Tofranil-PM 100mg Capsule

Manufacturer MALLINCKRODT Active Ingredient Imipramine Capsules(im IP ra meen) Pronunciation toe-FRAH-nil P.M. (for brand); im-IP-ra-meen (for generic)
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.
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Drug Class
Tricyclic Antidepressant (TCA)
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Pharmacologic Class
Norepinephrine and Serotonin Reuptake Inhibitor (NSRI)
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Pregnancy Category
Category D
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FDA Approved
Mar 1959
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DEA Schedule
Not Controlled

Overview

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What is this medicine?

Tofranil-PM is a medication used to treat depression and sometimes panic disorder. It belongs to a class of drugs called tricyclic antidepressants. It works by helping to restore the balance of certain natural chemicals in the brain. This specific form is an extended-release capsule, meaning it releases the medicine slowly over time, usually taken once a day at bedtime.
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How to Use This Medicine

Taking Your Medication Correctly

To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your medication and follow the instructions precisely. If you experience drowsiness after taking this medication, consult 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 start to feel better.

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 have questions 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 is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses. If you take your daily dose at bedtime and miss a dose, do not take the missed dose the next morning.
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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 the medication affects you, due to potential drowsiness or blurred vision.
  • Avoid sudden changes in position (e.g., standing up quickly) to minimize dizziness from orthostatic hypotension.
  • Maintain good oral hygiene due to dry mouth (a common side effect).
  • Stay hydrated to help with dry mouth and constipation.
  • Inform your doctor about all other medications, supplements, and herbal products you are taking, especially St. John's Wort.

Dosing & Administration

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Adult Dosing

Standard Dose: 100 mg orally once daily at bedtime (for Tofranil-PM extended-release capsule)
Dose Range: 75 - 300 mg

Condition-Specific Dosing:

depression: Initial: 75 mg/day in divided doses or once daily at bedtime, gradually increased to 150-200 mg/day. Max: 300 mg/day. Tofranil-PM 100mg is a specific extended-release strength, typically taken once daily.
panicDisorder: Initial: 25 mg/day, gradually increased to 75-150 mg/day. Max: 200 mg/day.
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Pediatric Dosing

Neonatal: Not established
Infant: Not established
Child: Not generally recommended for depression due to Black Box Warning. For nocturnal enuresis (off-label, generally not first-line): 25-75 mg orally once daily at bedtime (dosing varies by age/weight).
Adolescent: Not generally recommended for depression due to Black Box Warning. If used, initial 25-50 mg/day, gradually increased. Max: 100 mg/day.
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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 (e.g., 50% of usual dose) and monitor plasma levels. Imipramine and its metabolites are primarily eliminated by the kidneys.
Dialysis: Not significantly dialyzable. Use with caution, monitor for adverse effects.

Hepatic Impairment:

Mild: Use with caution, monitor for adverse effects.
Moderate: Significant reduction in dose (e.g., 50% of usual dose) recommended due to extensive hepatic metabolism. Monitor for adverse effects and consider plasma levels.
Severe: Contraindicated or not recommended due to extensive hepatic metabolism and risk of accumulation and toxicity.
Confidence: Medium

Pharmacology

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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 (muscarinic receptor blockade), antihistaminic (H1 receptor blockade), and alpha-1 adrenergic blocking properties, which contribute to its side effect profile.
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Pharmacokinetics

Absorption:

Bioavailability: 29-77% (variable due to significant first-pass metabolism)
Tmax: 1-2 hours (for immediate release); longer for extended-release formulations like Tofranil-PM
FoodEffect: Food may slightly delay absorption but does not significantly affect bioavailability.

Distribution:

Vd: 10-20 L/kg (large volume of distribution)
ProteinBinding: ~90% (primarily to alpha-1-acid glycoprotein and albumin)
CnssPenetration: Yes (readily crosses the blood-brain barrier)

Elimination:

HalfLife: Imipramine: 6-20 hours; Desipramine: 12-76 hours (highly variable)
Clearance: Not available (highly variable due to metabolism)
ExcretionRoute: Renal (approximately 80% as metabolites), Fecal (approximately 20%)
Unchanged: <5% (renal)
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Pharmacodynamics

OnsetOfAction: Antidepressant effects typically begin within 1-4 weeks; sedative effects may be immediate.
PeakEffect: Antidepressant effects peak after several weeks of consistent dosing.
DurationOfAction: Due to long half-life, once-daily dosing is effective, especially with extended-release formulations.

Safety & Warnings

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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. 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. Tofranil-PM is not approved for use in pediatric patients except for patients with nocturnal enuresis.
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Side Effects

Important Side Effects to Report to Your Doctor Immediately

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, seek medical attention right away:

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
Yellowing of the 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, which may be signs of 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 Blood Sugar Changes

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, seek medical attention right away:
Eye pain
Changes in eyesight
Swelling or redness in or around the eye

Serotonin Syndrome

A rare but potentially life-threatening condition called serotonin syndrome may occur, especially if you are taking certain other medications. Seek medical attention immediately 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

Other Possible Side Effects

While many people may not experience any side effects or only minor ones, it is essential to report any of the following symptoms to your doctor if they bother you or do not go away:
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

Reporting Side Effects

If you have any questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
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Seek Immediate Medical Attention If You Experience:

  • Worsening depression or thoughts about suicide or self-harm, especially at the beginning of treatment or after a dose change.
  • New or worsening anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (restlessness), hypomania, or mania.
  • Fast, pounding, or irregular heartbeat; chest pain; shortness of breath; fainting.
  • Severe dizziness or lightheadedness, especially when standing up.
  • Blurred vision, eye pain, or seeing halos around lights (may indicate acute narrow-angle glaucoma).
  • Difficulty urinating or severe constipation.
  • Seizures.
  • Fever, sore throat, or unusual bruising/bleeding (signs of blood dyscrasias).
  • Yellowing of skin or eyes (jaundice).
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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 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 medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
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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 down position, and exercise caution when climbing 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 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, consult with your doctor.

Potential Side Effects and Interactions

It may take several weeks to experience the full effects of this medication. Be aware that 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. In hot weather or during physical activity, drink plenty of fluids to prevent dehydration.

Medical Monitoring

Your doctor may require you to undergo 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.

Special Populations

If you are 65 years or older, use this medication with caution, as you may be more prone to side effects. Pregnant women or those planning to become pregnant should discuss the benefits and risks of taking this medication with their doctor.
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Overdose Information

Overdose Symptoms:

  • Severe drowsiness or confusion
  • Coma
  • Severe dry mouth
  • Blurred vision
  • Dilated pupils
  • Fast, irregular, or pounding heartbeat (tachycardia, arrhythmias)
  • Low blood pressure (hypotension)
  • Fever
  • Muscle rigidity
  • Overactive reflexes
  • Seizures
  • Respiratory depression
  • Cardiac arrest

What to Do:

Seek immediate emergency medical attention. Call 911 or Poison Control at 1-800-222-1222. Overdose can be fatal, especially in children.

Drug Interactions

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Contraindicated Interactions

  • Monoamine Oxidase Inhibitors (MAOIs) (risk of serotonin syndrome, hyperpyretic crises, convulsions, death)
  • Cisapride (risk of QT prolongation and arrhythmias)
  • Thioridazine (risk of QT prolongation and arrhythmias)
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Major Interactions

  • Other CNS depressants (e.g., alcohol, benzodiazepines, opioids, sedatives, hypnotics) - additive CNS depression
  • Anticholinergic agents (e.g., atropine, scopolamine, antihistamines, antipsychotics) - additive anticholinergic effects (severe constipation, urinary retention, paralytic ileus, hyperpyrexia)
  • Sympathomimetics (e.g., epinephrine, norepinephrine, phenylephrine, pseudoephedrine) - potentiated pressor response
  • QT-prolonging drugs (e.g., antiarrhythmics like quinidine, procainamide, amiodarone, sotalol; certain antipsychotics, macrolide antibiotics) - increased risk of ventricular arrhythmias
  • CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, quinidine, cimetidine) - significantly increased imipramine and desipramine plasma concentrations
  • Thyroid hormones - increased risk of cardiac arrhythmias and toxicity
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Moderate Interactions

  • Antihypertensives (e.g., guanethidine, clonidine, reserpine) - imipramine may antagonize their hypotensive effects
  • Anticoagulants (e.g., warfarin) - increased anticoagulant effect (monitor INR)
  • Cimetidine - increased imipramine levels
  • Methylphenidate - increased imipramine levels
  • Barbiturates - may decrease imipramine levels (enzyme induction)
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Minor Interactions

  • Not available (most interactions are clinically significant)

Monitoring

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Baseline Monitoring

Complete Medical History and Physical Exam

Rationale: To identify pre-existing conditions (e.g., cardiac disease, glaucoma, urinary retention, seizure disorder) that may contraindicate or require caution with imipramine.

Timing: Prior to initiation of therapy

Electrocardiogram (ECG)

Rationale: To assess for pre-existing cardiac conduction abnormalities or QT prolongation, especially in patients over 40 years old or with cardiac risk factors.

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 Tests (BUN, Creatinine)

Rationale: To assess renal function, as metabolites are 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 effects (e.g., agranulocytosis, thrombocytopenia).

Timing: Prior to initiation of therapy

Electrolytes (Potassium, Magnesium)

Rationale: To identify imbalances that could increase risk of cardiac arrhythmias.

Timing: Prior to initiation of therapy

Ophthalmologic Exam (intraocular pressure)

Rationale: To assess for narrow-angle glaucoma, which can be exacerbated by anticholinergic effects.

Timing: Prior to initiation of therapy (if risk factors present)

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Routine Monitoring

Blood Pressure and Heart Rate

Frequency: Regularly, especially during dose titration and in elderly patients

Target: Maintain within normal limits; monitor for orthostatic hypotension and tachycardia.

Action Threshold: Significant orthostatic drop (>20 mmHg systolic or >10 mmHg diastolic) or persistent tachycardia; consider dose reduction or alternative.

Electrocardiogram (ECG)

Frequency: Periodically, especially in elderly patients, those with cardiac risk factors, or at higher doses (e.g., >150 mg/day).

Target: Normal sinus rhythm, PR <200ms, QRS <100ms, QTc <450ms (men), <470ms (women).

Action Threshold: Significant QTc prolongation (>500ms or >60ms increase from baseline), new conduction abnormalities; consider dose reduction, discontinuation, or cardiology consult.

Serum Imipramine and Desipramine Levels (Therapeutic Drug Monitoring - TDM)

Frequency: Recommended for dose optimization, suspected non-adherence, toxicity, or poor response; typically after 5-7 days at a stable dose.

Target: Imipramine + Desipramine: 150-300 ng/mL (for depression)

Action Threshold: Levels outside therapeutic range; adjust dose accordingly, considering clinical response and side effects.

Mental Status and Clinical Response

Frequency: Weekly during initial titration, then monthly or as clinically indicated.

Target: Improvement in depressive symptoms, reduction in panic attacks.

Action Threshold: Worsening depression, emergence of suicidality, mania/hypomania, or severe adverse effects; reassess treatment plan.

Liver Function Tests (LFTs)

Frequency: Periodically, especially if signs of hepatic dysfunction or on long-term therapy.

Target: Within normal limits.

Action Threshold: Significant elevation (e.g., >3x ULN); investigate cause, consider discontinuation.

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Symptom Monitoring

  • Worsening depression
  • Suicidal thoughts or behavior (especially in young adults)
  • Unusual changes in behavior (e.g., agitation, irritability, anxiety, panic attacks, insomnia, impulsivity, aggression, hypomania, mania)
  • Cardiac symptoms (e.g., palpitations, dizziness, fainting, chest pain)
  • Anticholinergic effects (e.g., dry mouth, blurred vision, constipation, urinary retention)
  • Orthostatic hypotension (dizziness upon standing)
  • Seizures
  • Fever, sore throat, or other signs of infection (due to rare hematologic effects)

Special Patient Groups

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Pregnancy

Imipramine is Pregnancy Category D. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal withdrawal symptoms (e.g., respiratory distress, cyanosis, apnea, seizures, feeding difficulties, hypotonia, hypertonia, tremor, irritability, constant crying) have been reported in neonates exposed to TCAs during the third trimester.

Trimester-Specific Risks:

First Trimester: Limited data, but some studies suggest a possible association with congenital malformations (e.g., cardiovascular defects), though causality is not definitively established. Risk appears low.
Second Trimester: Generally considered safer than first or third trimester, but still Category D. Monitor for fetal growth.
Third Trimester: Risk of neonatal withdrawal syndrome and persistent pulmonary hypertension of the newborn (PPHN) if exposed late in pregnancy. Avoid use in the third trimester if possible.
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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. Due to the potential for serious adverse reactions in the nursing infant (e.g., sedation, anticholinergic effects, cardiac effects), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Monitor infant for drowsiness, poor feeding, and weight gain.

Infant Risk: L3 (Moderately Safe - some concern, monitor infant)
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Pediatric Use

Imipramine is not approved for use in pediatric patients for depression due to the Black Box Warning regarding increased risk of suicidal thoughts and behavior. Its use for nocturnal enuresis is generally reserved for cases unresponsive to other measures, and careful risk-benefit assessment is required. Children are more sensitive to anticholinergic effects and cardiac effects.

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Geriatric Use

Elderly patients are more sensitive to the anticholinergic, sedative, and hypotensive effects of imipramine. They are also at increased risk for cardiac conduction disturbances and orthostatic hypotension. Lower initial doses and slower titration are recommended. Monitor closely for adverse effects, especially cardiac and CNS effects. Consider therapeutic drug monitoring.

Clinical Information

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Clinical Pearls

  • Imipramine is a potent TCA with significant anticholinergic, antihistaminic, and alpha-1 adrenergic blocking properties, which contribute to its side effect profile (e.g., dry mouth, constipation, sedation, orthostatic hypotension).
  • Due to its cardiac effects (e.g., QTc prolongation, conduction delays), a baseline ECG is crucial, especially in patients over 40 or with pre-existing cardiac conditions.
  • Therapeutic drug monitoring (TDM) of imipramine and desipramine levels can be useful for optimizing dose, assessing adherence, and investigating toxicity or lack of response.
  • The Black Box Warning for suicidality in children, adolescents, and young adults is critical; close monitoring for clinical worsening and suicidality is essential.
  • Withdrawal symptoms (e.g., nausea, vomiting, dizziness, headache, anxiety, agitation, sleep disturbances) can occur if discontinued abruptly; taper dose gradually.
  • Tofranil-PM is an extended-release formulation, typically taken once daily at bedtime, which can improve adherence and minimize daytime sedation.
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Alternative Therapies

  • Other Tricyclic Antidepressants (TCAs): Amitriptyline, Nortriptyline, Doxepin, Desipramine, Clomipramine
  • Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram
  • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Venlafaxine, Duloxetine, Desvenlafaxine
  • Atypical Antidepressants: Bupropion, Mirtazapine, Trazodone
  • For panic disorder: SSRIs, SNRIs, benzodiazepines (short-term)
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Cost & Coverage

Average Cost: Varies widely by pharmacy and formulation (generic vs. brand) per 30 capsules
Generic Available: Yes
Insurance Coverage: Generally Tier 1 or 2 for generic imipramine; brand Tofranil-PM may be higher tier or require prior authorization.
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General Drug Facts

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. 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 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 quantity, and the time it occurred.