Tofranil-PM 75mg 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 D
FDA Approved
Mar 1959
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tofranil-PM is a medication used to treat depression. It belongs to a class of drugs called tricyclic antidepressants (TCAs). It works by helping to restore the balance of certain natural substances (neurotransmitters) in the brain. Because Tofranil-PM is an extended-release capsule, it is usually taken once a day, typically at bedtime, to help manage 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 your medication, discuss this with your doctor, as they may need to adjust your dose 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, check with your pharmacist for guidance on the best disposal method. You may also want to inquire about 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, discuss this with your doctor, as they may need to adjust your dose 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, check with your pharmacist for guidance on the best disposal method. You may also want to inquire about 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
- Take exactly as prescribed, usually once daily at bedtime. Do not crush, chew, or open the capsule.
- Avoid alcohol, as it can increase drowsiness and other side effects.
- Be cautious when driving or operating machinery until you know how this medication affects you, as it can cause drowsiness, dizziness, or blurred vision.
- Avoid sudden changes in position (e.g., standing up quickly from a sitting or lying position) to prevent dizziness or lightheadedness due to orthostatic hypotension.
- Maintain good oral hygiene and use sugarless candy/gum for dry mouth.
- Increase fiber and fluid intake to help with constipation.
- Inform your doctor about all other medications, supplements, and herbal products you are taking, especially St. John's Wort.
- Do not stop taking this medication suddenly without consulting your doctor, as it can lead to withdrawal symptoms.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
75 mg orally once daily at bedtime (Tofranil-PM)
Dose Range:
75 - 200 mg
Condition-Specific Dosing:
Depression (outpatient):
Initially 75 mg once daily at bedtime; may increase by 25-50 mg/day every few days as tolerated, up to 150 mg/day. Max 200 mg/day.
Depression (hospitalized):
Initially 100-150 mg once daily at bedtime; may increase gradually up to 200 mg/day. Max 300 mg/day (rarely).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not indicated for depression. For nocturnal enuresis (imipramine HCl, not Tofranil-PM): 25-75 mg orally once daily at bedtime, depending on age/weight.
Adolescent:
Not indicated for depression due to Black Box Warning. For nocturnal enuresis (imipramine HCl, not Tofranil-PM): 50-75 mg orally once daily at bedtime.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor for adverse effects.
Moderate:
Use with caution; consider lower doses and monitor plasma levels if available.
Severe:
Use with caution; consider significant dose reduction (e.g., 50%) and monitor plasma levels. Avoid if possible.
Dialysis:
Not significantly dialyzable. Use with caution; consider lower doses.
Hepatic Impairment:
Mild:
Use with caution; monitor for adverse effects.
Moderate:
Consider significant dose reduction (e.g., 50%) and monitor plasma levels. Avoid if possible.
Severe:
Contraindicated or not recommended due to extensive hepatic metabolism and risk of accumulation and toxicity.
Pharmacology
Mechanism of Action
Imipramine is a tricyclic antidepressant (TCA) that primarily inhibits the reuptake of norepinephrine (NE) and serotonin (5-HT) at the presynaptic neuronal membrane, thereby increasing the concentration of these neurotransmitters in the synaptic cleft. It also possesses significant anticholinergic, antihistaminic (H1), and alpha-1 adrenergic blocking properties, which contribute to its side effect profile.
Pharmacokinetics
Absorption:
Bioavailability:
29-77% (variable due to significant first-pass metabolism)
Tmax:
Imipramine: 6-12 hours (Tofranil-PM, extended-release); Desipramine (active metabolite): 9-24 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
Elimination:
HalfLife:
Imipramine: 6-20 hours; Desipramine: 12-40 hours (Tofranil-PM provides sustained release, extending effective half-life)
Clearance:
Variable, dependent on hepatic metabolism
ExcretionRoute:
Renal (approximately 80%), Fecal (approximately 20%)
Unchanged:
<5%
Pharmacodynamics
OnsetOfAction:
Antidepressant effects: 2-4 weeks; Sedative/anticholinergic effects: within hours to days
PeakEffect:
Antidepressant effect: 4-6 weeks
DurationOfAction:
Long, due to long half-life and active metabolite; allows for once-daily dosing with extended-release formulation.
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 Tofranil-PM 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 High or Low Blood Sugar
Inform your doctor if you experience any signs of high or low blood sugar, including:
Breath that smells like fruit
Dizziness
Fast breathing
Fast heartbeat
Feeling confused, sleepy, or weak
Flushing
Headache
Unusual thirst or hunger
Passing urine more often
Shaking or sweating
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 called serotonin syndrome may occur, especially if you are 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, stomach upset, 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 have concerns about other symptoms, contact your doctor for guidance. 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 High or Low Blood Sugar
Inform your doctor if you experience any signs of high or low blood sugar, including:
Breath that smells like fruit
Dizziness
Fast breathing
Fast heartbeat
Feeling confused, sleepy, or weak
Flushing
Headache
Unusual thirst or hunger
Passing urine more often
Shaking or sweating
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 called serotonin syndrome may occur, especially if you are 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, stomach upset, 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 have concerns about other symptoms, contact your doctor for guidance. 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/behaviors, especially at the beginning of treatment or after a dose change.
- New or worsening anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (restlessness), hypomania, or mania.
- Severe dizziness or fainting (signs of orthostatic hypotension).
- Fast, pounding, or irregular heartbeat.
- Difficulty urinating or severe constipation.
- Blurred vision or eye pain.
- Seizures.
- Fever, sore throat, or other signs of infection (rare, but serious).
- Yellowing of the skin or eyes (jaundice), dark urine, or persistent nausea/vomiting (signs of liver problems).
- Rash or severe 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. Be sure to describe the symptoms 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 determine if it is safe for you to take this medication with your other medications and health issues. Never start, stop, or change the dosage 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. Be sure to describe the symptoms 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 determine if it is safe for you to take this medication with your other medications and health issues. Never start, stop, or change the dosage 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, rise slowly from a sitting or lying position. Be cautious when navigating stairs.
Stopping the Medication
Do not abruptly 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. 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. Additionally, you may be more susceptible to sunburn. Avoid exposure to direct 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
You may need to undergo an electrocardiogram (ECG) 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 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, rise slowly from a sitting or lying position. Be cautious when navigating stairs.
Stopping the Medication
Do not abruptly 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. 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. Additionally, you may be more susceptible to sunburn. Avoid exposure to direct 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
You may need to undergo an electrocardiogram (ECG) 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 confusion
- Severe dry mouth
- Blurred vision
- Dilated pupils
- Fast, irregular, or pounding heartbeat (tachycardia, arrhythmias)
- Low blood pressure (hypotension)
- Fever
- Muscle rigidity or spasms
- Agitation, hallucinations, delirium
- Seizures
- Coma
- Respiratory depression
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. For poison control, call 1-800-222-1222. Bring the medication bottle with you.
Drug Interactions
Contraindicated Interactions
- Monoamine Oxidase Inhibitors (MAOIs) (risk of serotonin syndrome, hypertensive crisis)
- Cisapride (risk of QT prolongation and arrhythmias)
Major Interactions
- Other QT-prolonging drugs (e.g., antiarrhythmics like quinidine, procainamide, amiodarone, sotalol; certain antipsychotics like thioridazine, ziprasidone; macrolide antibiotics; fluoroquinolones) - increased risk of torsades de pointes.
- CNS depressants (e.g., alcohol, benzodiazepines, opioids, hypnotics, sedatives) - additive CNS depression.
- Anticholinergic agents (e.g., atropine, scopolamine, antihistamines, antipsychotics) - additive anticholinergic effects (severe constipation, urinary retention, paralytic ileus, hyperpyrexia).
- CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, quinidine, cimetidine) - significantly increase imipramine and desipramine plasma concentrations, increasing toxicity risk.
- Sympathomimetics (e.g., epinephrine, norepinephrine, phenylephrine, pseudoephedrine) - potentiated pressor response, risk of hypertensive crisis.
- Thyroid hormones - increased risk of cardiac arrhythmias and toxicity.
Moderate Interactions
- Antihypertensives (e.g., guanethidine, clonidine, reserpine) - imipramine may antagonize their hypotensive effects.
- Other antidepressants (e.g., SSRIs, SNRIs) - increased risk of serotonin syndrome if combined with other serotonergic agents.
- Anticoagulants (e.g., warfarin) - potential for increased anticoagulant effect (monitor INR).
- Barbiturates - may decrease imipramine plasma levels due to enzyme induction.
- Nicotine - may decrease imipramine plasma levels.
Minor Interactions
- Oral contraceptives - may increase imipramine plasma levels.
- Grapefruit juice - may inhibit CYP3A4, potentially increasing imipramine levels (minor effect).
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess for pre-existing cardiac conduction abnormalities or QT prolongation, especially in elderly patients or those with cardiac history, due to imipramine's potential for cardiotoxicity.
Timing: Prior to initiation of therapy
Blood Pressure (BP) and Heart Rate (HR)
Rationale: To establish baseline and monitor for orthostatic hypotension or tachycardia.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs)
Rationale: To assess hepatic function, as imipramine is extensively metabolized by the liver.
Timing: Prior to initiation of therapy
Renal Function (BUN, Creatinine)
Rationale: To assess renal function, as metabolites are primarily renally excreted.
Timing: Prior to initiation of therapy
Complete Blood Count (CBC) with differential
Rationale: To establish baseline and monitor for rare but serious hematologic abnormalities (e.g., agranulocytosis, thrombocytopenia).
Timing: Prior to initiation of therapy
Electrolytes (Potassium, Magnesium)
Rationale: To assess for electrolyte imbalances that could predispose to arrhythmias.
Timing: Prior to initiation of therapy
Weight
Rationale: To establish baseline and monitor for weight changes.
Timing: Prior to initiation of therapy
Psychiatric Evaluation (mood, suicidality, anxiety)
Rationale: To establish baseline symptom severity and monitor for changes, including emergence of suicidality or mania.
Timing: Prior to initiation of therapy
Routine Monitoring
Blood Pressure (BP) and Heart Rate (HR)
Frequency: Weekly during dose titration, then periodically (e.g., monthly) or as clinically indicated.
Target: Maintain within patient's normal range; monitor for orthostatic changes.
Action Threshold: Significant orthostatic hypotension (e.g., >20 mmHg drop in systolic BP) or persistent tachycardia (>100 bpm) may require dose adjustment or discontinuation.
Electrocardiogram (ECG)
Frequency: Periodically (e.g., annually) or as clinically indicated, especially in elderly patients, those with cardiac disease, or at higher doses.
Target: Normal sinus rhythm, PR <200 ms, QRS <100 ms, QTc <450 ms (men), <470 ms (women).
Action Threshold: New onset arrhythmias, significant PR/QRS/QTc prolongation (e.g., QTc >500 ms or increase >60 ms from baseline) may require dose reduction or discontinuation.
Plasma Imipramine + Desipramine Levels (Therapeutic Drug Monitoring)
Frequency: Not routinely required, but useful in cases of suspected toxicity, non-response, or significant drug interactions.
Target: 150-300 ng/mL (combined imipramine and desipramine)
Action Threshold: Levels >300 ng/mL associated with increased risk of toxicity; levels <150 ng/mL may indicate subtherapeutic dosing.
Weight
Frequency: Periodically (e.g., every 3-6 months).
Target: Maintain stable weight.
Action Threshold: Significant or undesirable weight gain may warrant intervention or alternative therapy.
Mental Status (mood, suicidality, anxiety, agitation, mania)
Frequency: Regularly, especially during initial therapy and dose changes.
Target: Improvement in target symptoms, absence of suicidality or emergent mania.
Action Threshold: Worsening depression, emergence of suicidal thoughts/behaviors, or signs of mania/hypomania require immediate reassessment and intervention.
Symptom Monitoring
- Worsening depression
- Suicidal thoughts or behaviors
- Unusual changes in behavior (e.g., agitation, irritability, anxiety, panic attacks, insomnia, aggressiveness, impulsivity, akathisia, hypomania, mania)
- Anticholinergic effects (e.g., dry mouth, blurred vision, constipation, urinary retention)
- Orthostatic hypotension (dizziness upon standing)
- Cardiac symptoms (e.g., palpitations, chest pain, syncope)
- Seizures
- Fever, sore throat, or other signs of infection (rare, but indicative of blood dyscrasias)
- Jaundice or other signs of liver dysfunction
Special Patient Groups
Pregnancy
Category D. Imipramine crosses the placenta. Use during pregnancy is generally not recommended unless the potential benefit outweighs the potential risk to the fetus. Neonates exposed to TCAs in the third trimester may experience withdrawal symptoms (e.g., respiratory distress, cyanosis, apnea, seizures, feeding difficulties, hypotonia, hypertonia, tremor, irritability, vomiting, hypoglycemia) or anticholinergic effects.
Trimester-Specific Risks:
First Trimester:
Limited data, but some studies suggest a possible association with congenital malformations, though causality is not definitively established. Risk appears low.
Second Trimester:
Generally considered safer than first or third trimester, but still Category D.
Third Trimester:
Increased risk of neonatal withdrawal symptoms and anticholinergic effects in the newborn.
Lactation
L3 (Moderately safe). Imipramine and its active metabolite desipramine are excreted into breast milk. While levels are generally low, potential for adverse effects in the infant (e.g., sedation, poor feeding, irritability, anticholinergic effects) exists. Monitor breastfed infant for drowsiness, poor feeding, and weight gain. Consider alternative therapies or therapeutic drug monitoring if used.
Infant Risk:
Low to moderate; monitor for sedation, irritability, poor feeding, and anticholinergic effects.
Pediatric Use
Tofranil-PM is not indicated for pediatric use for depression due to the Black Box Warning regarding increased risk of suicidality in children, adolescents, and young adults. Imipramine HCl (immediate release) is used for nocturnal enuresis in children, but with careful consideration of risks and benefits.
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/day) and titrate slowly. Increased risk of falls, cognitive impairment, and cardiac adverse events (e.g., orthostatic hypotension, arrhythmias). Close monitoring is essential.
Clinical Information
Clinical Pearls
- Tofranil-PM is an extended-release formulation, allowing for once-daily dosing, typically at bedtime, which can improve adherence and leverage its sedating properties.
- Imipramine has significant anticholinergic side effects (dry mouth, constipation, blurred vision, urinary retention), which can be particularly bothersome in elderly patients.
- Cardiotoxicity (e.g., QTc prolongation, arrhythmias, orthostatic hypotension) is a major concern, especially in overdose or in patients with pre-existing cardiac conditions. ECG monitoring is crucial.
- Therapeutic drug monitoring (TDM) for combined 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 weeks to reach steady state and for full antidepressant effects to manifest.
- Withdrawal symptoms can occur if discontinued abruptly; taper dose gradually over several weeks.
Alternative Therapies
- Other Tricyclic Antidepressants (TCAs): Nortriptyline, Amitriptyline, Doxepin
- Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Venlafaxine, Duloxetine, Desvenlafaxine
- Atypical Antidepressants: Bupropion, Mirtazapine, Trazodone
- Monoamine Oxidase Inhibitors (MAOIs): Phenelzine, Tranylcypromine (reserved for refractory cases due to significant interactions)
- Electroconvulsive Therapy (ECT) for severe or refractory depression
Cost & Coverage
Average Cost:
$50 - $200 per 30 capsules (generic 75mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (generic), Tier 3 or higher (brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information. It is vital to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider for guidance.
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 detailed information, including the name of the medication taken, the quantity, and the time it occurred.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information. It is vital to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider for guidance.
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 detailed information, including the name of the medication taken, the quantity, and the time it occurred.