Savella

Name: Savella

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Pharmacology

Mechanism of Action

SNRI; has no affinity for other neurotransmitter receptors (including gamma-aminobutyric acid [GABA], beta-adrenergic, opiate, histaminergic, and benzodiazepine receptors) and has no MAOI activity

Absorption

Bioavailability: 85-90%

Peak plasma time: 2-4 hr

Distribution

Protein bound: 13%

Vd: 400 L

Metabolism

Metabolized to several metabolites

Elimination

Half-life: L-isomer, 6-8 hr; D-isomer, 8-10 hr

Excretion: Urine (55%)

Drug Interactions

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.

  • Furazolidone
  • Iproniazid
  • Isocarboxazid
  • Linezolid
  • Methylene Blue
  • Moclobemide
  • 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
  • Almotriptan
  • Amisulpride
  • Amitriptyline
  • Amoxapine
  • Amtolmetin Guacil
  • Anagrelide
  • Ancrod
  • Anisindione
  • Antithrombin III Human
  • Apixaban
  • Aripiprazole
  • Aspirin
  • Avitriptan
  • Bemiparin
  • Benperidol
  • Bivalirudin
  • Bromfenac
  • Bufexamac
  • Buprenorphine
  • Bupropion
  • Celecoxib
  • Chlorpromazine
  • Choline Salicylate
  • Cilostazol
  • Citalopram
  • Clonixin
  • Clopidogrel
  • Clovoxamine
  • Clozapine
  • Cyclobenzaprine
  • Danaparoid
  • Defibrotide
  • Dermatan Sulfate
  • Desirudin
  • Desvenlafaxine
  • Dexibuprofen
  • Dexketoprofen
  • Dextromethorphan
  • Diclofenac
  • Dicumarol
  • Diflunisal
  • Dipyridamole
  • Dipyrone
  • Dolasetron
  • Donepezil
  • Droxicam
  • Duloxetine
  • Edoxaban
  • Eletriptan
  • Epoprostenol
  • Eptifibatide
  • Escitalopram
  • Etodolac
  • Etofenamate
  • Etoricoxib
  • Felbinac
  • Femoxetine
  • Fenoprofen
  • Fentanyl
  • Fepradinol
  • Feprazone
  • Floctafenine
  • Fluconazole
  • Flufenamic Acid
  • Fluoxetine
  • Fluphenazine
  • Flurbiprofen
  • Fluvoxamine
  • Fondaparinux
  • Frovatriptan
  • Granisetron
  • Haloperidol
  • Heparin
  • Ibuprofen
  • Iloprost
  • Indomethacin
  • Iobenguane I 123
  • Ketoprofen
  • Ketorolac
  • Lamifiban
  • Levomilnacipran
  • Lexipafant
  • Lithium
  • Lorcaserin
  • Lornoxicam
  • Loxapine
  • Loxoprofen
  • Lumiracoxib
  • Meclofenamate
  • Mefenamic Acid
  • Meloxicam
  • Meperidine
  • Mesoridazine
  • Metoclopramide
  • Mirtazapine
  • Molindone
  • Morniflumate
  • Nabumetone
  • Nadroparin
  • Naproxen
  • Naratriptan
  • Nefazodone
  • Nepafenac
  • Niflumic Acid
  • Nimesulide
  • Nimesulide Beta Cyclodextrin
  • Olanzapine
  • Oxaprozin
  • Oxycodone
  • Oxyphenbutazone
  • Palonosetron
  • Parecoxib
  • Paroxetine
  • Pentosan Polysulfate Sodium
  • Perphenazine
  • Phenindione
  • Phenprocoumon
  • Phenylbutazone
  • Piketoprofen
  • Pimozide
  • Piroxicam
  • Pranoprofen
  • Proglumetacin
  • Promazine
  • Propyphenazone
  • Proquazone
  • Quetiapine
  • Risperidone
  • Rivaroxaban
  • Rizatriptan
  • Rofecoxib
  • Salicylic Acid
  • Salsalate
  • Sertraline
  • Sibrafiban
  • Sibutramine
  • Sodium Salicylate
  • Sulfinpyrazone
  • Sulindac
  • Sulodexide
  • Sumatriptan
  • Tapentadol
  • Tenoxicam
  • Thioridazine
  • Thiothixene
  • Tiaprofenic Acid
  • Ticlopidine
  • Tirofiban
  • Tolfenamic Acid
  • Tolmetin
  • Tramadol
  • Trazodone
  • Trifluoperazine
  • Tryptophan
  • Valdecoxib
  • Venlafaxine
  • Vilazodone
  • Vortioxetine
  • Warfarin
  • Xemilofiban
  • Zimeldine
  • Ziprasidone
  • Zolmitriptan

Savella Overview

Savella is a prescription medication used to treat fibromyalgia. Savella belongs to a group of drugs called serotonin and norepinephrine reuptake inhibitors (SNRIs), which work by stopping the movement of pain signals in the brain.

This medication comes in tablet form and is usually taken 2 times a day, with or without food.

Common side effects include nausea, constipation, and headache. Savella can also cause dizziness or drowsiness. Do not drive or operate heavy machinery until you know how Savella affects you.

Side Effects of Savella

Serious side effects have been reported with Savella. See the “Drug Precautions” section.

Common side effects include the following:

  • nausea
  • headache
  • constipation
  • dizziness
  • insomnia
  • hot flush
  • sweating
  • vomiting
  • palpitations
  • increased heart rate
  • dry mouth
  • high blood pressure

This is not a complete list of Savella side effects. Ask your doctor or pharmacist for more information.

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

Savella Overdose

If you take too much Savella, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include extreme drowsiness, slow heart rate, weak pulse, fainting, and slow breathing (breathing may stop).

Savella Dosage and Administration

Savella is given orally with or without food.

Taking Savella with food may improve the tolerability of the drug.

Recommended Dosing

The recommended dose of Savella is 100 mg/day (50 mg twice daily).

Based on efficacy and tolerability dosing may be titrated according to the following schedule:

Day 1: 12.5 mg once

Days 2-3: 25 mg/day (12.5 mg twice daily)

Days 4-7: 50 mg/day (25 mg twice daily)

After Day 7: 100 mg/day (50 mg twice daily)

Based on individual patient response, the dose may be increased to 200 mg/day (100 mg twice daily).

Doses above 200 mg/day have not been studied.

Savella should be tapered and not abruptly discontinued after extended use [see Dosage and Administration (2.4) and Warnings and Precautions (5.7)].

Patients with Renal Insufficiency

No dosage adjustment is necessary in patients with mild renal impairment.

Savella should be used with caution in patients with moderate renal impairment.

For patients with severe renal impairment (indicated by an estimated creatinine clearance of 5-29 mL/min), the maintenance dose should be reduced by 50% to 50 mg/day (25 mg twice daily).

Based on individual patient response, the dose may be increased to 100 mg/day (50 mg twice daily).

Savella is not recommended for patients with end-stage renal disease.

Patients with Hepatic Insufficiency

No dosage adjustment is necessary for patients with hepatic impairment.

As with any drug, caution should be exercised in patients with severe hepatic impairment.

Discontinuing Savella

Withdrawal symptoms have been observed in clinical trials following discontinuation of milnacipran, as with other serotonin and norepinephrine re-uptake inhibitors (SNRIs) and selective serotonin re-uptake inhibitors (SSRIs). Patients should be monitored for these symptoms when discontinuing treatment. Savella should be tapered and not abruptly discontinued after extended use [see Warnings and Precautions (5.7)].

Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of a MAOI intended to treat psychiatric disorders and initiation of therapy with Savella. Conversely, at least 5 days should be allowed after stopping Savella before starting a MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

Use of Savella with other MAOIs such as Linezolid or Methylene Blue

Do not start Savella in a patient being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)].

In some cases, a patient already receiving Savella therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, Savella should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with Savella may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with Savella is unclear. The clinician should nevertheless be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].

Drug Abuse and Dependence

Controlled Substance

Milnacipran is not a controlled substance.

Abuse

Milnacipran did not produce behavioral signs indicative of abuse potential in animal or human studies.

Dependence

Milnacipran produces physical dependence, as evidenced by the emergence of withdrawal symptoms following drug discontinuation, similar to other SNRIs and SSRIs. These withdrawal symptoms can be severe. Thus, Savella should be tapered and not abruptly discontinued after extended use [see Warnings and Precautions (5.7)].

For Healthcare Professionals

Applies to milnacipran: oral tablet

General

The most commonly reported side effects were nausea, constipation, headache, dizziness, insomnia, and hot flush.[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 39%), constipation (up to 16%)
Common (1% to 10%): Vomiting, dry mouth, abdominal pain/upper abdominal pain, diarrhea, dyspepsia, gastroesophageal reflux disease, flatulence, abdominal distension
Uncommon (0.1% to 1%): Gastritis, stomatitis, hemorrhoids
Postmarketing reports: Acute pancreatitis[Ref]

Nervous system

Very common (10% or more): Headache (up to 19%), dizziness (up to 11%)
Common (1% to 10%): Migraine, paresthesia, tremor, tension headache, hypoesthesia, dysesthesia, somnolence, dysgeusia, convulsions (including grand mal), loss of consciousness, Parkinsonism, memory impairment
Uncommon (0.1% to 1%): Syncope, vertigo
Rare (0.01% to 0.1%): Balance disorder, cerebrovascular accident
Frequency not reported: Serotonin syndrome[Ref]

Dermatologic

Very common (10% or more): Hyperhidrosis (up to 14%)
Common (1% to 10%): Rash, pruritus, night sweats
Uncommon (0.1% to 1%): Urticaria
Rare (0.01% to 0.1%): Photosensitivity reaction
Postmarketing reports: Erythema multiforme, Stevens Johnson syndrome, ecchymosis/cutaneous or mucosal bleeding[Ref]

Cardiovascular

Very common (10% or more): Hot flush (up to 12%)
Common (1% to 10%): Palpitations, hypertension, increased heart rate, increased blood pressure, tachycardia, chest pain, chest discomfort, flushing
Uncommon (0.1% to 1%): Arrhythmia, extrasystoles, hypotension, orthostatic hypotension, Raynaud's phenomena
Rare (0.01% to 0.1%): Acute coronary syndrome, angina pectoris
Frequency not reported: Contusion, peripheral edema
Postmarketing reports: Supraventricular tachycardia, hypertensive crisis[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 12%)
Common (1% to 10%): Anxiety, depression, stress, irritability, agitation
Uncommon (0.1% to 1%): Suicidal ideation, panic attack, confusion, hallucination, nightmares, decreased libido
Frequency not reported: Physical dependence
Postmarketing reports: Aggression, anger, delirium, homicidal ideation, elimination of psychomotor inhibition with suicidal risk, mood switch with episodes of mania, reactivation of delusions in patients with psychosis[Ref]

Genitourinary

Common (1% to 10%): Dysuria, ejaculation disorder, erectile dysfunction, ejaculation failure, prostatitis, scrotal pain, testicular pain, testicular swelling, urinary hesitation, urinary retention, urethral pain, decreased urine flow, cystitis, urinary tract infection
Uncommon (0.1% to 1%): Pollakiuria, metrorrhagia
Rare (0.01% to 0.1%): Amenorrhea[Ref]

Other

Common (1% to 10%): Chills, pyrexia, fatigue, fall, pain
Uncommon (0.1% to 1%): Tinnitus, feeling of body temperature change[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, fibromyalgia, muscle spasms, arthralgia, pain in extremity
Postmarketing reports: Rhabdomyolysis[Ref]

Respiratory

Common (1% to 10%): Upper respiratory tract infection, dyspnea, sinusitis, nasopharyngitis
Uncommon (0.1% to 1%): Dyspnea
Rare (0.01% to 0.1%): Epistaxis[Ref]

Metabolic

Common (1% to 10%): Decreased or increased weight, hypercholesterolemia, decreased appetite
Postmarketing reports: Hyponatremia, anorexia[Ref]

Ocular

Common (1% to 10%): Blurred vision
Uncommon (0.1% to 1%): Dry eye, mydriasis, reduced visual acuity
Postmarketing reports: Accommodation disorder[Ref]

Immunologic

Common (1% to 10%): Influenza[Ref]

Hepatic

Uncommon (0.1% to 1%): Increased hepatic enzymes
Rare (0.01% to 0.1%): Hepatitis
Postmarketing reports: Cytolytic hepatitis[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity[Ref]

Renal

Frequency not reported: Cystitis
Postmarketing reports: Acute renal failure[Ref]

Hematologic

Postmarketing reports: Leukopenia, neutropenia, thrombocytopenia[Ref]

Endocrine

Postmarketing reports: Hyperprolactinemia, galactorrhea[Ref]

Some side effects of Savella may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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