Generic Name: milnacipran HCl (mil-na-cip-ran)

Brand Names: Savella®

Classification: Antidepressant - SSRI
(Selective Serotonin Reuptake Inhibitors)

Issue Date: January 14, 2009

Savella is expected to be available by prescription in April of 2009.

The U.S. Food and Drug Administration (FDA) has approved Savella (milnacipran HCl), a selective serotonin and norepinephrine dual reuptake inhibitor for the management of Fibromyalgia (FM). Although the exact mechanism by which Savella improves the symptoms of FM is unknown, some researchers believe that abnormalities in certain brain neurotransmitters may be central to FM. Savella blocks the reuptake of both norepinephrine and serotonin, with greater selectivity for the inhibition of norepinephrine reuptake in vitro. This may be the mechanism by which Savella acts to improve the symptoms of FM.

• Before Using This Medicine
• Precautions While on this Medicine
• Side Effects

Do not take Savella together with a monoamine oxidase inhibitor (MAOI) such as:

• Isocarboxazid (Marplan®)
• Phenelzine (Nardil®)
• Rasagiline (Azilect®)
• Selegiline (Eldepryl®, Emsam®)
• Tranylcypromine (Parnate®)

You must wait at least 14 days after stopping an MAOI before you can take Savella.

SSRI antidepressants may cause serious or life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Savella, do not stop taking the medication without first talking to your doctor.

Blood pressure and heart rate should be monitored prior to initiating treatment with Savella and periodically throughout treatment. SSRIs, including Savella, have been associated with reports of increases in blood pressure and heart rate. Pre-existing hypertension, tachyarrhythmias and other cardiac diseases should be treated before starting therapy with Savella.

Savella should be used with caution in patients with significant hypertension or cardiac disease. For patients who experience a sustained increase in blood pressure or heart rate while receiving Savella, either dose reduction or discontinuation should be considered.

Savella should be prescribed with caution in patients with a history of:

• seizure disorder
• mania
• controlled narrow-angle glaucoma

Savella has been associated with mild elevations of ALT and AST. Rarely, fulminant hepatitis has been reported in patients treated with milnacipran. Savella should be discontinued in patients who develop jaundice or other evidence of liver dysfunction and should not be resumed unless another cause can be established.

Savella should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease.

As with other SNRIs and SSRIs withdrawal symptoms have been observed following discontinuation of milnacipran. A gradual dose reduction is recommended.

Hyponatremia, (an electrolyte disturbance), may occur as a result of treatment with SSRIs and SNRIs, including Savella. Discontinuation should be considered for patients with symptomatic hyponatremia.

SSRIs and SNRIs, including Savella, may increase the risk of bleeding events. Patients should be cautioned regarding the risk of bleeding associated with concomitant use of Savella and NSAIDs, aspirin, warfarin or other drugs that affect coagulation.

Male patients with a history of obstructive uropathies may experience higher rates of genitourinary adverse events.

Savella is unlikely to be involved in clinically significant pharmacokinetic drug interactions. Pharmacodynamic interactions of Savella with other drugs can occur.

Savella contains FD&C Yellow No. 5, which may cause allergic-type reactions in susceptible persons.

In clinical trials, the most frequently occurring adverse reaction was nausea. The most commonly occurring adverse reactions (greater than or equal to 5% and twice that of placebo) were:

• constipation
• hot flush
• hyperhidrosis
• vomiting
• palpitations
• heart rate increased
• dry mouth
• hypertension

Savella is not used to treat depression, but it acts like medicines that are used to treat depression (antidepressants) and other psychiatric disorders.

Read the Medication Guide that comes the antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts or actions with antidepressant medicines. Talk to your or your family member's healthcare provider about:

• all risks and benefits of treatment with antidepressant medicines
• all treatment choices for depression or other serious mental illness

Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.

Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manicdepressive illness) or suicidal thoughts or actions.

• Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.


• Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.


• Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• new or worse irritability
• attempts to commit suicide
• acting aggressive, being angry, or violent
• new or worse depression
• acting on dangerous impulses
• new or worse anxiety
• an extreme increase in activity and talking
• feeling very agitated or restless (mania)
• panic attacks
• other unusual changes in behavior or mood
• trouble sleeping (insomnia)

What else you should know about antidepressant medicines:

• Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.


• Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.


• Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.


• Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.


• Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child's healthcare provider for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA1088.

Side Effects

The clinical development program demonstrated that Savella was safe and generally well tolerated. The most frequently occurring adverse reaction was nausea. Other common adverse reactions reported in these clinical trials were:

• constipation
• hot flush
• hyperhidrosis
• vomiting
• palpitations
• heart rate increased
• dry mouth
• hypertension

The majority of adverse reactions reported were mild to moderate in nature.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.