Imipramine

Imipramine is also used occasionally to treat eating disorders and panic disorders. Talk to your doctor about the possible risks of using this medication for your condition.

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

Tofranil, Tofranil-PM

Use of imipramine during pregnancy has not been adequately evaluated.

Available evidence suggests that imipramine may be excreted in breast milk and may be harmful to the infant.

CYP2D6 is a protein in your body that is involved in the elimination of imipramine and other drugs from your body. Some patients have less of this protein in their bodies, affecting how much of the drug gets eliminated. Levels of CYP2D6 can vary greatly between individuals, and those having less of this protein are known as "poor metabolizers." 

CYP2D6 testing is done to determine whether you are a poor metabolizer. If you are a poor metabolizer, the levels of imipramine in your blood can become too high. As a result, you may be at an increased risk of having more side effects from imipramine. 

Your doctor may adjust your dose of imipramine if you are a poor metabolizer. 

Imipramine is a prescription medication used to treat depression and bedwetting in children.

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

Before taking imipramine, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to imipramine or to any of its ingredients
• have liver problems
• have heart problems
• have kidney problems
• have diabetes
• are pregnant or breastfeeding

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

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

Report any new or worsening symptoms to your doctor, 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:

• blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;

• a light-headed feeling, like you might pass out;

• new or worsening chest pain, pounding heartbeats or fluttering in your chest;

• sudden numbness or weakness, problems with vision, speech, or balance;

• fever, sore throat;

• confusion, hallucinations, unusual thoughts or behavior;

• painful or difficult urination;

• seizure (convulsions); or

• jaundice (yellowing of the skin or eyes).

Common side effects may include:

• tingly feeling, weakness, lack of coordination;

• dry mouth, nausea, vomiting, constipation, diarrhea;

• vision changes, 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.

In the U.S.

• Tofranil
• Tofranil-PM

Available Dosage Forms:

• Tablet
• Capsule

Therapeutic Class: Antidepressant

Pharmacologic Class: Antidepressant, Tricyclic

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

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

• Abdominal or stomach pain
• agitation
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain or discomfort
• clay-colored stools
• cold sweats
• confusion about identity, place, and time
• continuing ringing or buzzing or other unexplained noise in the ears
• cough or hoarseness
• dark urine
• decrease in the frequency of urination
• difficulty in passing urine (dribbling)
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• double vision
• dry mouth
• false beliefs that cannot be changed by facts
• fast, pounding, or irregular heartbeat or pulse
• feeling, seeing, or hearing things that are not there
• feeling that others are watching you or controlling your behavior
• feeling that others can hear your thoughts
• fever with or without chills
• flushed, dry skin
• general feeling of tiredness or weakness
• hearing loss
• hostility
• hyperventilation
• inability to move the arms, legs, or facial muscles
• irritability
• itching or rash
• lack of coordination
• lethargy
• loss of balance control
• lower back or side pain
• mood or mental changes
• muscle spasm or jerking of all extremities
• muscle trembling, jerking, or stiffness
• nightmares
• pain or discomfort in the arms, jaw, back, or neck
• painful or difficult urination
• pinpoint red or purple spots on the skin
• rapid weight gain
• redness of the face, neck, arms, and occasionally, upper chest
• restlessness
• seizures
• shakiness and unsteady walk
• slow speech
• sore throat
• stiffness of the limbs
• stupor
• sweating
• swelling of the face, ankles, legs, or hands
• talking, feeling, and acting with excitement
• trouble sleeping
• twisting movements of the body
• uncontrolled movements, especially of the face, neck, and back
• unusual behavior
• unusual tiredness or weakness
• weakness in the arms, hands, legs, or feet
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Bluish color of fingernails, lips, skin, palms, or nail beds
• cold, clammy skin
• decreased awareness or responsiveness
• difficult or troubled breathing
• disorientation
• fast, weak pulse
• hallucinations
• irregular, fast, slow, or shallow breathing
• severe sleepiness

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

• Bigger, dilated, or enlarged pupils (black part of the eye)
• black tongue
• decreased interest or ability in sexual intercourse
• difficulty having a bowel movement (stool)
• enlargement of the breast
• hives or welts
• increase in sexual ability, desire, drive, or performance
• increased sensitivity of the eyes to light
• increased urge to urinate during the night
• peculiar taste
• redness or other discoloration of the skin
• severe sunburn
• swelling of the testicles
• swelling of the breasts or breast soreness in both females and males
• swollen, painful, or tender lymph glands on the side of the face or neck
• unexpected or excess milk flow from the breasts
• waking to urinate at night

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

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

A. Acute: Oral LD50 ranges are as follows:

Rat 355 to 682 mg/kg
Dog 100 to 215 mg/kg

Depending on the dosage in both species, toxic signs proceeded progressively from depression, irregular respiration and ataxia to convulsions and death,

B. Reproduction/Teratogenic: The overall evaluation may be summed up in the following manner:

Oral: Independent studies in three species (rat, mouse, and rabbit) revealed that when Imipramine Hydrochloride is administered orally in doses up to approximately 2-1/2 times the maximum human dose in the first 2 species and up to 25 times the maximum human dose in the third species, the drug is essentially free horn teratogenic potential. In the three species studied, only one instance of fetal abnormality occurred (in the rabbit) and in that study there was likewise an abnormality in the control group. However, evidence does exist from the rat studies that some systemic and embryotoxic potential is demonstrable. This is manifested by reduced litter size, a slight increase in the stillborn rate, and a reduction in the mean birth weight.

Manufactured by:
Leading Pharma, LLC
Fairfield, NJ 07004
Rev. 01 10/16

Depression: Oral:

Outpatients: Initial: 75 mg daily; may increase gradually to 150 mg daily. May be given in divided doses or as a single bedtime dose; Maintenance 50-150 mg daily; maximum: 200 mg daily

Inpatients: Initial: 100-150 mg daily; may increase gradually to 200 mg daily; if no response after 2 weeks, may further increase to 250-300 mg daily. May be given in divided doses or as a single bedtime dose; maximum: 300 mg daily.

Bulimia nervosa (off-label use): Oral: Initial: 50 mg at bedtime; increase gradually based on response and tolerability up to 300 mg at bedtime (Agras 1987; Mitchell 1990; Pope 1983).

Neuropathic pain (off-label use): Oral: Note: Not the preferred TCA (Bril 2011; Dworkin 2007). Initial: 50 mg once daily or in divided doses twice daily; increase gradually up to 150 mg daily (Kvinesdal 1984; Sindrup 2003) or to a dosage sufficient to achieve an imipramine plus desipramine plasma concentration of 113-170 ng/mL (SI: 400-600 nmol/L) (Sindrup 1989; Sindrup 1990)

Panic disorder (off-label use): Oral: Initial: 10 mg once daily; increase gradually to a usual dose of 75-300 mg daily (APA 2009; Bandelow 2008)

Post-traumatic stress disorder (PTSD) (off-label use): Oral: Initial: 50 mg once daily; increase gradually to 200-300 mg once daily to achieve blood levels in the therapeutic range (>150 ng/mL) (Frank 1988; Kosten 1991)

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddod 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of imipramine.

Allow 14 days to elapse between discontinuing imipramine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Use with other MAO inhibitors (linezolid or IV methylene blue):

Do not initiate imipramine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition (Zyvox prescribing information; methylene blue prescribing information).

If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving imipramine and potential benefits outweigh potential risks, discontinue imipramine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume imipramine 24 hours after the last dose of linezolid or IV methylene blue.

Applies to imipramine: compounding powder, intramuscular solution, oral capsule, oral tablet

General

The most commonly reported side effects were tremors, increased weight, dry mouth, and constipation.[Ref]

Hypersensitivity

Very rare (less than 0.01%): Systemic anaphylactic/anaphylactoid reactions[Ref]

Psychiatric

Common (1% to 10%): Confusional states (especially in the elderly), hallucinations, disorientation, delusions, anxiety, restlessness, agitation, insomnia, nightmares, hypomania, exacerbation of psychosis, sleep disorders, emotional instability, swings from depression to hypomania or mania
Very rare (less than 0.01%): Aggression[Ref]

Cardiovascular

Very common (10% or more): Sinus tachycardia, electrocardiogram abnormalities (e.g., ST and T wave changes), hot flushes, orthostatic hypotension
Common (1% to 10%): Arrhythmias, palpitations, conduction disorders (e.g., widening of QRS complex, bundle branch block, PR changes)
Very rare (less than 0.01%): Cardiac failure, QT interval prolongation, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation, torsades de pointes, hypertension, stroke, vasospasm
Frequency not reported: Myocardial infarction, heart block, precipitation of congestive heart failure, flushing, collapse, cardiac decompensation, peripheral vasospastic reactions[Ref]

Nervous system

Very common (10% or more): Tremors
Common (1% to 10%): Dizziness, headache, somnolence, paraesthesia
Rare (less than 0.1%): Convulsions
Very rare (less than 0.01%): Myoclonus, extrapyramidal disorder, ataxia, speech
disorders, abnormal electroencephalogram, tinnitus
Frequency not reported: Numbness, tingling, incoordination, peripheral neuropathy, seizures, drowsiness, nervousness, syncope[Ref]

Hepatic

Common (1% to 10%): Elevated transaminases
Very rare (less than 0.01%): Hepatitis (with or without jaundice), acute hepatitis, hepatic
necrosis
Frequency not reported: Jaundice (simulating obstructive), altered liver function[Ref]

Endocrine

Very rare (less than 0.01%): Inappropriate antidiuretic hormone (ADH) secretion syndrome, breast enlargement (female), galactorrhea (female)
Frequency not reported: Gynecomastia (male), increased or decreased libido, impotence, testicular swelling[Ref]

Hematologic

Very rare: (less than 0.01%): Bone marrow depression (including agranulocytosis, eosinophilia, thrombocytopenia, leucopenia), purpura, petechiae[Ref]

Gastrointestinal

Very common (10% or more): Dry mouth, constipation
Common (1% to 10%): Nausea, vomiting
Rare (less than 0.1%): Sublingual adenitis
Very rare (less than 0.01%): Dental caries, ileus paralytic, stomatitis, abdominal disorders, tongue ulceration
Frequency not reported: Epigastric distress, diarrhea, peculiar taste, abdominal cramps, parotid swelling[Ref]

Metabolic

Very common (10% or more): Increased weight
Common (1% to 10%): Anorexia
Very rare (less than 0.01%): Elevation or depression of blood sugar levels, weight loss
Frequency not reported: Hyponatremia[Ref]

Dermatologic

Very common (10% or more): Hyperhidrosis
Common (1% to 10%): Skin rash, urticaria, allergic dermatitis
Very rare (less than 0.01%): Pruritus, photosensitivity reactions, alopecia, skin hyperpigmentation[Ref]

Other

Common (1% to 10%): Fatigue
Very rare (less than 0.01%): Asthenia, edema (localized or generalized), pyrexia, sudden death
Frequency not reported: Weakness, proneness to falling, tiredness, drug fever[Ref]

Genitourinary

Common (1% to 10%): Micturition disorder
Very rare (less than 0.01%): Urinary retention
Frequency not reported: Dilation of the urinary tract, urinary frequency[Ref]

Ocular

Common (1% to 10%): Blurred vision, disturbances of accommodation, decreased lacrimation
Very rare (less than 0.01%): Mydriasis, glaucoma[Ref]

Respiratory

Very rare (less than 0.01%): Allergic alveolitis (pneumonitis) with or without eosinophilia[Ref]

Musculoskeletal

Frequency not reported: Increased risk of bone fractures[Ref]

Some side effects of imipramine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Tablets:
6 years to 12 years:
Initial dose: 25 mg orally per day
Maintenance dose: 50 mg orally per day
Maximum dose: 2.5 mg/kg/day

12 years to 18 years:
Initial dose: 25 mg orally per day
Maintenance dose: 75 mg orally per day
Maximum dose: 2.5 mg/kg/day

Comments:
-This dose should be given one hour before bedtime.
-In early night bedwetters, the drug is more effective given earlier and in divided amounts, i.e., 25 mg in mid afternoon, repeated at bedtime.
-Dosage should be tapered off gradually.

Use: Temporary adjunctive therapy in reducing enuresis in children aged 6 years and older

Renal dysfunction: Use with caution

Monitoring:
-Psychiatric: Patients should be monitored for worsening and emergence of suicidal thoughts.

Patient advice:
-Patients should be cautioned accordingly since this drug may impair the mental and/or physical abilities required for the performance of operating an automobile or machinery.

Summary of Use during Lactation

Milk levels of imipramine and its metabolite are low and have not been detected in the serum of breastfed infants. Immediate side effects have not been reported and a limited amount of follow-up has found no adverse effects on infant growth and development. Imipramine use during breastfeeding would usually not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Some experts consider imipramine one of the antidepressants of choice for nursing mothers.[1][2] Other agents with may be preferred when large doses are required or while nursing a newborn or preterm infant.

Drug Levels

Imipramine is metabolized to desipramine which has antidepressant activity equal to that of imipramine. Desipramine is metabolized to 2-hydroxydesipramine which has antidepressant activity equal to that of desipramine.[3]

Maternal Levels. Two women who were taking imipramine 50 mg daily for panic disorder had imipramine and desipramine breastmilk levels measured 1 month postpartum (time after dose not stated). In one, levels of impiramine and desipramine were 91 and 185 mcg/L, respectively. In the other only trace quantities were detected.[4]

A mother who was 1 month postpartum began taking imipramine for depression. Sixteen days after initiation, milk imipramine plus desipramine levels ranged from 21 to 59 mcg/L at various times while taking a dose of 200 mg daily. There was no clear-cut relationship of milk levels to the time since the dose.[5]

Four mothers who were taking imipramine in doses of 75 to 150 mg daily had milk samples taken 12 to 15 hours after their daily dose. Milk imipramine plus desipramine levels ranged from 48 to 622 mcg/L, with little correlation to dosage. Foremilk levels were lower than hindmilk levels.[6] Using the hindmilk data from this study, an exclusively breastfed infant would receive an estimated maximum of 2.9% of the maternal weight-adjusted dosage.

Infant Levels. Two infants had serum level measurements of imipramine plus desipramine while breastfeeding. One infant whose mother began imipramine 75 mg daily 2 weeks postpartum and was breastfed for 7 weeks had a serum level of 0.6 mcg/L. Another infant was breastfed for 17 weeks after his mother began imipramine 100 mg daily 8 weeks postpartum and later decreased to 75 mg daily. His average of 3 serum levels was 5.5 mcg/L (range 3.3 to 7.4 mcg/L). Time after the dose was not stated.[6]

One 5.9-week-old infant who was breastfed 10 to 12 times daily had no detectable serum imipramine or desipramine (both <25 mcg/L) during maternal use of imipramine 75 mg daily. Another 17-week-old infant who was breastfed 10 to 12 times daily had no detectable serum imipramine (<20 mcg/L) or desipramine (<35 mcg/L) during maternal use of imipramine 150 mg daily.[7]

Effects in Breastfed Infants

No behavioral or physical changes were noted in a 6-week-old breastfed infant whose mother had been taking imipramine 200 mg/day at bedtime for 15 days.[5]

Follow-up for 1 to 3 years in 14 breastfed infants whose mothers were taking imipramine in an average dosage of 161 mg daily (range 125 to 225 mg daily) found no adverse effects on growth and development.[8]

Four infants were breastfed for 7 to 18 weeks during maternal use of imipramine 75 to 150 mg daily starting at 2 weeks (3 infants) and 8 weeks (1 infant) postpartum. Formal testing indicated no adverse effects on infant development up to 30 months of age. The mother of 1 infant was taking haloperidol along with imipramine 150 mg daily.[6]

In another study, 25 infants whose mothers took a tricyclic antidepressant during pregnancy and lactation were tested formally between 15 to 71 months and found to have normal growth and development. Some of the mothers were taking imipramine.[9]

Six postpartum mothers diagnosed with panic disorder were successfully treated with imipramine 25 to 35 mg (mean 28 mg) daily starting at a mean of 5.9 weeks postpartum. Mothers were treated for a mean of 9.3 weeks. All mothers reported that no adverse effects occurred in their infants.[10]

Effects on Lactation and Breastmilk

Imipramine has caused increased prolactin levels and gynecomastia in nonpregnant, nonnursing patients.[11][12] Galactorrhea has been reported rarely.[13][14] The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 30% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge.[15] The antidepressants used by the mothers were not specified.

Alternate Drugs to Consider

Nortriptyline, Paroxetine, Sertraline

References

1. di Scalea TL, Wisner KL. Pharmacotherapy of postpartum depression. Expert Opin Pharmacother. 2009;10:2593-607. PMID: 19874247

2. National Health Service (England). National Institute for Health and Clinical Excellence. Antenatal and postnatal mental health: clinical management and service guidance, clinical guideline no. 45. 2007. http://www.nice.org.uk

3. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID: 15169695

4. Ware MR, DeVane CL. Imipramine treatment of panic disorder during pregnancy. J Clin Psychiatry. 1990;51:482-4. PMID: 2228984

5. Sovner R, Orsulak PJ. Excretion of imipramine and desipramine in human breast milk. Am J Psychiatry. 1979;136:451-2. PMID: 426114

6. Yoshida K, Smith B, Craggs M et al. Investigation of pharmacokinetics and possible adverse effects in infants exposed to tricyclic antidepressants in breast-milk. J Affective Disord. 1997;43:225-37. PMID: 9186793

7. Birnbaum CS, Cohen LS, Bailey JW et al. Serum concentrations of antidepressants and benzodiazepines in nursing infants: a case series. Pediatrics. 1999;104:e11. PMID: 10390297

8. Misri S, Sivertz K. Tricyclic drugs in pregnancy and lactation: a preliminary report. Int J Psychiatry Med. 1991;21:157-71. PMID: 1894455

9. Nulman I, Rovet J, Stewart DE et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry. 2002;159:1889-95. PMID: 12411224

10. Uguz F, Aydin A, Ak M et al. Low-dose imipramine for the treatment of panic disorder during postpartum period: A retrospective analysis of 6 cases. J Clin Psychopharmacol. 2016;36:292-3. PMID: 27035490

11. Turkington RW. Prolactin secretion in patients treated with various drugs: phenothiazines, tricyclic antidepressants, reserpine, and methyldopa. Arch Intern Med. 1972;130:349-54. PMID: 4560178

12. Turkington RW. Serum prolactin levels in patients with gynecomastia. J Clin Endocrinol Metab. 1972;34:62-6. PMID: 5061776

13. Klein JJ SRWR. Galactorrhea due to imipramine. Report of a case. N Engl J Med. 1964;271:510-2. PMID: 14172465

14. Mahasuar R, Majhi P, Ravan JR. Euprolactinemic galactorrhea associated with use of imipramine and escitalopram in a postmenopausal woman. Gen Hosp Psychiatry. 2010;32:341.e11-3. PMID: 20430243

15. Venkatesh KK, Castro VM, Perlis RH et al. Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression. Am J Obstet Gynecol. 2017;216:S466-S467.