Norpramin

The usual adult dose is 100-200 mg at bedtime or divided every 12 hours. The maximum dose is 300 mg daily.

Frequency Not Defined

Common

• Fatigue
• Lethargy
• Sedation
• Weakness
• Constipation
• Dry mouth
• Blurred vision

Less Common

• Agitation
• Anxiety
• Headache
• Insomnia
• Nausea
• Vomiting
• Sweating

Infrequent

• ECG changes, orthostatic hypotension, tachycardia
• Confusion, dizziness, paresthesia
• Extrapyramidal symptoms
• Rash
• Elevated LFTs
• Sexual dysfunction
• Tinnitus

Rare

• Seizure
• Agranulocytosis
• Eosinophilia
• Leukopenia
• Thrombocytopenia
• SIADH

Norpramin is a prescription medication used to treat the symptoms of depression. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Norpramin falls into category C. Safe use of Norpramin during pregnancy and lactation has not been established; therefore, if it is to be given to pregnant patients, nursing mothers, or women of childbearing potential, the possible benefits must be weighed against the possible hazards to mother and child. Animal reproductive studies have been inconclusive.

Taking this medicine with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking desipramine with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor if you have used an "SSRI" antidepressant in the past 5 weeks, such as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, or vilazodone.

You must wait at least 5 weeks after stopping fluoxetine (Prozac) before you can take desipramine.

Many drugs can interact with desipramine. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

• any other antidepressant;

• St. John's wort;

• tryptophan (sometimes called L-tryptophan);

• medicine to treat mood disorders, thought disorders, or mental illness--buspirone, lithium, and many others;

• migraine headache medicine--rizatriptan, sumatriptan, zolmitriptan, and others; or

• narcotic pain medicine--fentanyl, tramadol.

This list is not complete and many other drugs can interact with desipramine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Major Depressive Disorder

Management of major depressive disorder.104

Results of several studies of TCAs in preadolescent and adolescent patients with major depression indicate lack of overall efficacy in this age group.

Panic Disorder

Has been used for the management of panic disorder† with or without agoraphobia†.a

Eating Disorders

Has been used for the management of eating disorders† (e.g., bulimia†, anorexia nervosa†) with equivocal results; avoid use in underweight individuals and in those exhibiting suicidal ideation.a

Bipolar Disorder

Has been used for the short-term management of acute depressive episodes in bipolar disorder†.a b

TCAs associated with a greater risk of precipitating hypomania or manic episodes than other classes of antidepressants;a b should always be used in combination with a mood stabilizer (e.g., lithium).b

Schizophrenia

Has been used for the management of acute depressive episodes (in combination with an antipsychotic) in patients with schizophrenia†.a

Postherpetic Neuralgia

Among the drugs of choice for the symptomatic treatment of postherpetic neuralgia†.a

Insomnia

Less effective for insomnia† and associated with more serious adverse reactions than conventional hypnotics.a

Attention Deficit Hyperactivity Disorder (ADHD)

Not recommended for use in children with ADHD†.101 102 103 (See Pediatric Use under Cautions.)

It is very important that your doctor check your progress at regular visits to allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

For some teenagers and young adults, this medicine can increase thoughts of suicide. Tell your doctor right away if you start to feel more depressed and have thoughts about hurting yourself. Report any unusual thoughts or behaviors that trouble you, especially if they are new or are getting worse quickly. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Do not take desipramine with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]). Do not start taking desipramine during the 2 weeks after you stop a MAO inhibitor and wait 2 weeks after stopping desipramine 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 intestinal symptoms, a sudden high body temperature, an extremely high blood pressure, or severe convulsions.

Desipramine may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use desipramine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), linezolid (Zyvox®), lithium (Eskalith®, Lithobid®), methylene blue, 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 desipramine.

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

This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants (medicines that cause drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies or colds, sedatives, tranquilizers, or sleeping medicines, prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

This medicine may raise or lower your blood sugar. If you are diabetic and notice a change in the results of your blood or urine sugar tests, check with your doctor.

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

Check with your doctor immediately if you have vision changes, such as blurred vision, difficulty reading, or eye pain, during or after treatment. This could be a sign of a serious eye problem.

This medicine may cause some people to become 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 drowsy or not alert.

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 (eg, St. John's wort) or vitamin supplements.

• It is used to treat low mood (depression).
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Norpramin affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• It may take a few weeks to see the full effect.
• If you have been taking this medicine for many weeks, talk with your doctor before stopping. You may want to slowly stop Norpramin.
• You may have some heart tests before starting this medicine. Talk with your doctor.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• Some people may have a higher chance of eye problems with Norpramin. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
• An unsafe heartbeat that is not normal (long QT on ECG) has happened with this medicine. Sudden deaths have rarely happened in people taking Norpramin. Talk with the doctor.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Norpramin (desipramine) while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Norpramin is indicated for the treatment of depression.

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Norpramin and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions” is available for Norpramin. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Norpramin.

Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

Patients should be advised that taking Norpramin can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS-Clinical Worsening and Suicide Risk). Therefore, Norpramin (desipramine hydrochloride) is not recommended for use in children.

Anyone considering the use of Norpramin in a child or adolescent must balance the potential risks with the clinical need (see also ADVERSE REACTIONS-Cardiovascular).

General

It is important that this drug be dispensed in the least possible quantities to depressed outpatients, since suicide has been accomplished with this class of drug (see WARNINGS-Clinical Worsening and Suicide Risk). Ordinary prudence requires that children not have access to this drug or to potent drugs of any kind; if possible, this drug should be dispensed in containers with child-resistant safety closures. Storage of this drug in the home must be supervised responsibly.

If serious adverse effects occur, dosage should be reduced or treatment should be altered.

Norpramin therapy in patients with manic-depressive illness may induce a hypomanic state after the depressive phase terminates.

The drug may cause exacerbation of psychosis in schizophrenic patients.

Both elevation and lowering of blood sugar levels have been reported.

Leukocyte and differential counts should be performed in any patient who develops fever and sore throat during therapy; the drug should be discontinued if there is evidence of pathologic neutrophil depression.

Clinical experience in the concurrent administration of ECT and antidepressant drugs is limited. Thus, if such treatment is essential, the possibility of increased risk relative to benefits should be considered.

This drug should be discontinued as soon as possible prior to elective surgery because of possible cardiovascular effects. Hypertensive episodes have been observed during surgery in patients taking desipramine hydrochloride.

Drug Interactions

Drugs Metabolized by P450 2D6.

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

Close supervision and careful adjustment of dosage are required when this drug is given concomitantly with anticholinergic or sympathomimetic drugs.

Patients should be warned that while taking this drug their response to alcoholic beverages may be exaggerated.

If Norpramin is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of Norpramin and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive. Both the sedative and anticholinergic effects of the major tranquilizers are also additive to those of Norpramin.

Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) and serotonergic drugs may potentially cause life threatening adverse events (See CONTRAINDICATIONS, WARNINGS, and DOSAGE AND ADMINISTRATION).

Included in the following listing are a few adverse reactions that have not been reported with this specific drug. However, the pharmacologic similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when Norpramin is given.

Cardiovascular:

Hypotension, hypertension, palpitations, heart block, myocardial infarction, stroke, arrhythmias, premature ventricular contractions, tachycardia, ventricular tachycardia, ventricular fibrillation, sudden death

There has been a report of an "acute collapse" and "sudden death" in an 8-year-old (18 kg) male, treated for 2 years for hyperactivity.

There have been additional reports of sudden death in children. (See PRECAUTIONS-Pediatric Use)

Psychiatric:

Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis

Neurologic:

Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures; alterations in EEG patterns; tinnitus

Symptoms attributed to Neuroleptic Malignant Syndrome have been reported during desipramine use with and without concomitant neuroleptic therapy.

Anticholinergic:

Dry mouth, and rarely associated sublingual adenitis; blurred vision, disturbance of accommodation, mydriasis, increased intraocular pressure; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of urinary tract

Allergic:

Skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight), edema (of face and tongue or general), drug fever, cross-sensitivity with other tricyclic drugs

Hematologic:

Bone marrow depressions including agranulocytosis, eosinophilia, purpura, thrombocytopenia

Gastrointestinal:

Anorexia, nausea and vomiting, epigastric distress, peculiar taste, abdominal cramps, diarrhea, stomatitis, black tongue, hepatitis, jaundice (simulating obstructive), altered liver function, elevated liver function tests, increased pancreatic enzymes

Endocrine:

Gynecomastia in the male, breast enlargement and galactorrhea in the female; increased or decreased libido, impotence, painful ejaculation, testicular swelling; elevation or depression of blood sugar levels; syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Other:

Weight gain or loss; perspiration, flushing; urinary frequency, nocturia; parotid swelling; drowsiness, dizziness, proneness to falling, weakness and fatigue, headache; fever; alopecia; elevated alkaline phosphatase

Withdrawal Symptoms:

Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.

Applies to desipramine: oral tablet

Along with its needed effects, desipramine (the active ingredient contained in Norpramin) 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 while taking desipramine:

• Abdominal or stomach pain
• anxiety
• black, tarry stools
• blurred or double vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain or discomfort
• confusion about identity, place, and time
• convulsions
• cough or hoarseness
• dark urine
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• fainting
• fast, irregular, pounding, or racing heartbeat or pulse
• inability to move the arms, legs, or facial muscles
• inability to speak
• irritability
• light-colored stools
• lightheadedness
• loss of appetite
• loss of bladder control
• muscle spasms or jerking of all extremities
• nausea
• nightmares
• pain or discomfort in the arms, jaw, back, or neck
• painful or difficult urination
• pinpoint red or purple spots on the skin
• pounding in the ears
• rash
• restlessness
• seeing, hearing, or feeling things that are not there
• shakiness and unsteady walk
• slow speech
• sore throat and fever
• sores, ulcers, or white spots on the lips or in the mouth
• stiffness of the limbs
• sudden loss of consciousness
• sweating
• swelling
• swollen glands
• talking, feeling, and acting with excitement
• trouble sleeping
• twisting body movements
• unsteadiness, trembling, or problems with muscle control or coordination
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• yellow eyes and skin

Some side effects of desipramine 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:

• Abdominal or stomach cramps
• bigger, dilated, or enlarged pupils (black part of the eye)
• bloating
• constipation
• decrease in the frequency of urination
• decrease in urine volume
• decreased interest in sexual intercourse
• diarrhea
• difficulty in passing urine (dribbling)
• hair loss or thinning of the hair
• inability to have or keep an erection
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse
• increased sensitivity of the eyes to light
• loss in sexual ability, desire, drive, or performance
• painful urination
• swelling of the breasts or breast soreness in both females and males
• swelling or inflammation of the mouth
• unexpected or excess milk flow from breasts in females