Promethazine Interactions
- Amantadine
- Amoxapine
- Amphetamine
Antacids
Antidiabetic Agents
Antimuscarinics
Antipsychotics
Anxiolytics, Sedatives, and Hypnotics
- Benzphetamine
- Bromocriptine
- Buprenorphine
- Butorphanol
- Cyclobenzaprine
- Dextroamphetamine
- Disopyramide
- Doxercalciferol
- Dronabinol, THC
- Entacapone
- Epinephrine
- Ethanol
- Ethotoin
- Fosphenytoin
General Anesthetics
- Levodopa
- Maprotiline
- Metoclopramide
Monoamine oxidase inhibitors (MAOIs)
- Nabilone
- Nalbuphine
Opiate agonists
- Orphenadrine
- Palonosetron
- Pentazocine
- Pergolide
Phenothiazines
- Phenytoin
Photosensitizing Agents
- Pramipexole
- Pregabalin
Radiopaque Contrast Agents
- Ropinirole
Sedating H1-blockers
Skeletal Muscle Relaxants
- Tolcapone
- Tramadol
- Trazodone
Tricyclic antidepressants
- Trimethobenzamide
Promethazine Interactions
Where possible, the use of promethazine with other phenothiazines should be done with caution. Additive cardiac effects (e.g., QT prolongation), CNS effects (e.g., extrapyramidal symptoms, sedation), or antimuscarinic/anticholinergic effects may occur. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. It is recommended that the concurrent use of MAOIs with drugs possessing anticholinergic activity be avoided, since their effects and those of other anticholinergic drugs are potentiated and may become severe. Most manufacturers recommend that antihistamines not be used within two weeks of therapy with a MAOI.
Promethazine (as a phenothiazine-family drug) may lower the seizure threshold and therefore be associated with an increased risk of seizures when given concurrently with tramadol. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with tramadol. Tramadol should be avoided or administered very cautiously to patients receiving promethazine, and other risk factors for seizures should be screened.
Antipsychotics in combination with promethazine have been associated with an increased risk for neuroleptic malignant syndrome. Also, depending on the specific agent, additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs with antimuscarinic activity. The following drugs are known to possess anticholinergic properties and should be used together cautiously: antimuscarinics, amantadine, amoxapine, clozapine, cyclobenzaprine, disopyramide, maprotiline, olanzapine, orphenadrine, other sedating H1-blockers, and tricyclic antidepressants. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, buprenorphine, butorphanol, dronabinol, THC, ethanol, haloperidol, general anesthetics, nabilone, nalbuphine, opiate agonists, pentazocine, pregabalin, risperidone, skeletal muscle relaxants, trazodone, and other sedating H1-blockers. Additional respiratory depressant agents in combination with promethazine should be avoided in children and administered in reduced dosage with close monitoring to other patients receiving promethazine. Concurrent use of cannabinoids with sedating H1-blockers such as promethazine may result in additive tachycardia, which may be pronounced.
Promethazine can cause extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion. An increased incidence of extrapyramidal symptoms may occur if promethazine is used concurrently with other agents capable of causing these reactions (e.g., metoclopramide).
Phenothiazines like promethazine may inhibit the clinical antiparkinsonian response to bromocriptine, cabergoline, levodopa, pergolide, pramipexole, or ropinirole therapy by blocking dopamine receptors in the brain. Medications like entacapone, tolcapone, pramipexole or ropinirole may also cause additive drowsiness when combined with promethazine. In general, the use of a phenothiazine-type drug should be avoided in patients requiring therapy for Parkinson’s disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to levodopa or other treatments.
Phenothiazines have been reported to inhibit and reverse the vasopressor effect of epinephrine; therefore, if treatment with a vasopressor agent is necessary in a patient who has been receiving promethazine, norepinephrine should be used.
It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Since promethazine is a phenothiazine antihistamine, it should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet (UV) exposure.
The concurrent use of trimethobenzamide with other medications that cause CNS depression (e.g., phenothiazines like promethazine) may potentiate the CNS effects of either trimethobenzamide or the other medication. These drugs may represent duplicate therapies for emesis as well.
Phenothiazines can cause QT interval prolongation and should be used cautiously in combination with palonosetron; however, the incidence of QT interval prolongation with palonosetron is rare and this potential additive interaction has not been specifically studied.
The combination of anticonvulsants (e.g., ethotoin, phenytoin or fosphenytoin) and phenothiazines should be approached with caution. The phenothiazines are known to lower seizure threshold, and this may be a particular risk for patients receiving anticonvulsants. Additive CNS depression may also occur.
Dextroamphetamine and other amphetamines (e.g., amphetamine or benzphetamine) may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. This effect may be clinically important if a patient is receiving an antihistamine agent for sedation induction, such as with promethazine.
Antacids may reduce the oral bioavailability of the phenothiazines. To avoid this interaction, administer the phenothiazine at least 1 hour before or 2 hours after an antacid medication.
Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Promethazine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors including promethazine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if promethazine is coadministered with doxercalciferol.
[ Last revised: 6/30/2006 12:44:00 PM ]
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