CJC-1295 and SSRIs (Sertraline, Escitalopram): Drug Interaction Guide

Does CJC-1295 interact with sertraline or escitalopram?

CJC-1295 is an investigational long-acting analogue of growth hormone-releasing hormone [1]. In the human studies it acted on the pituitary, raising growth hormone and, through GH, IGF-I [1][2]. After a single subcutaneous injection of the DAC form, mean GH rose 2- to 10-fold for 6 days or more, mean IGF-I rose 1.5- to 3-fold for 9 to 11 days, and the estimated half-life was 5.8 to 8.1 days [2].

Sertraline and escitalopram block serotonin reuptake [5]. Their labels warn about serotonin syndrome, bleeding, low sodium and activation of mania [4][6]. Sertraline's label also advises caution in patients with risk factors for QTc prolongation [4]. None of these warnings concerns the growth hormone axis.

What the Zoloft label treats as an interaction

Zoloft's label contraindicates MAOIs and pimozide. It also flags other serotonergic drugs, medicines that affect bleeding, highly protein-bound drugs such as warfarin, CYP2D6 substrates such as desipramine and metoprolol, phenytoin, and drugs that prolong the QTc interval [4]. Its serotonin syndrome warning names triptans, tricyclics, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines and St John's wort, and notes the syndrome can occur with Zoloft alone [4]. CJC-1295 is not among the examples in the Zoloft interaction table, but that does not settle whether an interaction occurs [4]. The escitalopram label carries the same serotonin syndrome class warning [6].

Side effects that could be confused

In the two CJC-1295 DAC trials in healthy adults, injection-site reactions occurred in about 70% of treated subjects in study 1 and in all treated subjects in study 2. Headache occurred in 63% versus 14% on placebo, and flushing, warmth and transient low blood pressure in about 30% of treated subjects in study 1, mostly at the higher doses [1][2]. Transient diarrhea and dizziness were also reported [1]. No serious adverse reactions were reported in these trials [1][2]. In a separate study of healthy men, a single dose of 60 or 90 micrograms/kg produced dose-dependent increases in heart rate [1].

The sertraline label describes serotonin syndrome as agitation, hallucinations or delirium; fast heart rate, labile blood pressure, dizziness, sweating, flushing and high temperature; tremor, rigidity, myoclonus and hyperreflexia; seizures; and nausea, vomiting or diarrhea [4]. Flushing, diarrhea, dizziness and a faster heart rate appear on both lists [4][1]. Shared symptoms do not show a shared mechanism. The Zoloft label says to discontinue Zoloft and any serotonergic drugs immediately if serotonin syndrome symptoms occur, and to start supportive treatment [4].

FDA's briefing also says the developer withdrew CJC-1295 DAC from clinical trials in 2006 after a participant in a phase 2 trial died. The data were never published, so a causal link is neither shown nor excluded [1].