Milnacipran Safe, Effective for Long-Term Treatment of Fibromyalgia

Jenny Ko, PharmD

May 20, 2011

 

AUSTIN, TX—Sustained long-term efficacy and tolerability of milnacipran—in some cases, exceeding three years of continuous usage—is supported in the treatment of patients with fibromyalgia, according to results of an open-label study presented during the American Pain Society's 30th Annual Scientific Meeting.

Fibromyalgia is a chronic disorder characterized by widespread pain and other symptoms that adversely impact function and health-related quality of life. For that reason, durable efficacy is an important treatment goal, noted Lesley Arnold, MD, from the University of Cincinnati College of Medicine, Cincinnati, OH, and colleagues.
To determine long-term efficacy of milnacipran, which is approved for the management of fibromyalgia, treatment effects were evaluated in 1,227 patients in a safety and efficacy study over a period that could exceed three years. Eligible patients were those with fibromyalgia who had successfully completed previous studies of milnacipran. The multicenter, open-label, flexible-dose study comprised a two-week washout period, a two-week dose-escalation period (to milnacipran 100mg/day), an 8-week stable-dose period (at milnacipran 100mg/day), and a flexible-dose period (milnacipran 50–200mg/day) for the remainder of the study. Key efficacy outcomes included 24-hour visual analog scale (VAS) and weekly recall pain (0–100 scale), Patient Global Impression of Change (PGIC), Patient Global Disease Status (PGDS), SF-36 Physical Component Summary (SF-36 PCS), and the Brief Pain Inventory (BPI).
Of the 1,227 patients, 47.7% were considered completers; 206 patients reached the final visit and 379 were enrolled when the study was terminated. Efficacy results were reported as mean changes from study baseline following the two-week washout period. At the final visit, patients treated with milnacipran demonstrated a mean (SEM) improvement from baseline in 24-hour VAS recall pain scores of 23.1 points (1.82) (observed cases). Improvements in VAS weekly recall pain, BPI scores, global status (PGIC, PGDS), and physical function (SF-36 PCS) were all observed with milnacipran treatment.
Over the three-year study, the most common treatment-emergent adverse events were nausea (25.9%), headache (13.4%), hypertension (11.2%), and sinusitis (10.4); 20.9% of patients discontinued the study due to these events, primarily nausea.

http://www.clinicaladvisor.com/milnacipran-safe-effective-for-long-term-treatment-of-fibromyalgia/article/203390/

Antiepileptic Drugs for Fibromyalgia Reviewed

April 8, 2011

Fibromyalgia syndrome (FMS) is a difficult-to-treat chronic pain condition with relatively few specifically approved and effective pharmacotherapies. A recent review examined the relative benefits and harms of pregabalin, the only antiepileptic FDA approved for fibromyalgia, and the antiseizure medication gabapentin in the treatment of FMS. However, the evidence supporting their efficacy was somewhat disappointing.
Writing in the Journal of Pain, researchers from the Oregon Health & Science University, School of Medicine, Portland, Oregon, report conducting an extensive literature search for studies of any antiepileptic drug compared with placebo or another antiepileptic agent in a randomized controlled trial (RCT) or observational study [Siler et al. 2011]. Only 8 studies were discovered matching those inclusion criteria: 7 of pregabalin (Lyrica®) that included 2,964 subjects total, and 1 trial of gabapentin (eg, Neurontin® and generics) that enrolled 150 participants. Populations studied included predominantly women aged 47 to 50 years.
Short-term (8-14 weeks), response rates with both drugs at various doses, and reducing mean pain scores by 30% from baseline, were modestly greater than placebo — pregabalin 26% to 50%; gabapentin up to a 51%; compared with 19% to 35% response rates with placebo. [Note: these data are taken from body text of article, which differs from the abstract.] Study withdrawals due to adverse events were significantly greater in pregabalin groups compared with placebo, with relative risks increasing as dose was increased. Gabapentin had similar drop-out rates but not statistically different from placebo (possibly due to the small sample size in this trial).

Compared with placebo, both drugs had greater rates of side effects. Dizziness, headache, somnolence, and edema were the most commonly reported adverse events for both drugs. Dizziness was most common with pregabalin (38%), while headache (27%) was more prevalent with gabapentin. Additionally, weight gain was more common with pregabalin than placebo, whereas sedation and light-headedness occurred more often with gabapentin than placebo.
A follow-up analysis found that about 25% of the pain relief associated with pregabalin was significantly correlated with combined improvements in anxiety and depression. Examination of the impact of other factors such as age, race, gender, and socioeconomic status on the benefits or harms associated with pregabalin or gabapentin was not possible due to narrow inclusion criteria and limited reporting in the studies.
There were important methodological differences between the pregabalin and gabapentin trials and, without head-to-head clinical studies, the authors state it is not possible to conclude if pregabalin or gabapentin is superior. While it appeared that gabapentin was slightly more efficacious, the drug incurred significantly higher rates of headache than pregabalin and it was studied in only a single, small-scale RCT.
The authors believe that results of their review indicate that pregabalin and gabapentin can be used for the treatment of fibromyalgia with moderate benefits in the short-term. However, clinicians must be cautious not to generalize these results to other, unstudied antiepileptic drugs, and the limitations of this evidence with regard to the populations included, durations studied, and the potentials for important differences in adverse effect profiles between the drugs should be taken into account.

COMMENTARY: In a prior UPDATES article we discussed comparisons of pregabalin with duloxetine (Cymbalta®) and milnacipran (Savella®) — both of which are selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants and FDA-approved for treating FMS. All 3 drugs were found to have short-term (up to 6 months) efficacy; although they differed in their adverse effect profiles, with pregabalin appearing to be most advantageous except in patients with depressed mood. There were some limitations of the trials and none compared all 3 drugs head-to-head.
In the present review by Siler and colleagues, the internal validity of the included RCTs was judged as being rather low. This was due to unclear methods of blinding, allocation concealment, and randomization. While the gabapentin trial was government funded, the pregabalin RCTs were supported by the pharmaceutical manufacturer. All of these factors can engender significant bias in research studies, as discussed in our recent UPDATES article on “Making Sense of Pain Research: Part 3.” Both pregabalin and gabapentin were better than placebo in reducing pain in the short-term; however, in absolute terms the magnitude of beneficial effects were limited, with half of patients (at most) experiencing a 30% decrease in pain (while up to one-third had a similar response with placebo). The authors note that the Numbers-Needed-to-Treat, or NNTs, for both drugs were not impressive; specifically, for every 5 patients treated with gabapentin or 8 patients treated with pregabalin (rather than placebo) for 8 to 14 weeks, 1 additional patient would have a response of at least a 30% improvement in symptoms. According to Siler et al., NNTs of 2 to 4 are considered favorable for drug therapies [although their reference source for this assumption is unclear].
Of pregabalin responders, beneficial effects dissipated over time and only about one-third continued to have response at 6 months. While this rate of continued response was better than for those who were switched to placebo, it is still disappointing, the authors believe, considering the long-term duration of FMS symptoms in most patients.
The authors further note that, from an evidence-based medicine perspective, the major components in assessing strength of evidence are: 1) precision of estimates, 2) directness and consistency of evidence, 3) risk of bias, and 4) magnitude of effect. They believe that the overall body of evidence in their review would merit only a low strength of evidence ranking. Furthermore, the clinical applicability (external validity) of the studies was limited by the short duration of all clinical trials and the selective patient population.
A benchmark for therapeutic success in studies to date of antidepressant and antiepileptic agents for FMS appears to be a 30% improvement in symptoms. We have previously described in an UPDATE [here] that 30% to 36% improvements in pain are generally considered by patients as being moderate, with 50% or greater improvements deemed more desirable. This helps to explain why multidrug therapies that combine to increase improvement are commonplace in patients with FMS.
Indeed, Siler and colleagues recommend that better, longer-term comparative trials are needed, which adopt a more “pragmatic” design. That is, including large numbers of patients, with a wide variety of baseline symptoms and comorbidity, and taking multiple medications. However, such “real world” trials can be extremely difficult to construct, conduct, and interpret. And, as we have noted before, pharmacotherapy is only one piece of the puzzle when it comes to successful management of FMS, which often benefits more from multimodal approaches as part of a comprehensive pain management program.
http://updates.pain-topics.org/2011/04/antiepileptic-drugs-for-fibromyalgia.html

Prescription Drug List Available to Help Fibromyalgia Patients

Fibromyalgia Prescriptions Drug List Includes Cymbalta, Lyrica and Savella

Common events that can cause Fibromyalgia to worsen include: weather extremes (either too cold or too humid), physical activity extremes (too much or too little), stress, and poor sleep.  It is rare for fibromyalgia patients to experience a restful night’s sleep; they usually have trouble falling asleep or, once asleep, there will be frequent awakenings.  Poor sleep patterns lead to increased pain and increased pain results in poor sleep patterns, creating a self-destructing loop.  It follows then that it is not uncommon for fibromyalgia patients to suffer from major depression, which may result in the inability to focus (known as “fibro fog”), feelings of hopelessness, and not wanting to participate in favorite activities.

Manging Fibromyalgia

Aside from the administering of a prescription drug list medicine, there are techniques used to manage fibromyalgia, however, such as exercising at least three times a week, which has been shown to decrease pain and improve one’s general health (but it should not be overdone as that can increase pain). Monitoring dietary intake has also been known ease the condition, as certain foods seem to aggravate it (aspartame, MSG, caffeine and tomatoes for instance). Other techniques include managing stress situations, which decreases fibromyalgia symptoms and finally, acupuncture, which can help relieve pain in some patients.  Trying the recommended strategies in combination with a medicines prescription from the Fibromyalgia prescription drug list can substantially improve the patient’s symptoms and quality of life.

http://www.prescriptiondrugs.com/trackback/12956

Forest Laboratories; Savella

Savella, which is approved for the management of fibromyalgia, posted sales of $24.6 million, up significantly from the year-earlier sales of $15.4 million. Sales are being driven by the company's promotional efforts.
Savella was launched in late April 2009. We believe the product may have multi-hundred million dollar potential. In early October 2010, Savella was moved into tier II unrestricted coverage on several managed care organizations. Improved formulary access should help boost sales. Forest Labs entered into a collaboration and distribution agreement with Janssen to commercialize Bystolic and Savella in Canada.
http://www.prnewswire.com/news-releases/zacks-analyst-blog-highlights-comerica-incorporated-sterling-bancshares-citigroup-forest-laboratories-and-ironwood-pharmaceuticals-114201369.html

Savella: Forest Laboratories Inc.

Forest Laboratories Inc. (NYSE: FRX) is scheduled to release fiscal third-quarter earnings before the opening bell on Tuesday, January 18, 2011. Analysts, on average, expect the company to report earnings of 99 cents per share on revenue of $1.10 billion. In the year-ago period, the company reported earnings of 97 cents per share on revenue of $1.06 billion.

Forest Laboratories, Inc. develops, manufactures, and sells branded and generic forms of ethical drug products. The Company’s United States products are marketed directly, or detailed, to physicians by its salesforces. Its principal products include Lexapro to treat depression; Namenda to treat Alzheimer's disease; Bystolic, beta-blocker to treat hypertension; and Savella for the treatment of fibromyalgia.

Forest Laboratories is trying hard to come up with new drugs that can help replace lost revenue when its antidepressant drug Lexapro goes off patent in March 2012.  The drug generated $2.3 billion in revenue last year. Similarly, the company's Alzheimer's drug Namenda faces patent expiration in April 2015. According to IMS Health, Namenda had U.S. sales of $1.2 billion for the twelve months ended March 31, 2010.

Late in October, the company said that U.S. Food and Drug Administration approved Teflaro for the treatment of community-acquired bacterial pneumonia. Forest expects Teflaro to be available to wholesalers by January 2011. Early in November, Forest Laboratories and Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) reported positive top-line results from a late-stage clinical trial assessing the efficacy and safety of investigational drug linaclotide in patients with irritable bowel syndrome with constipation. The companies expect to submit an NDA with the FDA for both the IBS-C and CC indications in the third quarter of calendar year 2011Last month, Forest Laboratories Ireland Limited, a wholly owned subsidiary of Forest Laboratories, Inc. and Gruenenthal entered into a license agreement for the co-development and commercialization of a novel oral small molecule analgesic, GRT 6005, and its follow-on compound GRT 6006. Both compounds were discovered and developed by Gruenenthal and represent novel first in class molecules with unique pharmacological and pharmacokinetic profiles that may enhance their effect in certain pain conditions. Early in January, Forest Laboratories and Almirall S.A. said that their lung disease drug aclidinium met its primary endpoints in a late stage clinical trial. Regulatory submissions in Europe and the US for aclidinium bromide monotherapy are both planned for mid 2011. Forest Laboratories has licensed US rights for aclidinium from Almirall, while Almirall maintains rights for the rest of the world. The companies are jointly involved in the development of the compound.

Among other developments, Forest Laboratories entered into a definitive collaboration and distribution agreement for Bystolic and Savella in Canada with Janssen Pharmaceutica NV and Janssen pharmaceutical respectively, on behalf of Janssen Inc., which will market the products in Canada.

http://www.themarketfinancial.com/forest-laboratories-inc-nyse-frx-q3-earnings-preview/121277

Central Neuropathic Pain

Central Neuropathic Pain: Cymbalta--- Another Failed Trial

December 29, 2010

Summary

Treatment of neuropathic pain remains an enigmatic dilemma for most physicians.  Presently there are no drugs FDA approved for central neuropathic pain.  The use of drugs utilized for diabetic peripheral neuropathy and fibromyalgia, most notably Cymbalta (Eli Lilly), Lyrica (Pfizer) and Savella (Forest), as well as generics such as  gabapentin, tricyclic antidepressants and older anticonvulsants remain the mainstay of therapy.

Analysis

Central neuropathic pain remains relatively treatment resistant, with most patients not achieving more than 30% pain relief.  Many patients with traumatic spinal cord injury with severe neuropathic pain choose no pain medication, given the minimal effect and high side effects of conventional (non-intrathecal) medications.  This double blind placebo controlled trial of Cymbalta (duloxetine, Eli Lilly) in patients with central neuropathic pain secondary to spinal cord injury or stroke, while showing a trend favoring Cymbalta, failed to show a statistically significant result for the primary endpoint.
The absence of a statistically significant endpoint means no clinically meaningful result, and no new label.
Nuedexta, Avanir's combination of ultra-low dose (10mg) quinidine with 20 mg of dextromethorphan showed a robust and rapid response in multiple sclerosis patient's with central neuropathic pain.  Although recently approved for PBA (Pseudobulbar affect), the effect seen in central neuropathic pain in MS patients was dramatic, and in additive to that achieved by concomitant use of narcotic or non-narcotic analgesics.  Avanir has released similar exemplary data for patients suffering diabetic peripheral neuropathy.
Central neuropathic pain remains an open field.  There are presently no drugs FDA approved for central neuropathic pain in the US, and only one (Lyrica) outside the US. With the upcoming launch of Nuedexta for PBA, and the positive data seen previously in double blind placebo controlled trials in MS pain, one can only hope that Avanir will follow Eli Lilly and soon fund trials in central neuropathic pain.  A successful trial of Nuedexta in central neuropathic pain could be expected to add markedly to Avanir's valuation.
http://www.glgroup.com/News/Central-Neuropathic-Pain--Cymbalta----Another-Failed-Trial-52020.html

Savella: Cypress Bio Bought by Ramius

 

Zacks Equity Research

December 17, 2010

Product Portfolio at Cypress Bio
With this acquisition, Royalty Pharma will gain access to Cypress Bio’s Savella royalty stream. Savella, which is indicated for the treatment of fibromyalgia, is the only marketed product at Cypress Bio.
Savella has been developed under an agreement with Forest Labs and Cypress Bio receives a 15% royalty on product sales. The company was previously co-promoting Savella with Forest Labs. However, the co-promotion agreement was terminated in August 2010.
http://www.zacks.com/stock/news/44844/Cypress+Bio+Bought+by+Ramius

MILNACIPRIN: SAVELLA

Milnacipran

(mil na' si pran)

Last revised: April 1, 2009.

U.S. National Library of Medicine
National Institutes of Health

National Center for Biotechnology Information

U.S. National Library of Medicine

National Institutes of Health

Important Warning:

Milnacipran is not used to treat depression, but it belongs to the same class of medications as many antidepressants. Before you take milnaciprin, you should be aware of the risks of taking antidepressants because taking milnaciprin may carry similar risks. During clinical studies, this type of antidepressant ('mood elevator') caused a small number of children, teenagers, and young adults (up to 24 years of age) to become suicidal (thinking about harming or killing oneself or planning or trying to do so). Children, teenagers, and young adults who take antidepressants to treat depression or other mental illnesses may be more likely to become suicidal than children, teenagers, and young adults who do not take antidepressants to treat these conditions. However, experts are not sure about how great this risk is and how much it should be considered in deciding whether a child or teenager should be treated with an antidepressant or antidepressant-like medication. Children younger than 18 years of age should not normally take milnacipran, but in some cases, a doctor may decide that milnacipran is the best medication to treat a child's condition.

You should know that your mental health may change in unexpected ways when you take milnacipran even if you are an adult over 24 years of age. You may become suicidal, especially at the beginning of your treatment and any time that your dose is increased or decreased. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: new or worsening depression; thinking about harming or killing yourself or planning or trying to do so; extreme worry; agitation; panic attacks; difficulty falling asleep or staying asleep; aggressive behavior; irritability; acting without thinking; severe restlessness; and frenzied, abnormal excitement. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.

Your healthcare provider will want to see you often while you are taking milnacipran, especially at the beginning of your treatment. Be sure to keep all appointments for office visits with your doctor.

The doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with milnacipran. Read the information carefully and ask your doctor or pharmacist if you have any questions. You also can obtain the Medication Guide from the FDA website: http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/UCM096273.

No matter what your age, before you take an antidepressant, you or your caregiver should talk to your doctor about the risks and benefits of treating your condition with milnaciprin or with other treatments. You should also talk about the risks and benefits of not treating your condition. Although taking milnaciprin or similar medications may increase the risk that you will become suicidal, you should know that there are other things that also increase this risk. If you have depression or another mental illness, there is a greatly increased risk that you will become suicidal. This risk is higher if you or anyone in your family has or has ever had bipolar disorder (mood that changes from depressed to abnormally excited), mania (frenzied, abnormally excited mood), or has thought about or attempted suicide. Talk to your doctor about your condition, symptoms, and personal and family medical history. You and your doctor will decide what type of treatment is right for you.

Why is this medication prescribed?

Milnacipran is used to treat fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep). Milnacipran is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amount of serotonin and norepinephrine, natural substances that help stop the movement of pain signals in the brain.

How should this medicine be used?

Milnacipran comes as a tablet to be taken by mouth. It is usually taken two times a day. Milnacipran may be taken with or without food, but taking it with food will decrease the chance that milnacipran will upset your stomach. Take milnacipran at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take milnacipran exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor will start you on a low dose of milnacipran and gradually increase your dose during the first week of treatment.

Milnacipran may help control the symptoms of fibromyalgia, but will not cure it. Do not stop taking milnacipran without talking to your doctor. If you suddenly stop taking milnacipran, you may experience withdrawal symptoms such as mood changes, irritability, agitation, dizziness, numbness or tingling in the hands or feet, anxiety, confusion, headache, tiredness, difficulty falling asleep or staying asleep, ringing in the ears, abnormal excitement, or seizures. Your doctor will probably decrease your dose gradually.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before taking milnacipran,

• tell your doctor and pharmacist if you are allergic to milnacipran, aspirin, any other medications, or tartrazine (FD&C Yellow No 5).
• tell your doctor if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate), or if you have stopped taking an MAO inhibitor within the past 14 days. Your doctor will probably tell you not to take milnacipran. If you stop taking milnacipran, you should wait at least 5 days before you start to take an MAO inhibitor.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, or herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin); and other antidepressants; aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); clonidine (Catapres); clomipramine (Anafranil); digoxin (Lanoxicaps, Digitek, Lanoxin); diuretics ('water pills'); duloxetine (Cymbalta); epinephrine (Epipen, Primatene Mist); lithium (Eskalith, Lithobid); medications for anxiety, mental illness, pain, or seizures; medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig); sedatives; selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); sleeping pills, tramadol, tranquilizers, and venlafaxine (Effexor). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what nutritional supplements you are taking, especially tryptophan or 5-HTP.
• tell your doctor if you have glaucoma (increased pressure in the eye that may lead to vision loss). Your doctor will probably tell you not to take milnacipran.
• tell your doctor if you drink or have ever drunk large amounts of alcohol and if you have or have ever had high blood pressure; seizures; an irregular heartbeat; an enlarged or inflamed prostate (a male reproductive gland); difficulty urinating; or heart, kidney, or liver disease. .
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking milnacipran, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking milnacipran.
• you should know that milnacipran may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• talk to your doctor about the safe use of alcoholic beverages while you are taking milnacipran.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

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.

What side effects can this medication cause?

Milnacipran may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• vomiting
• constipation
• stomach pain
• weight loss
• dry mouth
• feeling of extreme facial warmth and/or redness
• increased sweating
• headache
• dizziness
• blurred vision
• difficulty falling or staying asleep
• decreased sexual desire or ability
• pain or swelling of the testicles
• difficulty urinating
• rash
• itching

Some side effects can be serious. If you experience any of these symptoms call your doctor immediately:

• hallucinations (seeing things or hearing voices that do not exist)
• confusion
• difficulty concentrating
• memory problems
• weakness
• unsteady walking that may cause falling
• seizures
• fainting
• coma (loss of consciousness for a period of time)
• slowed or stopped breathing
• fast or pounding heartbeat
• difficulty breathing
• extreme tiredness
• lack of energy
• loss of appetite
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• flu-like symptoms
• black and tarry stools
• red blood in stools
• bloody vomit
• vomit that looks like coffee grounds
• unusual bleeding or bruising
• nosebleeds
• tiny red spots directly under the skin

Milnacipran may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/Safety/MedWatch] or by phone [1-800-332-1088].

What storage conditions are needed for this medicine?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• extreme sleepiness
• confusion
• dizziness
• coma (loss of consciousness for a period of time)
• slowed or stopped heartbeat and breathing

What other information should I know?

Keep all appointments with your doctor. Your doctor will check your blood pressure and pulse regularly during your treatment with minalcipran.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

In this page

• Why is this medication prescribed?
• How should this medicine be used?
• Other uses for this medicine
• What special precautions should I follow?
• What special dietary instructions should I follow?
• What should I do if I forget a dose?
• What side effects can this medication cause?
• What storage conditions are needed for this medicine?
• In case of emergency/overdose
• What other information should I know?
• Brand names

American Society of Health-System Pharmacists, Disclaimer

AHFS® Consumer Medication Information. © Copyright, 2010. The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.

The following brand names are from RxNorm, a standardized nomenclature for clinical drugs produced by the National Library of Medicine:

Brand names

• Savella

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000495