Tofranil-PM 125mg 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
Antidepressant
Pharmacologic Class
Tricyclic Antidepressant (TCA); Norepinephrine and Serotonin Reuptake Inhibitor (NSRI)
Pregnancy Category
Category C
FDA Approved
Mar 1959
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tofranil-PM is a medication called a tricyclic antidepressant (TCA). It works by helping to balance certain natural chemicals in your brain that affect mood. It's used to treat depression. The 'PM' means it's an extended-release capsule designed to be taken once a day, usually at bedtime, to help with symptoms of depression.
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 this medication, discuss it 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. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs available 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 this medication, discuss it 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. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs available 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
- Take exactly as prescribed, usually once daily at bedtime. Do not crush, chew, or open the capsule.
- Avoid alcohol and other CNS depressants, as they can increase drowsiness and other side effects.
- Be aware of potential for drowsiness or dizziness, especially when starting the medication or increasing the dose. Avoid driving or operating heavy machinery until you know how it affects you.
- Rise slowly from a sitting or lying position to prevent dizziness from low blood pressure.
- Manage common side effects like dry mouth (sugar-free candy/gum, sips of water), constipation (increase fiber and fluids), and blurred vision (usually temporary).
- Do not stop taking this medication suddenly without consulting your doctor, as it can lead to withdrawal symptoms.
- Report any new or worsening symptoms, especially changes in mood, behavior, or thoughts of self-harm, to your doctor immediately.
- Inform your doctor and pharmacist about all other medications, supplements, and herbal products you are taking to avoid harmful interactions.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
75 mg to 150 mg daily, given as a single dose at bedtime (for Tofranil-PM, extended-release). May be increased to 200 mg daily if needed. Max 300 mg daily for hospitalized patients.
Dose Range:
75 - 300 mg
Condition-Specific Dosing:
Depression (outpatient):
75 mg to 150 mg daily, usually as a single bedtime dose. Initial: 75 mg daily, may increase by 25 mg to 50 mg increments up to 150 mg daily. Maintenance: 50 mg to 150 mg daily.
Depression (hospitalized):
Initial: 100 mg to 150 mg daily in divided doses, gradually increased to 200 mg daily. Max 300 mg daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not indicated for depression in children under 12. For nocturnal enuresis (Tofranil, not PM): 6-12 years: 25-50 mg at bedtime. >12 years: 50-75 mg at bedtime.
Adolescent:
For depression: Initial 30-40 mg daily, may increase to 75-100 mg daily in divided doses or as a single bedtime dose. Max 100 mg daily.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment recommended, monitor for adverse effects.
Moderate:
Use with caution, consider lower doses and monitor plasma levels if available.
Severe:
Use with caution, consider lower doses and monitor plasma levels if available. Imipramine and its metabolites are primarily eliminated renally.
Dialysis:
Not significantly dialyzable due to high protein binding and large volume of distribution. Use with caution, monitor for adverse effects.
Hepatic Impairment:
Mild:
Use with caution, monitor for adverse effects.
Moderate:
Use with caution, consider lower doses and monitor plasma levels. Imipramine is extensively metabolized by the liver.
Severe:
Contraindicated or use with extreme caution at significantly reduced doses. Monitor closely for toxicity. Imipramine is extensively metabolized by the liver.
Pharmacology
Mechanism of Action
Imipramine is a tricyclic antidepressant (TCA) that primarily inhibits the reuptake of norepinephrine and serotonin at presynaptic neuronal membranes in the central nervous system (CNS). This leads to increased concentrations of these neurotransmitters in the synaptic cleft, enhancing their activity. It also has significant anticholinergic, antihistaminic, and alpha-1 adrenergic blocking properties, which contribute to its side effect profile.
Pharmacokinetics
Absorption:
Bioavailability:
29-77% (highly variable due to first-pass metabolism)
Tmax:
1-2 hours (for immediate release); Tofranil-PM (extended release) would have a delayed Tmax, typically 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:
86-95%
CnssPenetration:
Yes (readily crosses the blood-brain barrier)
Elimination:
HalfLife:
9-24 hours (imipramine); 12-54 hours (desipramine)
Clearance:
Not readily available, but extensive hepatic metabolism.
ExcretionRoute:
Approximately 80% renal (as metabolites), 20% fecal.
Unchanged:
<5% (imipramine); <1% (desipramine)
Pharmacodynamics
OnsetOfAction:
Antidepressant effects typically begin within 1-4 weeks, with full effect seen after 4-6 weeks.
PeakEffect:
Peak plasma concentrations for Tofranil-PM are typically 6-12 hours post-dose. Clinical peak effect for depression is weeks.
DurationOfAction:
Due to long half-life, once-daily dosing is appropriate for extended-release formulations. Effects persist as long as drug is present.
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
While rare, some people may experience severe and potentially life-threatening side effects when 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 or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of high or low blood pressure, including:
+ Severe headache or dizziness
+ Passing out or changes in eyesight
Confusion or hallucinations (seeing or hearing things that are not there)
Trouble sleeping or experiencing bad dreams
Erectile dysfunction or changes in sex interest
Fever, chills, or sore throat
Unexplained bruising or bleeding, or 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, or changes in balance
Drooping on one side of the face or blurred eyesight
Ringing in the ears
Burning, numbness, or tingling sensations that are not normal
Trouble controlling body movements, twitching, or changes in balance
Trouble swallowing or speaking
Seizures
Severe constipation or stomach pain (which may be signs of a severe bowel problem)
Trouble passing urine
Swelling
Mouth irritation or mouth sores
Enlarged breasts or nipple discharge
Swelling of the testicles
Hair loss
Additional Warnings
Some people may be at a higher risk of developing eye problems when taking this medication. Your doctor may recommend an eye exam to assess your risk. If you experience eye pain, changes in eyesight, or swelling or redness in or around the eye, contact your doctor immediately.
There is also a risk of a severe and potentially life-threatening condition called serotonin syndrome, especially when taking certain other medications. Seek medical help right away if you experience:
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
Common Side Effects
Most people taking this medication will not experience severe side effects, but may still encounter some minor issues. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Dizziness, drowsiness, tiredness, or weakness
Dry mouth
Constipation, diarrhea, stomach pain, upset stomach, vomiting, or decreased appetite
Changes in taste
Stomach cramps
Weight gain or loss
Excessive sweating
Flushing
Headache
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when 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 or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of high or low blood pressure, including:
+ Severe headache or dizziness
+ Passing out or changes in eyesight
Confusion or hallucinations (seeing or hearing things that are not there)
Trouble sleeping or experiencing bad dreams
Erectile dysfunction or changes in sex interest
Fever, chills, or sore throat
Unexplained bruising or bleeding, or 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, or changes in balance
Drooping on one side of the face or blurred eyesight
Ringing in the ears
Burning, numbness, or tingling sensations that are not normal
Trouble controlling body movements, twitching, or changes in balance
Trouble swallowing or speaking
Seizures
Severe constipation or stomach pain (which may be signs of a severe bowel problem)
Trouble passing urine
Swelling
Mouth irritation or mouth sores
Enlarged breasts or nipple discharge
Swelling of the testicles
Hair loss
Additional Warnings
Some people may be at a higher risk of developing eye problems when taking this medication. Your doctor may recommend an eye exam to assess your risk. If you experience eye pain, changes in eyesight, or swelling or redness in or around the eye, contact your doctor immediately.
There is also a risk of a severe and potentially life-threatening condition called serotonin syndrome, especially when taking certain other medications. Seek medical help right away if you experience:
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
Common Side Effects
Most people taking this medication will not experience severe side effects, but may still encounter some minor issues. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Dizziness, drowsiness, tiredness, or weakness
Dry mouth
Constipation, diarrhea, stomach pain, upset stomach, vomiting, or decreased appetite
Changes in taste
Stomach cramps
Weight gain or loss
Excessive sweating
Flushing
Headache
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor. 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 suicidal thoughts/behavior (especially in young adults)
- New or worsening anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (restlessness), hypomania, or mania
- Severe dizziness or fainting (orthostatic hypotension)
- Fast, pounding, or irregular heartbeat (palpitations, arrhythmias)
- Chest pain
- Difficulty urinating or inability to urinate
- Severe constipation or abdominal pain (suggesting paralytic ileus)
- Blurred vision or eye pain (especially with sudden onset, could indicate angle-closure glaucoma)
- Fever, sore throat, or other signs of infection (could indicate blood dyscrasias)
- Yellowing of skin or eyes (jaundice), dark urine, severe stomach pain (signs of liver problems)
- Seizures
- Rash or allergic reaction
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:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
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 increase the risk of 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 problems with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other medications and health conditions. 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:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
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 increase the risk of 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 problems with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
Important Warnings and Precautions
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 undergoing certain types of surgery. If you need to stop taking this medication, your doctor will provide guidance on when to resume taking it after your surgery or procedure.
Caution with Daily Activities
Until you understand how this medication affects you, avoid driving and engaging in activities that require alertness. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying down position. Be cautious when climbing stairs.
Discontinuing the Medication
Do not stop taking this medication abruptly without consulting your doctor, as this may increase the risk of side effects. If you need to discontinue this medication, your doctor will instruct you on how to gradually stop taking it.
Special Considerations
If you have diabetes (high blood sugar), closely monitor your blood sugar levels. Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter medications that may cause drowsiness, consult with your doctor.
Delayed Effects and Sun Sensitivity
It may take several weeks to experience the full effects of this medication. You may be more susceptible to sunburn, so avoid exposure to sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard against the sun.
Heat and Fluid Loss
Be cautious in hot weather or during physical activity, and drink plenty of fluids to prevent dehydration.
Electrocardiogram (ECG) Monitoring
Your doctor may require an ECG test before starting this medication and during treatment. Discuss this with your doctor.
Allergies and Age-Related Considerations
If you are allergic to tartrazine (FD&C Yellow No. 5), inform your doctor, as some products contain this ingredient. If you are 65 years or older, use this medication with caution, as you may be more prone to side effects.
Pregnancy and Breastfeeding
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 undergoing certain types of surgery. If you need to stop taking this medication, your doctor will provide guidance on when to resume taking it after your surgery or procedure.
Caution with Daily Activities
Until you understand how this medication affects you, avoid driving and engaging in activities that require alertness. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying down position. Be cautious when climbing stairs.
Discontinuing the Medication
Do not stop taking this medication abruptly without consulting your doctor, as this may increase the risk of side effects. If you need to discontinue this medication, your doctor will instruct you on how to gradually stop taking it.
Special Considerations
If you have diabetes (high blood sugar), closely monitor your blood sugar levels. Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter medications that may cause drowsiness, consult with your doctor.
Delayed Effects and Sun Sensitivity
It may take several weeks to experience the full effects of this medication. You may be more susceptible to sunburn, so avoid exposure to sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard against the sun.
Heat and Fluid Loss
Be cautious in hot weather or during physical activity, and drink plenty of fluids to prevent dehydration.
Electrocardiogram (ECG) Monitoring
Your doctor may require an ECG test before starting this medication and during treatment. Discuss this with your doctor.
Allergies and Age-Related Considerations
If you are allergic to tartrazine (FD&C Yellow No. 5), inform your doctor, as some products contain this ingredient. If you are 65 years or older, use this medication with caution, as you may be more prone to side effects.
Pregnancy and Breastfeeding
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 coma
- Confusion, agitation, hallucinations
- Dilated pupils
- Fast, irregular, or pounding heartbeat (tachycardia, arrhythmias)
- Low blood pressure (hypotension)
- Seizures
- Respiratory depression (slow, shallow breathing)
- Urinary retention
- Dry mouth, hot, flushed skin
- Muscle rigidity or spasms
- Hyperthermia (high body temperature)
What to Do:
Seek immediate emergency medical attention. Call 911 or Poison Control (1-800-222-1222). Overdose can be fatal, especially due to cardiac and CNS effects. Treatment is supportive, including gastric lavage, activated charcoal, continuous ECG monitoring, and management of arrhythmias, hypotension, and seizures.
Drug Interactions
Contraindicated Interactions
- Monoamine Oxidase Inhibitors (MAOIs) (risk of serotonin syndrome, hyperpyretic crises, convulsions, death)
- Cisapride (risk of QT prolongation, arrhythmias)
- Thioridazine (risk of QT prolongation, arrhythmias)
Major Interactions
- Other CNS depressants (e.g., alcohol, benzodiazepines, opioids) (additive CNS depression)
- Anticholinergic agents (e.g., atropine, scopolamine, antihistamines) (additive anticholinergic effects, paralytic ileus)
- Sympathomimetics (e.g., epinephrine, norepinephrine, phenylephrine) (potentiated pressor response)
- Antiarrhythmics (e.g., quinidine, propafenone, flecainide) (increased risk of arrhythmias, QT prolongation)
- SSRIs (e.g., fluoxetine, paroxetine) (inhibition of imipramine metabolism, increased TCA levels, serotonin syndrome risk)
- Cimetidine (inhibition of imipramine metabolism, increased TCA levels)
- Thyroid hormones (increased risk of cardiac arrhythmias)
- Anticoagulants (e.g., warfarin) (potential for increased anticoagulant effect)
- Clonidine (potential for hypertensive crisis upon clonidine withdrawal)
Moderate Interactions
- Barbiturates (may decrease imipramine levels)
- Phenytoin (imipramine may increase phenytoin levels, phenytoin may decrease imipramine levels)
- Oral contraceptives (may increase imipramine levels)
- Nicotine (may decrease imipramine levels)
- Grapefruit juice (may increase imipramine levels)
- St. John's Wort (risk of serotonin syndrome)
Minor Interactions
- Not typically categorized as minor for TCAs due to broad interaction profile.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To establish baseline and monitor for blood dyscrasias (rare, but serious).
Timing: Prior to initiation
Electrocardiogram (ECG)
Rationale: To assess for pre-existing cardiac conduction abnormalities, especially in elderly or those with cardiac history, due to risk of QT prolongation and arrhythmias.
Timing: Prior to initiation
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, as imipramine is extensively metabolized by the liver.
Timing: Prior to initiation
Renal Function Tests (BUN, Creatinine)
Rationale: To assess baseline renal function, especially in elderly or those with renal impairment.
Timing: Prior to initiation
Blood Pressure (BP) and Heart Rate (HR)
Rationale: To establish baseline and monitor for orthostatic hypotension and tachycardia.
Timing: Prior to initiation
Weight
Rationale: To establish baseline and monitor for weight changes.
Timing: Prior to initiation
Psychiatric Evaluation (mood, suicidality)
Rationale: To establish baseline severity of depression and assess for risk of suicidality.
Timing: Prior to initiation
Routine Monitoring
Blood Pressure (BP) and Heart Rate (HR)
Frequency: Regularly, especially during dose titration and in elderly patients.
Target: Maintain within normal limits, monitor for orthostatic changes.
Action Threshold: Significant orthostatic hypotension (e.g., >20 mmHg drop in systolic BP) or persistent tachycardia.
ECG
Frequency: Periodically, especially with dose increases, in elderly, or those with cardiac risk factors. Annually for long-term therapy.
Target: Normal sinus rhythm, PR, QRS, QT intervals within normal limits for age/sex.
Action Threshold: Significant QT prolongation (>500 ms or >60 ms increase from baseline), new arrhythmias, or conduction disturbances.
Liver Function Tests (LFTs)
Frequency: Periodically, especially if symptoms of hepatic dysfunction develop.
Target: Within normal limits.
Action Threshold: Significant elevation of transaminases (e.g., >3x ULN).
Complete Blood Count (CBC)
Frequency: Periodically, especially if signs of infection or unexplained bleeding/bruising occur.
Target: Within normal limits.
Action Threshold: Significant leukopenia, agranulocytosis, or thrombocytopenia.
Therapeutic Drug Monitoring (TDM) - Imipramine + Desipramine levels
Frequency: Consider for non-responders, those with adverse effects, suspected non-adherence, or significant drug interactions. Typically after 5-7 half-lives (e.g., 1-2 weeks after dose change).
Target: 150-300 ng/mL (sum of imipramine and desipramine)
Action Threshold: Levels outside therapeutic range, especially above 300 ng/mL (increased toxicity risk) or below 150 ng/mL (potential for non-response).
Weight
Frequency: Periodically (e.g., every 3-6 months).
Target: Stable or within acceptable range.
Action Threshold: Significant or undesirable weight gain.
Psychiatric Status (mood, suicidality, anxiety, sleep, energy)
Frequency: Regularly, especially during initial treatment and dose changes (weekly for first 4 weeks, then monthly).
Target: Improvement in depressive symptoms, absence of suicidal ideation.
Action Threshold: Worsening depression, emergence or worsening of suicidal thoughts/behaviors, agitation, mania/hypomania.
Symptom Monitoring
- Dry mouth
- Constipation
- Blurred vision
- Urinary retention
- Dizziness/lightheadedness (especially on standing)
- Sedation/drowsiness
- Tremor
- Sweating
- Nausea/vomiting
- Sexual dysfunction
- Agitation/restlessness
- Insomnia
- New or worsening suicidal thoughts or behavior
- Mania/hypomania (e.g., elevated mood, increased energy, decreased need for sleep, racing thoughts)
- Seizures
- Cardiac symptoms (e.g., palpitations, chest pain, fainting)
Special Patient Groups
Pregnancy
Use during pregnancy should only be considered if the potential benefit justifies the potential risk to the fetus. Imipramine crosses the placenta. Neonates exposed to TCAs in the third trimester have developed withdrawal symptoms (e.g., respiratory distress, cyanosis, apnea, seizures, feeding difficulties, hypotonia, hypertonia, tremor, jitteriness, irritability, constant crying).
Trimester-Specific Risks:
First Trimester:
Some studies suggest a possible, but not consistently proven, increased risk of congenital malformations (e.g., limb reduction defects, cardiovascular defects). Data are conflicting and generally do not show a consistent pattern of major malformations.
Second Trimester:
Risk of withdrawal symptoms in neonate if exposure continues into third trimester.
Third Trimester:
Increased risk of neonatal withdrawal symptoms (e.g., respiratory distress, feeding difficulties, irritability, tremor, seizures) and persistent pulmonary hypertension of the newborn (PPHN) if exposed late in pregnancy.
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. Monitor infants for sedation, poor feeding, and weight gain. Use with caution, or consider an alternative if possible.
Infant Risk:
L3 (Moderate risk) - Monitor infant for drowsiness, poor feeding, and weight gain. Consider therapeutic drug monitoring in the infant if concerns arise.
Pediatric Use
Not approved for depression in children under 12 years. For nocturnal enuresis, it is used in children 6 years and older (Tofranil, not PM). Black Box Warning regarding increased risk of suicidality in children, adolescents, and young adults. Close monitoring is essential.
Geriatric Use
Elderly patients are more sensitive to the anticholinergic, sedative, and hypotensive effects of imipramine. Start with lower doses (e.g., 30-40 mg daily) and titrate slowly. Increased risk of orthostatic hypotension, falls, cognitive impairment, and cardiac conduction abnormalities. Monitor ECG, blood pressure, and cognitive function closely. Consider lower target therapeutic plasma levels.
Clinical Information
Clinical Pearls
- Tofranil-PM is an extended-release formulation, designed for once-daily dosing, typically at bedtime, to minimize daytime sedation and improve adherence.
- Imipramine has significant anticholinergic side effects (dry mouth, constipation, blurred vision, urinary retention), which can be particularly bothersome in the elderly.
- Orthostatic hypotension is a common and potentially serious side effect, especially at treatment initiation and dose increases. Advise patients to rise slowly.
- Cardiac conduction abnormalities (e.g., QT prolongation, widened QRS) are a concern, especially in overdose or in patients with pre-existing cardiac disease. ECG monitoring is crucial.
- Therapeutic drug monitoring (TDM) for imipramine and desipramine levels can be useful in cases of non-response, suspected toxicity, or significant drug interactions.
- Due to its long half-life and active metabolite, it takes several days to reach steady-state plasma concentrations and weeks for full antidepressant effect.
- Abrupt discontinuation can lead to withdrawal symptoms (e.g., nausea, vomiting, dizziness, headache, irritability, sleep disturbance). Taper slowly when discontinuing.
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, Desvenlafaxine
- Atypical Antidepressants: Bupropion, Mirtazapine, Trazodone
- Electroconvulsive Therapy (ECT)
- Psychotherapy (e.g., Cognitive Behavioral Therapy - CBT)
Cost & Coverage
Average Cost:
$50 - $200 per 30 capsules (125mg)
Generic Available:
Yes
Insurance Coverage:
Typically Tier 1 or Tier 2 for generic imipramine. Brand name Tofranil-PM may be Tier 3 or require prior authorization.
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, it's crucial to seek immediate medical attention. Call your local poison control center or visit the emergency room right away. When seeking help, be prepared to provide detailed information about the overdose, including the name of the medication taken, the amount consumed, and the time it occurred.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, it's crucial to seek immediate medical attention. Call your local poison control center or visit the emergency room right away. When seeking help, be prepared to provide detailed information about the overdose, including the name of the medication taken, the amount consumed, and the time it occurred.