Pronunciation:

mil-NA-si-pran

Brand Names:

• Savella

Dosage Forms:

• Tablet

Warnings:

Milnacipran hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders. Antidepressants increased the risk compared with placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of such drugs in a child, adolescent, or young adult must balance this risk with the clinical need. Short term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24 years; there was a reduction in risk with antidepressants compared with placebo in adults aged 65 or older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on milnacipran hydrochloride should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Milnacipran hydrochloride is not approved for use in the treatment of MDD. Milnacipran hydrochloride is not approved for use in pediatric patients .

Classifications:

Therapeutic—

Central Nervous System Agent

Pharmacologic—

Serotonin/Norepinephrine Reuptake Inhibitor

Uses of This Medicine:

Milnacipran is used to treat a condition called fibromyalgia, which causes muscle pain and stiffness. It belongs to a group of medicines known as selective serotonin and norepinephrine reuptake inhibitors (SSNRIs). These medicines work by increasing the activity of certain chemicals in the brain called serotonin and norepinephrine.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of milnacipran in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of milnacipran in the elderly. However, elderly patients are more likely to have hyponatremia (low sodium in the blood) and age-related kidney problems, which may require an adjustment in the dose for patients receiving milnacipran.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Isocarboxazid
• Linezolid
• Methylene Blue
• Metoclopramide
• Ozanimod
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Selegiline
• Tranylcypromine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Alfentanil
• Almotriptan
• Amifampridine
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Anileridine
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Avitriptan
• Bemiparin
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Betrixaban
• Bivalirudin
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buspirone
• Butorphanol
• Cangrelor
• Carbamazepine
• Celecoxib
• Certoparin
• Chlorpheniramine
• Choline Salicylate
• Cilostazol
• Citalopram
• Clomipramine
• Clonixin
• Clopidogrel
• Cocaine
• Codeine
• Cyclobenzaprine
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Desipramine
• Desirudin
• Desvenlafaxine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Dibenzepin
• Diclofenac
• Difenoxin
• Diflunisal
• Digoxin
• Dihydrocodeine
• Diphenoxylate
• Dipyridamole
• Dipyrone
• Dolasetron
• Donepezil
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Eletriptan
• Enoxaparin
• Epinephrine
• Epoprostenol
• Eptifibatide
• Escitalopram
• Ethylmorphine
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenfluramine
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Frovatriptan
• Gepirone
• Granisetron
• Heparin
• Hydrocodone
• Hydromorphone
• Hydroxyamphetamine
• Hydroxytryptophan
• Ibuprofen
• Iloprost
• Imipramine
• Indomethacin
• Iobenguane I 123
• Iobenguane I 131
• Ketobemidone
• Ketoprofen
• Ketorolac
• Lasmiditan
• Lepirudin
• Levoketoconazole
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Meperidine
• Metaxalone
• Methadone
• Methamphetamine
• Methotrexate
• Mirtazapine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nadroparin
• Nalbuphine
• Naproxen
• Naratriptan
• Nefazodone
• Nepafenac
• Nicomorphine
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Norepinephrine
• Nortriptyline
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Palonosetron
• Papaveretum
• Parecoxib
• Paregoric
• Parnaparin
• Paroxetine
• Pentazocine
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Piketoprofen
• Piritramide
• Piroxicam
• Pranoprofen
• Prasugrel
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Remifentanil
• Reviparin
• Rivaroxaban
• Rizatriptan
• Rofecoxib
• Salicylic Acid
• Salsalate
• Selexipag
• Sertraline
• Sibutramine
• Sodium Salicylate
• St John's Wort
• Sufentanil
• Sulfinpyrazone
• Sulindac
• Sulodexide
• Sumatriptan
• Tapentadol
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tilidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Tramadol
• Trazodone
• Treprostinil
• Trimipramine
• Tryptophan
• Valdecoxib
• Venlafaxine
• Vilazodone
• Vorapaxar
• Vortioxetine
• Warfarin
• Ziprasidone
• Zolmitriptan

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Bleeding problems or
• Depression, history of or
• Enlarged prostate or
• Glaucoma, angle-closure or
• Heart disease or
• Heart rhythm problems (eg, tachyarrhythmia) or
• Hypertension (high blood pressure) or
• Hyponatremia (low sodium in the blood) or
• Liver disease or
• Mania, history of or
• Painful or difficult urination, history of or
• Seizures, history of or
• Urinary tract blockage—Use with caution. May make these conditions worse.

• Kidney disease, end-stage—Use is not recommended in patients with this condition.

• Kidney disease, moderate or severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of This Medicine:

Take this medicine only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

You may take this medicine with or without food.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For treatment of fibromyalgia:
    • Adults—At first, 12.5 milligrams (mg) once a day on Day 1. 12.5 mg 2 times a day on Days 2 to 3. 25 mg 2 times a day on Days 4 to 7. 50 mg 2 times a day after Day 7. Your doctor may adjust your dose as needed. However, the dose is usually not more than 200 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is important that your doctor check your progress at regular visits to allow for changes in your dose and to help reduce any side effects. Blood and urine tests may be needed to check for any unwanted effects.

Milnacipran may cause some teenagers and young adults to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. If you or your caregiver notice any of these unwanted effects, tell your doctor right away. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Do not take this medicine during 14 days after stopping a monoamine oxidase inhibitor (MAOI) (eg, isocarboxazid [Marplan®], linezolid [Zyvox®], methylene blue injection, phenelzine [Nardil®], selegiline [Eldepryl®], or tranylcypromine [Parnate®]). Do not take an MAO inhibitor for at least 5 days after stopping milnacipran. Talk to your doctor about this if you have questions.

Make sure your doctor knows if you are also using aspirin, NSAIDs (eg, ibuprofen, naproxen, Advil®, Aleve®, Celebrex®, Motrin®), or a blood thinner (eg, warfarin, Coumadin®). Milnacipran may increase your risk of bleeding problems when taken together with these medicines.

This medicine may cause a serious condition called serotonin syndrome when taken with certain medicines such as St. John's wort, buspirone, fentanyl, lithium, tryptophan, amphetamines, other medicines to treat depression, or some pain or migraine medicines (eg, rizatriptan [Maxalt®], sumatriptan [Imitrex®], tramadol [Ultram®], or zolmitriptan [Zomig®]. Check with your doctor first before taking any other medicines. Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there.

You will also need to have your blood pressure and pulse measured before starting and while you are using this medicine. If you notice any change to your recommended blood pressure or pulse rate, call your doctor right away. If you have questions about this, talk to your doctor.

Check with your doctor right away if you have clay-colored stools, dark urine, decreased appetite, fever, headache, itching, loss of appetite, nausea and vomiting, skin rash, stomach pain or tenderness, swelling of the feet or lower legs, unusual tiredness or weakness, or yellow eyes or skin. These may be symptoms of a serious liver problem.

Avoid drinking alcohol while you are using this medicine.

This medicine may cause some people to become less alert than they are normally. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

This medicine may cause hyponatremia (low sodium in the blood). This is more common in elderly patients, those who are taking diuretic medicines for high blood pressure, or those who have decreased amounts of fluid in the body due to severe diarrhea or vomiting. Check with your doctor right away if you have confusion, headache, memory problems, trouble concentrating, weakness, or feel unsteady when standing.

Do not stop using this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely to decrease the chance of side effects, including actions that are out of control, agitation, anxiety, confusion, continuing ringing or buzzing or other unexplained noise in the ears, dizziness, headache, hearing loss, irritability, nervousness, seizures, talking, feeling, and acting with excitement, trouble sleeping, or unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness.

Check with your doctor right away if you have decreased interest in sexual intercourse, delayed or inability to have and orgasm in women, inability to have or keep an erection in men, or loss in sexual ability, desire, drive, or performance. These could be symptoms of sexual dysfunction.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Blurred vision

body aches or pain

chills

cough

difficulty with breathing

dizziness

ear congestion

fast, irregular, pounding, or racing heartbeat or pulse

fear or nervousness

fever

headache

increased sweating

loss of voice

nasal congestion

pounding in the ears

runny nose

slow or fast heartbeat

sneezing

sore throat

unusual tiredness or weakness

Less common

Back pain

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

chest pain, discomfort, or tightness

chills

decrease in frequency of urination

decrease in urine volume

difficult or painful urination

difficulty in passing urine (dribbling)

frequent urination

groin pain

muscle aches

pain or burning with urination

shakiness in the legs, arms, hands, or feet

swollen, tender prostate

Rare

Bladder pain

bloating or swelling of the face, arms, hands, lower legs, or feet

bloody or cloudy urine

bruise

discouragement

fall

feeling sad or empty

frequent urge to urinate

full or bloated feeling

heartburn

increased or decreased weight

irritability

lack of appetite

loss of interest or pleasure

lower back or side pain

pressure in the stomach

rapid weight gain

swelling of the stomach area

tingling of the hands or feet

tiredness

trouble concentrating

trouble sleeping

unusual weight gain or loss

vomiting

Incidence not known

Agitation

black, tarry stools

bleeding gums

blistering, peeling, or loosening of the skin

blood in the urine or stools

coma

confusion as to time, place, or person

dark-colored urine

delayed or inability to have an orgasm

decreased interest in sexual intercourse

decreased urine output

diarrhea

difficulty with swallowing

general tiredness and weakness

high fever

holding false beliefs that cannot be changed by fact

inability to have or keep an erection

increased sweating

increased thirst

itching

joint or muscle pain

light-colored stools

loss in sexual ability, desire, drive, or performance

loss of balance control

loss of consciousness

mask-like face

muscle cramps or spasms

muscle pain or stiffness

overactive reflexes

pinpoint red spots on the skin

poor coordination

red skin lesions, often with a purple center

red, irritated eyes

restlessness

seeing, hearing, or feeling things that are not there

seizures

severe muscle stiffness

shuffling walk

slowed movements

slurred speech

sores, ulcers, or white spots on the lips or in the mouth

stiffness of the arms and legs

sweating

swelling of the face, ankles, fingers, or lower legs

swollen glands

talking or acting with excitement you cannot control

tic-like (jerky) movements of the head, face, mouth, and neck

tiredness

trembling and shaking of the fingers and hands

twitching

unusual bleeding or bruising

unusual excitement, nervousness, or restlessness

unusually pale skin

upper right abdominal or stomach pain

weight gain

yellow eyes and skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Feeling of warmth

headache, severe and throbbing

redness of the face, neck, arms, and occasionally, upper chest

sudden sweating

Less common

Decreased appetite

rash

stomach pain

swelling of the testes

Rare

Acid or sour stomach

belching

bloated

change in taste

excess air or gas in the stomach or intestines

full feeling

heartburn

indigestion

irritability

loss of taste

night sweats

passing gas

sleepiness or unusual drowsiness

stomach discomfort or upset

Incidence not known

Swelling of the breasts or unusual milk production

unexpected or excess milk flow from the breasts

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.