That is, it is a selective mixed agonist–antagonist of the estrogen receptors (ERs), with estrogenic actions in some tissues and antiestrogenic actions in other tissues. The medication has estrogenic effects in bone, partial estrogenic effects in the uterus and liver, and antiestrogenic effects in the breasts. The affinity of toremifene for the ER is similar to that of tamoxifen. In studies using rat ER, toremifene had about 1.4% and tamoxifen had about 1.6% of the affinity of estradiol for the ER. The affinities (Ki) of toremifene at the human ERs have been reported as 20.3 ± 0.1 nM for the ERα and 15.4 ± 3.1 nM for the ERβ. In other rat ER studies, toremifene had 3–9% of the affinity of estradiol for the ER while its metabolites N-desmethyltoremifene and 4-hydroxytoremifene had 3–5% and 64–158% of the affinity of estradiol for the ER, respectively. The affinity of another metabolite, 4-hydroxy-N-desmethyltoremifene, was not assessed. 4-Hydroxytoremifene showed about 100-fold higher antiestrogenic potency than toremifene in vitro in one study, but not in another. 4-Hydroxy-N-desmethyltoremifene has also been found to be strongly antiestrogenic in vitro. The metabolites of toremifene, particularly 4-hydroxytoremifene, may contribute importantly to the clinical activity of the medication. On the other hand, some authorities consider toremifene not to be a prodrug.Toremifene is very similar to tamoxifen and shares most of its properties. There are some indications that toremifene may be safer than tamoxifen as it is not a hepatocarcinogen in animals and may have less potential for genotoxicity.
The label recommends that caution should be exercised when treating people with liver damage, severe kidney disease, and severe hypertension, and in children, adolescents and young adults due to the increased risk of suicidal ideation. Side effects
The common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating. Bupropion has the highest incidence of insomnia of all second-generation antidepressants, apart from desvenlafaxine. It is also associated with about 20% increased risk of headache.Bupropion raises blood pressure in some people. One study showed an average rise of 6 mm Hg in sysolic blood pressure in 10% of patients. The prescribing information notes that hypertension, sometimes severe, is observed in some people taking bupropion, both with and without pre-existing hypertension. Safety of bupropion in people with cardiovascular conditions and its general cardiovascular safety profile remain unclear due to the lack of data.Seizure is a rare but serious adverse effect of bupropion. It is strongly dose-dependent: for the immediate release preparation, the seizure incidence is 0.4% at the dose 300–450 mg per day; the incidence climbs almost ten-fold for the higher than recommended dose of 600 mg. For comparison, the incidence of unprovoked seizure in the general population is 0.07 to 0.09%, and the risk of seizure for a variety of other antidepressants is generally between 0 and 0.5% at the recommended doses.Cases of liver toxicity leading to death or liver transplantation have been reported for bupropion.