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Savella
milnacipran
Black Box Warnings .
Suicidality
milnacipran is an SNRI, similar to drugs used for tx of depression and other psychiatric disorders; incr. suicidality risk in children, adolescents, and young adults with major depressive or other psychiatric disorders; weigh risk vs. benefit; in short-term studies of antidepressants vs. placebo, suicidality risk not incr. in patients >24 yo, and risk decr. in patients 65 yo and older; depression and certain other psychiatric disorders themselves associated with incr. suicide risk; observe all patients for clinical worsening, suicidality, or unusual behavior changes; advise families and caregivers of need for close observation and communication with prescriber; not approved for peds use or tx of major depressive disorders
Adult Dosing .
Dosage forms: TAB: 12.5 mg, 25 mg, 50 mg, 100 mg; TAB (4-wk titration pack): 12.5 mg x5, 25 mg x8, and 50 mg x42
fibromyalgia
- [50 mg PO bid]
- Start: 12.5 mg PO qd x1 day, then 12.5 mg PO bid x2 days, then 25 mg PO bid x4 days, then 50 mg PO bid; Max: 200 mg/day; Info: taper dose gradually to D/C
renal dosing
- [see below]
- CrCl > 50: no adjustment; CrCl 30-49: not defined, caution advised; CrCl 5-29: decr. usual maintenance dose by 50%, max 100 mg/day; ESRD: avoid use
- HD/PD: not defined
hepatic dosing
- [see below]
- Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: not defined, caution advised; chronic hepatic disease: avoid use
Peds Dosing .
Peds dosing is currently unavailable or not applicable for this drug.
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- MAO inhibitor use within 14 days
- hepatic disease, chronic
- alcohol abuse
- abrupt withdrawal
- caution: patients <25 yo
- caution: elderly patients
- caution: hepatic impairment
- caution: CrCl <50
- caution: seizure history
- caution: hypomania history
- caution: mania history
- caution: suicidal patients
- caution: HTN
- caution: cardiovascular disease
- caution: arrhythmia
- caution: hypovolemia
- caution: hyponatremia
- caution: glaucoma, angle-closure
- caution: uropathy, obstructive
- caution: dysuria history
- caution: bleeding risk
Drug Interactions .
Overview
milnacipran
SNRI
- antiplatelet effects
- CNS depression
- hypertensive effects
- hyponatremia
- lowers seizure threshold
- serotonergic effects
- tachycardia
- add MAO inhibitor to Interaction Check if recent (14 days) use
Contraindicated
- isocarboxazid
- linezolid
- methylene blue injection
- phenelzine
- safinamide
- selegiline transdermal
- tranylcypromine
Avoid/Use Alternative
- 5-HTP
- albuterol
- aldesleukin
- alfentanil
- almotriptan
- amifampridine
- amitriptyline
- amoxapine
- amphetamine
- black cohosh
- bromocriptine
- buprenorphine
- buspirone
- butalbital
- butorphanol
- carbamazepine
- citalopram
- clomipramine
- clonidine
- cocaine
- codeine
- cyclobenzaprine
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- digoxin
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- ergotamine
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- ethanol
- fenfluramine
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- trimipramine
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- vilazodone
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Monitor/Modify Tx
- abiraterone acetate
- abrocitinib
- acalabrutinib
- acebutolol
- acetazolamide
- ado-trastuzumab emtansine
- afatinib
- albuterol inhaled
- aliskiren
- alpha-tocopherol (vitamin E)
- alprazolam
- alteplase
- amiloride
- amlodipine
- anacaulase topical
- anagrelide
- angiotensin II
- antithrombin
- apixaban
- aprocitentan
- arformoterol inhaled
- argatroban
- armodafinil
- asciminib
- asparaginase
- aspirin
- atenolol
- atogepant
- atomoxetine
- atropine
- atropine ophthalmic
- avapritinib
- axitinib
- azilsartan medoxomil
- baclofen intrathecal
- benazepril
- benzphetamine
- benztropine
- betamethasone
- betaxolol
- bevacizumab
- binimetinib
- bismuth subsalicylate
- bisoprolol
- bivalirudin
- brentuximab vedotin
- brigatinib
- bromelain
- bromfenac ophthalmic
- budesonide
- bumetanide
- bupropion
- cabazitaxel
- cabozantinib
- caffeine
- caffeine citrate
- calaspargase
- candesartan cilexetil
- cangrelor
- cannabis
- caplacizumab
- captopril
- carfilzomib
- carvedilol
- celecoxib
- chlordiazepoxide
- chlorothiazide
- chlorpromazine
- chlorthalidone
- cilostazol
- cisplatin
- clevidipine
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- clopidogrel
- clorazepate
- collagenase clostridium histolyticum
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- corticotropin
- cortisone
- cyclophosphamide
- cyclosporine
- cysteamine
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- danazol
- danshen
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- dasatinib
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- deflazacort
- desflurane
- desmopressin
- deuruxolitinib
- dexamethasone
- dexmedetomidine
- dexmedetomidine injection
- diazepam
- diclofenac
- diclofenac ophthalmic
- diclofenac topical
- dicyclomine
- diethylpropion
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- diltiazem
- dimethyl fumarate
- dinutuximab
- diosmin
- dipyridamole
- diroximel fumarate
- dobutamine
- dopamine
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- droperidol
- droxidopa
- enalapril
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- epinephrine
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- etodolac
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- etrasimod
- evening primrose oil
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- fenoprofen
- fenugreek
- fingolimod
- fludrocortisone
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- flurbiprofen
- flurbiprofen ophthalmic
- formoterol inhaled
- fosinopril
- fostamatinib
- fremanezumab
- fruquintinib
- gabapentin
- gabapentin enacarbil
- galcanezumab
- garlic
- gefitinib
- gemtuzumab ozogamicin
- ginkgo
- glycopyrrolate
- guanfacine
- heparin
- hoodia
- hydralazine
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- ibrutinib
- ibuprofen
- ibuprofen lysine
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- iloprost inhaled
- imatinib
- indapamide
- indomethacin
- iopamidol
- irbesartan
- isoflurane
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- levothyroxine
- licorice
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- magnesium citrate
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- mannitol
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- nabumetone
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- niacin (vitamin B3)
- nicardipine
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- nilotinib
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- nisoldipine
- norepinephrine
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- oxytocin
- ozanimod
- pacritinib
- pazopanib
- pegaspargase
- penicillin G
- pentobarbital
- pentosan polysulfate sodium
- pentoxifylline
- perindopril
- perphenazine
- pexidartinib
- phendimetrazine
- phenobarbital
- phenoxybenzamine
- phentermine
- phentolamine
- phenylephrine
- phenylephrine injection
- phenylephrine nasal
- phenylephrine ophthalmic
- phenylephrine rectal
- pindolol
- piperacillin
- piroxicam
- pirtobrutinib
- plasminogen, human
- polyethylene glycol
- polyethylene glycol/electrolytes
- ponatinib
- ponesimod
- porfimer
- pralsetinib
- prasugrel
- prazosin
- prednisolone
- prednisone
- pregabalin
- primidone
- propofol
- propranolol
- pseudoephedrine
- quazepam
- quetiapine
- quinapril
- ramipril
- ramucirumab
- ranibizumab
- regorafenib
- remibrutinib
- remimazolam
- resveratrol
- reteplase
- revakinagene taroretcel
- rimegepant
- ripretinib
- rivaroxaban
- romidepsin
- ropinirole
- rotigotine transdermal
- salmeterol inhaled
- salsalate
- saw palmetto
- selinexor
- selpercatinib
- selumetinib
- sepiapterin
- sevoflurane
- siponimod
- sirolimus albumin-bound
- solriamfetol
- sorafenib
- sotatercept
- spironolactone
- sulfate bowel prep
- sulindac
- sunitinib
- suvorexant
- tacrolimus
- tagraxofusp
- telmisartan
- temazepam
- tenecteplase
- terazosin
- terbutaline
- teriflunomide
- testosterone
- thioridazine
- thiothixene
- thyroid
- ticagrelor
- timolol
- tipranavir
- tirofiban
- tisotumab vedotin
- tivozanib
- tolmetin
- torsemide
- tovorafenib
- trametinib
- trandolapril
- treprostinil
- triamcinolone
- triamterene
- triazolam
- trospium
- ubrogepant
- upadacitinib
- vadadustat
- valproic acid
- valsartan
- vamorolone
- vandetanib
- vasopressin
- verapamil
- vilanterol inhaled
- viloxazine
- vinpocetine
- voclosporin
- vorapaxar
- warfarin
- willow bark
- zaleplon
- zanubrutinib
- zavegepant
- ziconotide
- ziv-aflibercept
- zolpidem
Caution Advised
- allopurinol
- amantadine
- apomorphine
- apraclonidine ophthalmic
- aripiprazole bimonthly injection
- aripiprazole lauroxil
- aripiprazole monthly injection
- aripiprazole oral
- asenapine
- baclofen
- brexpiprazole
- brimonidine ophthalmic
- brimonidine topical
- brivaracetam
- brompheniramine
- busulfan
- cannabidiol
- carbinoxamine
- cariprazine
- carisoprodol
- cenobamate
- cetirizine
- chamomile, German
- chlophedianol
- chlorambucil
- chlorcyclizine
- chlorpheniramine
- chlorzoxazone
- clemastine
- clozapine
- cyproheptadine
- dantrolene
- darifenacin
- deutetrabenazine
- dexbrompheniramine
- dexchlorpheniramine
- dichlorphenamide
- difelikefalin
- difenoxin
- dimenhydrinate
- diphenhydramine
- diphenoxylate
- domperidone
- efavirenz
- elinzanetant
- entacapone
- entrectinib
- ethanol (in some formulations)
- ethosuximide
- felbamate
- fesoterodine
- flibanserin
- foslevodopa
- fosphenytoin
- ganaxolone
- glofitamab
- hydroxychloroquine
- iloperidone
- lacosamide
- lamotrigine
- levetiracetam
- levocetirizine
- levodopa
- linvoseltamab
- lofexidine
- loxapine
- lurasidone
- meclizine
- melatonin
- meprobamate
- methocarbamol
- methsuximide
- metyrapone
- metyrosine
- molindone
- mosunetuzumab
- naltrexone
- paliperidone
- passion flower
- perampanel
- pheniramine
- phenytoin
- pimozide
- pramipexole
- prochlorperazine
- pyrilamine
- ramelteon
- repotrectinib
- risperidone
- rufinamide
- scopolamine
- sodium picosulfate
- solifenacin
- stiripentol
- tasimelteon
- tetrabenazine
- thiotepa
- tiagabine
- tizanidine
- tolcapone
- tolterodine
- topiramate
- treosulfan
- trifluoperazine
- trihexyphenidyl
- triprolidine
- valbenazine
- valerian
- vigabatrin
- zonisamide
Adverse Reactions .
Serious Reactions
- suicidality
- depression exacerbation
- hypomania
- mania
- serotonin syndrome
- seizures
- SIADH
- hyponatremia
- glaucoma, angle-closure
- HTN
- hypertensive crisis
- tachycardia
- takotsubo cardiomyopathy
- urinary retention
- bleeding
- hepatotoxicity
- pancreatitis
- erythema multiforme
- Stevens-Johnson syndrome
- withdrawal symptoms if abrupt D/C
Common Reactions
- nausea
- vomiting
- headache
- migraine
- constipation
- insomnia
- dizziness
- palpitations
- tachycardia
- hyperhidrosis
- HTN
- xerostomia
- anxiety
- abdominal pain
- pruritus
- rash
- respiratory infection
- chest pain
- chest discomfort
- flushing
- tremor
- paresthesia
- hypoesthesia
- weight loss
- appetite decr.
- ALT or AST elevated
- blurred vision
- rigors
- dyspnea
- dysuria
- urinary retention
- urinary hesitancy
- urethral pain
- libido decr. (male patients)
- abnormal ejaculation
- erectile dysfunction
- testicular pain
- sexual dysfunction
Safety/Monitoring .
Monitoring Parameters
Cr at baseline; BP, HR at baseline, then periodically; symptoms of suicidality, clinical worsening, and/or unusual behavior changes, especially during initial tx or after dose changes
Pregnancy/Lactation .
Pregnancy
Clinical Summary
weigh risk/benefit during pregnancy, especially in 3rd trimester; no human data available, though risk of neonatal withdrawal symptoms or serotonin syndrome based on limited human data with other SNRIs; possible risk of embryo-fetal toxicity, including skeletal variation, based on conflicting animal data at up to 1.5x MRHD; risk of postpartum hemorrhage based on human data with SNRIs, especially if used within 1mo before delivery
Lactation
Clinical Summary
weigh risk/benefit while breastfeeding; inadequate human data available to assess risk of infant harm, though drug excreted into milk; inadequate human data available to assess effects on milk production
Pharmacology .
Metabolism: for milnacipran: liver minimally; CYP450: unknown
Excretion: for milnacipran: urine primarily (55% unchanged); Half-life: 6-8h
Subclass: Fibromyalgia
Mechanism of Action
for milnacipran: exact mechanism of action unknown; inhibits norepinephrine and serotonin reuptake
Formulary .
No Formulary Selected
Manufacturer/Pricing .
Manufacturer: AbbVie Inc.
DEA/FDA: Rx
Retail Price
Estimated prices only. For current pricing, visit GoodRx.
oral tablet:
- 12.5 mg (60 ea): $439.00
- 25 mg (60 ea): $439.00
- 50 mg (60 ea): $439.00
- 100 mg (60 ea): $439.00
oral tablet:
- 12.5 mg and 25 mg and 50 mg (1 titration pack, 4 weeks): $403.00
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