Clomipramine

314.86

314.85

206-144-2

NUV44L116D

169865

DTXSID6022844

C61608

QN06AA04|N06AA04|N - Nervous system

2933990090

6.5

5.2

white to off-white powder

1.1±0.1 g/cm3

189.5 °C

160-170 °C

216.4±28.7 °C

1.582

1.44e-02 g/L

Clomipramine hydrochloride capsules should be stored in tight containers at a temperature of 20-25 deg C and protected from moisture. When stored as directed, the capsules have an expiration date of 3 years following the date of manufacture.

4.07X10-7 mm Hg at 25 deg C (est)

Oral-rat LD50: 613 mg/kg; Oral-Mouse LD50: 380 mg/kg

Thermal decomposition releases toxic nitrogen oxides and chloride fumes

Henry's Law constant = 7.48X10-9 atm-cu m/mol at 25 °C (est)

pKa = 8.98 (amine) (est)

174.3 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|174.4 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated]

Crystals from acetone-ether/methanol-ether. MW 351.31. MP 189-190 °C ...; also reported as crystals from acetone; mp 191-5-192 °C... Freely soluble in water, methanol, methylene chloride; practically insoluble in ethyl ether, benzene /Clomipramine hydrochloride/|Hydroxyl radical reaction rate constant = 2.94X10-10 cu cm/molec-sec at 25 °C (est)

Ⅱ

3265

3

20/21/22

36

HN9055000

Xn

The warehouse is ventilated, low temperature and dry; stored separately from food materials

P264, P270, P301+P312, P330, P501

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Clomipramine tablets. ... Indications for use /in dogs/. For use as part of a comprehensive behavioral management program to treat separation anxiety in dogs greater than 6 months of age. ... Limitations: Federal law restricts this drug to use by or on the order of a licensed veterinarian.|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl clomipramine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Clomipramine hydrochloride/|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Clomipramine hydrochloride is included on this list. /Clomipramine hydrochloride/

highly toxic

Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.

Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. Serum aminotransferase elevations during clomipramine therapy are reported in 1% to 3% of patients and the abnormalities were usually mild, asymptomatic and transient, reversing even with continuation of medication. As with many tricyclic antidepressants, rare instances of clinically apparent acute liver injury have been reported in patients taking clomipramine. The clinical features of cases of drug induced liver disease from clomipramine have not been well defined. The acute liver injury caused by tricyclic antidepressants typically arises within 1 to 4 weeks of starting the medication and presents with fatigue followed by dark urine and jaundice. Both hepatocellular and cholestatic patterns of injury have been described. The injury is usually mild-to-moderate in severity and recovery is rapid when the tricyclic is discontinued. Immunoallergic features such as rash, fever and eosinophilia are not common and autoantibodies are generally not detected. Fatal cases are extremely rare.

Limited data suggest that demethylation of clomipramine may be reduced with chronic alcohol consumption. In one study, the clearance of clomipramine via demethylation was decreased substantially and the ratio of blood clomipramine to desmethylclomipramine concentrations at steady state was higher in recently detoxified alcoholic patients (abstinence periods ranged from 4-20 weeks) compared with a control group of patients with no history of alcoholism.|The plasma concentration of clomipramine has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (eg, cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (eg, barbiturates, phenytoin), and such an effect may be anticipated with clomipramine as well. Administration of clomipramine has been reported to increase the plasma levels of phenobarbital, if given concomitantly.|Several tricyclic antidepressants have been reported to block the pharmacologic effects of guanethidine, clonidine, or similar agents, and such an effect may be anticipated with clomipramine because of its structural similarity to other tricyclic antidepressants.|Close supervision and careful adjustment of dosage are required when clomipramine is administered with anticholinergic or sympathomimetic drugs.|For more Interactions (Complete) data for Clomipramine (11 total), please visit the HSDB record page.

... Patients genetically deficient in hydroxylation accumulate demethyl-clomipramine at high concentrations that can produce serious side effects and/or nonresponse. ...

Clomipramine is approximately 97-98% bound to plasma proteins, principally to albumin and possibly to α₁-acid glycoprotein. Desmethylclomipramine is 97-99% bound to plasma proteins.

... Four clomipramine-treated breastfeeding mother-infant pairs were assessed for serum concentrations of clomipramine, N-desmethylclomipramine, and corresponding 8-hydroxymetabolites. Although the mothers exhibited a wide range of serum concentrations, the parent drug and metabolites were either nondetectable or below the quantifiable limit in the sera of all infants. ...

May be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder). Unlabeled indications include: depression, panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy (limited evidence), autistic disorder (limited evidence), trichotillomania (limited evidence), onchophagia (limited evidence), stuttering (limited evidence), premature ejaculation, and premenstrual syndrome.|FDA Label|As an aid in the treatment of separation related disorders in dogs manifested by destruction and inappropriate elimination (defecation and urination) and only in combination with behavioural modification techniques.

Clomipramine is a tricyclic antidepressant used in the therapy of obsessive-compulsive disorder. Clomipramine can cause mild and transient serum enzyme elevations and is rare cause of clinically apparent acute liver injury.

Antidepressant Agents

Tricyclic Antidepressive Agents; Serotonin Uptake Inhibitors|Clomipramine hydrochloride capsules are indicated for the treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD). The obsessions or compulsions must cause marked distress, be time consuming, or significantly interfere with social or occupational functioning, in order to meet the DSM-III-R (circa 1989) diagnosis of OCD. /Included in US product label/|/VET THER/ The efficacy and tolerability of clomipramine in the treatment of separation anxiety in dogs was tested in a prospective, randomized, double-blind, placebo-controlled, parallel-group, international multicenter clinical trial. For a diagnosis of separation anxiety, dogs had to exhibit at least one of the following signs in the absence of their owner: destruction, defecation, urination and/or vocalization, as well as the behaviour suggestive of "hyper-attachment" to their owner. A total of 95 dogs were randomized to receive one of the three treatments for 2-3 months: "standard-dose" clomipramine (1 to <2 mg/kg, PO, q. 12 hr); "low-dose" clomipramine (0.5 to <1 mg/kg, PO, q. 12 hr); and placebo (PO, q. 12 hr). All dogs received behavioural therapy. Dogs were examined at four time points (days 0, 28, 56 and 84) after the initiation of therapy. Improvement in each dog's behaviour at days 28, 56 and 84 was evaluated in comparison to its behaviour at day 0.The results showed that, compared to placebo, dogs receiving standard-dose clomipramine were rated improved at least three times faster for the signs destruction, defecation and urination. At most time points, more dogs in the standard-dose clomipramine group were rated improved for the signs destruction, defecation and urination, and in an owner's global assessment of the dog's overall behaviour (p<0.05 at certain time points). However, there were no statistically significant differences at any time point between the standard dose and the placebo groups in the sign vocalization. The low-dose clomipramine group produced no statistically significant effect when compared with placebo. Mild and transient vomiting was noted as a side effect of clomipramine in a small number of dogs.It is concluded that addition of standard-dose (1 to <2 mg/kg, PO, q. 12 hr) clomipramine to conventional behavioural therapy for 2-3 months ameliorated the signs of separation anxiety in dogs.

/BOXED WARNING/ Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of clomipramine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Clomipramine hydrochloride capsules are not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).|Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants. This risk may persist until clinically important remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term, placebo-controlled studies of antidepressants (ie, selective serotonin-reuptake inhibitors and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders. An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age, and a reduced risk was observed in adults 65 years of age or older. It currently is unknown whether the suicidality risk extends to longer-term use (ie, beyond several months); however, there is substantial evidence from placebo-controlled maintenance trials in adults with major depressive disorder that antidepressants can delay the recurrence of depression.|The risk of suicidality in FDA's pooled analysis differed across the different psychiatric indications, with the highest incidence observed in the major depressive disorder studies. ...The average risk of such events was 4% among children and adolescents receiving these drugs, twice the risk (2%) that was observed among those receiving placebo. ... In addition, although there was considerable variation in risk among the antidepressants, a tendency toward an increase in suicidality risk in younger patients was found for almost all drugs studied. It is currently unknown whether the suicidality risk in pediatric patients extends to longer-term use (i.e., beyond several months).|As a result of this analysis and public discussion of the issue, FDA has directed manufacturers of all antidepressants to add a boxed warning to the labeling of their products to alert clinicians of this suicidality risk in children and adolescents and to recommend appropriate monitoring and close observation of patients receiving these agents. The drugs that are the focus of the revised labeling are all drugs included in the general class of antidepressants, including those that have not been studied in controlled clinical trials in pediatric patients, since the available data are not adequate to exclude any single antidepressant from an increased risk. In addition to the boxed warning and other information in professional labeling on antidepressants, FDA currently recommends that a patient medication guide explaining the risks associated with the drugs be provided to the patient each time the drugs are dispensed.|For more Drug Warnings (Complete) data for Clomipramine (57 total), please visit the HSDB record page.

Among reports from other countries of clomipramine overdose, the lowest dose associated with a fatality was 750 mg.

Clomipramine has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. While a variety of withdrawal symptoms have been described in association with clomipramine discontinuation, there is no evidence for drug seeking behavior, except for a single report of potential clomipramine abuse by a patient with a history of dependence on codeine, benzodiazepines, and multiple psychoactive drugs. The patient received clomipramine hydrochloride for depression and panic attacks and appeared to become dependent after hospital discharge.

Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α₁ and β₁ receptors are sensitized, α₂ receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system. (See all compounds classified as Antidepressive Agents, Tricyclic.)|Compounds that specifically inhibit the reuptake of serotonin in the brain. (See all compounds classified as Serotonin Uptake Inhibitors.)

Well absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occurred 2-6 hours following oral administration of a single 50 mg dose. The peak plasma concentration ranged from 56 ng/mL to 154 mg/mL (mean, 92 ng/mL). There are large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine.|Urine (51-60%) and feces via biliary elimination (24-32%)|~ 17 L/kg (range: 9-25 L/kg). Clomipramine is capable of distributing into the cerebrospinal fluid, the brain, and into breast milk.|Clomipramine hydrochloride appears to be well absorbed from the GI tract following oral administration. However, extensive first-pass metabolism decreases its oral bioavailability to about 50%. The oral capsules and solution of clomipramine hydrochloride reportedly are bioequivalent. Food does not appear to substantially affect the bioavailability of clomipramine from the capsules.|In one case report, plasma clomipramine concentrations were measured in an infant whose mother was receiving clomipramine hydrochloride 125 mg daily during pregnancy. ... After the first week postpartum, the mother's dosage of clomipramine hydrochloride was increased to 150 mg daily and the concentration of clomipramine in milk was 80-160% of the concurrent plasma clomipramine concentration at steady state. ...|Peak plasma clomipramine concentrations of approximately 56-154 ng/mL (mean: 92 ng/mL) usually occur within 2-6 hours (mean: 4.7 hours) following oral administration of a single 50-mg dose of clomipramine hydrochloride. Like other tricyclic antidepressants, clomipramine exhibits considerable interindividual variation in plasma concentrations achieved with a given dose due, at least in part, to genetic differences in the metabolism of the drug.|Following multiple-dose oral administration of clomipramine, steady-state plasma concentrations of the drug generally are achieved within about 1-2 weeks. Steady-state plasma desmethylclomipramine (the principal metabolite) concentrations may be achieved at about the same time as steady-state plasma clomipramine concentrations or later. In some cases, plasma desmethylclomipramine concentrations have been observed to continue to increase during 4-6 weeks of administration of a constant dosage of clomipramine hydrochloride. Plasma concentrations of desmethylclomipramine generally exceed those of the parent drug following multiple daily dosing of clomipramine hydrochloride.|For more Absorption, Distribution and Excretion (Complete) data for Clomipramine (13 total), please visit the HSDB record page.

Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown.|The exact metabolic fate of clomipramine has not been fully elucidated. Clomipramine appears to be extensively metabolized to desmethylclomipramine and other metabolites and their glucuronide conjugates. Desmethylclomipramine, the principal metabolite, is formed by N-demethylation of clomipramine. Other metabolites of clomipramine include 8-hydroxyclomipramine, 2-hydroxyclomipramine, and clomipramine N-oxide, which appear to be formed via 8-hydroxylation, 2-hydroxylation, and N-oxidation, respectively. The metabolites of desmethylclomipramine include 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which apparently are formed via 8-hydroxylation and N-demethylation, respectively. Although desmethylclomipramine is pharmacologically active, its efficacy in obsessive-compulsive disorder is not known. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine also are pharmacologically active but the clinical importance of their presence remains unknown.|The hydroxylation of clomipramine and desmethylclomipramine appears to be under genetic control (similar to that of debrisoquine and sparteine). In healthy adults who were phenotyped for debrisoquine hydroxylation, extensive metabolizers were distinguishable from poor metabolizers with regard to the extent of hydroxylation of desmethylclomipramine. Blood concentrations of desmethylclomipramine were higher than expected in a limited number of patients who subsequently were found to be poor metabolizers. Limited data suggest that CYP2D6, a cytochrome P-450 isoenzyme implicated in the sparteine/debrisoquine oxidation polymorphism, is involved in the 8-hydroxylation of clomipramine and desmethylclomipramine and in the 2-hydroxylation of clomipramine. In addition, demethylation of clomipramine may involve CYP2C, which is implicated in the S-mephenytoin oxidation polymorphism, and CYP1A2.|The fate of clomipramine (CMI) and its main demethylated metabolite demethylclomipramine (DCMI) was studied in two strains of Swiss mice (NMRI and CD1) after intraperitoneal injection. A study of its distribution among various tissues showed that fixation was most marked in lungs, perirenal fat and kidneys, and only moderate in the brain. The pharmacokinetic parameters of both molecules were determined in brain tissue and plasma. Absorption was rapid (tmax CMI = 14 min), metabolism prompt (tmax DCMI = 17 or 18 min according to the breed) and elimination rapid from both plasma and brain tissue. The first two stages were similar in the two strains, but elimination of CMI from both plasma and brain was faster in the NMRI mice (plasma t1/2 = 53 min against 165 min in the CD1 mice). Both values were well below that reported for man (mean plasma t1/2 = 24 hr). ...|Clomipramine has known human metabolites that include 10-hydroxy-clomipramine, 2-hydroxy-clomipramine, 8-hydroxy-clomipramine, and N-Desmethylclomipramine.

Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to saturable kinetics (i.e. metabolism).|The elimination half-life of clomipramine averages approximately 32 hours (range: 19-37 hours) and that of desmethylclomipramine averages about 69 hours (range: 54-77 hours) following a single, 150-mg oral dose of the drug.|To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. 6 male and 6 female Beagles. Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. ... For clomipramine, after IV administration, elimination half-life was 5 hours ...|/The objective of this study was/ to determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following single-dose and repeated-dose oral administration at various dosages. ... Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. ... Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated-dose administration but remained short in all groups (< or = 4 hours).

Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α₁-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.|The pharmacology of clomipramine is complex and in many ways resembles that of other antidepressants, particularly those agents (eg, selective serotonin-reuptake inhibitors, trazodone) that predominantly potentiate the pharmacologic effects of serotonin (5-HT). Although clomipramine's principal pharmacologic effect in vitro is the selective inhibition of serotonin reuptake, in vivo the drug's pharmacologic activity is not so selective because of the action of its demethylated metabolite, desmethylclomipramine, as an inhibitor of norepinephrine reuptake. As a result of this and other effects, clomipramine also shares the pharmacologic profile of other tricyclic antidepressants.|The precise mechanism of action that is responsible for the efficacy of clomipramine in the treatment of obsessive-compulsive disorder is unclear. However, because of its pronounced potency in blocking serotonin reuptake at the presynaptic neuronal membrane and its efficacy in the treatment of obsessive-compulsive disorder, a serotonin hypothesis has been developed to explain the pathogenesis of the condition. The hypothesis postulates that a dysregulation of serotonin is responsible for obsessive-compulsive disorder and that clomipramine is effective because it corrects this imbalance.|Clomipramine and its principal metabolite, desmethylclomipramine, have been shown to block the reuptake of serotonin and norepinephrine, respectively, at the presynaptic neuronal membrane. The effects of serotonin and norepinephrine may thus be potentiated. However, it has been suggested that postsynaptic receptor modification is mainly responsible for the antidepressant action observed during long-term administration of antidepressant agents. During long-term therapy with most antidepressants (eg, tricyclic antidepressants, monoamine oxidase [MAO] inhibitors), these adaptive changes generally consist of subsensitivity of the noradrenergic adenylate cyclase system in association with a decrease in the number of beta-adrenergic receptors; such effects on noradrenergic receptor function commonly are referred to as "down-regulation." In addition, some antidepressants reportedly decrease the number of 5-HT binding sites following chronic administration.|Clomipramine's principal metabolite, desmethylclomipramine, is an inhibitor of norepinephrine reuptake. Clomipramine decreases the concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG), a metabolite of norepinephrine, in CSF in patients with obsessive-compulsive disorder. Patients with depressive affective (mood) disorders (e.g., major depressive episode) also exhibit decreases in concentrations of 5-HIAA and MHPG in CSF during treatment with clomipramine. The decrease in the concentration of 5-HIAA in CSF was correlated with inhibition of the in vitro uptake of 3H-serotonin in plasma. The change in concentration of MHPG in CSF during clomipramine therapy was correlated with amelioration of depression.|For more Mechanism of Action (Complete) data for Clomipramine (10 total), please visit the HSDB record page.

N-[3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-t-yl)propyl]-N,N',N'-trimethylpropane-1,3-diamine|3-(3-chloro-5H-dibenzo[b,f]azepin-5-yl]-N,N-dimethylpropan-1-amine|3-(3,7-dichloro-10,11-dihydro-5H-dibenzol[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine|3-chloro-5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine|For more Impurities (Complete) data for Clomipramine (11 total), please visit the HSDB record page.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ ... Four clomipramine-treated breastfeeding mother-infant pairs were assessed for serum concentrations of clomipramine, N-desmethylclomipramine, and corresponding 8-hydroxymetabolites. Although the mothers exhibited a wide range of serum concentrations, the parent drug and metabolites were either nondetectable or below the quantifiable limit in the sera of all infants. No adverse clinical effects were observed. ...|/SIGNS AND SYMPTOMS/ Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. Other CNS manifestations may include drowsiness, stupor, ataxia, restlessness, agitation, delirium, severe perspiration, hyperactive reflexes, muscle rigidity, athetoid and choreiform movements. Cardiac abnormalities may include tachycardia, signs of congestive heart failure, and in very rare cases, cardiac arrest. Respiratory depression, cyanosis, shock, vomiting, hyperpyrexia, mydriasis, and oliguria or anuria may also be present.|/SIGNS AND SYMPTOMS/ Abrupt or gradual discontinuation of tricyclic antidepressants may precipitate withdrawal symptoms. The most common of these are general somatic or gastrointestinal distress, anxiety and agitation, sleep disturbance, akathisia, parkinsonism, paradoxical behavioral activation and mania. There are very few reports of withdrawal reactions following discontinuation of clomipramine ...|/CASE REPORTS/ In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with clomipramine either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg. The 10 nonfatal cases involved doses of up to 5000 mg, accompanied by plasma levels of up to 1010 ng/mL. All 10 patients completely recovered.|For more Human Toxicity Excerpts (Complete) data for Clomipramine (25 total), please visit the HSDB record page.

Anafranil

Formulations: (AHFS, 2009)

Analyte: clomipramine hydrochloride; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /clomipramine hydrochloride/|Analyte: clomipramine hydrochloride; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards /clomipramine hydrochloride/|Analyte: clomipramine hydrochloride; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 254 nm and comparison to standards /clomipramine hydrochloride/|Analyte: clomipramine HCl; matrix: pharmaceutical preparation (capsule); procedure: infrared absorption spectrophotometry with comparison to standards (chemical identification) /clomipramine hydrochloride/|For more Analytic Laboratory Methods (Complete) data for Clomipramine (9 total), please visit the HSDB record page.

Analyte: clomipramine hydrochloride; matrix: pharmaceutical preparation; procedure: high-performance liquid chromatography with electrochemical detection|Analyte: clomipramine hydrochloride; matrix: pharmaceutical preparation; procedure: capillary electrophoresis with ultraviolet detection at 254 nm|Analyte: clomipramine hydrochloride; matrix: blood (whole), urine; procedure: high-performance liquid chromatography with UV detection at 200.5 nm and comparison to standards (chemical identification)|Analyte: clomipramine hydrochloride; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 226 nm, 254 nm, 400 nm; limit of quantitation: 7 ng/mL (UV 226 nm, UV 400 nm); 10 ng/mL (UV 254 nm)|Analyte: clomipramine hydrochloride; matrix: blood (serum), tissue (brain, liver), urine; procedure: high-performance liquid chromatography with ultraviolet detection at 254; limit of quantitation: 50 ng/mL (serum, urine); 500 ng/mL (tissue)

Veterinary drugs -> Clomicalm -> EMA Drug Category|Psychoanaleptics -> Veterinary pharmacotherapeutic group|Pharmaceuticals