A once-a-day oral
milnacipran modified release formulation has been developed. The formulation comprises an
extended release dosage unit (optionally containing the
immediate release portion) coated with delayed release
coating. The
milnacipran composition, when administered orally, first passes through the
stomach releasing from zero to less than 10% of the total
milnacipran dose and then enters the intestines where
drug is released slowly over an extended period of time. The release profile is characterized by a 0.05-4 hours
lag time period during which less than 10% of the total milnacipran
dose is released followed by a slow or
extended release of the remaining
drug over a defined period of time. The composition provides
in vivo drug plasma levels characterized by Tmax at 4-10 hours and an approximately linear drop-off thereafter and Cmax below 3000 ng / ml, preferably below 2000 ng / ml, and most preferably below 1000 ng / ml. The composition allows milnacipran to be delivered over approximately 24 hours, when administered to a patient in need, resulting in diminished incidence or decreased intensity of common milnacipran side effects such as sleep disturbance,
nausea,
vomiting, headache, tremulousness,
anxiety,
panic attacks,
palpitations,
urinary retention, orthostatic hypotension,
diaphoresis,
chest pain,
rash,
weight gain,
back pain,
constipation, vertigo, increased sweating, agitation, hot flushes, tremors, fatigue,
somnolence, dyspepsia, dysoria, nervousness,
dry mouth,
abdominal pain,
irritability, and
insomnia.