Clomipramine

What is Clomipramine?

• Clomipramine (Anafrani), is an antiobsessional drug that belongs to the class (dibenzazepine) of pharmacologic agents known as tricyclic antidepressants.

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Clomipramine

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What are the uses of this medicine?

• Clomipramine (Anafrani), is used for the treatment of obsessions and compulsions in patients with Obsessive-Compulsive Disorder (OCD).
• Obsessions are recurrent, persistent ideas, thoughts, images, or impulses that are ego-dystonic.
• Compulsions are repetitive, purposeful, and intentional behaviors performed in response to an obsession or in a stereotyped fashion, and are recognized by the person as excessive or unreasonable.

How does this medicine work?

• Clomipramine (kloe mip' ra meen) is a dibenzazepine derived tricyclic antidepressant which acts by inhibition of serotonin reuptake within synaptic clefts in the central nervous system, thus increasing brain serotonin levels. Clomipramine also has some blocking activity at postsynaptic dopamine receptors.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• with a history of hypersensitivity to clomipramine or other tricyclic antidepressants.
• with a monoamine oxidase (MAO) inhibitor.

• Clomipramine cannot be used during the acute recovery period after a myocardial infarction.

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Be sure to mention any of the following:

• other tricyclic antidepressants such as amitriptyline (Elavil), amoxapine (Asendin), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil).
• monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate). If you stop taking clomipramine, you should wait at least 14 days before you start to take an MAO inhibitor.
• anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); benztropine (Cogentin)
• cimetidine (Tagamet)
• clonidine (Catapres)
• dicyclomine (Bentyl)
• digoxin (Lanoxin)
• disulfiram
• flecainide (Tambocor)
• guanethidine (Ismelin)
• haloperidol (Haldol)
• levodopa (Sinemet, Dopar)
• medications for nausea, dizziness, or mental illness
• methylphenidate (Concerta, Metadate, Ritalin)
• oral contraceptives
• phenobarbital
• phenytoin
• propafenone (Rythmol)
• quinidine
• secobarbital (Seconal)
• sedatives
• selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac, Sarafem), sertraline (Zoloft), and paroxetine (Paxil)
• tranquilizers
• trihexyphenidyl (Artane)

Is this medicine FDA approved?

• Clomipramine is used in the therapy of obsessive-compulsive disorder and was approved for this indication in the United States in 1989.

How should this medicine be used?

Recommended dosage: Initial Treatment/Dose Adjustment (Adults):

• Treatment with clomipramine should be initiated at a dosage of 25 mg daily and gradually increased, as tolerated, to approximately 100 mg during the first 2 weeks.
• During initial titration, clomipramine should be given in divided doses with meals to reduce gastrointestinal side effects. Thereafter, the dosage may be increased gradually over the next several weeks, up to a maximum of 250 mg daily.

Initial Treatment/Dose Adjustment (Children and Adolescents):

• As with adults, the starting dose is 25 mg daily and should be gradually increased (also given in divided doses with meals to reduce gastrointestinal side effects) during the first 2 weeks, as tolerated, up to a daily maximum of 3 mg/kg or 100 mg, whichever is smaller.
• Thereafter, the dosage may be increased gradually over the next several weeks up to a daily maximum of 3 mg/kg or 200 mg.

Administration:

• Clomipramine comes as a capsule to take by mouth. At the beginning of treatment, clomipramine is usually taken three times a day with meals as the body adjusts to the medication. After several weeks of treatment, clomipramine is usually taken once a day at bedtime.
• Take clomipramine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
• Your doctor may start you on a low dose of clomipramine and gradually increase your dose.
• It may take several weeks or longer for you to feel the full benefit of clomipramine.
• Continue to take clomipramine even if you feel well.
• Do not stop taking clomipramine without talking to your doctor.
• If you suddenly stop taking clomipramine, you may experience withdrawal symptoms.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As capsules of 25, 50 and 75 mg for oral administration.

This medicine is available in fallowing brand namesː

• Anafrani

What side effects can this medication cause?

The most common side effects of this medicine may include:

• dry mouth
• constipation
• nausea
• dyspepsia
• anorexia
• nervous system complaints, including somnolence, tremor, dizziness, nervousness, and myoclonus
• genitourinary complaints, including changed libido, ejaculatory failure, impotence, and micturition disorder
• other miscellaneous complaints, including fatigue, sweating, increased appetite, weight gain, and visual changes

Less common, but serious side effects may include:

• Suicide
• Cardiovascular Effects
• Psychosis, Confusion, And Other Neuropsychiatric Phenomena
• Mania/Hypomania
• Hepatic Changes
• Hematologic Changes
• Central Nervous System Effects
• Sexual Dysfunction
• Weight Changes
• Withdrawal Symptoms

What special precautions should I follow?

• Since depression is a commonly associated feature of OCD, the risk of suicide must be considered.
• Caution is necessary in treating patients with known cardiovascular disease, and gradual dose titration is recommended.
• Patients treated with clomipramine have been reported to show a variety of neuropsychiatric signs and symptoms including delusions, hallucinations, psychotic episodes, confusion, and paranoia.
• Activation of mania or hypomania has also been reported in a small proportion of patients with affective disorder treated with marketed tricyclic antidepressants, which are closely related to clomipramine.
• clomipramine was occasionally associated with elevations in SGOT and SGPT. Caution is indicated in treating patients with known liver disease, and periodic monitoring of hepatic enzyme levels is recommended in such patients.
• Postmarketing reports of leukopenia, agranulocytosis, thrombocytopenia, anemia, and pancytopenia in association with clomipramine hydrochloride capsules USP use. As is the case with tricyclic antidepressants to which clomipramine is closely related, leukocyte and differential blood counts should be obtained in patients who develop fever and sore throat during treatment with clomipramine.
• When clomipramine and a neuroleptic were used concomitantly, the cases were sometimes considered to be examples of a neuroleptic malignant syndrome.
• The rate of sexual dysfunction in male patients with OCD who were treated with clomipramine in the premarketing experience was markedly increased.
• Weight gain was reported in patients receiving clomipramine.
• As with closely related tricyclic antidepressants, concurrent administration of clomipramine with electroconvulsive therapy may increase the risks.
• Prior to elective surgery with general anesthetics, therapy with clomipramine should be discontinued.
• As with closely related tricyclic antidepressants, clomipramine should be used with caution in the following:
• (1)Hyperthyroid patients or patients receiving thyroid medication, because of the possibility of cardiac toxicity;
• (2)Patients with increased intraocular pressure, a history of narrow-angle glaucoma, or urinary retention, because of the anticholinergic properties of the drug;
• (3)Patients with tumors of the adrenal medulla (e.g., pheochromocytoma, neuroblastoma) in whom the drug may provoke hypertensive crises;
• (4)Patients with significantly impaired renal function.
• A variety of withdrawal symptoms have been reported in association with abrupt discontinuation of clomipramine. It is recommended that the dosage be tapered gradually and the patient monitored carefully during discontinuation
• Clomipramine can cause mild and transient serum enzyme elevations and is rare cause of clinically apparent acute liver injury.
• Clomipramine hydrochloride capsules USP has been found in human milk.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma.
• Other CNS manifestations may include drowsiness, stupor, ataxia, restlessness, agitation, delirium, severe perspiration, hyperactive reflexes, muscle rigidity and 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.

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary.
• If signs of toxicity occur at any time during this period, extended monitoring is required.
• All patients suspected of tricyclic overdose should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by activated charcoal.
• Emesis is contraindicated.
• Intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used.
• Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium, or phenytoin.
• Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).
• Hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic poisoning.
• Seizures should be controlled with benzodiazepines, or if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms.
• Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Can this medicine be used in pregnancy?

• Pregnancy Category C.
• There are no adequate or well-controlled studies in pregnant women.
• Withdrawal symptoms, including jitteriness, tremor, and seizures, have been reported in neonates whose mothers had taken clomipramine until delivery.
• Clomipramine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Can this medicine be used in children?

• Safety and effectiveness in the pediatric population other than pediatric patients with OCD have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• Clomipramine Hydrochloride

Inactive ingredients:

• Gelatin
• Magnesium Stearate
• Silicon Dioxide
• Titanium Dioxide
• Ferric Oxide Yellow
• Starch, Corn

Who manufactures and distributes this medicine?

• Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel
• Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY

What should I know about storage and disposal of this medication?

• Store at 20°-25°C (68°-77°F).
• Dispense in well-closed containers with a child-resistant closure.
• Protect from moisture.
• Dispense in tight container (USP).

• Dailymed label info on Clomipramine
• FDA Clomipramine

Clomipramine Resources
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The following are antidepressant subclasses and drugs

MAO Inhibitors Isocarboxazid, Phenelzine, Tranylcypromine

SNRIs Duloxetine, Levomilnacipran, Venlafaxine

SSRIs Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Vilazodone, Vortioxetine

Tricyclics Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine

Miscellaneous Bupropion, Flibanserin, Mirtazapine, Nefazodone, Trazodone