cause false positive urine drug screening tests for methadone, opiates, and PCP. This is not dangerous, but if you're subject to drug testing — for employment, legal reasons, or medical monitoring — inform the testing facility that you are taking doxylamine succinate/pyridoxine hydrochloride. A confirmatory mass spectrometry test will distinguish the false positive.

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The Bottom Line

Always give your provider and pharmacist a complete list of every medication, supplement, and substance you're using before starting Diclegis. The most important rule: avoid alcohol and all CNS depressants. Never combine with MAO inhibitors. For more information on what Diclegis is and how it's dosed, see what is Diclegis? For side effect information, see Diclegis side effects.