Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

VENLAFAXINE HYDROCHLORIDE

NFPA

PRODUCT USE

Antidepressant whose action is believed to be associated with the potentiation of
neurotransmitter activity in the CNS. Venlafaxine and its active metabolite
desmethylvenlafaxine (ODV) are potent inhibitors of neuronal serotonin and norepinephrine
uptake and weak inhibitors of dopamine uptake. Both have no significant affinity for
muscarinic, histaminergic, or alpha- 1- adrenergic receptors in vitro. Pharmacologic
activity at these receptors is hypothesised to be associated with the various
anticholinergic, sedative and cardiovascular effects seen with other psychotropic drugs.
Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity.

SYNONYMS

C17-H28-Cl-N-O2, C17-H28-Cl-N-O2, "cyclohexanol, 1-[2-(dimethylamino)-1-(4-
methoxyphenyl)ethyl]-, hydrochloride", "cyclohexanol, 1-[2-(dimethylamino)-1-(4-
methoxyphenyl)ethyl]-, hydrochloride", (R/S)-1-[2-(dimethylamino)-1-(4-
methoxyphenyl)ethyl]cyclohexanol, (R/S)-1-[2-(dimethylamino)-1-(4-
methoxyphenyl)ethyl]cyclohexanol, hydrochloride, (+/-)-1-[alpha-((dimethylamino)methyl]-p-
methoxybenzyl]cyclohexanol, (+/-)-1-[alpha-((dimethylamino)methyl]-p-
methoxybenzyl]cyclohexanol, Efexor, WY-45030, antidepressant

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

None

EMERGENCY OVERVIEW

RISK

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Although ingestion is not thought to produce harmful effects, the material may still be damaging to the health of the individual following ingestion, especially where pre-  existing organ (e.g. liver, kidney) damage is evident. Present definitions of harmful or toxic substances are generally based on doses producing mortality (death) rather than those producing morbidity (disease, ill-health). Gastrointestinal tract discomfort may produce nausea and vomiting. In an occupational setting however, ingestion of insignificant quantities is not thought to be cause for concern.  Accidental ingestion of the material may be damaging to the health of the individual.  for venlafaxine:  In overdose, somnolence is the most commonly reported symptom. Convulsion and mild sinus tachycardia have also been reported. Treatment is associated with sustained dose-  dependent increases in blood pressure. Treatment-related anxiety, nervousness, insomnia and anorexia have also been reported. Significant weight loss may be an undesirable effect of treatment. Hypomania or mania, and seizure has been reported in a small number of patients. Other adverse reactions headache, asthenia, infection, chills, chest pain, trauma, vasodilation, increased blood pressure/ hypertension, tachycardia, postural hypotension, sweating, rash, pruritus, nausea, constipation, diarrhoea, vomiting, dyspepsia, flatulence, somnolence, dry mouth, dizziness, insomnia, nervousness, anxiety, tremor, abnormal dreams, hypertonia, paraesthesia, decreased libido, agitation, confusion,  abnormal thoughts, depersonalisation, depression, urinary retention, twitching, yawning, blurred vision, taste perversion, tinnitus, mydriasis, abnormal ejaculation/ orgasm, impotence, urinary frequency, impaired urination, disturbed orgasm, menstrual disorders, dysphagia, eructation, ecchymosis, somnolence, peripheral oedema, weight gain, emotional lability, trismus vertigo, bronchitis, dyspnea, abnormal vision, ear pain, anorgasmia, dysuria, haematuria, metrorrhagia, impaired urination, vaginitis, dry mouth, neck pain, and sweating.  Dose-dependent effects included chills, nausea, agitation, dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation. A statistically significant increase in serum cholesterol was also  reported. Infrequent or rare effects included enlarged abdomen, allergic reactions, cyst, facial oedema, hangover, hernia, moniliasis, neck rigidity, sub- sternal chest pain, pelvic pain, photosensitivity reactions, appendicitis, body odour, halitosis, ulcer, withdrawal symptoms, angina pectoris, extrasystoles, hypotension, peripheral vascular disorder (cold feet and hands), syncope, thrombophlebitis, arrhythmia, first-degree atrioventricular block, bradycardia, bundle branch block, mitral valve disorder, mucocutaneous haemorrhage, sinus bradycardia, varicose vein, colitis, oedema of the tongue, oesophagitis, gastritis, gastroenteritis, gingivitis, glossitis, rectal haemorrhage, hemorrhoids, melena, stomatitis, stomach ulcer, mouth ulcerations, cheilitis,  cholecystitis, cholelithiasis, haematemesis, gum haemorrhage, hepatitis, ileitis, jaundice, oral moniliasis, intestinal obstruction, proctitis, increased salivation, soft stools, discolouration of the tongue, oesophageal ulcer, peptic ulcer syndrome, goiter, hyperthyroidism, hypothyroidism, leukocytosis, leukopenia, lymphadenopathy, lymphocytosis,  thrombocytopenia, thrombocythemia, basophilia, cyanosis, eosinophilia, abnormal erythrocytes and WBC, diabetes mellitus, glycosuria, hypercholesteraemia, hyperglycaemia, hyperlipaemia, hyperrubicaemia, hypoglycaemia, hypokalaemia, increased thirst, alcohol intolerance, bilirubinaemia, gout, haemochromatosis, hyperkalaemia, hyperphosphataemia, hypoglycaemic reaction, hyponatraemia, hypophosphataemia, hypoproteinaemia, uraemia, arthritis, arthrosis, bone pain, bone spurs, bursitis, joint disorder, myasthenia, tenosynovitis, osteoporosis, apathy, ataxia, circumoral paraesthesia, CNS stimulation, euphoria, hallucinations, hostility, hyperaesthesia, hyperkinaesia, hypertonia, hypotonia,  incoordination, increased libido, manic reactions, myoclonus, neuralgia, neuropathy, paranoid reaction, psychosis, psychotic depression, sleep disturbance, abnormal speech, stupor, torticollis, akathisia, alkinaesia, alcohol abuse, aphasia, bradykinaesia, cerebrovascular accident, loss of consciousness, delusions, dementia, dystonia, hypokinaesia, neuritis, nystagmus, increased reflexes, seizures, acne, alopecia, brittle nails, contact dermatitis, dry skin, herpes simplex, herpes zoster, maculopapular rash, urticaria, dermal atrophy, exfoliative dermatitis, fungal dermatitis, lichenoid dermatitis, discolouration of the hair, eczema, furuncolosis, hirsutism, skin hypertrophy,  leukoderma, psoriasis, pustular rash, vesiculobullous rash, asthma, chest congestion, epistaxis, hyperventilation, laryngismus, laryngitis, pneumonia, voice alterations, atelectasis, haemoptysis, hypoxia, pleurisy, pulmonary embolus, sleep apnea, increased sputum, cataract, conjunctivitis, corneal lesion, diplopia, dry eyes, exophthalmos, eye pain, otitis media, parosmia, photophobia, subconjunctival haemorrhage, loss of taste, visual field defect, blepharitis, chromatopsia, conjunctival oedema, deafness, glaucoma, hyperacusis, keratitis labrynthitis, miosis, papilloedema, decreased pupillary reflex, schleritis, albuminuria, amenorrhoea, kidney calculus, cystitis, leukorrhea, menorrhagia, nocturia, bladder pain, breast pain, kidney pain, polyuria, prostatitis, pyelonephritis, pyuria, urinary incontinence,urinary urgency, uterine fibroids, enlarged uterine haemorrhage, vaginal haemorrhage, vaginal moniliasis, abortion, breast engorgement, breast enlargement, calcium crystalluria, female lactation, hypomenorrhea, menopause, prolonged erection, uterine spasm.  Since any psychoactive drug may impair judgement, thinking or motor skills, exposed individuals should be cautious in operating machinery.  Adverse reactions, some serious, have been reported in patients who have recently discontinued monoamine oxidase inhibitor (MAOI) therapy or who have discontinued venlafaxine therapy prior to initiation of an MAOI.  Reactions include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia, with features resembling neuroleptic malignant syndrome, seizures, and death. In patients receiving antidepressants with similar action to venlafaxine in combination there have been reports of serious, sometimes fatal reactions. For a selective serotonin reuptake inhibitor, these include hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.  Certain cases present with features resembling neuroleptic malignant syndrome. Severe hypothermia and sometimes fatal seizures have been reported with combined use of tricyclics and MAOIs.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals.  

SKIN

  The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Open cuts, abraded or irritated skin should not be exposed to this material.  Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected.  

INHALED

  The material is not thought to produce either adverse health effects or irritation of the respiratory tract following inhalation (as classified using animal models). Nevertheless, adverse effects have been produced following exposure of animals by at least one other route and good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting.  Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled.  

CHRONIC HEALTH EFFECTS

  Long-term exposure to the product is not thought to produce chronic effects adverse to the health (as classified using animal models); nevertheless exposure by all routes should be minimized as a matter of course.  Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Prime symptom is breathlessness; lung shadows show on X-ray.  Venlafaxine given by gavage to mice for 18 months (up to 120 mg/kg/day) and to rats for 24 months (up to 120 mg/kg/day) did not induce tumours.  Venlafaxine and the major metabolite desvenlafaxine were not mutagenic in the Ames reverse mutation assay in Salmonella or the CHO/HGPRT mammalian cell forward gene mutation assay, the in vitro BALB/c-3T3 mouse cell transformation assay, the sister chromatid exchange assay in cultured CHO  cells, or in the in vivo chromosomal aberration assay in rat bone marrow. desvenlafaxine was not mutagenic in the in vitro CHO cell chromosomal aberration assay. There was a clastogenic response in th in vitro chromosomal aberration assay in rat bone marrow in male rats receiving 200 times, on a mg/kg basis, or 50 times on a mg/m2 basis, the maximum human daily dose. The no-effect dose was 67 times (mg/kg) or 17 times (mg/m2) the human dose.  Reproduction and fertility studies in rats showed no effects on male and female fertility up to oral doses 8 times that of the maximum recommended human dose (mg/kg basis). Venlafaxine did not cause malformations in offspring of rats and rabbits given 11 times (rat) or 12 times (rabbit) the maximum recommended human daily dose on a mg/kg basis. In rats, however, there was a decrease in pup weight, and an increase in stillborn pups and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. These effects occurred at 10 times the maximum human dose (mg/kg basis).