Tofranil-PM 150mg Capsules
WARNING: Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like depression, nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.This drug is not approved for use in children. Talk with the doctor. @ COMMON USES: It is used to treat depression.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Tricyclic Antidepressant (TCA)
Pharmacologic Class
Norepinephrine and Serotonin Reuptake Inhibitor (NSRI)
Pregnancy Category
Category D
FDA Approved
Mar 1959
DEA Schedule
Not Controlled
Overview
What is this medicine?
Imipramine is a medication used to treat depression and sometimes panic disorder or bedwetting in children. It works by helping to restore the balance of certain natural substances (neurotransmitters) in the brain. It belongs to a group of medicines called tricyclic antidepressants (TCAs).
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your medication and follow the instructions closely. If you experience drowsiness after taking your medication, consult with your doctor, as they may need to adjust your dosage or the timing of when you take it. Continue taking your medication as directed by your doctor or healthcare provider, even if you're feeling well.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom. Keep all medications in a secure location, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult with your pharmacist for guidance on the best disposal method. You may also want to explore drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses. If you take your daily dose at bedtime and miss a dose, do not take the missed dose the next morning.
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your medication and follow the instructions closely. If you experience drowsiness after taking your medication, consult with your doctor, as they may need to adjust your dosage or the timing of when you take it. Continue taking your medication as directed by your doctor or healthcare provider, even if you're feeling well.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom. Keep all medications in a secure location, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult with your pharmacist for guidance on the best disposal method. You may also want to explore drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses. If you take your daily dose at bedtime and miss a dose, do not take the missed dose the next morning.
Lifestyle & Tips
- Avoid alcohol and other CNS depressants, as they can increase drowsiness and other side effects.
- Be cautious when driving or operating machinery until you know how this medication affects you, due to potential for drowsiness, dizziness, or blurred vision.
- Rise slowly from a sitting or lying position to minimize dizziness from orthostatic hypotension.
- Manage dry mouth with sugar-free candy, gum, or artificial saliva.
- Increase fluid and fiber intake to help with constipation.
- Avoid excessive heat exposure, as imipramine can impair sweating and increase risk of heatstroke.
- Do not stop taking this medication suddenly without consulting your doctor, as withdrawal symptoms can occur.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
For depression, initial 75 mg/day, gradually increased to 150-200 mg/day. Tofranil-PM (imipramine pamoate) 150mg is typically given once daily at bedtime. Max 300 mg/day.
Dose Range:
75 - 300 mg
Condition-Specific Dosing:
depression:
Initial 75 mg/day, maintenance 150-200 mg/day (up to 300 mg/day in hospitalized patients).
panicDisorder:
Initial 25 mg/day, gradually increase to 75-150 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For nocturnal enuresis (ages 6 years and older): Initial 25 mg 1 hour before bedtime. If inadequate, may increase to 50 mg (6-12 years) or 75 mg (over 12 years). Max 2.5 mg/kg/day.
Adolescent:
For depression: Initial 25-50 mg/day, gradually increase to 100 mg/day (max 150 mg/day). For nocturnal enuresis: 75 mg at bedtime.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but use with caution.
Moderate:
Use with caution; consider lower doses and monitor for adverse effects.
Severe:
Use with caution; consider lower doses and monitor for adverse effects. Imipramine and its metabolites are primarily eliminated renally.
Dialysis:
Not significantly dialyzable. Use with caution; monitor for adverse effects.
Hepatic Impairment:
Mild:
Use with caution; consider lower doses.
Moderate:
Significant dose reduction required; monitor plasma levels and for adverse effects.
Severe:
Contraindicated or not recommended due to extensive hepatic metabolism and risk of accumulation.
Confidence:
Medium
Pharmacology
Mechanism of Action
Imipramine is a tricyclic antidepressant (TCA) that primarily inhibits the reuptake of norepinephrine (NE) and serotonin (5-HT) into presynaptic neurons, thereby increasing the concentrations of these neurotransmitters in the synaptic cleft. It also possesses significant anticholinergic, antihistaminic, and alpha-1 adrenergic blocking properties, which contribute to its side effect profile.
Pharmacokinetics
Absorption:
Bioavailability:
Variable (29-77%) due to extensive first-pass metabolism.
Tmax:
Imipramine (immediate release): 1-3 hours; Tofranil-PM (pamoate, extended release): 6-12 hours.
FoodEffect:
Food may delay absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
10-20 L/kg (large volume of distribution).
ProteinBinding:
>90% (primarily to albumin and alpha-1 acid glycoprotein).
CnssPenetration:
Yes (readily crosses the blood-brain barrier).
Elimination:
HalfLife:
Imipramine: 6-20 hours; Desipramine: 12-40 hours.
Clearance:
Approximately 0.5-1.5 L/kg/hr (highly variable).
ExcretionRoute:
Primarily renal (approximately 80% as metabolites), with some fecal excretion (approximately 20%).
Unchanged:
<5% (imipramine); <1% (desipramine)
Pharmacodynamics
OnsetOfAction:
Antidepressant effects typically begin within 2-4 weeks. Sedative and anticholinergic effects may be seen earlier.
PeakEffect:
Full therapeutic effect for depression may take 4-6 weeks.
DurationOfAction:
Due to long half-lives of parent drug and active metabolite, effects persist for 24 hours, allowing once-daily dosing for extended-release formulations.
Safety & Warnings
BLACK BOX WARNING
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 imipramine 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.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high or low blood pressure, including:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Confusion
Hallucinations (seeing or hearing things that are not there)
Sleep disturbances, such as trouble sleeping or bad dreams
Erectile dysfunction or changes in sex interest
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Yellow skin or eyes (jaundice)
Chest pain or pressure
Fast or abnormal heartbeat
Shortness of breath
Sudden weight gain or swelling in the arms or legs
Weakness on one side of the body
Trouble speaking or thinking
Changes in balance
Drooping on one side of the face
Blurred eyesight
Ringing in the ears
Burning, numbness, or tingling sensations
Trouble controlling body movements
Twitching
Seizures
Severe constipation or stomach pain (may indicate a bowel problem)
Trouble passing urine
Swelling
Mouth irritation or mouth sores
Enlarged breasts or nipple discharge
Swelling of the testicles
Hair loss
Monitoring for Eye Problems
Some people may be at a higher risk of developing eye problems while taking this medication. Your doctor may recommend an eye exam to assess your risk. If you experience any of the following symptoms, contact your doctor immediately:
Eye pain
Changes in eyesight
Swelling or redness in or around the eye
Serotonin Syndrome: A Potentially Life-Threatening Condition
There is a risk of developing serotonin syndrome, a severe and potentially deadly condition, especially when taking certain other medications. If you experience any of the following symptoms, seek medical attention right away:
Agitation
Changes in balance
Confusion
Hallucinations
Fever
Fast or abnormal heartbeat
Flushing
Muscle twitching or stiffness
Seizures
Shivering or shaking
Excessive sweating
Severe diarrhea, upset stomach, or vomiting
Severe headache
Other Possible Side Effects
While many people may not experience any side effects or only minor ones, it is essential to be aware of the following possible side effects:
Dizziness
Drowsiness
Fatigue
Weakness
Dry mouth
Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Changes in taste
Stomach cramps
Weight gain or loss
Excessive sweating
Flushing
Headache
If you experience any of these side effects or any other symptoms that concern you, contact your doctor for advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high or low blood pressure, including:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Confusion
Hallucinations (seeing or hearing things that are not there)
Sleep disturbances, such as trouble sleeping or bad dreams
Erectile dysfunction or changes in sex interest
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Yellow skin or eyes (jaundice)
Chest pain or pressure
Fast or abnormal heartbeat
Shortness of breath
Sudden weight gain or swelling in the arms or legs
Weakness on one side of the body
Trouble speaking or thinking
Changes in balance
Drooping on one side of the face
Blurred eyesight
Ringing in the ears
Burning, numbness, or tingling sensations
Trouble controlling body movements
Twitching
Seizures
Severe constipation or stomach pain (may indicate a bowel problem)
Trouble passing urine
Swelling
Mouth irritation or mouth sores
Enlarged breasts or nipple discharge
Swelling of the testicles
Hair loss
Monitoring for Eye Problems
Some people may be at a higher risk of developing eye problems while taking this medication. Your doctor may recommend an eye exam to assess your risk. If you experience any of the following symptoms, contact your doctor immediately:
Eye pain
Changes in eyesight
Swelling or redness in or around the eye
Serotonin Syndrome: A Potentially Life-Threatening Condition
There is a risk of developing serotonin syndrome, a severe and potentially deadly condition, especially when taking certain other medications. If you experience any of the following symptoms, seek medical attention right away:
Agitation
Changes in balance
Confusion
Hallucinations
Fever
Fast or abnormal heartbeat
Flushing
Muscle twitching or stiffness
Seizures
Shivering or shaking
Excessive sweating
Severe diarrhea, upset stomach, or vomiting
Severe headache
Other Possible Side Effects
While many people may not experience any side effects or only minor ones, it is essential to be aware of the following possible side effects:
Dizziness
Drowsiness
Fatigue
Weakness
Dry mouth
Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Changes in taste
Stomach cramps
Weight gain or loss
Excessive sweating
Flushing
Headache
If you experience any of these side effects or any other symptoms that concern you, contact your doctor for advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Worsening depression or new/worsening suicidal thoughts/behaviors, especially at the beginning of treatment or after dose changes.
- Signs of mania (e.g., increased energy, racing thoughts, severe insomnia, unusual happiness or irritability).
- Severe dizziness or fainting (orthostatic hypotension).
- Fast, pounding, or irregular heartbeat.
- Difficulty urinating or severe constipation.
- Blurred vision or eye pain.
- Fever, sore throat, or other signs of infection (rare, but can indicate blood dyscrasias).
- Seizures.
- Yellowing of skin or eyes (jaundice), dark urine, severe stomach pain (signs of liver problems).
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
If you have recently had a heart attack.
If you have taken certain medications for depression or Parkinson's disease within the last 14 days, including isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline, as this may lead to very high blood pressure.
If you are currently taking linezolid or methylene blue, as these medications can interact with this drug.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other treatments and health issues. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
If you have recently had a heart attack.
If you have taken certain medications for depression or Parkinson's disease within the last 14 days, including isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline, as this may lead to very high blood pressure.
If you are currently taking linezolid or methylene blue, as these medications can interact with this drug.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other treatments and health issues. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
Important Warnings and Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will provide guidance on when to resume taking it after the surgery or procedure.
Caution with Daily Activities
Until you understand how this medication affects you, avoid driving and other tasks that require alertness. To minimize the risk of dizziness or fainting, stand up slowly after sitting or lying down, and exercise caution when climbing stairs.
Stopping the Medication
Do not suddenly stop taking this medication without consulting your doctor, as this may increase the risk of side effects. If you need to discontinue the medication, your doctor will provide instructions on how to gradually stop taking it.
Special Considerations
If you have diabetes (high blood sugar), closely monitor your blood sugar levels while taking this medication. Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter medications that may cause drowsiness, discuss the potential risks with your doctor.
Delayed Effects and Sun Sensitivity
It may take several weeks to experience the full effects of this medication. Additionally, you may be more susceptible to sunburn, so avoid exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear.
Heat and Fluid Loss
Be cautious in hot weather or during physical activity, and drink plenty of fluids to prevent dehydration.
Medical Monitoring
Your doctor may recommend an electrocardiogram (ECG) before starting this medication and during treatment. If you are allergic to tartrazine (FD&C Yellow No. 5), a component of some products, inform your doctor.
Age and Pregnancy Considerations
If you are 65 or older, use this medication with caution, as you may be more prone to side effects. If you are pregnant or plan to become pregnant, discuss the benefits and risks of taking this medication with your doctor.
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will provide guidance on when to resume taking it after the surgery or procedure.
Caution with Daily Activities
Until you understand how this medication affects you, avoid driving and other tasks that require alertness. To minimize the risk of dizziness or fainting, stand up slowly after sitting or lying down, and exercise caution when climbing stairs.
Stopping the Medication
Do not suddenly stop taking this medication without consulting your doctor, as this may increase the risk of side effects. If you need to discontinue the medication, your doctor will provide instructions on how to gradually stop taking it.
Special Considerations
If you have diabetes (high blood sugar), closely monitor your blood sugar levels while taking this medication. Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter medications that may cause drowsiness, discuss the potential risks with your doctor.
Delayed Effects and Sun Sensitivity
It may take several weeks to experience the full effects of this medication. Additionally, you may be more susceptible to sunburn, so avoid exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear.
Heat and Fluid Loss
Be cautious in hot weather or during physical activity, and drink plenty of fluids to prevent dehydration.
Medical Monitoring
Your doctor may recommend an electrocardiogram (ECG) before starting this medication and during treatment. If you are allergic to tartrazine (FD&C Yellow No. 5), a component of some products, inform your doctor.
Age and Pregnancy Considerations
If you are 65 or older, use this medication with caution, as you may be more prone to side effects. If you are pregnant or plan to become pregnant, discuss the benefits and risks of taking this medication with your doctor.
Overdose Information
Overdose Symptoms:
- Severe drowsiness or confusion
- Agitation, hallucinations
- Dilated pupils
- Fast, irregular, or pounding heartbeat (arrhythmias)
- Low blood pressure (hypotension)
- Seizures
- Coma
- Respiratory depression
- Hyperthermia
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Overdose can be fatal, especially due to cardiac toxicity.
Drug Interactions
Contraindicated Interactions
- Monoamine Oxidase Inhibitors (MAOIs): Risk of serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes). Allow at least 14 days between discontinuing MAOIs and starting imipramine, and vice versa.
- Cisapride: Increased risk of QT prolongation and ventricular arrhythmias.
Major Interactions
- QT-prolonging drugs (e.g., Class IA and III antiarrhythmics, some antipsychotics, macrolide antibiotics, fluoroquinolones): Additive risk of QT prolongation and torsades de pointes.
- CNS Depressants (e.g., alcohol, benzodiazepines, opioids, sedatives, hypnotics): Potentiation of CNS depression.
- Anticholinergic agents (e.g., atropine, benztropine, antihistamines, some antipsychotics): Potentiation of anticholinergic effects (e.g., severe constipation, urinary retention, paralytic ileus, hyperpyrexia).
- Sympathomimetics (e.g., epinephrine, norepinephrine, phenylephrine, pseudoephedrine): Potentiation of cardiovascular effects (e.g., hypertension, arrhythmias).
- CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, quinidine, cimetidine): Significantly increase imipramine and desipramine plasma concentrations, increasing risk of toxicity. Dose reduction of imipramine may be necessary.
- Thyroid hormones: Increased risk of cardiac arrhythmias and enhanced antidepressant effects.
Moderate Interactions
- Antihypertensives (e.g., guanethidine, clonidine, reserpine): Imipramine may antagonize the hypotensive effects of these drugs.
- Anticoagulants (e.g., warfarin): TCAs may potentiate the effects of oral anticoagulants, requiring closer monitoring of INR.
- Barbiturates: May decrease imipramine plasma levels due to enzyme induction.
- Nicotine: May decrease imipramine plasma levels due to enzyme induction.
Minor Interactions
- Oral contraceptives: May increase or decrease TCA levels; monitor for efficacy/toxicity.
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess for pre-existing cardiac conduction abnormalities or risk factors for arrhythmias, especially in elderly patients or those with cardiac disease.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: Imipramine is extensively metabolized by the liver; to assess baseline hepatic function.
Timing: Prior to initiation of therapy.
Renal Function (BUN, Creatinine)
Rationale: To assess baseline renal function, as metabolites are renally excreted.
Timing: Prior to initiation of therapy.
Blood Pressure (BP) and Heart Rate (HR)
Rationale: To establish baseline and monitor for orthostatic hypotension and tachycardia.
Timing: Prior to initiation of therapy (supine and standing).
Psychiatric Evaluation (Mood, Suicidality)
Rationale: To establish baseline severity of depression, assess for suicidality, and rule out bipolar disorder (risk of mania).
Timing: Prior to initiation of therapy.
Routine Monitoring
Plasma Imipramine and Desipramine Levels
Frequency: After 5-7 days of stable dosing, then periodically as needed (e.g., with dose changes, suspected non-adherence, or toxicity).
Target: 150-300 ng/mL (sum of imipramine and desipramine).
Action Threshold: Levels above 300 ng/mL may increase risk of toxicity (e.g., cardiac arrhythmias, seizures); levels below 150 ng/mL may indicate subtherapeutic dosing.
Electrocardiogram (ECG)
Frequency: Periodically, especially in elderly patients, those with cardiac risk factors, or at higher doses.
Target: Normal PR, QRS, QT intervals.
Action Threshold: Significant prolongation of PR, QRS (>100 ms), or QTc (>450 ms in males, >470 ms in females) may warrant dose reduction or discontinuation.
Blood Pressure (BP) and Heart Rate (HR)
Frequency: Regularly, especially during dose titration.
Target: Within patient's normal range.
Action Threshold: Significant orthostatic hypotension (e.g., drop >20 mmHg systolic or >10 mmHg diastolic) or persistent tachycardia.
Mental Status and Suicidality Assessment
Frequency: Frequent monitoring, especially during initial therapy and dose changes.
Target: Improvement in mood, absence of suicidal ideation.
Action Threshold: Worsening depression, emergence of suicidal thoughts or behaviors, agitation, mania/hypomania.
Symptom Monitoring
- Orthostatic hypotension (dizziness upon standing)
- Anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention)
- Sedation or drowsiness
- Tachycardia or palpitations
- Tremor
- Nausea, vomiting
- Weight gain
- Sexual dysfunction
- Agitation, anxiety, insomnia
- Signs of mania/hypomania (in bipolar patients)
- New or worsening suicidal thoughts/behaviors
Special Patient Groups
Pregnancy
Imipramine is classified as Pregnancy Category D. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal withdrawal symptoms have been reported.
Trimester-Specific Risks:
First Trimester:
Limited data on teratogenicity, but some studies suggest a possible association with limb reduction defects, though causality is not established. Risk is generally considered low.
Second Trimester:
Risk of fetal exposure and potential for adverse effects on fetal development.
Third Trimester:
Risk of neonatal withdrawal syndrome (e.g., respiratory distress, cyanosis, irritability, feeding difficulties, seizures, tremors, hypertonia/hypotonia) if exposed late in pregnancy. Cardiac effects (tachycardia, arrhythmias) have also been reported in neonates.
Lactation
Imipramine and its active metabolite, desipramine, are excreted into breast milk. The American Academy of Pediatrics considers imipramine to be a drug for which the effect on the nursing infant is unknown but may be of concern. Use with caution.
Infant Risk:
Monitor breastfed infants for sedation, poor feeding, weight gain, and anticholinergic effects (e.g., constipation, urinary retention). Consider therapeutic drug monitoring in the infant if concerns arise. Lower doses or alternative agents may be preferred, especially in neonates.
Pediatric Use
Imipramine has a Black Box Warning for increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults. It is approved for nocturnal enuresis in children 6 years and older. Use for depression in pediatric patients should be carefully considered, balancing risks and benefits, with close monitoring for suicidality and behavioral changes.
Geriatric Use
Elderly patients are more sensitive to the anticholinergic, sedative, and cardiovascular (orthostatic hypotension, cardiac conduction abnormalities) side effects of imipramine. Start with lower doses and titrate slowly. Monitor ECG, blood pressure, and for cognitive impairment. Avoid in patients with severe cardiac disease, glaucoma, or prostatic hypertrophy.
Clinical Information
Clinical Pearls
- Imipramine has a narrow therapeutic index; therapeutic drug monitoring (TDM) of plasma imipramine and desipramine levels can be useful, especially in cases of non-response, suspected toxicity, or significant drug interactions.
- Due to its significant anticholinergic and alpha-1 adrenergic blocking effects, imipramine is often less tolerated than newer antidepressants (SSRIs, SNRIs).
- Cardiac conduction abnormalities (e.g., QRS widening, QT prolongation) are a significant concern, especially in overdose or in patients with pre-existing cardiac disease. Baseline and periodic ECGs are recommended.
- Orthostatic hypotension is common, particularly in the elderly, and can lead to falls.
- Tofranil-PM (imipramine pamoate) was an extended-release formulation, typically dosed once daily at bedtime, which could improve adherence and reduce peak-related side effects compared to immediate-release formulations.
- Withdrawal symptoms (e.g., nausea, vomiting, dizziness, headache, anxiety, agitation, sleep disturbances) can occur if discontinued abruptly; taper dose gradually.
Alternative Therapies
- Other Tricyclic Antidepressants (TCAs): Amitriptyline, Nortriptyline, Doxepin, Desipramine (active metabolite of imipramine)
- Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Venlafaxine, Duloxetine
- Atypical Antidepressants: Bupropion, Mirtazapine
- Electroconvulsive Therapy (ECT) for severe depression
Cost & Coverage
Average Cost:
Not applicable (Tofranil-PM discontinued) Not applicable
Generic Available:
Yes
Insurance Coverage:
Tier 1 or 2 (for generic imipramine)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, do not share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which is a patient fact sheet that provides important information. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, consult with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.