دسیپرامین
Desipramine Hydrochloride (Norpramin)
دسیپرامین

نام ژنریک

Desipramine Hcl

شکل دارویی

اشكال دارويي:


Tablet: 25mg

موارد مصرف

موارد و مقدار مصرف


افسردگي


بزرگسالان: روزانه mg 200-100 خوراكي در دوزهاي منقسم مصرف مي‌شود و حداكثر تا دوز mg 300 افزايش مي‌يابد. مي‌توان كل دوز روزانه را هر شب تجويز نمود.


سالمندان و نوجوانان- روزانه mg 100-25 خوراكي كه به تدريج تا حداكثر دوز mg 100 (حداكثر دوز mg 150 در حالات بسيار شديد) افزايش مي‌يابد.


مكانيسم اثر


اثر ضد افسردگي: اين دارو با مهار برداشت مجدد نور اپي‌نفرين و سروتونين در انتهاهاي عصبي CNS (نورون‌هاي پيش سيناپسي )، باعث افزايش غلظت اين ناقل‌ها در شكاف‌هاي سيناپسي مي‌شود. دزي پرامين، برداشت نور اپي‌نفرين را بيش از سروتونين مهار مي‌كند. اثرات آرام بخشي، آنتي كولينرژيك و كاهنده فشار خون اين دارو كمتر از پيش داروي آن (ايمي پرامين) مي‌باشد.

موارد منع مصرف

تداخل دارويي


1- دارو-دارو : مصرف همزمان دزي پرامين با داروهاي ضد آريتمي، پيموزايد، و هورمون‌هاي تيروئيد، ممكن است خطر آريتمي‌هاي قلبي و ناهنجاري‌هاي هدايتي قلب را افزايش دهد.


- باربيتوراتها ممكن است متابوليسم دزي پرامين را افزايش و اثر آن را كاهش دهند.


- بتابلوكرها، سايمتيدين، ضدبارداري‌هاي هورموني، و متيل فنيدات ممكن است متابوليسم دزي پرامين را مهار نموده و سطح آن را افزايش دهند.


- مصرف همزمان دزي پرامين با كلونيدين، كنترل فشار خون را مختل نموده و خطر افزايش فشار خون وخيم را افزايش مي‌دهد.


- داروهايي كه با واسطه CYP2D6 متابوليزه مي‌شوند، مثل ديگر ضد افسردگي‌ها، كاربامازپين، فنوتيازين‌ها و ضد آريتمي‌هاي كلاس 1C (مثل فلكائينيد و پروپافنون )، ممكن است سطح سرمي دزي پرامين را افزايش دهند.


- فلوكستين، فلووكسامين، پاروكستين و سرترالين ممكن است سطح دزي پرامين را افزايش دهند.


- مهاركننده‌هاي MAO ممكن است در مصرف همزمان با دزي پرامين ، باعث تحريك شديد CNS، هايپرپيركسي و تشنج شوند. از مصرف همزمان خودداري شود.


- كينولون‌ها (مثل سيپروفلوكساسين) ممكن است ريسك آريتمي‌هاي خطرناك را افزايش دهند.


- مصرف همزمان دزي پرامين با وارفارين ممكن است PT و INR و ريسك خونريزي را افزايش دهد.


2- دارو- گياه: مصرف همزمان دزي پرامين با روغن گل مغربي (evening primrose oil) ممكن است باعث تشنج شود.


3- دارو- شيوه زندگي: مصرف سيگار با كاهش سطح دزي پرامين، اثر آن را كاهش مي‌دهد.


قرار گرفتن در معرض نور آفتاب، خطر حساسيت به نور را به همراه دارد.


اثر بر آزمايشهاي تشخيصي


- ممكن است سطح گلوكز خون را افزايش يا كاهش دهد.


- ممكن است سطح تست‌هاي عملكرد كبدي را افزايش و شمارش WBC را كاهش دهد.

موارد قابل توجه

-

تداخل دارویی

عوارض جانبي


اعصاب مركزي: بي‌قراري ، اضطراب، گيجي، گيجي، تحريك پذيري، سردرد، عصبانيت، احساس ناراحتي، لرزش، ضعف، تغييرات EEG، واكنشهاي اكستراپيراميدال، تشنج.


قلبي- عروقي: افت فشار خون وضعيتي ، تاكيكاردي، تغييرات ECG، افزايش فشار خون.


دستگاه گوارش: بي‌اشتهايي، يبوست، خشكي دهان، تهوع، ايلئوس فلجي، استفراغ.


چشم: تاري ديد، ميدرياز.


گوش: وزوز گوش.


ادراري- تناسلي: احتباس ادراري.


متابوليك: هايپرگليسمي، هايپوگليسمي.


پوست: عرق سرد، حساسيت به نور، راش، كهير.


ساير عوارض: واكنشهاي ازدياد حساسيت.


پس از قطع ناگهاني درمان طولاني‌مدت: سردرد، ناخوشي، تهوع.


مسموميت و درمان


علائم- 12 ساعت اول مسموميت حاد ، فاز تحريكي است كه با فعاليت بيش از حد آنتي كولينرژيكي (بي قراري، تحريك، گيجي، توهم، علائم پاركينسوني، هايپرترمي، تشنج، احتباس ادراري، خشكي غشاهاي مخاطي، گشادي مردمك‌ها، يبوست و ايلئوس) همراه است و با فاز مهاري CNS شامل هايپوترمي ، كاهش يا حذف رفلكس‌ها، خواب آلودگي، افت فشار خون، سيانوز، و نامنظم شدن ضربان قلب (تاكيكاردي، اختلالات هدايتي و اثرات شبه كينيدين روي ECG) دنبال مي‌شود.


شدت مسموميت با پهن شدن كمپلكس QRS مشخص مي‌شود كه معمولاً نشان دهنده سطح سرمي بيش از ng/ml 1000 است. عموماً سطح سرمي كمك كننده نيست. به دنبال افت فشار، افت ونتيلاسيون و تشنج ممكن است اسيدوز متابوليك بروز نمايد.


درمان: درمان علامتي و حمايتي است؛ حفظ راه هوايي، تنظيم دماي بدن و حفظ تعادل آب و الكتروليت‌ها بسيار مهم است. القاي استفراغ ممنوع است. مي‌توان اقدام به شستشوي معده و تجويز ذغال فعال نمود. دياليز اثر كمي دارد. بدون توجه به مقدار مصرف شده، بيمار از هر لحاظ بايد پايش شود.


فيزوستيگمين ممكن است با احتياط براي تصحيح اختلالات قلبي عروقي يا كوما به كار رود ، هرچند كه تجويز بسيار سريع آن مي‌تواند منجر به تشنج شود. تشنج را با ديازپام يا فني‌توئين تزريقي، آريتمي را با فني توئين يا ليدوكائين تزريقي و اسيدوز را با بيكربنات سديم بايد درمان نمود. همچنين آريتمي‌ها و افت فشار خون را مي‌توان با بيكربنات سديم، مايعات يا وازوپرسورها درمان نمود. باربيتورات‌ها را نبايد تجويز نمود، زيرا اين داروها ممكن است اثرات تضعيف تنفسي و عصبي را تشديد نمايند.

مکانیزم اثر

عوارض جانبي


اعصاب مركزي: بي‌قراري ، اضطراب، گيجي، گيجي، تحريك پذيري، سردرد، عصبانيت، احساس ناراحتي، لرزش، ضعف، تغييرات EEG، واكنشهاي اكستراپيراميدال، تشنج.


قلبي- عروقي: افت فشار خون وضعيتي ، تاكيكاردي، تغييرات ECG، افزايش فشار خون.


دستگاه گوارش: بي‌اشتهايي، يبوست، خشكي دهان، تهوع، ايلئوس فلجي، استفراغ.


چشم: تاري ديد، ميدرياز.


گوش: وزوز گوش.


ادراري- تناسلي: احتباس ادراري.


متابوليك: هايپرگليسمي، هايپوگليسمي.


پوست: عرق سرد، حساسيت به نور، راش، كهير.


ساير عوارض: واكنشهاي ازدياد حساسيت.


پس از قطع ناگهاني درمان طولاني‌مدت: سردرد، ناخوشي، تهوع.


مسموميت و درمان


علائم- 12 ساعت اول مسموميت حاد ، فاز تحريكي است كه با فعاليت بيش از حد آنتي كولينرژيكي (بي قراري، تحريك، گيجي، توهم، علائم پاركينسوني، هايپرترمي، تشنج، احتباس ادراري، خشكي غشاهاي مخاطي، گشادي مردمك‌ها، يبوست و ايلئوس) همراه است و با فاز مهاري CNS شامل هايپوترمي ، كاهش يا حذف رفلكس‌ها، خواب آلودگي، افت فشار خون، سيانوز، و نامنظم شدن ضربان قلب (تاكيكاردي، اختلالات هدايتي و اثرات شبه كينيدين روي ECG) دنبال مي‌شود.


شدت مسموميت با پهن شدن كمپلكس QRS مشخص مي‌شود كه معمولاً نشان دهنده سطح سرمي بيش از ng/ml 1000 است. عموماً سطح سرمي كمك كننده نيست. به دنبال افت فشار، افت ونتيلاسيون و تشنج ممكن است اسيدوز متابوليك بروز نمايد.


درمان: درمان علامتي و حمايتي است؛ حفظ راه هوايي، تنظيم دماي بدن و حفظ تعادل آب و الكتروليت‌ها بسيار مهم است. القاي استفراغ ممنوع است. مي‌توان اقدام به شستشوي معده و تجويز ذغال فعال نمود. دياليز اثر كمي دارد. بدون توجه به مقدار مصرف شده، بيمار از هر لحاظ بايد پايش شود.


فيزوستيگمين ممكن است با احتياط براي تصحيح اختلالات قلبي عروقي يا كوما به كار رود ، هرچند كه تجويز بسيار سريع آن مي‌تواند منجر به تشنج شود. تشنج را با ديازپام يا فني‌توئين تزريقي، آريتمي را با فني توئين يا ليدوكائين تزريقي و اسيدوز را با بيكربنات سديم بايد درمان نمود. همچنين آريتمي‌ها و افت فشار خون را مي‌توان با بيكربنات سديم، مايعات يا وازوپرسورها درمان نمود. باربيتورات‌ها را نبايد تجويز نمود، زيرا اين داروها ممكن است اثرات تضعيف تنفسي و عصبي را تشديد نمايند.

فارماكوكینتیك

موارد منع مصرف و احتياط


موارد منع مصرف: حساسيت به دارو ، كساني كه طي 14 روز اخير يكي از داروهاي مهاركننده MAO را دريافت كرده‌اند ، بيماراني كه در فاز حاد بهبودي MI هستند. واكنش حساسيت متقاطع ممكن است بين سه‌ حلقه‌ اي‌ هاي دي بنزازپيني رخ دهد.


موارد احتياط: بيماراني كه هورمون‌هاي تيروئيدي دريافت مي‌كنند ، سابقه تشنج، احتباس ادراري، بيماري تيروئيدي يا قلبي- عروقي، گلوكوم، بيماران افسرده با افكار خودكشي. براي اين بيماران در هر بار ويزيت بايد مقادير كمي تجويز شود.

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: ضدافسردگي سه حلقه‌اي دي بنزازپين.


طبقه‌بندي درماني: ضد افسردگي.


طبقه‌بندي مصرف در بارداري: رده C


ملاحظات اختصاصي


هشدار: دارو بايد با حداقل تعداد براي بيمار تجويز شود ، زيرا ممكن است به قصد خودكشي مورد استفاده قرار گيرد.


1- پيش از تجويز دزي پرامين، بايد فشار خون در حالت‌هاي ايستاده و نشسته اندازه‌گيري شود تا افت فشار خون وضعيتي، در صورت وجود، آشكار شود.


2- در طول هفته‌هاي اول درمان، نسبت به اثر آرام بخشي اين دارو تحمل ايجاد مي‌شود.


3- علائم عدم تحمل دارو عبارتند از: گيجي، سرگيجه و افت فشار خون وضعيتي. در اين صورت دوز دارو بايد كاهش يابد.


4- اين دارو نبايد بطور ناگهاني قطع شود. قطع مصرف آن بايد تدريجي و طي 3 تا 6 هفته صورت گيرد.


5- اين دارو بايد حداقل 48 ساعت پيش از اعمال جراحي، به طور موقت قطع شود.


6- اين دارو ممكن است باعث القاي هايپومانيا در بيماران مبتلا به اختلال دوقطبي شود.


نكات قابل توصيه به بيمار


1- دارو بايد شب‌ها موقع خواب مصرف شود تا خواب آلودگي هنگام روز به حداقل برسد.


2- اثرات كامل دارو ممكن است تا 4 هفته يا بيشتر پس از شروع درمان ظاهر نشود.


3- براي جلوگيري از سرگيجه و افت فشار وضعيتي، تا 30 دقيقه پس از مصرف دوز دارو، بايد دراز كشيده و از تغيير وضعيت ناگهاني بخصوص هنگام برخاستن از حالت نشسته بايد خودداري نمود.


4- بيمار بايد اثرات غير معمول يا ناخوشايند مثل گيجي، اختلالات حركتي، ضربان سريع قلب، سرگيجه، غش، و اختلال در ادرار كردن را به اطلاع پزشك خود برساند.


5- استفاده از آدامس‌هاي بدون قند و آب نبات يا يخ مي‌تواند به رفع خشكي دهان كمك كند.


6- حفظ مرتب بهداشت دهان و دندان براي جلوگيري از پوسيدگي دندان‌ها بسيار اهميت دارد.


مصرف در سالمندان: سالمندان به عوارض قلبي عروقي و آنتي كولينرژيك دارو حساس ترند.


مصرف در كودكان: مصرف دزي پرامين در كودكان زير 12 سال توصيه نمي‌شود. مرگ ناگهاني در كودكان مصرف كننده گزارش شده است.


مصرف در شيردهي: دارو با غلظتهاي معادل غلظت سرمي مادر، در شير ظاهر مي‌شود. مزايا و مضرات مصرف دارو بايد سنجيده شود.

Desipramine Hydrochloride (Norpramin)

NORPRAMIN®
(desipramine hydrochloride) Tablets USP

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 NORPRAMIN (desipramine 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. NORPRAMIN (desipramine hydrochloride) is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric Use.)

DRUG DESCRIPTION

NORPRAMIN® (desipramine hydrochloride USP) is an antidepressant drug of the tricyclic type, and is chemically: 5H-Dibenz[bflazepine-5-propanamine,10,11-dihydro-A/-methyl-, monohydrochloride.

NORPRAMIN (desipramine hydrochloride) structural formula illustration

Inactive Ingredients

The following inactive ingredients are contained in all dosage strengths: acacia, calcium carbonate, corn starch, D&C Red No. 30 and D&C Yellow No. 10 (except 10 mg and 150 mg), FD&C Blue No. 1 (except 50 mg, 75 mg, and 100 mg), hydrogenated soy oil, iron oxide, light mineral oil, magnesium stearate, mannitol, polyethylene glycol 8000, pregelatinized corn starch, sodium benzoate (except 150 mg), sucrose, talc, titanium dioxide, and other ingredients.

What are the possible side effects of desipramine (Norpramin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have any of these serious side effects:

  • fast,...

Read All Potential Side Effects and See Pictures of Norpramin »

What are the precautions when taking desipramine hydrochloride (Norpramin)?

See also the Warning section.

Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or to other tricyclic antidepressants (e.g., amitriptyline); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have a certain medical condition. Before using this medicine, consult your doctor or pharmacist if you have had: a recent heart attack.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., asthma, chronic bronchitis), certain eye problems (e.g., glaucoma, increased intraocular pressure), diabetes,...

Read All Potential Precautions of Norpramin »

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

NORPRAMIN (desipramine hydrochloride) is indicated for the treatment of depression.

DOSAGE AND ADMINISTRATION

Not recommended for use in children (see WARNINGS).

Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients compared to hospitalized patients, who are closely supervised. Dosage should be initiated at a low level and increased according to clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a period of time and should be at the lowest dose that will maintain remission.

Usual Adult Dose

The usual adult dose is 100 to 200 mg per day. In more severely ill patients, dosage may be further increased gradually to 300 mg/day if necessary. Dosages above 300 mg/day are not recommended. Dosage should be initiated at a lower level and increased according to tolerance and clinical response. Treatment of patients requiring as much as 300 mg should generally be initiated in hospitals, where regular visits by the physician, skilled nursing care, and frequent electrocardiograms (ECGs) are available.

The best available evidence of impending toxicity from very high doses of NORPRAMIN (desipramine hydrochloride) is prolongation of the QRS or QT intervals on the ECG. Prolongation of the PR interval is also significant, but less closely correlated with plasma levels. Clinical symptoms of intolerance, especially drowsiness, dizziness, and postural hypotension, should also alert the physician to the need for reduction in dosage. Initial therapy may be administered in divided doses or a single daily dose. Maintenance therapy may be given on a once-daily schedule for patient convenience and compliance.

Adolescent and Geriatric Dose

The usual adolescent and geriatric dose is 25 to 100 mg daily.

Dosage should be initiated at a lower level and increased according to tolerance and clinical response to a usual maximum of 100 mg daily. In more severely ill patients, dosage may be further increased to 150 mg/day. Doses above 150 mg/day are not recommended in these age groups.

Initial therapy may be administered in divided doses or a single daily dose.

Maintenance therapy may be given on a once-daily schedule for patient convenience and compliance.

HOW SUPPLIED

10 mg blue coated tablets imprinted 68-7

NDC 0068-0007-01: bottles of 100

25 mg yellow coated tablets imprinted NORPRAMIN (desipramine hydrochloride) 25

NDC 0068-0011-01: bottles of 100

50 mg green coated tablets imprinted NORPRAMIN (desipramine hydrochloride) 50

NDC 0068-0015-01: bottles of 100

75 mg orange coated tablets imprinted NORPRAMIN (desipramine hydrochloride) 75

NDC 0068-0019-01: bottles of 100

100 mg peach coated tablets imprinted NORPRAMIN (desipramine hydrochloride) 100

NDC 0068-0020-01: bottles of 100

150 mg white coated tablets imprinted NORPRAMIN (desipramine hydrochloride) 150

NDC 0068-0021-50: bottles of 50

NORPRAMIN (desipramine hydrochloride) tablets should be stored at room temperature, preferably below 86°F (30°C). Protect from excessive heat. Dispense in tight container.

Rev. October 2009. Mfd for: sanofi-aventis U.S. LLC Bridgewater, NJ 08807 © 2009 sanofi-aventis U.S. LLC

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

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 (desipramine hydrochloride) is given.

Cardiovascular: Hypotension, hypertension, palpitations, heart block, myocardial infarction, stroke, arrhythmias, premature ventricular contractions, tachycardia, ventricular tachycardia, ventricular fibril-lation, 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 reten-tion, 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, thrombocy-topenia

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.

Read the Norpramin (desipramine hydrochloride) Side Effects Center for a complete guide to possible side effects »

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 selective serotonin reuptake inhibitors (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 (desipramine hydrochloride) 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 (desipramine hydrochloride) 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 (desipramine hydrochloride) .

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, 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 trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. 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 with antide-pressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.

Table 1

Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated
  Increases Compared to Placebo
< 18 14 additional cases
18-24 5 additional cases
  Decreases Compared to Placebo
25-64 1 fewer case
>65 6 fewer cases

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for NORPRAMIN (desipramine hydrochloride) should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Screening Patients for Bipolar Disorder

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that NORPRAMIN (desipramine hydrochloride) is not approved for use in treating bipolar depression.

General

Extreme caution should be used when this drug is given in the following situations:

  1. In patients with cardiovascular disease, because of the possibility of conduction defects, arrhythmias, tachycardias, strokes, and acute myocardial infarction.
  2. In patients who have a family history of sudden death, cardiac dysrhythmias, or cardiac conduction disturbances.
  3. In patients with a history of urinary retention or glaucoma, because of the anticholinergic properties of the drug.
  4. In patients with thyroid disease or those taking thyroid medication, because of the possibility of cardiovascular toxicity, including arrhythmias.
  5. In patients with a history of seizure disorder, because this drug has been shown to lower the seizure threshold. Seizures precede cardiac dysrhythmias and death in some patients. This drug is capable of blocking the antihypertensive effect of guanethidine and similarly acting compounds.

The patient should be cautioned that this drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. In patients who may use alcohol excessively it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage.

Use in Pregnancy

Safe use of NORPRAMIN (desipramine hydrochloride) 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.

Geriatric Use

Clinical studies of NORPRAMIN (desipramine hydrochloride) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Lower doses are recommended for elderly patients. (See DOSAGE AND ADMINISTRATION.) The ratio of 2-hydroxydesipramine to desipramine may be increased in the elderly, most likely due to decreased renal elimination with aging.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

NORPRAMIN (desipramine hydrochloride) use in the elderly has been associated with a proneness to falling as well as confusional states. (See ADVERSE REACTIONS.)

PRECAUTIONS

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 (desipramine hydrochloride) 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 (desipramine hydrochloride) . 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 (desipramine hydrochloride) .

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.

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) (desipramine hydro-chloride) is not recommended for use in children.

Anyone considering the use of NORPRAMIN (desipramine hydrochloride) 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 (desipramine hydrochloride) 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.

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Deaths may occur from overdosage with this class of drugs. Overdose of desipramine has resulted in a higher death rate compared to overdoses of other tricyclic antidepressants. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible. There is no specific antidote for desipramine overdosage.

Oral LD50

The oral LD50 of desipramine is 290 mg/kg in male mice and 320 mg/kg in female rats.

Manifestations of Overdosage

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 antidepressant toxicity. Early changes in the QRS complex include a widening of the terminal 40 msec with a rightward axis in the frontal plane, recognized by the presence of a terminal S wave in Lead 1 and AVL and an R wave in AVR. Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypother-mia, hyperpyrexia, or any of the symptoms listed under ADVERSE REACTIONS.

Management

Aggressive supportive care and serum alkalinization are the mainstays of therapy.

General

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 dys-rhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. Follow ECG, renal function, CPK, and arterial blood gasses as clinically indicated. There are case reports of patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of significant poisoning prior to death, and most received inadequate gastrointestinal decontamination. Monitoring of plasma drug levels should not guide management of the patient.

Gastrointestinal Decontamination

Emesis is contraindicated. Activated charcoal should be administered to patients who present early after an overdose.

Cardiovascular

A maximal limb-lead QRS duration widening to greater than 100 msec is a significant indicator of toxicity, specifically for the risk of seizures and, eventually, cardiac dysrhythmias. Serum alkalinization with intravenous sodium bicarbonate and hyperventilation (as needed) should be instituted in patients manifesting significant toxicity such as QRS widening. Dysrhythmias despite adequate alkalemia may respond to overdrive pacing, beta-agonist infusions, and magnesium therapy. Type 1A and 1C antiarrhythmics are generally contraindicated (eg, quinidine, disopyramide, and procainamide).

CNS

In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines. If these are ineffective or seizures recur, other anticonvulsants (eg, phenobarbital, propofol) may be used.

Psychiatric Follow-up

Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Pediatric Management

The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

CONTRAINDICATIONS

NORPRAMIN (desipramine hydrochloride) should not be given in conjunction with, or within 2 weeks of, treatment with an MAO inhibitor drug; hyperpyretic crises, severe convulsions, and death have occurred in patients taking MAO inhibitors and tricyclic antidepressants. When NORPRAMIN (desipramine hydrochloride) is substituted for an MAO inhibitor, at least 2 weeks should elapse between treatments. NORPRAMIN (desipramine hydrochloride) should then be started cautiously and should be increased gradually.

NORPRAMIN (desipramine hydrochloride) is contraindicated in the acute recovery period following myocardial infarction. It should not be used in those who have shown prior hypersensitivity to the drug. Cross-sensitivity between this and other dibenzazepines is a possibility.

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Available evidence suggests that many depressions have a biochemical basis in the form of a relative deficiency of neurotransmitters such as norepinephrine and serotonin. Norepinephrine deficiency may be associated with relatively low urinary 3-methoxy-4-hydroxyphenyl glycol (MHPG) levels, while serotonin deficiencies may be associated with low spinal fluid levels of 5-hydroxyindoleacetic acid. While the precise mechanism of action of the tricyclic antidepressants is unknown, a leading theory suggests that they restore normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system. Evidence indicates that the secondary amine tricyclic antidepressants, including NORPRAMIN (desipramine hydrochloride) , may have greater activity in blocking the re-uptake of norepinephrine. Tertiary amine tricyclic antidepressants, such as amitriptyline, may have greater effect on serotonin re-uptake.

NORPRAMIN (desipramine hydrochloride) is not a monoamine oxidase (MAO) inhibitor and does not act primarily as a central nervous system stimulant. It has been found in some studies to have a more rapid onset of action than imipramine. Earliest therapeutic effects may occasionally be seen in 2 to 5 days, but full treatment benefit usually requires 2 to 3 weeks to obtain.

Metabolism

Tricyclic antidepressants, such as desipramine hydrochloride, are rapidly absorbed from the gas-trointestinal tract. Tricyclic antidepressants or their metabolites are to some extent excreted through the gastric mucosa and reabsorbed from the gastrointestinal tract. Desipramine is metabolized in the liver and approximately 70% is excreted in the urine.

The rate of metabolism of tricyclic antidepressants varies widely from individual to individual, chiefly on a genetically determined basis. Up to a 36-fold difference in plasma level may be noted among individuals taking the same oral dose of desipramine. The ratio of 2-hydroxydesipramine to desipramine may be increased in the elderly, most likely due to decreased renal elimination with aging.

Certain drugs, particularly the psychostimulants and the phenothiazines, increase plasma levels of concomitantly administered tricyclic antidepressants through competition for the same metabolic enzyme systems. Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressants. Conversely decreases in plasma levels of the tricyclic antidepressants have been reported upon discontinuation of cimetidine which may result in the loss of the therapeutic efficacy of the tricyclic antidepressant. Other substances, particularly barbiturates and alcohol, induce liver enzyme activity and thereby reduce tricyclic antidepressant plasma levels. Similar effects have been reported with tobacco smoke.

Research on the relationship of plasma level to therapeutic response with the tricyclic antidepressants has produced conflicting results. While some studies report no correlation, many studies cite therapeutic levels for most tricyclics in the range of 50 to 300 nanograms per milliliter. The therapeutic range is different for each tricyclic antidepressant. For desipramine, an optimal range of therapeutic plasma levels has not been established.

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Medication Guide

Norpramin®
(desipramine hydrochloride) Tablets USP

Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions

Read the Medication Guide that comes with your, or your family member's, antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member's, healthcare provider about:

  • all risks and benefits of treatment with antidepressant medicines
  • all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

  1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
  2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
  3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
    • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
    • Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
    • Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

  • thoughts about suicide or dying
  • attempts to commit suicide
  • new or worse depression
  • new or worse anxiety
  • feeling very agitated or restless
  • panic attacks
  • trouble sleeping (insomnia)
  • new or worse irritability
  • acting aggressive, being angry, or violent
  • acting on dangerous impulses
  • an extreme increase in activity and talking (mania)
  • other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

  • Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
  • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
  • Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
  • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
  • Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child's healthcare provider for more information.

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

You may also report side effects to sanofi-aventis U.S. at 1-800-633-1610.

This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Medication Guide

Norpramin®
(desipramine hydrochloride) Tablets USP

Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions

Read the Medication Guide that comes with your, or your family member's, antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member's, healthcare provider about:

  • all risks and benefits of treatment with antidepressant medicines
  • all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

  1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
  2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
  3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
    • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
    • Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
    • Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

  • thoughts about suicide or dying
  • attempts to commit suicide
  • new or worse depression
  • new or worse anxiety
  • feeling very agitated or restless
  • panic attacks
  • trouble sleeping (insomnia)
  • new or worse irritability
  • acting aggressive, being angry, or violent
  • acting on dangerous impulses
  • an extreme increase in activity and talking (mania)
  • other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

  • Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
  • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
  • Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
  • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
  • Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child's healthcare provider for more information.

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

You may also report side effects to sanofi-aventis U.S. at 1-800-633-1610.

This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.

Last reviewed on RxList: 12/7/2009
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Norpramin Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

DESIPRAMINE - ORAL

(des-IP-ra-meen)

COMMON BRAND NAME(S): Norpramin

WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. Therefore, it is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.

Tell the doctor immediately if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

USES: Desipramine is used to treat depression. This medication may improve your mood, sleep, appetite, and energy level and may help restore your interest in daily living. This medication belongs to a class of medications called tricyclic antidepressants. It works by restoring the balance of a certain natural substance (norepinephrine) in the brain.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to treat panic disorder and certain types of ongoing pain.

HOW TO USE: Read the Medication Guide available from your pharmacist. Consult your doctor or pharmacist if you have any questions.

Take this medication by mouth with or without food, usually 1-3 times daily or as directed by your doctor. Dosage is based on your medical condition and response to therapy. Your doctor may start you at a low dose and gradually increase your dose. Usually, the daily dose will not be more than 300 milligrams for adults and 150 milligrams for teenagers and the elderly. This medication may make you sleepy or wakeful. Therefore, depending on how this medication affects you, your doctor may direct you to take the entire dose once daily either in the morning or at bedtime.

Follow your doctor's instructions carefully. Do not take more or less medication or take it more frequently than prescribed. Your condition will not improve any faster and your risk of side effects will increase. Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day.

It is important to continue taking this medication even if you feel well. Do not suddenly stop taking this medication without consulting your doctor. Some conditions may become worse when the drug is abruptly stopped. Your dose may need to be gradually decreased.

This medication does not work right away. It may take 2 to 3 weeks before you experience the full benefits when this medication is used for depression.

Inform your doctor if your condition persists or worsens.

Disclaimer

Norpramin Consumer (continued)

SIDE EFFECTS: Headache, nausea, dizziness, drowsiness, nervousness, trouble sleeping, blurred vision, increased appetite, weight gain, constipation and dry mouth may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes (e.g., confusion, depression, hallucinations, memory problems), enlarged/painful breasts, unusual breast milk production, irregular/painful menstrual periods, muscle stiffness/twitching, restlessness, ringing in the ears, sexual problems (e.g., decreased sexual ability, changes in desire), shakiness (tremors), numbness/tingling of the hands/feet, pain/redness/swelling of arms or legs, trouble urinating, severe vomiting.

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), severe stomach/abdominal pain, dark urine, yellowing of eyes/skin.

Seek immediate medical attention if any of these rare but very serious side effects occur: chest pain, slow/fast/irregular heartbeat, seizures, fainting, slurred speech, weakness on one side of the body, vision changes.

This drug may rarely cause a serious nervous system disorder (neuroleptic malignant syndrome). Seek immediate medical attention if you notice any of the following rare but very serious side effects: muscle stiffness, high fever, increased sweating, fast heartbeat, sudden mental/mood changes, change in the amount of urine.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

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

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Norpramin (desipramine hydrochloride) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: See also the Warning section.

Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or to other tricyclic antidepressants (e.g., amitriptyline); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have a certain medical condition. Before using this medicine, consult your doctor or pharmacist if you have had: a recent heart attack.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., asthma, chronic bronchitis), certain eye problems (e.g., glaucoma, increased intraocular pressure), diabetes, eating disorders (e.g., bulimia), heart problems (e.g., arrhythmias, coronary artery disease), liver problems, kidney problems, personal or family history of other mental/mood conditions (e.g., bipolar disorder, schizophrenia), seizures, overactive thyroid (hyperthyroidism), trouble urinating (e.g., due to enlarged prostate), any condition that may increase your risk of seizures (e.g., alcohol/sedative dependency, use of electroconvulsive therapy, brain injury/disease such as stroke), certain types of tumors (e.g., pheochromocytoma, neuroblastoma).

Desipramine may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that require immediate medical attention. The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may affect the heart rhythm (see also Drug Interactions section). Before using desipramine, tell your doctor or pharmacist if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using desipramine safely.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or drowsy or cause blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.

To decrease dizziness and lightheadedness, get up slowly when rising from a seated or lying position.

This drug may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

If you have diabetes, this drug may make it harder to control your blood sugar levels. Check your blood sugar regularly as directed by your doctor. Tell your doctor immediately if you have symptoms such as increased thirst/urination, shakiness, unusual sweating, or hunger. Your anti-diabetic medication or diet may need to be adjusted.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at a greater risk for heart problems or mental/mood changes (e.g., confusion, agitation) while using this drug.

Caution is advised when using this drug in children. (See also the Warning section.)

This medication should be used only when clearly needed during pregnancy. Infants born to mothers who have taken similar medications during pregnancy may have symptoms such as trouble urinating, prolonged sleepiness, shaking, and seizures. Discuss the risks and benefits with your doctor.

This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Disclaimer

Norpramin Consumer (continued)

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious, possibly fatal interactions may occur: arbutamine, disopyramide, sibutramine, MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine).

Avoid taking MAO inhibitors within 2 weeks before, during and after treatment with this medication. In some cases a serious, possibly fatal drug interaction may occur.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting desipramine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anticholinergics (e.g., atropine, belladonna alkaloids, scopolamine, drugs for Parkinson's disease such as benztropine), inhaled bronchodilators (e.g., albuterol, salmeterol), certain drugs for high blood pressure (e.g., clonidine, guanadrel, guanethidine, reserpine), digoxin, nasal decongestants (e.g., epinephrine, phenylephrine), levodopa, lithium, stimulants (e.g., amphetamine, epinephrine, methylphenidate), thyroid supplements, valproic acid, drugs affecting liver enzymes that remove desipramine from your body (e.g., alcohol, barbiturates such as phenobarbital, cimetidine, cisapride, haloperidol, certain drugs for heart rhythm such as flecainide/propafenone, halofantrine, HIV protease inhibitors such as amprenavir/fosprenavir, phenothiazines such as thioridazine, pimozide, certain anti-seizure drugs such as carbamazepine/phenytoin, antidepressants such as duloxetine/fluoxetine/fluvoxamine/trazodone, St. John's wort, terbinafine).

Cigarette smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking.

Many drugs besides desipramine may affect the heart rhythm (QT prolongation in the EKG), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, sparfloxacin, macrolide antibiotics (such as erythromycin), among others. Therefore, before using desipramine, report all medications you are currently using to your doctor or pharmacist.

Also report the use of drugs which might increase seizure risk (decrease seizure threshold) when combined with this medication such as bupropion, isoniazid (INH), theophylline, or tramadol, among others. Consult your doctor or pharmacist for details.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-anxiety drugs (e.g., diazepam), anti-seizure drugs (e.g., levetiracetam), drugs for motion sickness (e.g., meclizine).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-containing ingredients or decongestants that could increase your heart rate or blood pressure. Ask your pharmacist about the safe use of those products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fast/irregular heartbeat, fainting, hallucinations, seizures.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., blood count, EKG, kidney function tests) may be performed regularly to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store in a tightly closed container at room temperature below 86 degrees F (30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised September 2011. Copyright(c) 2011 First Databank, Inc.

Norpramin Patient Information Including Side Effects

Brand Names: Norpramin

Generic Name: desipramine (Pronunciation: des IP ra meen)

What is desipramine (Norpramin)?

Desipramine is a tricyclic antidepressant. Desipramine affects chemicals in the brain that may become unbalanced.

Desipramine is used to treat symptoms of depression.

Desipramine may also be used for other purposes not listed in this medication guide.

Desipramine 10 mg-GG

round, white, imprinted with GG 63

Desipramine 100 mg-GG

round, white, imprinted with GG 167

Desipramine 150 mg-GG

round, white, imprinted with GG 168

Desipramine 25 mg-GG

round, white, imprinted with GG 64

Desipramine 50 mg-GG

round, white, imprinted with GG 65

Desipramine 75 mg-GG

round, white, imprinted with GG 166

Norpramin 10 mg

round, blue, imprinted with 68-7

What are the possible side effects of desipramine (Norpramin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have any of these serious side effects:

  • fast, pounding, or uneven heart rate;
  • seizure (convulsions);
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden headache, problems with vision, speech, or balance;
  • easy bruising or bleeding, unusual weakness;
  • tremors, restless muscle movements in your eyes, tongue, jaw, or neck;
  • very stiff (rigid) muscles, high fever, sweating, confusion, tremors, feeling like you might pass out;
  • urinating less than usual or not at all;
  • extreme thirst with headache, nausea, vomiting, and weakness;
  • skin rash, severe tingling or numbness, pain and muscle weakness; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • vomiting, constipation;
  • dry mouth, unpleasant taste;
  • weakness, lack of coordination;
  • feeling anxious, restless, dizzy, or drowsy;
  • sleep problems (insomnia), nightmares;
  • blurred vision, trouble concentrating, headache, ringing in your ears;
  • breast swelling (in men or women); or
  • decreased sex drive, impotence, or difficulty having an orgasm.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Norpramin (desipramine hydrochloride) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about desipramine (Norpramin)?

Do not use this medication if you have recently had a heart attack, or if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Side Effects Centers

Norpramin Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking desipramine (Norpramin)?

Do not use this medication if you are allergic to desipramine, or if you have recently had a heart attack.

Do not use desipramine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take desipramine before the MAO inhibitor has cleared from your body.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely take desipramine:

  • heart disease, or a history of heart attack, stroke, or seizures;
  • a family history of sudden death related to a heart rhythm disorder;
  • bipolar disorder (manic-depression);
  • schizophrenia or other mental illness;
  • liver disease;
  • overactive thyroid;
  • diabetes (desipramine may raise or lower blood sugar);
  • glaucoma; or
  • problems with urination.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Tell your doctor if you have worsening symptoms of depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Desipramine may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether desipramine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Older adults may be more likely to have side effects from this medication.

Do not give desipramine to anyone under 18 years old without the advice of a doctor.

How should I take desipramine (Norpramin)?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Your doctor may occasionally change your dose to make sure you get the best results from this medication. Follow the directions on your prescription label.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking desipramine. You may need to stop using the medicine for a short time.

Do not stop using desipramine without first talking to your doctor. You may need to use less and less before you stop the medication completely. Stopping this medication suddenly could cause you to have unpleasant side effects.

It may take a few weeks of using this medicine before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve during treatment.

Store desipramine at room temperature away from moisture and heat.

Side Effects Centers

Norpramin Patient Information including If I Miss a Dose

What happens if I miss a dose (Norpramin)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Norpramin)?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of desipramine can be fatal. Symptoms may include uneven heartbeats, extreme drowsiness, vomiting, blurred vision, confusion, hallucinations, muscle stiffness, feeling hot or cold, seizure (convulsions), or coma.

What should I avoid while taking desipramine (Norpramin)?

Avoid drinking alcohol. It can cause dangerous side effects when taken together with desipramine.

Grapefruit and grapefruit juice may interact with desipramine. Discuss the use of grapefruit products with your doctor before increasing or decreasing the amount of grapefruit products in your diet.

Desipramine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Desipramine can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun.

What other drugs will affect desipramine (Norpramin)?

Cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures or anxiety can add to sleepiness caused by desipramine. Tell your doctor if you regularly use any of these medicines, or any other antidepressants.

Before taking desipramine, tell your doctor if you have used an "SSRI" antidepressant in the past 5 weeks, such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), or sertraline (Zoloft).

Tell your doctor about all other medicines you use, especially:

  • cimetidine (Tagamet); or
  • heart rhythm medications such as flecainide (Tambocor), propafenone (Rhythmol), or quinidine (Cardioquin, Quinidex, Quinaglute).

This list is not complete and there are many other medicines that can interact with desipramine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

Where can I get more information?

Your pharmacist can provide more information about desipramine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 9.02. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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Side Effects Centers

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