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During the climacteric period, several symptoms exist that motivate women to seek medical advice; one of the most common is the hot flush, which presents in 75%–85% of these during a variable time span. For the treatment of hot flush, several non-hormonal treatments exist; among them, veralipride has shown to be a useful treatment of vasomotor symptoms during the climacteric period. In recent times, several medical societies have discredited its use. The purpose of this review, therefore, is to define a measured position in relation to the use of this drug. On completion of this review, it was possible to conclude that this drug has an antidopaminergic mechanism of action. The recommended schedule is: 100 mg/day for 20 days, with 10 days drug free. Since the risk of undesirable secondary effects such as galactorrhea, mastodynia, and extrapyramidal can increase with use, no more than 3 treatment cycles are recommended. This drug has a residual effect that can allow drug-free intervals, which permit a longer time between schedules.
During the climacteric period, several symptoms exist that motivate women to seek medical advice. One of the most frequent is the hot flush, which presents in 75%–85% of these for a variable time span.
The hot flush is defined as a sudden hot sensation in the face, neck, and chest, which can have different intensity and frequency during the day and night and can be accompanied by sweating, flushing, throbs, anxiety, or irritability.1 The hot flush has an average duration of 4 minutes but can last from a few seconds to 10 minutes.2
For hot flushes to occur, estradiol serum levels need to have decreased. This produces changes in hypothalamic neurotransmitters such as those synthesized in noradrenergic and dopaminergic neurons. The increase in noradrenergic tone modifies the opioid system and in concert with the decrease in dopaminergic tone modifies the release of gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH),3 which traduce an increase in its pulsatility. These neurotransmitters by themselves promote instability of the thermoregulatory center and condition vasomotor symptoms.4 Also, it has been observed that estrogen deficiency is associated with a decrease in serotonin levels allowing hot flushes to occur, probably due to an interconnection between this neurotransmitter and noradrenaline.5
For the treatment of climacteric symptoms, several drugs have been used with different results in relation to their effectiveness and secondary effects.6 The most representative studies with these drugs are shown in Table 1.
Veralipride is another drug that has shown its effectiveness, and it has been considered a good therapeutic alternative for climacteric-related vasomotor symptoms when a contraindication or non-acceptance of hormone therapy (HT) exists. Veralipride can also be used in association with other drugs that do not confer any control of vasomotor symptoms; for example, raloxifene, whose main indication is for postmenopausal women with risk of or established osteopenia-osteoporosis.31
Veralipride has been used for a long time. Recent studies have proved its efficiency in the recommended dose of 100 mg/day;32 however, at this time some medical societies33 and government organizations34 have discredited its use due to its secondary adverse effects. The still in use Mexican Official Norm for the prevention and control of perimenopausal and postmenopausal diseases in women establishes that the drug can be useful in the control of vasomotor symptoms.35
For all previously exposed the purpose of this work is to review the current evidence with veralipride and define a measured position without bias in relation to its use.
Veralipride is a dopaminergic antagonist of receptor D2, whose formula is N-[allyl-1 pyrrolidinyl-2) methyl] dimethoxy-2,3-sulfamoyl-5 benzamide.36 This drug induces prolactin secretion without any estrogenic or progestagenic effects. Serum levels of follicle stimulating hormone, LH, estradiol, and estrone aren’t modified.37 However, some studies have reported that LH can decrease. Prolactin increase and LH decrease can be explained by a stimulation of endogenous opioid activity.3,38 This drug is well absorbed when administered orally, achieving maximal concentrations at 2.5 hours. It is poorly metabolized and is eliminated in the urine and feces. After oral administration, the half-life is 4 hours, and 44% is excreted without any changes in urine in the first 120 hours.3
When evaluating hot flushes, frequency and intensity are taken in account. With veralipride, it has been reported that since the 4th treatment day, hot flushes begin to subside.3 In other studies in which veralipride has been compared against placebo, it has been reported that there is a statistically significant reduction in frequency as well as in intensity of hot flushes after 20 days of continuous treatment at a dose of 100 mg/day.3
When comparing veralipride with HT, a decrease in frequency of hot flushes of 80% versus 100% and of intensity of 71% versus 100%, respectively, has been observed.7
Most of the studies agree that the decrease of hot flushes with veralipride use is from 48.0% to 89.9% depending on time of use and method of administration.
Several ways of prescribing veralipride have been reported and not always in accordance with the product directions – many times due to ignorance and others with the idea of decreasing the secondary effects such as hyper-prolactinemia as well as those extrapyramidal.
Leo et al indicate that every veralipride prescription schedule must be individualized, and that 6 cycles of treatment are not associated with addiction.3
One of the main secondary effects of veralipride use is hyperprolactinemia, which may or may not be accompanied by galactorrhea, and can disappear at 48 hours of treatment withdrawal,39 other studies indicate that the normalization of prolactin levels can take 2 or 3 weeks.45 Reported prolactin levels after 2 cycles have been 106.2 ± 41.5 ng/mL;39 others have reported levels 10 times higher than those at baseline.46 A clinical study reported that after veralipride administration at a dose of 100 mg/day for 6 months on alternate days or months, the prolactin levels were not higher than 21 ng/mL.7 Other reported secondary effects have been galactorrhea, headache, nervousness, insomnia, depression, mastodynia, and weight increase.
The most serious effects that have been reported with veralipride use are those extrapyramidal, such as acute dyskinesia, tardive dyskinesia, Parkinsonism, postural tremor, myoclonia, and dystonia. Many of these have been related to over-dosage and due to the lack of prescription instruction follow-up; however, this it is not always the case.10,42,46,47 See Table 3.
It’s worth mentioning that the Pharmacovigilance committee from the laboratory that produces this drug in Mexico has reported that sales in 5 years have been 2,265,729 pieces. In this time they have been informed of only 35 adverse effects. Of these, 21 have been attributed to incorrect medication use: anxiety (6), depression (6), abnormal movements (2), weight gain (2), lower limb pain (2), neck rigidity (1), galactorrhea (1), and muscular weakness (1). Those which presented after adequate drug intake numbered 14: insomnia (3), nervousness (2), fear (2), fine tremor (1), irritability (1), lack of appetite (1), mastitis (1), galactorrhea (1), pain (1), and head pain (1).52
After the review of several non-hormonal options for the treatment of climacteric hot flushes it can be concluded that for a drug to be considered as a good option for the treatment of vasomotor symptoms, an evaluation of the risk-benefit of the chosen therapy is always needed, and this must be well supported by clinical studies that evaluate safety parameters.53
Those women than can be candidates for veralipride use must achieve an adequate clinical profile, which means they will lack any history of tardive dyskinesia, Parkinsonism, acute dyskinesia, postural tremor, myoclonia, dystonia, hyperprolactinemia, breast fibrocystic disease, depression, and breast cancer.37
After this review it can be concluded that veralipride is a good option, and a safe drug if recommended doses are respected.3 Its high effectiveness in the control of vasomotor symptoms allows a high number of patients to be benefited.
The presentation of secondary adverse events is decreased using this medicament at a dose no greater than 100 mg/day, for short time spans, and leaving drug-free intervals between schedules. The drug-free intervals will not decrease drug favorable effects due to the drug’s residual effect as shown before.
It’s worth investigating safety aspects in the Latin-American population as well as the use of low-dose. Recently, the Mexican Association for the Study of the Climacteric, gave the following recommendations when veralipride is prescribed.
The author reports no conflicts of interest in this work.