MILNACIPRAN
HAZARDTEXT ®
Information to help in the initial response for evaluating chemical incidents
-IDENTIFICATION
SYNONYMS
(+/-)-[1R(S),2S(R)]-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide hydrochloride Molecular formula: C15H22N2O
IDENTIFIERS
USES/FORMS/SOURCES
Milnacipran is available as 12.5 mg, 25 mg, 50 mg, and 100 mg film-coated tablets for oral administration (Prod Info SAVELLA(R) oral tablets, 2009).
-CLINICAL EFFECTS
GENERAL CLINICAL EFFECTS
- USES: Selective serotonin and norepinephrine reuptake inhibitor (SSNRI) used in the management of fibromyalgia.
- PHARMACOLOGY: Inhibits neuronal norepinephrine and serotonin reuptake; thus potentiating the serotonergic and noradrenergic activity in the CNS.
- TOXICOLOGY: Primarily sympathomimetic activity, potential for serotonin syndrome.
- EPIDEMIOLOGY: Several deliberate poisonings with milnacipran have been reported in postmarketing experience. Fatalities are rare.
MILD TO MODERATE TOXICITY: Somnolence, nausea and vomiting are common. Tachycardia and hypertension have been reported. SEVERE TOXICITY: Milnacipran may cause seizures and serotonin syndrome. Acute stress cardiomyopathy developed in a woman after ingesting 3000 mg of milnacipran.
COMMON: Headache, nausea and vomiting, constipation, hypertension, tachycardia and palpitations. Elevated liver enzymes have been reported.
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
-FIRST AID
FIRST AID AND PREHOSPITAL TREATMENT
- Prehospital activated charcoal is not recommended because of the potential for somnolence and rarely, seizures.
-RANGE OF TOXICITY
MINIMUM LETHAL EXPOSURE
- CASE REPORT: A 42-year-old woman was found dead in her car surrounded by empty medication containers (anetholtrithione, bromazepam, chlorazepate, heptaminol, prazepam and venlafaxine). A bottle with residual of a white suspension was also found, and it's contents were identified to be milnacipran and sertraline. Toxicologic analysis revealed eight psychotropic molecules in the victim's blood; all were within therapeutic concentrations except for milnacipran. Femoral and cardiac serum concentrations of milnacipran were 21.5 and 21 mg/L, respectively (approximately 40 times the usual maximum prescribed concentration). Autopsy found slight mitral prolapse, polyvisceral congestion and approximately 20 grams of whitish substance in the victim's stomach. The authors speculate the victim ingested about 4 grams of milnacipran, and suspect milnacipran's pharmacokinetics played a part in this fatal intoxication (Fanton et al, 2008).
MAXIMUM TOLERATED EXPOSURE
- Acute intoxications have been reported with ingestions up to 2.8 grams of milnacipran; however few clinical details are available. The most common symptoms associated with acute intoxications are nausea, vomiting and somnolence (Prod Info SAVELLA(R) oral tablets, 2009).
- CASE SERIES: Fanton et al (2008) details three cases of intentional milnacipran overdose with favorable outcomes (Fanton et al, 2008):
The first case involved an ingestion of 950 mg milnacipran (9 times the recommended dose) resulting in sleepiness and a complication of amenorrhea-galactorrhea three days postingestion. The patient was treated with activated charcoal and diuresis. The second case reported serum milnacipran levels of 0.334 g/L, along with alcohol (1.33 g/L), resulting in somnolence that resolved under simple surveillance. The third case was a multi-drug ingestion with an estimated milnacipran intake of 1.4 grams. The milnacipran serum concentration was 3 mg/L, and toxic concentration of meprobamate was also reported. Isolated impairment of consciousness (GCS of 5) occurred; however a favorable recovery was made.
- CASE REPORT: A 59-year-old woman developed coma, respiratory failure, autonomic instability, fever, tremor, and acute cardiac dysfunction after ingesting 3000 mg of milnacipran. Following supportive care, she recovered gradually. It is suggested that the combination of paroxetine taken therapeutically and milnacipran overdose could have caused serotonin syndrome in this patient (Levine et al, 2011).
- Carcinogenicity Ratings for CAS92623-85-3 :
ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed EPA (U.S. Environmental Protection Agency, 2011): Not Listed IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed MAK (DFG, 2002): Not Listed NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed
TOXICITY AND RISK ASSESSMENT VALUES
- EPA Risk Assessment Values for CAS92623-85-3 (U.S. Environmental Protection Agency, 2011):
-STANDARDS AND LABELS
WORKPLACE STANDARDS
- ACGIH TLV Values for CAS92623-85-3 (American Conference of Governmental Industrial Hygienists, 2010):
- AIHA WEEL Values for CAS92623-85-3 (AIHA, 2006):
- NIOSH REL and IDLH Values for CAS92623-85-3 (National Institute for Occupational Safety and Health, 2007):
- OSHA PEL Values for CAS92623-85-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
- OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS92623-85-3 (U.S. Occupational Safety and Health Administration, 2010):
ENVIRONMENTAL STANDARDS
- EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS92623-85-3 (U.S. Environmental Protection Agency, 2010):
- EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS92623-85-3 (U.S. Environmental Protection Agency, 2010):
- EPA RCRA Hazardous Waste Number for CAS92623-85-3 (U.S. Environmental Protection Agency, 2010b):
- EPA SARA Title III, Extremely Hazardous Substance List for CAS92623-85-3 (U.S. Environmental Protection Agency, 2010):
- EPA SARA Title III, Community Right-to-Know for CAS92623-85-3 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):
- DOT List of Marine Pollutants for CAS92623-85-3 (49 CFR 172.101 - App. B, 2005):
- EPA TSCA Inventory for CAS92623-85-3 (EPA, 2005):
LABELS
- NFPA Hazard Ratings for CAS92623-85-3 (NFPA, 2002):
-PERSONAL PROTECTION
SUMMARY
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
PROTECTIVE CLOTHING
- CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 92623-85-3.
-PHYSICAL HAZARDS
FIRE HAZARD
- FLAMMABILITY CLASSIFICATION
- NFPA Flammability Rating for CAS92623-85-3 (NFPA, 2002):
- FIRE CONTROL/EXTINGUISHING AGENTS
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
- NFPA Extinguishing Methods for CAS92623-85-3 (NFPA, 2002):
EVACUATION PROCEDURES
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
- AIHA ERPG Values for CAS92623-85-3 (AIHA, 2006):
- DOE TEEL Values for CAS92623-85-3 (U.S. Department of Energy, Office of Emergency Management, 2010):
- AEGL Values for CAS92623-85-3 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 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62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):
- NIOSH IDLH Values for CAS92623-85-3 (National Institute for Occupational Safety and Health, 2007):
CONTAINMENT/WASTE TREATMENT OPTIONS
-PHYSICAL/CHEMICAL PROPERTIES
MOLECULAR WEIGHT
- 282.8 g/mol (Prod Info Savella(R) oral tablets, 2013)
DESCRIPTION/PHYSICAL STATE
- Milnacipran hydrochloride is a white to off-white crystalline powder that is freely soluble in water, methanol, ethanol, chloroform, and methylene chloride, and sparingly soluble in diethyl ether. The melting point is 179 degrees C (Prod Info Savella(R) oral tablets, 2013).
FREEZING/MELTING POINT
SOLUBILITY
Milnacipran hydrochloride is freely soluble in methanol, ethanol, chloroform, and methylene chloride. It is sparingly soluble in diethyl ether (Prod Info Savella(R) oral tablets, 2013).
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- 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
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