Milnacipran 50mg capsules

There is limited clinical experience with milnacipran overdose in humans. In clinical trials, cases of acute ingestions up to 1000 mg daily were reported with none being fatal F3925. In postmarketing experience, fatal outcomes have been reported for acute overdoses primarily involving multiple drugs but also with milnacipran only F3925.

The most common signs and symptoms of overdose included increased blood pressure, cardio-respiratory arrest, changes in the level of consciousness (ranging from somnolence to coma), confusional state, dizziness, and increased hepatic enzymes [F3919, F3922, F3925].

There are no adequate and well-controlled studies in pregnant women [F3919, F3922, F3925]. In fact, milnacipram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [F3919, F3922, F3925].

Neonates exposed to SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding [F3919, F3922, F3925]. Such complications can arise immediately upon delivery.

Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying [F3919, F3922, F3925]. These features are consistent with either a direct toxic effect of SNRI class drugs like milnacipran or, possibly, a drug discontinuation syndrome [F3919, F3922, F3925]. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [F3919, F3922, F3925].

The effect of milnacipran on labor and delivery in humans is unknown [F3919, F3922, F3925].

Milnacipran should be used during labor and delivery only if the potential benefits outweigh the potential risks [F3919, F3922, F3925].

There are no adequate and well-controlled studies in nursing mothers [F3919, F3922, F3925]. It is not known if milnacipran is excreted in human milk [F3919, F3922, F3925]. Studies have shown that levomilnacipran is excreted into the milk of lactating rats [F3919, F3922, F3925].

Subsequently, possible excretion into human milk possesses the potential for serious adverse reactions in nursing infants [F3919, F3922, F3925]. As a consequence, breastfeeding by women treated with levomilnacipran should be considered only if the potential benefits outweigh the potential risks to the child [F3919, F3922, F3925].

Milnacipran is not indicated for use in children under 18 years of age due to concerns over the potential for agitation-type emotional and behavioral changes, as well as suicidal ideation and/or behavior [F3919, F3922, F3925].

SNRIs like milnacipran have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [F3919, F3922, F3925].

Levomilnacipran was not mutagenic when evaluated in vitro in a bacterial mutagenicity study (Ames test) and not genotoxic in a mouse lymphoma study [F3919, F3922, F3925]. It was not clastogenic in an in vivo micronucleus assay in rats [F3919, F3922, F3925].

The potential effects of levomilnacipran on gonadal function, mating behavior, reproductive performance and early pregnancy were evaluated in rats at oral doses of 0, 10, 30, or 100 mg/kg/day [F3919, F3922, F3925].

The NOAEL was 100 mg/kg/day based on reductions in body weight gain and food consumption [F3919, F3922, F3925]. There were no levomilnacipran effects on male and female fertility parameters [F3919, F3922, F3925].

In the rat and rabbit embryo/fetal development studies, decreases in maternal body weight gain and food consumption were noted [F3919, F3922, F3925]. In the fetuses, increases in the incidence of ossification anomalies were noted but were of no toxicological significance [F3919, F3922, F3925].

In both species, the NOAEL was determined to be 100 mg/kg/day, a dose which represents a rat or rabbit animal-to-human exposure margin of 9-fold and 4-fold, respectively relative to the human exposure from 120 mg/day of levomilnacipran [F3919, F3922, F3925].

Material safety data for milnacipran has documented the LD50 oral value in the rat model as being 213 mg/kg MSDS.