Endoxifen

Evidence to Experience with Endoxifen
Discussion Points from an Online Continuous Medical Education Meet
Key Takeaways
Effectiveness and Safety of Endoxifen
Endoxifen is demonstrating its safety and efficacy in various patient populations, including adults, the elderly, and across different psychiatric conditions. Notably, endoxifen’s use is increasing in Bipolar mania, Borderline Personality Disorder (BPD) and Mania with co-morbid substance use and Impulsivity
Endoxifen’s Role in Managing Mania with Co-Morbid Substance Use
An extensive pooled analysis, drawing from both monosubstance and polysubstance cases associated with mania, was presented, with specific instances observed in the Mumbai and Chennai regions. Endoxifen exhibited notable effectiveness in regulating both manic symptoms and substance misuse, encompassing substances such as alcohol, nicotine, and even cannabis.
A Promising Future with Prudent Surveillance
While endoxifen has demonstrated a commendable safety and efficacy record in numerous patients, ongoing evaluation of potential long-term adverse events and rigorous post-marketing surveillance is underway to gain a more comprehensive understanding of the drug’s overall effectiveness profile.

Evidence to Experience with Endoxifen Minutes of Meeting – Online Continuous Medical Education

Since the half-life of endoxifen is notably extended, why not explore the possibility of alternate-day dosing?
The effectiveness of any medication depends not only on the half-life but also on a myriad of other factors, such as the disease’s severity, pharmacokinetic parameters (Absorption, Distribution, Metabolism, and Excretion – ADME), tolerability, relapse rates, drug resistance, and the presence of concurrent medical conditions. Consequently, while alternate-day dosing might be a viable approach, adhering to once-daily doses is advisable for optimum response.
Are there documented case reports of endoxifen’s use among the geriatric population?
In real-world scenarios, the administration of endoxifen has been done in individuals as old as 98 years. This is attributed to the fact that endoxifen, does not go under cytochrome P-450 metabolism, and hence exhibits minimal potential for drug-drug interactions. Therefore, it is considered relatively safe for elderly patients, who frequently present with a multitude of co-morbidities.
Could you elaborate on the mechanism of action of endoxifen in reducing cravings in patients with Alcohol Dependence Syndrome (ADS)?
Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity (Ref:Front Neurosci. 2018 Apr 12;12:244.)
The rationale behind using endoxifen for the treatment of Alcohol Dependence Syndrome is closely linked to its role in inhibiting protein kinase C. Selective inhibitors of PKCε catalytic activity may prove useful for decreasing ethanol consumption (Ref:. Neuropharmacology. 2016 Aug; 107: 40–48). Excessive activation of protein kinase C is associated with heightened impulsivity in patients. Evidence to Experience with Endoxifen Minutes of Meeting – Online Continuous Medical Education
This impulsive behavior, in turn, leads to increased consumption of addictive substances. Endoxifen plays a pivotal role in reducing such impulsivity, ultimately aiding in the mitigation of cravings.
Taking into consideration the history of ovarian cysts at a 16 mg dose, is it considered safe to prescribe endoxifen to patients with a family history of uterine cancers?
The level of risk of estrogen related side effects in women treated with Endoxifen would be dose and time dependent. Endoxifen dose of 8mg is very low to mimic significant estrogen related changes. Even if we look at Endoxifen ongoing clinical trials with breast cancer patients, higher doses of endoxifen, up to 160 mg are tried for anti-estrogen activity. (https://pubmed.ncbi.nlm.nih.gov/28854070/). Moreover Endoxifen 8mg dose is optimum dose to cross blood brain barrier and induce protein kinase C inhibition by being 4 times more potent than its parent molecule(Tamoxifen). In females with pre-existing conditions like PCOS & amenorrhea careful consideration of the risk-benefit ratio with Endoxifen is recommended.
Notably, it’s essential to underline that endoxifen is not causally linked to uterine cancer, as it does not participate in the formation of the alpha- sulphoxy metabolite, which is known to cause uterine cancer. This metabolite is solely associated with tamoxifen and not endoxifen. Evidence to Experience with Endoxifen Minutes of Meeting – Online Continuous Medical Education
Does endoxifen exhibit any influence on opioid-induced excessive sexual desire or an elevated libido stemming from other factors?
Much evidence has implicated PKCs in the effects of several drugs of abuse, and in behavioural responses to these drugs (Mol Neurobiol. 2004 Apr;29(2):139-54.) Endoxifen has the potential to diminish the utilization of opioids due to PKC inhibition activity, which, in turn, may contribute to the reduction of heightened sexual desire, particularly if it is linked to opioid use.
Is the utilization of endoxifen in individuals with seizure disorders deemed safe?
As of the present moment, the use of endoxifen in patients with seizure disorders remains safe.
Could you provide insights into the safety of using endoxifen during lactation?
Just like other psychiatric medications, the usage of endoxifen during pregnancy and lactation is not encouraged.
In cases of acute mania, can endoxifen be employed as a standalone treatment?
In milder episodes of mania, endoxifen can be utilized as a monotherapy. Clinical trials on 509 patients have revealed that endoxifen, when administered as the sole therapeutic agent, is associated with a substantial reduction in YMRS scores. Evidence to Experience with Endoxifen Minutes of Meeting – Online Continuous Medical Education
It is challenging to control hyperactivity and insomnia solely with endoxifen without resorting to benzodiazepines and atypical antipsychotics. Also, is there an off-label usage of endoxifen to consider?
For individuals grappling with moderate to severe mania, it is advisable to consider combining endoxifen with the prevailing treatment options. Endoxifen has least drug to drug interactions and this attribute facilitates its usage alongside mood stabilizers, antipsychotic agents, and even benzodiazepines. By doing so, one can harness the added advantage of achieving a faster remission of symptoms with the addition of endoxifen. The scope of endoxifen’s application is now coming out to be in a wide array of clinical indications such as mania with co-morbid substance use, borderline personality disorders (Cluster B personality disorders), Impulsivity and schizoaffective disorders.
Are there any recommended blood investigations for monitoring potential side effects associated with endoxifen?
Typically, therapeutic drug monitoring is not deemed necessary for endoxifen because it does not have a narrow therapeutic window. In females with pre- existing conditions like PCOS & amenorrhea careful consideration of the risk- benefit ratio with Endoxifen is recommended.
What role does endoxifen play in maintenance therapy?
Given the mounting utilization of endoxifen for prolonged treatment periods, it is being employed as a maintenance therapy. However, for individuals afflicted by rapid cycling, it is advisable to consider the inclusion of a mood stabilizer and/or an antipsychotic agent at a lower dose. This precautionary measure can reduce the probability of relapse. Evidence to Experience with Endoxifen Minutes of Meeting – Online Continuous Medical Education
Are there scientific studies focusing on childhood mania and the potential utilization of endoxifen in addressing internet and pornographic addictions? While there have been numerous instances across the nation where endoxifen has been administered to adolescent populations, especially for conditions such as adolescent ADHD; it is important to underline that such usage is not officially recommended for the pediatric population. That being said, since impulsivity often underpins addiction, endoxifen may hold promise in managing internet and pornographic addictions. This correlation arises from the fact that increased impulsivity is intrinsically linked to elevated levels of protein kinase C, and in such instances, endoxifen may prove beneficial.
What is the highest dosage of endoxifen you have prescribed?
As endoxifen adheres to linear pharmacokinetics, any escalation in the dosage leads to an exponential increase in its concentration within the bloodstream. Consequently, many psychiatrists have been experimenting with dosages as high as 16 mg. Additionally, there are instances where a few psychiatrists have ventured even further, prescribing doses of 24 mg, particularly in severe cases. However, it is advisable to start with the recommended dosage of 8 mg OD and then increase it to 16 mg based on clinical judgement.
Are there any specific recommendations regarding the use of endoxifen in children, and if so, in what age group?
As a general guideline, the utilization of endoxifen is not favored in the pediatric population. Nevertheless, emerging usage suggests that it has been tried among adolescents, particularly for indications such as adolescent ADHD. While endoxifen’s effectiveness in addressing inattention remains uncertain, it might offer advantages in managing hyperactivity & impulsivity in this age group. Evidence to Experience with Endoxifen Minutes of Meeting – Online Continuous Medical Education
Are there any notable drug-drug interactions that should be approached with caution when using endoxifen?
The administration of endoxifen with warfarin is not recommended.
Have there been any reported instances of hyponatremia associated with endoxifen usage?
Notably, endoxifen is not known to induce reductions in sodium concentrations or elicit adverse effects on sodium channels. Consequently, the likelihood of side effects such as hyponatremia occurring in association with endoxifen administration is not expected