Anafranil

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. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. 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 such as dizziness, nausea, vomiting, headache, weakness, sleep problems, fever, and irritability. Your doctor probably will decrease your dose gradually.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Anafranil is part of the drug class:

• Non selective monoamine reuptake inhibitors

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate)
• 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)
• linezolid (Zyvox)
• medications for nausea, dizziness, or mental illness
• methylene blue
• 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)

This is not a complete list of Anafranil drug interactions. Ask your doctor or pharmacist for more information.

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 hydrochloride 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 is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of clomipramine can be fatal.

Overdose symptoms may include vomiting, fast or uneven heart rate, loss of balance or coordination, extreme drowsiness, fever, severe sweating, stiff muscles, increased or decreased urination, blue lips or fingernails, weak or shallow breathing, fainting, seizure (convulsions) or coma.

• Mechanism of action in the management of OCD unknown but may involve inhibition of reuptake of serotonin.1 2 3 213 214 220

• Desmethylclomipramine inhibits norepinephrine reuptake;2 3 4 48 212 213 214 220 221 235 therefore, clomipramine also shares pharmacologic profile of other tricyclic antidepressants.235 238

• Exhibits marked anticholinergic activity, which may account for 3 4 288 289 sedation,1 65 238 242 adverse cardiovascular effects,1 2 193 222 235 339 and reduced seizure threshold (particularly at relatively high dosages).1 210

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to check for any unwanted effects. Blood tests may be needed to check for unwanted effects.

Clomipramine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some children, teenagers, and young adults to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you or your child have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you, or your caregiver notice any of these side effects, tell your doctor right away. Let the doctor know if you, your child, or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Do not take clomipramine with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], linezolid (Zyvox®), methylene blue, phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]). Do not start taking clomipramine during the 2 weeks after you stop a MAO inhibitor. Wait for 2 weeks after stopping clomipramine before you start taking a MAO inhibitor. If you take them together or do not wait 2 weeks, you may develop confusion, agitation, restlessness, stomach or bowel symptoms, a sudden high body temperature, an extremely high blood pressure, or severe convulsions.

Clomipramine may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use clomipramine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), lithium (Eskalith®, Lithobid®), tryptophan, St. John's wort, or some pain or migraine medicines (eg, sumatriptan, tramadol, Frova®, Maxalt®, Relpax®, Zomig®). Check with your doctor first before taking any other medicines with clomipramine.

This medicine may cause some people to become dizzy, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy, drowsy, or not alert.

Check with your doctor right away if you have a fever, chills, cough, sore throat, swollen, painful, or tender lymph glands in the neck, armpit, or groin, or yellow skin or eyes while using this medicine. These could be symptoms of a serious condition called drug reaction with eosinophilia and systemic symptoms (DRESS).

Clomipramine may lower the number of some types of blood cells in your body. Because of this, you may bleed or get infections more easily. To help with these problems, avoid being near people who are sick or have infections. Wash your hands often. Stay away from rough sports or other situations where you could be bruised, cut, or injured. Brush and floss your teeth gently. Be careful when using sharp objects, including razors and fingernail clippers.

Check with your doctor before using this medicine with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with clomipramine may worsen the side effects of this medicine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.

This medicine may cause men to have problems with sex. Check with your doctor if you are having an abnormal ejaculation or decreased sexual performance or desire.

Weight changes may occur during treatment with this medicine. Talk with your doctor if this is a concern for you.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are using this medicine. Taking clomipramine together with medicines used during surgery or emergency treatment may increase the risk of side effects.

Do not stop taking this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent possible worsening of your condition and reduce the possibility of withdrawal symptoms such as dizziness, headache, nausea, vomiting, trouble sleeping, irritability, high fever, or a general feeling of discomfort or illness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bladder pain
• bloody or cloudy urine
• blurred vision
• body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• confusion
• difficult, burning, or painful urination
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• excessive muscle tone
• fear or nervousness
• feeling sad or empty
• fever
• hearing changes
• irritability
• lower back or side pain
• muscle stiffness, tension, or tightness
• poor concentration
• rhythmic movement of muscles
• sneezing
• tightness of the chest
• trouble breathing
• unusual tiredness or weakness
• voice changes

• Anger that is hard to control
• breast enlargement
• burning feeling while urinating
• changes in vision
• chills
• decrease in the frequency of urination
• difficulty in passing urine (dribbling)
• difficulty in speaking
• dry mouth
• fast, irregular, pounding, or racing heartbeat or pulse
• headache, severe and throbbing
• hyperventilation
• irregular heartbeats
• irritability
• nausea or vomiting
• numbness, tingling, pain, or weakness in the hands or feet
• pain during sexual intercourse
• panic attacks
• paranoia
• rapidly changing moods
• restlessness
• shaking
• swelling of the face, fingers, feet, or lower legs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blistering, crusting, irritation, itching, or reddening of the skin
• change in taste
• constipation
• cracked, dry, or scaly skin
• change in interest in sexual intercourse
• diarrhea
• dry skin
• heartburn
• hives or welts, skin rash
• inability to have or keep an erection
• increased interest in sexual intercourse
• joint pain
• pimples
• redness of the face, neck, arms, and occasionally, upper chest
• shakiness in the legs, arms, hands, or feet
• stomach discomfort, upset, or pain
• swelling
• swollen joints
• trembling or shaking of the hands or feet

• Absent, missed, or irregular menstrual periods
• breast pain
• sores, ulcers, or white spots on the lips or tongue or inside the mouth

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Anafranil™ (clomipramine hydrochloride) Capsules USP is 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.

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.

The effectiveness of Anafranil for the treatment of OCD was demonstrated in multicenter, placebo-controlled, parallel-group studies, including two 10-week studies in adults and one 8-week study in children and adolescents 10 to 17 years of age. Patients in all studies had moderate-to-severe OCD (DSM-III), with mean baseline ratings on the Yale-Brown Obsessive Compulsive Scale (YBOCS) ranging from 26 to 28 and a mean baseline rating of 10 on the NIMH Clinical Global Obsessive Compulsive Scale (NIMH-OC). Patients taking CMI experienced a mean reduction of approximately 10 on the YBOCS, representing an average improvement on this scale of 35% to 42% among adults and 37% among children and adolescents. CMI-treated patients experienced a 3.5 unit decrement on the NIMH-OC. Patients on placebo showed no important clinical response on either scale. The maximum dose was 250 mg/day for most adults and 3 mg/kg/day (up to 200 mg) for all children and adolescents.

The effectiveness of Anafranil for long-term use (i.e., for more than 10 weeks) has not been systematically evaluated in placebo-controlled trials. The physician who elects to use Anafranil for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Pregnancy Category: C

Lactation: distributed in breast milk, do not nurse (AAP states effect on nursing infants is unknown but may be of concern)

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.