Goerbelsnatch asked
Is it ok to take hydroxyzine while on a course of Bactrim? I saw there are clinical studies that may suggest arrhythmia or long QT.
At a glance
- Both Bactrim (sulfamethoxazole; trimethoprim) and hydroxyzine are associated with QT prolongation, although rarely.
- QT prolongation with Bactrim has been seen during post-marketing experience and it isn't known if a definitive relationship exists. It nonetheless should be used cautiously in those with certain risk factors.
- QT prolongation with hydroxyzine has been seen during post-marketing experience. Several studies have noted that hydroxyzine appears to be a risk factor for cases of QT prolongation. Therefore, hydroxyzine is contraindicated in those with a known history of QT prolongation.
- The overall risk of combining Bactrim and hydroxyzine appears to be low, but should be used cautiously in those with certain risk factors for QT prolongation.
Answer
There is a potential interaction between Bactrim (sulfamethoxazole; trimethoprim) and hydroxyzine in that they are both associated with QT prolongation. However, it is thought to be rare and the interaction is more of a general precaution to be aware of in those with certain risk factors.
Most drug references will list this interaction as 'minor' or not at all since there is a lack of data regarding it.
The QT interval is measured via an electrocardiogram (EKG) and can be used as a predictor for cardiac events, such as ventricular tachycardia and torsade de pointes. A 'prolonged' QT-interval may put you more at the risk of these cardiac events.
The risk of QT prolongation with both Bactrim (sulfamethoxazole; trimethoprim) and hydroxyzine appears to be low, which is why this interaction doesn't come up very often.
In the next sections, I will discuss what is known about the risk of 'QT prolongation' with both drugs.
Bactrim And QT Prolongation
While initial clinical trials for Bactrim (sulfamethoxazole; trimethoprim) did not show adverse cardiac effects, QT prolongation, which has resulted in ventricular tachycardia and torsade de pointes, have been reported on occasion since the drug has been available on the market (this is known as post-marketing experience). The prescribing information for Bactrim discusses this.
Although post-marketing experience can be an excellent tool for discovering side effects when the drug is introduced to a larger population, by nature, they are voluntary case-reports. Unfortunately, it is challenging to determine whether or not a relationship between a drug and side effect exist.
Nevertheless, there are many studies (such as this one published in the British Journal of Clinical Pharmacology), that list Bactrim as a drug that could increase the risk of QT prolongation.
It isn't too difficult to find published case reports that suspect Bactrim as being a causative factor in situations where an individual experienced QT prolongation.
Since there is much we don't know about just how risky Bactrim is, a general precaution is advised in certain individuals, such as those who have the following cardiac conditions:
- Cardiac arrhythmias
- Congenital long QT syndrome
- Heart failure
- Prior heart attack
- High blood pressure
It also should be used cautiously if you are taking other drugs that could put you at risk for QT prolongation. This is where the potential interaction with hydroxyzine comes in.
Hydroxyzine And QT Prolongation
Like Bactrim, hydroxyzine has also been associated with QT prolongation during post-marketing experience.
Hydroxyzine is an antihistamine, similar to Benadryl (diphenhydramine), but is structurally different. Antihistamines, in general, are known to rarely cause QT prolongation. It seems to be more associated in cases of antihistamine overdose.
Interestingly enough, the labeling for hydroxyzine states that it is contraindicated in those with a known history of QT prolongation, unlike Bactrim, where it is just a precaution. This is most likely due to hydroxyzine having more published evidence that it can cause this side effect.
One large review study, published in Pharmacology Research & Perspectives, looked at case data relating to QT prolongation and hydroxyzine over a 60 year period (December 1955 to August 2016). It states the following:
Results from this analysis support the listing of hydroxyzine as a drug with "conditional risk of TdP" [torsades de pointes] and are in line with recommendations to limit hydroxyzine use in patients with known underlying risk factors for QT prolongation and/or TdP.
The study did note that every single case of QT prolongation involved underlying medical conditions or concomitant medications known to cause QT prolongation.
Interaction Concerns
Overall, Bactrim and hydroxyzine are associated with QT prolongation. The overall risk appears to be quite low but they should still be used cautiously together. They should certainly not be given together if you have a history of QT prolongation, especially since QT prolongation is a contraindication to hydroxyzine use alone.
In the presence of certain risk factors, use of the drugs together should be done more cautiously. Risk factors include:
- Cardiac disease
- Electrolyte imbalances
- Age (the elderly are more at risk)
- Sex (females are more at risk)
- Concomitant drugs
If you are going to be taking both of these drugs, it is essential to watch for any side effects that could be indicative of cardiac problems, such as:
- Dizziness, lightheadedness
- Palpitation
- Shortness of breath
- Irregular heartbeat
Your doctor will be your best resource to determine if the combination of Bactrim and hydroxyzine is right for you based on your current medical situation.
References
- Elsevier ClinicalKey: Bactrim (Accessed 1/25/19)
- Elsevier ClinicalKey: Hydroxyzine (Accessed 1/25/19)
- Risk factors for prolonged QTc among US adults: Third National Health and Nutrition Examination Survey. European Journal of Preventive Cardiology (Accessed 1/25/19)
- Bactrim Prescribing Information (Accessed 1/25/19)
- Drug-Induced Prolongation of the QT Interval. New England Journal of Medicine (Accessed 1/25/19)
- Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re‐evaluation of an established drug. PubMed (Accessed 1/25/19)
- QT prolongation and torsades de pointes after administration of trimethoprim-sulfamethoxazole. American Journal of Cardiology (Accessed 1/25/19)
- Drug-induced QT interval prolongation: mechanisms and clinical management. Therapeutic Advances in Drug Safety (Accessed 1/25/19)
- Non-antiarrhythmic drugs prolonging the QT interval: considerable use in seven countries. PubMed (Accessed 1/25/19)
- Atarax Patient Information Leaflet (Accessed 1/25/19)
- QT prolongation induced by hydroxyzine: a pharmacovigilance case report. PubMed (Accessed 1/25/19)