The incidence of cardiovascular and anticholinergic side effects was significantly lower compared to TCAs as a controlled study with over 3,300 patients revealed. Elevation of liver enzymes without signs of symptomatic liver disease has been infrequent. Mood swing to mania has also been seen and dictates termination of treatment. In psychotic patients emergence of delirium has been noticed. Milnacipran has a low incidence of sedation but improves sleep (both duration and quality) in depressed patients. In agitated patients or those with suicidal thoughts additive sedative/anxiolytic treatment is usually indicated. Interactions
MAOIs — hyperserotonergia (serotonin syndrome), potentially lethal hypertensive crisis
5-HT1 receptor agonists — coronary vasoconstriction with risk of angina pectoris and myocardial infarction
Epinephrine, norepinephrine (also in local anesthesia) — hypertensive crisis and/or possible cardiac arrhythmia
Clonidine — antihypertensive action of clonidine may be antagonized
Digitalis — hemodynamic actions increased
Triptans — there have been rare postmarketing reports of hyperserotonergia (serotonin syndrome). If concomitant treatment of milnacipran with a triptan is clinically warranted, careful observation of patient is advised when starting or increasing dosages. Alcohol — no interactions known; however, because milnacipran can cause mild elevation of liver enzymes, caution is recommended; the FDA advises against the concomitant use of alcohol and milnacipran

Pharmacology
Pharmacodynamics
Milnacipran inhibits the reuptake of serotonin and norepinephrine in an approximately 1:3 ratio, respectively.
Ecallantide (trade name Kalbitor) is a drug used for the treatment of hereditary angioedema (HAE) and in the prevention of blood loss in cardiothoracic surgery. It is an inhibitor of the protein kallikrein and a 60-amino acid polypeptide which was developed from a Kunitz domain through phage display to mimic antibodies inhibiting kallikrein. Medical uses
Angioedema
On November 27, 2009, ecallantide was approved by the FDA for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age. A single dose requires three separate injections, which are given under the skin.Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors. Adverse effects
The most common adverse effects are headache, nausea, fatigue and diarrhea. Less common, but observed in more than 5% of patients in clinical trials, are respiratory tract infections, fever, vomiting, itching and upper abdominal pain. Up to 4% of patients showed anaphylaxis, which led to a black box warning in the US. Interactions
As of 2011, no interaction studies have been conducted. Mechanism of action
HAE is caused by a mutation of the C1-inhibitor gene. Defective or missing C1-inhibitor permits activation of kallikrein, a protease that is responsible for liberating bradykinin from its precursor kininogen. An excess of bradykinin leads to fluid leakage from blood vessels, causing swelling of tissues typical of HAE. Ecallantide suppresses this pathogenetic mechanism by selectively and reversibly inhibiting the activity of plasma kallikrein. Ecallantides inhibitory constant (Ki) for kallikrein is 25 picoMolar, indicating high affinity.