Promethazine and dextromethorphan and Ziprasidone interaction
Promethazine and dextromethorphan and Ziprasidone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Ziprasidone label · effective 2026-06-09
…drugs, ziprasidone is contraindicated: • in patients with a known history of QT prolongation (including congenital long QT syndrome) • in patients with recent acute myocardial infarction • in patients with uncompensated heart failure Pharmacokinetic/pharmacodynamic studies between ziprasidone and other drugs that prolong the QT interval have not been performed.
An additive effect of ziprasidone and other drugs that prolong the QT interval cannot be excluded.
• Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone.
QT Prolongation and Risk of Sudden Death Ziprasidone use should be avoided in combination with other drugs that are known to prolong the QTc interval [see Contraindications (4.1) and Drug Interactions (7.4) ].
If concomitant use of ziprasidone with other serotonergic drugs is clinically warranted, inform patients of the increased risk of serotonin syndrome and monitor for symptoms.
From the Promethazine and dextromethorphan (Promethazine Hydrochloride and Dextromethorphan Hydrobromide) label · effective 2025-08-08
The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine…
The management of NMS should include 1) immediate discontinuation of promethazine, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available.
CNS Depressants – Promethazine may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced…
Neuroleptic Malignant Syndrome A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine alone or in combination with antipsychotic drugs.
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Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.