Thread by @renudhinakaran

I really wish I'd paid more attention to biology & chemistry in school! Learning about the pharmacodynamic & pharmacokinetic properties of medications is truly fascinating. I'm so enamored by the cytochrome P450 family of enzymes & the highly important CYP3A4. 1/ #NEISVoid

There is a long list of drugs which are either substrates, inhibitors and inducers of CYP3A4, which determines how these drugs are metabolised. Grapefruit juice can also inhibit this enzyme, which when coupled with a moderate or strong CYP3A4 inhibitor drug can be dangerous. 2/

While it may not directly cause QT prolongation, combining two drugs (one of which may cause QT prolongation) which are metabolised through this enzyme can lead to increased levels of this drug, increasing the risk. 3/

This does not mean that you can never use 2 inhibtors or two inducers or a combination ever. Given the long list of drugs that use CYP3AR, treatment would be impossible. Considering the potency of inhibition/induction, the risk vs. benefit, with close monitoring would be best. 4/

Going through the EPAR reports published by the EMA is by far the best place to start to understand whether the drug you take is contraindicated with the drug you're considering to add to your regimen or whether a dose adjustment with close monitoring would be an option. 5/

Given that a lot of #LongCovid folks are getting to start Ivabradine or Guanfacine, both of which are CYP3A4 inhibitors, and given that a considerable subset of this population also uses antihistamines for #MCAS and/or LABA inhalers for #asthma, understanding this will be key.

Just some notes: Ivabradine & Desloratadine are both weak inhibitors of CYP3A4. They are neither contraindicated for concomitant use, nor are they requited to be used with precaution. However Ivabradine is not recommended to be used with other QT prolonging medicinal products. 6/

Desloratadine has not shown to have QT prolonging effects in a statistically significant manner in studies but questions do linger, given the history of previous generation antihistamines. Also, these studies do state that the few cases of QT prolongation with desloratadine 7/

occurred in combination with other drugs with QT prolongation effects. To my best knowledge & search (through public sources), there is no study for interaction between the two drugs. Concomitant use should therefore be decided in consultation with a cardiologist. 8/

Personally, the farther away from Ivabradine I take desloratadine, the better I feel. There is indeed a dragging effect when I take them together. Given the half life of Ivabradine (2 hours) and the low dose I take of both drugs, so far it has been okay. I get regular ECGs. 9/

QT correction methods seem to vary (& my cardiologist always does a manual calculation). For men the upper QTc limit seems to be 450 and women 460 (although anything above 450 is shown as QT Prolongation in ECGs & some studies say the limit is 460 & 470 respectively). 10/

I'm not very confident about this part so please take it with a pinch of salt (or lots, if you have #POTS) and discuss with your cardiologist. A QTc of over 500 increases the risk for TdP (the very sexy sounding Torsades de Pointes), a specific type of arrhythmia. 11/

Unless you have congenital LQTS or are on a combination of drugs that can cause QT prolongation but are not sufficiently monitored (even then it seems to be extremely rare), it shouldn't be a problem. However, it is still good to get this cleared with your doctors. 12.