Imipramine (Tofranil) - Indications, Dosage, Side effects, Brands

Imipramine (Tofranil) is a tricyclic antidepressant drug that is primarily used to treat patients with depression, anxiety, and panic disorders.

Imipramine (Tofranil) Uses:

  • Childhood enuresis (imipramine hydrochloride only):

    • Give your child between 25 to 50 milligrams each day, either spread out during the day or as a single dose before bedtime.
    • This is a temporary extra treatment to help with bedwetting in children under six, but only after making sure there are no health issues through the required tests.

  • Major depressive disorder (unipolar):

    • Unipolar major depressive disorder treatment (MDD)

  • Off Label Use of Imipramine in Adults:

    • Bulimia nervosa.
    • Neuropathic pain.
    • Panic disorder.

Imipramine dose in adults:

Imipramine (Tofranil) Dose in the treatment of Major depressive disorder (unipolar):

  • P/O:
    • Initial:

      • If the initial dose is well-tolerated and shows a positive response, you can increase it by 25 to 50 milligrams per day.

      • Do this on a weekly basis until you reach the usual dose range of 100 to 300 milligrams per day.

  • Manufacturer's labeling:

Note: Current clinical practise might not be reflected in the dosing in the prescribed information.

    • Outpatients:

      • Initial:
        • Based on how well the body responds and the individual's tolerance, you can slowly increase the dose up to 200 milligrams per day, starting from 75 milligrams per day.
      • Usual maintenance dose:
        • You can take this medication either as a single dose before bedtime or divide it into multiple doses.
        • The recommended daily dose ranges from 50 to 150 milligrams.

    • Inpatients:

      • Initial:
        • The initial dose is 100 milligrams per day. Depending on how well it's tolerated and the response, the dose can be gradually increased up to 200 milligrams per day.
        • If there's no improvement after two weeks, the dosage may be raised to a range of 250 to 300 milligrams per day.
        • You can take this medication as a single bedtime dose or split it into multiple doses.

Imipramine (Tofranil) Dose in the treatment of Bulimia nervosa (off-label): P/O:

  • Initial:
    • Start with 50 milligrams at bedtime, and depending on how well your body responds and tolerates the medication, gradually increase the dosage up to 300 milligrams.

Imipramine (Tofranil) Dose in the treatment of Neuropathic pain (off-label): P/O:

Note:

Not preferred TCA.

  • Initial:

    • Take 50 milligrams once daily or split it into two doses and take it twice daily.

    • Once your plasma concentration of imipramine with desipramine reaches 113–170 ng/mL (SI: 400–600 nmol/L), you can gradually increase your dosage up to 150 milligrams per day.

Imipramine (Tofranil) Dose in the treatment of the Panic disorder (off-label):

  • P/O:
    • Initial:

      • Begin with a daily dose of 10 milligrams. Increase the dosage gradually over 3 to 5 weeks until you reach the target dose range of 100 to 300 milligrams per day.

      • The average doses in the studies ranged from 155 to 239 milligrams per day.

  • Discontinuation of therapy:

    • When discontinuing antidepressant medication that has been taken for more than three weeks, it's recommended to taper the dose gradually over a period of 2 to 4 weeks.

    • This helps reduce withdrawal symptoms and identifies any returning symptoms.

    • If there is a prior history of withdrawal symptoms or if the antidepressant was taken in high doses, a slower taper over 4 weeks may be necessary.

    • This is especially true if the medication has a short half-life (less than 24 hours), such as paroxetine or venlafaxine.

    • If withdrawal symptoms become severe, it's advisable to either resume the previously prescribed dose or decrease it more gradually.

    • For individuals receiving long-term treatment (more than six months), tapering over more than three months might be beneficial, particularly for those with a history of discontinuation syndrome.

    • It's important to note that there is limited data to establish precise tapering rates, so the process should be tailored to individual needs and monitored closely by a healthcare professional.

  • Switching antidepressants:

    • There's limited evidence on the best methods for switching antidepressants.

    • Two common approaches are cross titration, where you gradually stop the previous antidepressant while also gradually increasing the new one, and straight changeover, where you abruptly stop the first antidepressant and then start the new one at an equivalent or lower dose, gradually increasing it.

    • Cross-titration is generally recommended for most switches, but it's not advisable when transitioning to or from a MAO inhibitor.

    • The duration of cross-titration can vary (over 1-4 weeks) based on the individual's susceptibility to withdrawal symptoms and adverse effects.

    • A direct switch may be appropriate when moving to another agent in the same or similar class, like switching between two SSRIs, or when the antidepressant to be discontinued has been used for less than one week or for adverse effects.

    • When deciding on a switching strategy, consider factors such as the risk of discontinuation symptoms, potential drug interactions, other properties of the antidepressants (e.g., half-life, adverse effects, and pharmacodynamics), and the desired level of symptom control.

    • Individualized decisions, based on these considerations, should be made in consultation with a healthcare professional.

  • Switching to or from an MAOI:

  • It is important to wait for at least 14 days after stopping an MAOI before starting imipramine.

    • Similarly, wait for 14 days after stopping imipramine before starting an MAOI.

    • This time interval helps minimize the risk of adverse effects and interactions between these medications.

    • Always follow the guidance and instructions provided by your healthcare professional when making such transitions.

Imipramine dose in childrens:

  • Note:
    • The dosing presented is based on hydrochloride salt.

Imipramine (Tofranil) Dose in the treatment of Attention-deficit hyperactivity disorder:

  • Children ≥6 years and Adolescents:

    • P/O:

      • Initial:

        • In 1-3 divided doses, 1 mg/kg/day.
        • Titrate as required.

      • Max daily dose:

        • The recommended dosage is either 4 milligrams per kilogram of body weight per day or a fixed dose of 200 milligrams per day.

        • If the dose exceeds 2 milligrams per kilogram per day, it's advised to monitor serum concentrations.

        • The target concentration should be equal to or below 200 nanograms per milliliter.

        • Regular monitoring helps ensure that the medication is within the desired range for optimal effectiveness and safety.

Note:

    • According to the manufacturer's labeling, pediatric patients should not be given doses exceeding 2.5 milligrams per kilogram per day.
    • There have been reports of uncertain significance regarding ECG abnormalities in pediatric children who received twice this recommended dose.
    • It's important to adhere to the prescribed dosage guidelines to ensure the safety and well-being of pediatric patients.
    • Any concerns or observations should be promptly communicated to healthcare professionals for further evaluation.

Imipramine (Tofranil) Dose in the treatment of Depression: P/O:

Note:

    • Controlled clinical trials have not demonstrated that tricyclic antidepressants are more effective than a placebo in treating depression in children and adolescents.

    • Not suggested as a first-line treatment.

    • Patients with concomitant conditions may benefit.

  • Children ≥8 years:

    • The recommended starting dose is 5 milligrams per kilogram per day, divided into 2-3 doses.

    • Every three to four days, adjust the dosage as needed, increasing by increments of 1 milligram per kilogram.

    • In certain centers, a maximum daily dosage of 5 milligrams per kilogram has been used.

    • It is crucial to pay close attention, especially at doses below 3.5 milligrams per kilogram per day.

    • The manufacturer's labeling advises against using doses greater than 2.5 milligrams per kilogram per day in pediatric patients.

    • Pediatric patients who received twice this recommended dose reported ECG abnormalities of uncertain relevance.

    • Close monitoring and adherence to dosage guidelines are essential for the safety and well-being of patients.

  • Adolescents:

    • Initial:
      • 25-50 mg/day.
      • Increase gradually.
    • Max daily dose:
      • 100 mg/day in single or divided doses

Imipramine (Tofranil) Dose in the treatment of Enuresis:

  • Children ≥6 years and Adolescents:

    • P/O:

      • Initial:

        • If there is not enough improvement in the patient's condition after one week of therapy, consider increasing the dose by 25 milligrams per day.

        • This adjustment aims to enhance the therapeutic response and address any inadequate outcomes observed during the initial week of treatment.

      • Max daily dose:

        • The lesser of:

          • For children aged 6 to less than 12 years, the recommended dosage is either 2.5 milligrams per kilogram per day or a fixed dose of 50 milligrams per day.

          • For those aged 12 years and older, the recommended dose is 75 milligrams per day.

          • For early night bedwetters, it has been shown that the medication is more effective when administered earlier and in divided doses, such as 25 milligrams in the midafternoon and repeated at bedtime.

          • While medication is generally not used in children under the age of six, certain patients may consider it for children older than four years old.

          • The decision to use medication should be made in consultation with a healthcare professional, taking into account individual circumstances and considerations.

Note:

    • Imipramine is categorized as a third-line treatment for enuresis, meaning it is considered after other options have been explored.
    • This is primarily due to the potential risk of serious side effects associated with imipramine use, including but not limited to arrhythmias (irregular heartbeats), heart block, and seizures.
    • The decision to prescribe imipramine for enuresis should be carefully weighed against the potential risks, and it is typically recommended when other treatments have not been effective or are not suitable for the individual.
    • Close monitoring and supervision by a healthcare professional are crucial when using imipramine for this purpose.

  • Discontinuation of therapy:

    • When considering discontinuation of antidepressant therapy, it's important to recognize that non-illness-related events may induce stress or anxiety, which could be mistakenly attributed to antidepressant withdrawal.

    • To minimize potential stress, it may be beneficial to schedule the discontinuance for less stressful times.

    • When stopping antidepressant therapy, it's advisable to lower the dosage gradually.

    • This helps reduce the likelihood of experiencing discontinuation syndromes (withdrawal symptoms) and allows for the identification of resurfacing signs of the illness state, such as relapse.

    • There is limited data to support precise taper rates following sickness remission.

    • However, considering the antidepressant's half-life, both APA (American Psychiatric Association) and NICE (National Institute for Health and Care Excellence) recommendations suggest tapering medication over a minimum of a few weeks.

    • Antidepressants with shorter half-lives may require more conservative tapering.

    • For individuals on long-term antidepressant treatment (years), WFSBP (World Federation of Societies of Biological Psychiatry) guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation.

    • If intolerable discontinuation symptoms occur following a dose reduction, it is advisable to consider resuming the previously prescribed dose and/or decreasing the dose at a more gradual rate. Individualized decisions should be made in consultation with a healthcare professional.

MAO inhibitor recommendations:

  • A psychiatric condition is treated by using an MAO inhibitor, and 

switching to or from one:

  • When initiating imipramine, it is essential to wait for a period of 14 days after discontinuing the use of an MAO inhibitor that was employed for the treatment of psychiatric problems.
  • Similarly, allow a 14-day interval between stopping imipramine and starting an MAO inhibitor for psychiatric illnesses. This waiting period helps minimize the risk of adverse interactions between these medications.
  • Always follow the guidance provided by your healthcare professional when transitioning between these drugs.

Pregnancy Risk Category: C

  • The use of tricyclic antidepressants during pregnancy has been associated with reports of congenital abnormalities in humans.

  • However, it has not been definitively established that there is a causal relationship between the medication and these abnormalities.

  • Tricyclic antidepressants may also lead to irritability, convulsions, and jitteriness in newborns.

  • Pregnant women may need to make adjustments to their medication doses late in pregnancy to achieve mood stability due to physiological changes induced by pregnancy.

  • The American College of Obstetricians and Gynecologists (ACOG) recommends individualized treatment for depression during pregnancy.

  • A collaborative approach involving the pediatrician, obstetrician, primary healthcare physician, and mental healthcare practitioner is crucial in developing a treatment plan.

  • The American Psychiatric Association (APA) does not generally recommend medication treatment during pregnancy.

  • However, women who have stopped taking antidepressants during pregnancy or are at high risk of postpartum depression may consider reinstating their medications under medical supervision.

  • Both ACOG and APA have created treatment algorithms for managing depression in women during pregnancy and before conception.

  • Pregnant women who have been exposed to antidepressants are encouraged to participate in the National Pregnancy Registry for Antidepressants to contribute valuable information on medication outcomes during pregnancy.

Use of imipramine while breastfeeding

  • Imipramine and its active metabolite, desipramine, can be found in breast milk.

  • Concentrations of imipramine in maternal plasma may be similar to those in the mother's blood.

  • Based on limited data from five mother/infant pairs, the estimated exposure for a breastfed infant to imipramine at doses of 75-200 mg/day ranged from 0.1% to 7.5%.

  • It is important to closely monitor infants who are breastfed by mothers taking imipramine, even if adverse events have not been explicitly documented.

  • The presence of imipramine can also be detected in the urine of nursing babies.

  • Manufacturers generally do not recommend breastfeeding while taking imipramine due to the potential risks associated with exposure to the drug through breast milk.

  • Decisions regarding breastfeeding should be made in consultation with healthcare professionals, considering individual circumstances and weighing the potential benefits and risks for both the mother and the infant.

Imipramine (Tofranil) Dose in Kidney Disease:

  • In the manufacturer's labeling, there are no dosage adjustments provided.
  • Use cautiously.

Imipramine (Tofranil) Dose in Liver disease:

  • In the manufacturer's labeling, there are no dosage adjustments provided.
  • Use cautiously.
  • Reported for tricyclic antidepressants in general.

Side effects of Imipramine (Tofranil):

  • Cardiovascular:

    • Palpitations
    • Cardiac Failure
    • Myocardial Infarction
    • Heart Block
    • ECG Changes
    • Hypertension
    • Orthostatic Hypotension
    • Cerebrovascular Accident
    • Tachycardia
    • Cardiac Arrhythmia

  • Central Nervous System:

    • Taste Disorder
    • Anxiety
    • Restlessness
    • Confusion
    • Peripheral Neuropathy
    • Disorientation
    • Numbness
    • Drowsiness
    • Headache
    • Insomnia
    • Extrapyramidal Reaction
    • Hallucination
    • Hypomania
    • Falling
    • Nightmares
    • EEG Pattern Changes
    • Paresthesia
    • Fatigue
    • Dizziness
    • Psychosis
    • Delusions
    • Seizure
    • Ataxia
    • Tingling Sensation
    • Agitation

  • Dermatologic:

    • Skin Rash
    • Diaphoresis
    • Urticaria
    • Skin Photosensitivity
    • Pruritus
    • Alopecia

  • Endocrine & Metabolic:

    • Increased Libido
    • Decreased Serum Glucose
    • SIADH
    • Gynecomastia
    • Increased Serum Glucose
    • Weight Gain
    • Galactorrhea
    • Weight Loss
    • Decreased Libido

  • Gastrointestinal:

    • Vomiting
    • Anorexia
    • Stomatitis
    • Diarrhea
    • Melanoglossia
    • Intestinal Obstruction
    • Nausea
    • Epigastric Distress
    • Sublingual Adenitis
    • Constipation
    • Xerostomia
    • Abdominal Cramps

  • Genitourinary:

    • Urinary Retention
    • Impotence
    • Urinary Hesitancy
    • Testicular Swelling
    • Urinary Tract Dilation
    • Breast Hypertrophy

  • Hematologic & Oncologic:

    • Purpura
    • Eosinophilia
    • Thrombocytopenia
    • Petechia
    • Agranulocytosis

  • Hepatic:

    • Increased Serum Transaminases
    • Cholestatic Jaundice

  • Hypersensitivity:

    • Hypersensitivity

  • Neuromuscular & Skeletal:

    • Weakness
    • Tremor

  • Ophthalmic:

    • Angle-Closure Glaucoma
    • Accommodation Disturbance
    • Mydriasis
    • Blurred Vision

  • Otic:

    • Tinnitus

Contraindications to Imipramine (Tofranil):

  • There is a possibility of experiencing hypersensitivity to imipramine, and cross-reactivity may occur with other dibenzodiazepines.

  • This is particularly relevant during the acute recovery period after myocardial injury (MI).

  • When it comes to the use of MAO inhibitors, they may be administered concurrently with imipramine or within 14 days after discontinuing either imipramine or another MAO inhibitor for the treatment of psychiatric disorders.

  • Patients receiving intravenous methylene blue or linezolid should initiate the process as well, considering potential interactions.

  • There is limited evidence suggesting cross-reactivity between tricyclic antidepressants, like imipramine, and allergenic antidepressants.

  • Cross-sensitivity can be possible due to similarities in chemical structure and pharmacologic activities.

  • Individuals should be cautious, and decisions regarding medication choices should be made under the guidance of healthcare professionals.

Warnings and precautions

  • Anticholinergic effects

    • Imipramine may lead to anticholinergic side effects, such as constipation, xerostomia (dry mouth), and blurred vision.

    • Individuals with conditions like reduced gastrointestinal motility, increased intraocular pressure, angle-closure glaucoma, paralytic ileus, urinary retention, or benign prostatic hyperplasia (BPH) should exercise caution when using this medication.

    • It's important to note that imipramine produces a higher degree of anticholinergic blocking compared to other antidepressants.

    • This heightened anticholinergic activity contributes to the potential side effects mentioned above and emphasizes the need for careful consideration, especially in individuals with pre-existing conditions that may be exacerbated by anticholinergic effects.

    • Patients should discuss any concerns or pre-existing conditions with their healthcare provider before starting imipramine

  • Depression in the CNS:

    • CNS (central nervous system) depression induced by imipramine can result in mental or physical impairment.

    • It is crucial to advise patients about activities that demand mental alertness, including driving or operating machinery, as their ability to perform these tasks may be compromised.

    • Compared to other antidepressants, imipramine has a higher degree of sedative effects.

    • This heightened sedation underscores the importance of caution and awareness, particularly when engaging in activities that require concentration and coordination.

    • Patients should be informed of these potential effects to ensure their safety and well-being while taking imipramine.

  • Fractures

    • There is evidence suggesting that antidepressant treatment may contribute to preventing bone fractures.

    • However, it's important to note that if a person undergoing antidepressant treatment experiences persistent bone pain, tenderness, swelling, or bruising, it could be indicative of a fragility fracture.

    • In such cases, seeking medical attention is crucial for a thorough evaluation and appropriate management.

    • While antidepressants may have potential benefits for bone health, any concerns or symptoms related to bone health should be discussed with a healthcare professional for further assessment and guidance.

  • Hematologic effects

    • Rarely, tricyclic antidepressants (TCAs) like imipramine can lead to bone marrow suppression.

    • If you experience symptoms such as fever or sore throat, it's advisable to have a complete blood count (CBC) done.

    • In the presence of indications of neutrophil depression (a type of white blood cell), discontinuing imipramine is recommended.

    • Bone marrow suppression is a serious potential side effect, and prompt medical attention is essential if there are any signs or symptoms suggesting it.

    • Close monitoring, regular check-ups, and immediate reporting of any unusual symptoms to a healthcare professional are important for the safe use of imipramine or any other medications in this class.

  • Orthostatic hypotension

    • Imipramine carries a relatively high risk of causing orthostatic hypotension compared to other antidepressants.

    • Orthostatic hypotension is a drop in blood pressure that occurs when standing up from a sitting or lying position.

    • Patients who are at high risk for this effect, as well as those who cannot tolerate temporary drops in blood pressure (such as individuals with cerebrovascular disease, cardiovascular disease, or hypovolemia), should exercise caution when using imipramine.

    • Close monitoring of blood pressure and adjustments to the treatment plan may be necessary in such cases.

    • Individuals with concerns about their cardiovascular health or those with specific risk factors should discuss these with their healthcare provider before starting imipramine or any other medication in this class.

  • Photosensitization

    • Imipramine has been associated with photosensitization, a heightened sensitivity of the skin to sunlight.
    • To minimize the risk of skin reactions, it is advisable to avoid excessive exposure to the sun while taking this medication.
    • This includes taking precautions such as using sunscreen, wearing protective clothing, and limiting sun exposure, particularly during peak sunlight hours.
    • Patients should discuss any concerns or experiences of photosensitivity with their healthcare provider for appropriate guidance and recommendations.

  • Serotonin syndrome

    • Serotonergic drugs, including SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors), have the potential to cause serotonin syndrome (SS).

    • This risk is particularly elevated when these drugs are combined with other serotonergic medications like triptans, TCAs (tricyclic antidepressants), fentanyl, lithium, tramadol, buspirone, St. John's wort, or tryptophan.

    • Additionally, combining these drugs with agents that impair serotonin metabolism, such as MAO inhibitors for psychiatric disorders, intravenous methylene blue, zolid, linezolid, and intravenous methylene blue, can increase the risk of SS.

    • Patients taking serotonergic medications should be monitored carefully for signs of serotonin syndrome, which may include mental state changes like agitation and hallucinations, as well as symptoms like delirium and coma.

    • Prompt medical attention is crucial if symptoms of serotonin syndrome are suspected, as it can be a potentially life-threatening condition.

    • Serotonin syndrome also has other features, such as:
      • Autonomic instability 
      • Neuromuscular changes 
      • GI symptoms 
      • Seizures
    • Stop taking any serotonergic agents or treatment if you notice signs or symptoms.

  • Alcohol abuse disorder

    • In individuals with chronic alcohol abuse disorder, the pharmacokinetics (how the body processes the drug) of certain medications, including imipramine, may be altered.

    • Reports suggest that there can be an increase in drug clearance and a decrease in elimination half-life in individuals with chronic alcohol abuse.

    • These changes in pharmacokinetics can affect how the body absorbs, distributes, metabolizes, and eliminates the drug.

    • Therefore, individuals with a history of chronic alcohol abuse may require careful monitoring and adjustments in medication dosages to ensure the effectiveness and safety of treatment.

    • It is crucial for patients to inform their healthcare providers about their alcohol consumption habits so that appropriate considerations can be made in managing their medication.

  • Cardiovascular disease

    • Patients with a history of cardiovascular disease, including a stroke, myocardial infarction (MI), or tachycardia, should exercise caution when considering the use of imipramine.

    • This medication has a higher risk of causing conduction abnormalities compared to other antidepressants.

    • Imipramine has been identified as a substance that can potentially exacerbate myocardial dysfunction, as stated in a scientific statement by the American Heart Association.

    • The risk is considered moderate in magnitude.

    • Individuals with preexisting heart disease and elderly patients should be aware that higher doses of imipramine may lead to changes in baseline and periodic electrocardiograms (EKG).

    • Regular monitoring, including EKG assessments, may be recommended in such cases to ensure the cardiovascular safety of the medication.

    • Before starting imipramine, individuals with a history of cardiovascular issues should discuss their medical history with their healthcare provider to assess the potential risks and benefits.

  • Diabetes:

    • Patients with diabetes mellitus should exercise caution when using imipramine, as this medication may affect glucose regulation.
    • Imipramine can potentially influence blood glucose levels, and individuals with diabetes may need to monitor their blood sugar more closely while taking this medication.
    • It is important for individuals with diabetes to work closely with their healthcare provider to manage their condition effectively, considering potential interactions and effects on glucose regulation when using imipramine or any other medications.
    • Adjustments in diabetes management may be necessary, and regular monitoring is crucial to ensure optimal health and safety.

  • Hepatic impairment

    • Patients with hepatic impairment should be cautious.

  • Hypomania and mania:

    • Imipramine can potentially worsen psychosis in individuals with bipolar disorder or trigger a shift towards mania or hypomania.

    • Therefore, using imipramine as monotherapy is not recommended for patients with bipolar disorder.

    • In cases where patients present with depressive symptoms, it is important to assess for possible bipolar disorder.

    • It's crucial to note that the FDA (U.S. Food and Drug Administration) has not approved imipramine for the treatment of bipolar disorder.

    • Management of bipolar disorder typically involves mood stabilizers or other medications specifically indicated for bipolar disorder.

    • Individuals with depressive symptoms who may have underlying bipolar disorder should undergo thorough evaluation and receive appropriate treatment under the guidance of a healthcare professional.

  • Ocular effects

    • Imipramine use may result in mild pupillary dilation, which, in certain cases, can lead to narrow-angle glaucoma.
    • It is crucial for patients who have not undergone an iridectomy (a surgical procedure to create an opening in the iris) to reduce the risk of narrow-angle glaucoma to undergo evaluation.
    • This assessment is important to monitor for potential eye-related side effects and ensure the safety of individuals using imipramine, particularly in those at risk for glaucoma.
    • Patients should inform their healthcare providers about their eye health history, and regular eye examinations may be recommended during imipramine treatment.

  • Renal impairment

    • Patients with impaired renal function should be cautious.

  • Seizure disorder

    • Patients at high risk of seizures, particularly those with a history of seizures, brain damage, head trauma, alcohol use, or concurrent treatment with medications that may lower the seizure threshold, should be treated with caution when using imipramine.

    • Imipramine has been associated with an increased risk of seizures, and close monitoring is advisable in individuals with these risk factors.

    • It is essential for healthcare providers to assess the overall risk-benefit profile for each patient and consider alternative treatment options if the risk of seizures is deemed to be significant.

    • Patients should inform their healthcare providers about their medical history, including any history of seizures or other risk factors, to ensure the safe and effective use of imipramine or any other medications.

    • Regular monitoring and adjustment of treatment plans may be necessary to manage the risk of seizures in these individuals.

Imipramine: Drug Interaction

Risk Factor C (Monitor therapy)

Acetylcholinesterase Inhibitors

May reduce an anticholinergic agent's therapeutic impact.  Acetylcholinesterase Inhibitors' therapeutic impact may be reduced by anticholinergic drugs.

Ajmaline

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Alcohol (Ethyl)

Alcohol's CNS depressing effect may be amplified by CNS depressants (Ethyl).

Alfuzosin

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Alizapride

CNS depressants may have an enhanced CNS depressant impact.

Almotriptan

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for any signs  and symptoms of serotonin syndrome or serotonin poisoning, such as  hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status.

Alosetron

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for any  signs and symptoms of serotonin syndrome or serotonin poisoning, such as hyperreflexia, clonus,  hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status.

Alpha1-Agonists

Tricyclic Antidepressants may enhance the therapeutic effect of Alpha1Agonists. Tricyclic Antidepressants may diminish the therapeutic effect of Alpha1-Agonists.

Alpha2-Agonists (Ophthalmic)

The therapeutic benefit of alpha2-agonists may be diminished by tricyclic antidepressants (Ophthalmic).

Altretamine

Could make tricyclic antidepressants' orthostatic hypotensive effect stronger.

Amantadine

May strengthen an anticholinergic agent's anticholinergic action.

Amifampridine

Amifampridine may have a stronger neuroexcitatory and/or seizure-potentiating impact when combined  with substances with seizure threshold lowering potential.

Amphetamines

Tricyclic antidepressants may make amphetamines more harmful or poisonous.  The effects of amphetamines on the cardiovascular system may be amplified by tricyclic antidepressants.  Tricyclic antidepressants' serotonergic action may be strengthened by amphetamines.  Serotonin syndrome might occur from this. Management: When these drugs are combined, watch out for  enhanced cardiovascular effects as  well as signs and symptoms of serotonin syndrome/serotonin poisoning  (such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and  mental status abnormalities).

Anticholinergic Agents

Other anticholinergic agents' negative or hazardous effects might be amplified.

Antiemetics (5HT3 Antagonists)

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might  occur from this.  When these medications are taken together, it is important to watch out for any signs and  symptoms of serotonin syndrome or serotonin poisoning, such as hyperreflexia, clonus, hyperthermia,  diaphoresis,  tremor, autonomic instability, and changes in mental status. Alosetron, Ondansetron, and  Ramosetron are exceptions.

Antipsychotic Agents

Antipsychotic Agents' negative or toxic effects may be exacerbated by Serotonergic Agents (High Risk).  Particularly, serotonergic drugs may intensify the effects of dopamine blocking, thus raising the danger  of neuroleptic malignant syndrome.  Serotonergic agents' serotonergic action may be enhanced by  antipsychotic  drugs (High Risk). Serotonin syndrome might occur from this.

Antipsychotic Agents (Second Generation [Atypical])

Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications  

Aspirin

 Aspirin's antiplatelet action may be enhanced by tricyclic antidepressants (tertiary amine).

Benperidol

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Beta2-Agonists

Tricyclic antidepressants may make beta2 agonists more harmful or poisonous.

Blood Pressure Lowering Agents

May increase the hypotensive effects of agents associated with hypotension.

Botulinum Toxin-Containing Products

May strengthen an anticholinergic agent's anticholinergic action.

Brexanolone

Brexanolone's CNS depressing effects may be amplified by other CNS depressants.

Brimonidine (Topical

 CNS depressants may have an enhanced CNS depressant impact.

Brimonidine (Topical)

The hypotensive effects of blood pressure-lowering medications may be strengthened.

BusPIRone

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for any signs  and symptoms of serotonin syndrome or serotonin poisoning, such as hyperreflexia, clonus,  hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status.

Cannabidiol

May enhance the CNS depressant effect of CNS Depressants.

Cannabis

May enhance the CNS depressant effect of CNS Depressants.

CarBAMazepine

May decrease the serum concentration of Tricyclic Antidepressants.

Chloral Betaine

May enhance the adverse/toxic effect of Anticholinergic Agents.

Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

Cimetidine

May decrease the metabolism of Tricyclic Antidepressants.

Citalopram

Tricyclic Antidepressants may enhance the serotonergic effect of Citalopram. Tricyclic Antidepressants may increase the serum concentration of Citalopram. Citalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis,  tremor, autonomic instability, mental status changes) and increased TCA and citalopram concentrations/effects.

CloBAZam

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

CNS Depressants

May enhance the adverse/toxic effect of other CNS Depressants.

Cobicistat

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Cyclobenzaprine

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for  any signs  and symptoms  of serotonin syndrome or serotonin poisoning, such as hyperreflexia,  clonus,  hyperthermia, diaphoresis,  tremor, autonomic instability, and changes in mental status.

CYP2C19 Inducers (Moderate)

May lower the serum level of CYP2C19 substrates (High risk with Inducers).

CYP2D6 Inhibitors (Moderate)

CYP2D6 substrate metabolism may be decreased (High risk with Inhibitors).

Darunavir

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Desmopressin

Tricyclic antidepressants may intensify Desmopressin's harmful or hazardous effects.

Dexmethylphenidate-Methylphenidate

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  Management: When these medications are taken together, keep an eye out for any  serotonin   syndrome  or serotonin poisoning signs and symptoms (such as hyperreflexia,  clonus, hyperthermia, diaphoresis,  tremor, autonomic instability, and changes in mental status).

Dextromethorphan

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for any  signs and symptoms  of serotonin syndrome or serotonin poisoning, such as hyperreflexia, clonus,  hyperthermia,  diaphoresis,  tremor, autonomic instability, and changes in mental status.

Diazoxide

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Dimethindene (Topical)

CNS depressants may have an enhanced CNS depressant impact.

Doxylamine

CNS depressants may have an enhanced CNS depressant impact.  Management: The producer of the pregnancy-safe drug Diclegis (doxylamine/pyridoxine)  particularly advises against combining it with other CNS depressants.

Dronabinol

CNS depressants may have an enhanced CNS depressant impact.

DULoxetine

Tricyclic antidepressants' serotonergic action should be improved. Serotonin syndrome might occur from this.  Tricyclic Antidepressants' serum levels may rise when DULoxetine is used.  Management: If TCA is combined with other medications, keep an eye out for  any side effects and elevated TCA concentrations that could indicate serotonin syndrome or  serotonin toxicity (such as hyperreflexia, clonus,  hyperthermia, diaphoresis, tremor, autonomic instability,  and changes in mental status).

DULoxetine

The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications.

Eletriptan

May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Ergot Derivatives

May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Nicergoline.

Escitalopram

Tricyclic Antidepressants may enhance the serotonergic effect of Escitalopram. Escitalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined.

Esketamine

May enhance the CNS depressant effect of CNS Depressants.

FluvoxaMINE

May enhance the serotonergic effect of Tricyclic Antidepressants. FluvoxaMINE may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined.

Gastrointestinal Agents (Prokinetic)

Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

Glucagon

Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.

Guanethidine

Tricyclic Antidepressants may diminish the therapeutic effect of Guanethidine.

Herbs (Hypotensive Properties)

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

HydrOXYzine

 CNS depressants may have an enhanced CNS depressant impact.

Hypotension-Associated Agents

The hypotensive action of hypotension-associated agents may be strengthened by blood pressure  lowering medications.

Imatinib

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Itopride

Itopride's therapeutic impact may be diminished by anticholinergic drugs.

Kava Kava

CNS depressants' harmful or toxic effects could be increased.

Lasmiditan

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for any  signs and symptoms  of serotonin syndrome or serotonin poisoning, such as hyperreflexia, clonus,  hyperthermia, diaphoresis,  tremor, autonomic instability, and changes in mental status.

Levodopa-Containing Products

Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications.

Lorcaserin

Tricyclic antidepressants' serotonergic action should be improved. Serotonin syndrome might occur from this.  Tricyclic Antidepressants' serum levels may rise as a result of lorcaserin. Management: If TCA is combined with  other medications, keep an eye out for any  side effects and elevated TCA concentrations that could indicate  serotonin syndrome or serotonin  toxicity (such as hyperreflexia, clonus,  hyperthermia, diaphoresis,  tremor, autonomic instability, and changes in mental status).

Lormetazepam

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Lumacaftor

 May lower the serum level of CYP2C19 substrates (High risk with Inducers).

Lumefantrine

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Magnesium Sulfate

CNS depressants may have an enhanced CNS depressant impact.

Melatonin:

Imipramine's negative or hazardous effects could be increased.

Metaxalone

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for  any signs and symptoms of  serotonin syndrome or serotonin poisoning, such as hyperreflexia,  clonus, hyperthermia, diaphoresis,  tremor, autonomic instability, and changes in mental status.

MetyroSINE

The sedative effects of metyroSINE may be strengthened by CNS depressants.

MetyroSINE

Tricyclic antidepressants' harmful or hazardous effects could be increased.

Mianserin

May strengthen an anticholinergic agent's anticholinergic action.

Minocycline (Systemic)

CNS depressants may have an enhanced CNS depressant impact.

Mirabegron

Anticholinergic drugs may make Mirabegron's harmful or hazardous effects worse.

Molsidomine

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Nabilone

CNS depressants may have an enhanced CNS depressant impact.

Naftopidil

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Nefazodone

Tricyclic antidepressants may strengthen Nefazodone's serotonergic effects. Serotonin syndrome might result  from this.  When these medications are taken together, it is important to watch out for  any signs  and symptoms of serotonin syndrome or serotonin poisoning, such as hyperreflexia,  clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.

Nicergoline

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Nicorandil

 Nicorandil's hypotensive effects may be enhanced by tricyclic antidepressants.

Nicorandil

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Nitroglycerin

Nitroglycerin absorption may be decreased by anticholinergic agents.  Anticholinergic medications specifically have the potential to impede or prevent  the absorption of nitroglycerin  by reducing the breakdown of sublingual nitroglycerin pills.

Nitroprusside

Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications.

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective

Nonsteroidal Anti-Inflammatory Drugs' (Non-steroidal) antiplatelet action may be enhanced by Tricyclic  Antidepressants (Tertiary Amine) (COX-2 Selective).

Nonsteroidal Anti-Inflammatory Agents (Nonselective

Nonsteroidal Anti-Inflammatory Drugs' (Non-steroidal) antiplatelet action may be enhanced by Tricyclic  Antidepressants (Tertiary Amine) (Nonselective).

Ondansetron

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out  for any signs and symptoms of  serotonin syndrome or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor,  autonomic instability, and changes in mental status.

Oxitriptan

The serotonergic impact of oxitriptan may be enhanced by serotonergic agents (high risk).  Serotonin syndrome might occur from this. When these medications are taken together, it is important to  watch out for  any signs and symptoms of serotonin syndrome or serotonin poisoning,  such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status.

Panobinostat

 May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Peginterferon Alfa-2b

May lower the serum level of CYP2D6 substrates (High risk with Inhibitors). 

Pentoxifylline

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Perhexiline

The serum levels of perhexiline may increase when exposed to CYP2D6 Substrates (High Risk with Inhibitors).  The serum concentration of CYP2D6 Substrates may rise in response to perhexiline (High risk with Inhibitors).

Pholcodine

Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications.

Phosphodiesterase 5 Inhibitors

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Piribedil

Piribedil's CNS depressing effects may be enhanced by other CNS depressants.

Pramipexole

The sedative effects of pramipexole might be enhanced by CNS depressants.

Prostacyclin Analogues

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Protease Inhibitors

Tricyclic Antidepressants' serum levels can rise.

Quinagolide

The hypotensive effects of blood pressure-lowering medications may be strengthened.

QuiNINE

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Ramosetron

Ramosetron's constipating effects may be enhanced by anticholinergic drugs.

Ramosetron

Perhaps makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for  any signs and symptoms  of serotonin syndrome or serotonin poisoning, such as hyperreflexia,  clonus, hyperthermia, diaphoresis,  tremor, autonomic instability, and changes in mental status.

ROPINIRole

The sedative effects of CNS depressants may increase those of ROPINIRole.

Rotigotine

Rotigotine's sedative effects may be boosted by CNS depressants.

Rufinamide

CNS depressants' harmful or toxic effects could be increased.  Particularly, drowsiness and lightheadedness could be worsened.

Serotonergic Agents (High Risk, Miscellaneous)

Tricyclic antidepressants might make serotonergic agents more effective (High Risk, Miscellaneous).  Serotonin syndrome might occur from this. When these medications are taken together, it is important  to watch out for any signs  and symptoms of serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status.

Serotonergic Non-Opioid CNS Depressants

Serotonergic non-opioid CNS depressants may have a greater CNS depressive effect when used with tricyclic  antidepressants. Serotonergic non-opioid CNS depressants' serotonergic effects may be enhanced  by tricyclic antidepressants. Serotonin syndrome might occur from this. When these medications are taken  together, it is important  to watch out for any signs  and symptoms of serotonin syndrome or serotonin  poisoning, such as  hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic  instability, and changes in mental status.

Serotonin 5-HT1D Receptor Agonists (Triptans)

Makes serotonergic agents more effective (High Risk).  Serotonin syndrome might occur from this. When these medications are taken together, it is important  to watch out for any signs  and symptoms of serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status.

Serotonin/Norepinephrine Reuptake Inhibitors

Tricyclic antidepressants' serotonergic action should be improved. Serotonin syndrome might occur from this.  When using these drugs together, watch out for any changes in mental status and indicators of  serotonin  syndrome, such as hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, and autonomic instability.  DULoxetine is an exception.

Sertraline

Tricyclic antidepressants' serotonergic action should be improved.  Tricyclic Antidepressants' serum levels may rise in response to sertraline.  Management: If these medications are combined, keep an eye out for elevated TCA concentrations and  side effects,  as well as  signs and symptoms of serotonin syndrome and serotonin toxicity (such as  hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status).

Sodium Phosphates

Tricyclic antidepressants might make sodium phosphates' harmful or hazardous effects worse.  Specifically, patients with severe sodium phosphate-induced fluid/electrolyte imbalances may  be at a higher risk of seizures and/or losing consciousness.

St John's Wort

Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  Serotonergic Agents' serum concentration may be reduced by St. John's Wort (High Risk). When these medications  are taken together, it is important to watch out  for any signs and symptoms of serotonin syndrome or serotonin  poisoning, such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability,  and changes in mental status.

Sulfonylureas

Cyclical antidepressants might make sulfonylureas' hypoglycemia effect stronger.

Syrian Rue

Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  When these medications are taken together, it is important to watch out for any  signs and symptoms  of serotonin syndrome or serotonin poisoning, such as  hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic instability, and changes in mental status.

Tetrahydrocannabinol

CNS depressants may have an enhanced CNS depressant impact.

Tetrahydrocannabinol and Cannabidiol

CNS depressants may have an enhanced CNS depressant impact.

Thiazide and Thiazide-Like Diuretics

Thiazide and Thiazide-Like Diuretics' serum concentrations may be elevated by anticholinergic agents.

Thyroid Products

Tricyclic antidepressants' arrhythmogenic effects might be increased.  Tricyclic Antidepressants' stimulatory action may be strengthened by thyroid products. May lower the level of imipramine in the serum.

Tobacco (Smoked)

Anticholinergic drugs may intensify topiramate's harmful or toxic effects.

Topiramate

The anticholinergic action of other tricyclic antidepressants may be enhanced.

Tricyclic Antidepressants

Other tricyclic antidepressants may have a greater CNS depressive effect when used with them.  The serotonergic impact of other tricyclic antidepressants may be enhanced by tricyclic antidepressants.  Serotonin syndrome might occur from this. Increasing TCA side effects, such as serotonin syndrome/serotonin  toxicity, CNS depression, and anticholinergic effects, should be continuously monitored.

Trimeprazine

CNS depressants may have an enhanced CNS depressant impact.

Valproate Products

Tricyclic Antidepressants' serum levels can rise.

Vilazodone

Tricyclic antidepressants may improve Vilazodone's serotonergic effects. Serotonin syndrome might occur from this.  If these medications are taken together, keep an eye out for any signs and  symptoms of serotonin syndrome or  serotonin poisoning (such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability,  and changes in mental status).

Vitamin K Antagonists (eg, warfarin)

The anticoagulant action of vitamin K antagonists may be increased by tricyclic antidepressants.

Vortioxetine

Tricyclic antidepressants may improve Vortioxetine's serotonergic effects. Serotonin syndrome might occur from this.  If these medications are taken together, keep an eye out for any signs  and symptoms of serotonin syndrome or  serotonin poisoning (such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability,  and changes in mental status).

Yohimbine

Tricyclic Antidepressants may increase the serum concentration of Yohimbine.

Risk Factor D (Consider therapy modification)

Abiraterone Acetate

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.

Alpha-/Beta-Agonists

Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist.

Alpha2-Agonists

Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Exceptions: Apraclonidine; Brimonidine (Ophthalmic); Lofexidine.

Amifostine

Amifostine's hypotensive impact may be strengthened by blood pressure lowering medications.  Treatment: Blood pressure-lowering drugs need to be avoided for 24 hours before amifostine  is administered when used at chemotherapeutic doses. Amifostine should not be given if blood  pressure lowering treatment cannot be stopped.

Asunaprevir

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Barbiturates

May increase the metabolism of Tricyclic Antidepressants.

Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin.

Buprenorphine

CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.

Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

Cinacalcet

May increase the serum concentration of Tricyclic Antidepressants. Management: Seek alternatives when possible. If these combinations are used, monitor closely for increased effects/toxicity and/or elevated serum concentrations (when testing is available) of the tricyclic antidepressant.

CYP2C19 Inducers (Strong)

May speed up CYP2C19 substrate metabolism (High risk with Inducers).  Management: Take into account a substitute for one of the interfering medications.  Specific contraindications may apply to some combinations. the relevant manufacturer's label.

CYP2D6 Inhibitors (Strong)

CYP2D6 substrate metabolism may be decreased (High risk with Inhibitors).

Dabrafenib

May lower the serum level of CYP2C19 substrates (High risk with Inducers).  Management: When possible, look for substitutes for the CYP2C19 substrate.  If concurrent therapy cannot be avoided, pay special attention to the substrate's  clinical consequences  (particularly therapeutic effects).

Dacomitinib

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).  Management: Steer clear of using dacomitinib at the same time as CYP2D6 subtrates with a limited therapeutic  index.

Droperidol

CNS depressants may have an enhanced CNS depressant impact. Consider lowering the dosage of droperidol or  other CNS drugs (such as opioids or barbiturates)  when they are used concurrently.  In separate drug interaction monographs, exceptions to this  monograph are covered in more detail.

Enzalutamide

May lower the serum level of CYP2C19 substrates (High risk with Inducers).  For medications that CYP2C19 activates, active metabolite concentrations may decrease instead.  Treatment: Enzalutamide should not be used concurrently with CYP2C19 substrates that have a limited therapeutic  index. Enzalutamide use, as with the use of any other CYP2C19 substrate, should be done cautiously  and well monitored.

Flunitrazepam

Flunitrazepam's CNS depressing effects may be enhanced by other CNS depressants.

FLUoxetine

Tricyclic antidepressants' serotonergic action should be improved.  Tricyclic Antidepressants' serum levels may rise when Fluoxetine is used.  Management: If these medications are combined, keep an eye out for elevated TCA concentrations and  side effects,  as well as  signs and symptoms of serotonin syndrome and serotonin toxicity (such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability, and changes in mental status).

HYDROcodone

CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

Iohexol

Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.

Iomeprol

Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.

Iopamidol

Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.

Lemborexant

CNS depressants may have an enhanced CNS depressant impact.  Management: Due to the possibility of additive CNS depressant effects when lemborexant and  concurrent CNS depressants are administered concurrently, dosage modifications may be required.  Effects of CNS depressants must be closely monitored.

Lofexidine

The therapeutic impact of lofexidine may be diminished by tricyclic antidepressants.  Management: If at all possible, steer clear of this medication cocktail. When starting a combined  therapy and stopping either medicine, closely monitor blood pressure  if concurrent administration is necessary.  To do so, adjust the dosage.

Methotrimeprazine

CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.

Metoclopramide

May enhance the adverse/toxic effect of Tricyclic Antidepressants. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with tricyclic antidepressants for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome.

Obinutuzumab

The hypotensive effects of blood pressure-lowering medications may be strengthened.  Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before  the start of the obinutuzumab infusion and keeping them off  until 1 hour after the infusion is finished.

Opioid Agonists

CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

OxyCODONE

CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

PARoxetine

Tricyclic antidepressants' serotonergic action should be improved.  Tricyclic Antidepressants' serum levels may rise when PARoxetine is used.  Management: If these medications are combined, keep an eye out for elevated TCA concentrations  and side effects,  as well as signs and symptoms of serotonin syndrome and serotonin  toxicity (such as hyperreflexia,  clonus, hyperthermia, diaphoresis, tremor, autonomic instability,  and changes in mental status).

Perampanel

May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.

Pramlintide

May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.

QuiNIDine

Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Secretin

Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin.

Serotonergic Opioids (High Risk)

Tricyclic Antidepressants may intensify Serotonergic Opioids' CNS depressive effects (High Risk).  Tricyclic Antidepressants may have a stronger serotonergic effect when used with Serotonergic Opioids (High Risk).  Serotonin syndrome might occur from this. Management: Take into account different pharmacological combinations.  Keep an eye out for the warning signs and  symptoms of CNS depression and serotonin syndrome,  if they occur together.

Sodium Oxybate

CNS depressants may have an enhanced CNS depressant impact.  Management: Take into account substitutes for combined use. Reduce the doses of one or more  medications when simultaneous use is necessary. It is not advised to use sodium oxybate with  alcoholic beverages or hypnotic sedatives.

Suvorexant

CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.

Tapentadol

May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

Terbinafine (Systemic)

May increase the serum concentration of Imipramine. Management: Monitor for increased effects/toxicity of imipramine during concomitant administration with terbinafine. Reduced dosages of imipramine may be needed.

Zolpidem

CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.

Risk Factor X (Avoid combination)

Aclidinium

May enhance the anticholinergic effect of Anticholinergic Agents.

Azelastine (Nasal)

CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).

Bromopride

May enhance the adverse/toxic effect of Tricyclic Antidepressants.

Bromperidol

The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications.  Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol.

Bromperidol

CNS depressants may have an enhanced CNS depressant impact.

Cimetropium

The anticholinergic activity of cimetropium may be strengthened by anticholinergic agents.

Dapoxetine

Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  Treatment: Avoid using high-risk serotonergic medications with dapoxetine or within 7 days after stopping them.  Within 14 days of using a monoamine oxidase inhibitor, do not take dapoxetine. This combination is  listed on the labelling for dapoxetine as being harmful.

Dronedarone

Tricyclic Antidepressants may enhance the arrhythmogenic effect of Dronedarone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Eluxadoline

Anticholinergic Agents may enhance the constipating effect of Eluxadoline.

Fexinidazole [INT]

Tricyclic antidepressants may increase Fexinidazole's [INT] ability to extend QTc.

Glycopyrrolate (Oral Inhalation)

Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).

Glycopyrronium (Topical)

May enhance the anticholinergic effect of Anticholinergic Agents.

Iobenguane Radiopharmaceutical Products

Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose.

Ipratropium (Oral Inhalation)

May enhance the anticholinergic effect of Anticholinergic Agents.

Levosulpiride

Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.

Linezolid

May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome.

Methylene Blue

Tricyclic Antidepressants may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome.

Monoamine Oxidase Inhibitors (Antidepressant)

May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome.

Orphenadrine

CNS Depressants may enhance the CNS depressant effect of Orphenadrine.

Oxatomide

May enhance the anticholinergic effect of Anticholinergic Agents.

Oxomemazine

May enhance the CNS depressant effect of CNS Depressants.

Paraldehyde

CNS Depressants may enhance the CNS depressant effect of Paraldehyde.

Pitolisant

Tricyclic Antidepressants may diminish the therapeutic effect of Pitolisant.

Potassium Chloride

Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride.

Potassium Citrate

Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.

Rasagiline

Tricyclic antidepressants' serotonergic action should be improved. Serotonin syndrome might occur from this.

Revefenacin

 Revefenacin's anticholinergic action may be strengthened by anticholinergic agents.

Safinamide

May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome.

Selegiline

May enhance the serotonergic effect of Imipramine. This could result in serotonin syndrome.

Thalidomide

CNS Depressants may enhance the CNS depressant effect of Thalidomide.

Tiotropium

Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.

Umeclidinium

May enhance the anticholinergic effect of Anticholinergic Agents.

 

Monitoring parameters:

  • CBC
  • ECG 
  • Prior to & during initial therapy, monitor BP and heart rate.
  • Serum sodium in at-risk populations 
  • Evaluate mental status and suicide ideation 
  • Anxiety
  • Blood glucose.
  • Panic attacks.
  • Signs/symptoms of serotonin syndrome.
  • Weight & BMI
  • Social functioning

 

How to administer Imipramine (Tofranil)?

Initiate treatment with a low dose, preferably after the night meal. Increase the dose in increments of 25 mg every 3 - 5 days.

Mechanism of action of Imipramine (Tofranil):

  • Imipramine, like other tricyclic antidepressants, is believed to exert its therapeutic effects by inhibiting the reuptake of neurotransmitters, such as serotonin and norepinephrine, at the presynaptic neural membrane.

  • This inhibition leads to increased concentrations of these neurotransmitters in the synaptic cleft, enhancing their effects.

  • In addition to reuptake inhibition, imipramine has been found to have additional effects on receptors.

  • It can lead to the desensitization of adenyl cyclase, downregulation of beta-adrenergic receptors, and downregulation of serotonin receptors.

  • These various actions contribute to the overall impact on neurotransmission and are thought to play a role in the antidepressant effects of imipramine.

The onset of action:

  • Depression:
    • Individual responses vary, however, 4-8 weeks of treatment is needed before determining if a patient is partially or nonresponsive (APA 2010).

Absorption:

  • Well absorbed.
  • Not affected by food.

Protein binding:

  • 60%-96%.
  • Primarily to alpha1 acid glycoprotein & lipoproteins.
  • To a lesser extent albumin.

Metabolism:

  • Hepatic, primarily via CYP2D6 to desipramine (active) and other metabolites.
  • Significant first-pass effect.

Bioavailability:

  • 22%-77%.

Half-life elimination:

  • 8-21 hours.
  • Mean:
    • Children: 11 hours.
    • Adults: 16-17 hours.
  • Desipramine (active metabolite):
  • 22-28 hours

Time to peak

  • serum: 2-6 hours.

Excretion:

  • Urine (as metabolites; <5% unchanged)

International Brands of Imipramine:

  • Tofranil
  • NOVO-Pramine
  • PMS-Imipramine
  • Antidep
  • Bonil
  • Celamine
  • Chrytemin
  • Depram
  • Depramina
  • Depsol
  • Depsonil
  • Ethipramine
  • Eupramin
  • Feinalmin
  • Fronil
  • Imidol
  • Imilanyle
  • Imimine
  • Imine
  • Melipramin
  • Meripramin
  • Pinor
  • Pramin
  • Pryleugan
  • Seizuban
  • Sermonil
  • Talpramin
  • Tofranil
  • TofranilPM
  • Tofyram
  • Topramine

 

Imipramine Brand Names in Pakistan:

Imipramine 25 mg Tablets
Depna Saydon Pharmaceutical Industries (Pvt) Ltd.
Imidol Siza International (Pvt) Ltd.
Imipral Usawa Pharmaceuticals
Imipramin Delta Pharma (Pvt) Ltd.
Imipramine Rehman Medicine Co.
Imiprol Usawa Pharmaceuticals
Imira Weather Folds Pharmaceuticals
Tofranil Indus Pharma (Pvt) Ltd.

 

Imipramine 75 mg Tablets
Imiprol Usawa Pharmaceuticals

 

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