Levomilnacipran (US brand name Fetzima®) is a serotonin-norpinephrine reuptake inhibitor (SNRI) that is indicated for the treatment of depression. Here is key information about this medication.
Note: This page and its related pages contain the full text of the chapter on levomilnacipran (Fetzima®) in my book, The Latest Antidepressants. This webpage will always have the most up-to-date version of that chapter.
There is a little backstory to levomilnacipran. Levomilnacipran is derived from a drug called milnacipran. Milnacipran is a racemic mixture; levomilnacipran is one of its enantiomers. So, the manufacturer has done what is the same basic idea as going from citalopram to escitalopram. From a drug that is combination of two enantiomers to a drug that is the more active enantiomers. Milnacipran has been used in Europe for the treatment of major depressive disorder (MDD) for many years. Milnacipran is also FDA-approved in the US for treating fibromyalgia. But, milnacipran is not approved by the FDA for the treatment of major depressive disorder., This makes it hard for our patients with MDD to get their insurance companies to pay for milnacipran.
Major depressive disorder
Initial: 20 mg once daily, increased to 40 mg once daily after 2 days
Titrate: Increments of 40 mg at intervals of 2 or more days
Maximum: 120 mg once daily
Special Consideration (renal impairment)
Mild: No dosage adjustment necessary
Moderate: ≤ 80 mg once daily
Severe: ≤ 40 mg once daily
End-stage renal disease: Not recommended for treatment
1. Give approximately at same time each day
2. Do not crush or chew the capsule
3. May be given with or without food
Dosage forms and strengths
Extended-release capsules: 20 mg, 40 mg, 80 mg, and 120 mg
Please refer to Prescribing Information (see link below) for complete discussion of dosage, administration, warnings and precautions, contraindications, etc.
How should levomilnacipran be prescribed?
Since levomilnacipran is an extended-release preparation (even though it is just called Fetzima® rather than Fetzima-ER), it is given once a day.
Since the capsules contain extended-release beads, the capsules should be swallowed whole and should not be chewed, crushed or opened.
Capsules of levomilnacipran are available in 20, 40, 80, and 120 mg strengths. The capsules are of different colors and have the milligram strength written on them.
The recommended daily dose of levomilnacipran is 40 to 120 mg per day. It should be started at 20 mg once daily and increased to 40 mg once daily after two days. Then, a further increase in the dose can be made if needed and tolerated.
Absorption of levomilnacipran is not significantly affected by taking it with or without food. However, because nausea is the most common adverse effect, I personally would always recommend that patients take the capsules after they finish a meal.
The Prescribing Information for levomilnacipran states that patients should be advised to avoid simultaneous alcohol consumption as it may lead to accelerated release of levomilnacipran. However, I assume that this would apply only to not using alcohol around the same time as taking the levomilnacipran. If levomilnacipran is taken in the morning, as is usual, and alcohol is taken in the late evening, I don’t understand how the alcohol could cause accelerated release of the drug.
What precautions should be taken in prescribing levomilnacipran?
In patients with liver impairment, adjustment of the dose of levomilnacipran is usually not needed.
Since the main way that levomilnacipran is excreted is through the kidney, renal failure does have a significant effect on the dosing of levomilnacipran. The maximum dose of levomilnacipran in moderate renal failure is 80 mg/day. The maximum dose of levomilnacipran in severe renal failure is 40 mg/day.
Heart rate and blood pressure should be measured before starting levomilnacipran and then periodically during treatment. In patients who have preexisting hypertension, we should make sure that the blood pressure is controlled before starting levomilnacipran.
Because levomilnacipran can cause mydriasis (dilatation of the pupils), it should not be prescribed to patients with uncontrolled narrow angle glaucoma.
Urinary hesitation may occur in about 5% of patients on levomilnacipran. Patients may not report urinary hesitancy to us because they may not realize that the urinary hesitancy is a side effect of the levomilnacipran. That’s why we need to routinely ask patients who are on levomilnacipran whether they are having any urinary hesitancy.
So, what’s the bottom line about levomilnacipran?
In my opinion, among the serotonin-norepinephrine reuptake inhibitors, levomilnacipran is more different from the SSRIs than are other SNRIs. The ratio of its potency at inhibiting norepinephrine vs. serotonin reuptake is much greater than for previously available SNRIs. Also, this ratio does not significantly change across the dose range as it does for venlafaxine. Whether, and to what extent, this difference in mechanism of action translates into any real difference in patient outcomes is, of course, not yet known. For large groups of patients, there is no apparent difference, but it is possible that advantages may be demonstrated in the future for subgroups of patients or for individual patients.
In some clinical situations, greater norepinephrine reuptake inhibition is thought to be desirable. For example, when a patient is being switched from an SSRI to an SNRI due to lack of response to the SSRI. Or when the patient has significant pain due to any reason or has significant problems with decreased concentration. In such situations, it may be theoretically more appealing to use levomilnacipran than other SNRIs. However, as noted previously, there is no actual evidence yet that levomilnacipran is better for such patients than other SNRIs.
When a drug is potent at inhibiting norepinephrine reuptake, we tend to get increased heart rate, increased blood pressure, and orthostatic hypotension. So, we need to be careful when using levomilnacipran in patients at higher risk of cardiovascular adverse effects: the elderly, patients who have either low or high blood pressure, patients with preexisting cardiac disease.
Another adverse effect that seems to occur more often in patients on an SNRI than on an SSRI is hyperhidrosis or excessive sweating. This can be persistent and quite bothersome for some patients.
Overall, levomilnacipran is one more choice in our menu of options and has the potential to show some advantages over cheaper, generic SNRIs. It is always safe to end any presentation by saying that more research is needed!
Related Pages (For subscribers only)
Levomilnacipran (Fetzima®): Efficacy
Levomilnacipran (Fetzima®): Pharmacological Effects
Levomilnacipran (Fetzima®): Pharmacokinetics
Levomilnacipran (Fetzima®): Drug Interactions
Levomilnacipran (Fetzima®): Adverse Effects
Potential side effects of levomilnacipran (Fetzima®) handout
Levomilnacipran (Fetzima®): An organized list of references
Copyright 2015, Rajnish Mago, MD. All rights reserved. May not be reproduced in any form without express written permission.
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