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Amoxapine - Uses, Dosage, Side Effects, Precautions, and Warnings

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Amoxapine helps maintain mental balance. To learn more about it, read the article given below.

Medically reviewed by

Dr. Kaushal Bhavsar

Published At November 8, 2022
Reviewed AtNovember 8, 2022


Amoxapine is an antidepressant drug used to treat neurotic depressive disorders or psychotic depression. It helps with depression accompanied by anxiety or agitation. Treating depression can help to improve mood and enables one to enjoy well-being. The drug is available on a doctor's prescription. Amoxapine is a Food and Drug Administration (FDA) approved drug for treating treatment-resistant depression when the first and second-line medications have failed to improve the symptoms.

How Does Amoxapine Work?

Amoxapine is a second-generation tricyclic dibenzoxazepine antidepressant that acts by preventing the reuptake of norepinephrine in the neuronal synapses. The drug is rapidly and completely absorbed from the gastrointestinal tract. A single dose of Amoxapine's highest plasma concentration may occur within one or two hours of oral administration. It is widely distributed in the body's tissues, such as the lungs, spleen, kidneys, heart, and brain. Amoxapine is completely metabolized in the liver. The major metabolite of Amoxapine is 8-hydroxy Amoxapine, and the minor metabolite is 7-hydroxy Amoxapine, which has a half-life of approximately 30 and six hours, respectively. The drug is excreted in urine as conjugated metabolites.


  • Amoxapine is used to relieve symptoms of depression.

  • It is used to treat neurotic and reactive depressive disorders. This usually occurs in response to an external problem or stress. Neurotic depression is found in an emotionally unstable person and involves distress, anxiety, apprehension, and low self-esteem.

  • Amoxapine is indicated for treatment-resistant depression when the first and second-line medications are ineffective in improving the condition.


  • Amoxapine is not the first choice for treating depression. This is primarily because of its side effects, such as drowsiness, severe allergic reactions, or blurred vision.

  • Antidepressants such as Amoxapine can become ineffective, especially when taken for a long time. There may be a recurrence of symptoms after two to three months of effective drug work.

  • Amoxapine is not recommended in children (under 16 years) and older adults with a history of seizures.

  • It may take several weeks or longer to see the full effect of Amoxapine.

  • Amoxapine can potentially cause major neuroleptic effects and may cause high incidences of seizures and overdose deaths.

  • Amoxapine is less potent or less effective than other tricyclic antidepressants. It has a therapeutic dosage ranging from 200 mg to 400 mg per day.


1. Route of Administration- Oral

2. Dosage Strengths -

  • 25 mg.

  • 50 mg.

  • 100 mg.

  • 150 mg.

3. Dosage Forms-

  • 25 mg - white, round tablet imprinted with "25".

  • 50 mg - Light orange, round tablet imprinted with "50".

  • 100 mg - Blue, circular tablet with "100" imprinted.

  • 150 mg - Light orange, round tablet with Imprinted" 150".

The recommended effective dose is 200 mg to 300 mg daily.

The starting dose for an adult is 50 mg which may be taken two or three times a day.

Special Considerations:

  • Pregnancy - Amoxapine is a pregnancy category C drug. The medicine should be used during pregnancy if it gives benefits that justify the possible risk to the fetus.

  • Lactation - Amoxapine is excreted in human breast milk. The drug should be used with caution while administered to nursing women.

  • Pediatric Patients - Antidepressants such as Amoxapine have an increased risk of suicidal thinking and behavior in children and adolescents. These patients must be closely monitored for any changes in behavior and suicidal tendencies, especially during the initial one to two months of therapy and dosage adjustments. The use of Amoxapine is not approved in pediatric patients.

  • Geriatric Patients - Amoxapine can cause a movement condition called tardive dyskinesia with symptoms including uncontrollable facial movements, such as blinking or sticking the tongue out. This is more often seen in elderly women.

  • Renal Impairment - Renal clearance of Amoxapine is decreased in severe renal impairment. Dose reduction may be necessary for these patients.

  • Hepatic Impairment - Patients with liver impairment have a greater risk for adverse effects due to decreased drug clearance. The use of Amoxapine should be avoided in patients with liver disease.

Warnings and Contraindications


  • Pregnancy - The United States has categorized Amoxapine as a pregnancy category C. However, no controlled studies have been done on women during their pregnancy. Amoxapine may be prescribed to pregnant women only if the benefits outweigh the risks.

  • Breastfeeding - Amoxapine is detected in breast milk and may cause adverse effects in nursing infants.

  • Children - Amoxapine carries an FDA black box warning regarding suicidal tendencies in patients under 24 years of age and should be avoided.

  • Elderly - Older adults are likely to have unwanted effects such as movement disorders, unusual drowsiness, or age-related kidney and liver problems. These patients may require dose adjustment.

  • Hypersensitivity - Adverse cutaneous manifestations are common side effects of antidepressants, including rashes and hypersensitivity reactions such as urticaria, photosensitivity, or hyperpigmentation.

  • Epilepsy - Tricyclic antidepressants such as Amoxapine are contraindicated in patients with epilepsy or seizures.

  • Acute Myocardial Infarction Recovery - Amoxapine treatment should be avoided in patients in the acute recovery period after myocardial infarction.

  • Alcohol - Taking alcohol while using Amoxapine can increase the side effects of the drug, such as drowsiness, dizziness, or difficulty concentrating. Consumption of alcohol should be avoided when taking tricyclic antidepressants like Amoxapine.

Warnings and Precautions:

  • Major Depressive Disorders - The use of Amoxapine in patients with major depressive disorders can worsen their depression and decrease the risk of suicidal ideation.

  • QT Prolongation - Treatment with Amoxapine should be avoided in patients with increased QT interval (a heart rhythm disorder that causes fast heartbeats) or acute myocardial infarction, as the medicine may exacerbate the symptoms.

  • Bipolar Disorders - Treatment with Amoxapine can induce a hypomanic state (abnormally elevated and extreme changes in mood or emotions) in patients with underlying bipolar disorder.

  • Overactive Thyroid - Amoxapine should be used cautiously in patients with hyperthyroidism or receiving thyroid drugs. These drugs can produce cardiac arrhythmias or improper beating of the heart.

  • Neuroleptic Malignant Syndrome - Therapy with Amoxapine may be associated with the neuroleptic malignant syndrome, which has potentially fatal clinical manifestations such as hyperpyrexia (a condition where the body temperature can go above 106 degrees Fahrenheit due to changes in the hypothalamus), rigidity or tension in the muscle, a change in mental function, and symptoms of autonomic instability such as dizziness and fainting upon standing.

  • Diabetes Mellitus - Treatment with Amoxapine may increase blood glucose concentration, as it affects the endocrine system. The drug should be used with caution in patients with diabetes mellitus.

For Patients

What Is Depression?

Depression or clinical depression is a common but serious illness. It is classified as a mood disorder that affects one's mood and ability to perform day-to-day activities. People experiencing depression have low productivity and can have chronic health conditions. Depression can cause severe symptoms, such as constant sadness or fearful mood, constantly irritated, lack of interest in any activity, restlessness, decreased energy, difficulty concentrating, difficulty sleeping, or suicide attempts or thoughts of death. Depression can be treated effectively with medications and psychotherapy.

Why Is Amoxapine Prescribed to Treat Symptoms of Depression?

  • Amoxapine is a tricyclic antidepressant that works on the central nervous system by increasing certain chemicals in the brain. This helps in maintaining mental balance.

  • Amoxapine is a good choice for people whose depression is resistant to other drugs.

  • It helps to keep more serotonin and norepinephrine available to the brain and helps to elevate mood.

  • Doses up to 300 mg can be taken once a day.

Facts One Should Know About Amoxapine:

  • Children and teenagers taking Amoxapine are more likely to become suicidal than children not taking this medication. The suicidal tendency is usually seen at the treatment's beginning or when the dose is increased or decreased.

  • Antidepressants such as Amoxapine can cause severe drowsiness and dizziness. It is advised to avoid driving or doing anything that may require one to focus.

  • The drug should not be taken if one has taken a monoamine oxidase (MAO) inhibitor in the past two weeks, as it may cause severe drug interaction.

How Should One Take Amoxapine?

  • Amoxapine is available as a tablet that is to be taken by mouth.

  • It can be taken once or more times a day. If taken once a day, it should be taken at bedtime.

  • It is usually taken with or without food.

  • The drug should be taken at the same time each day.

  • The dosage of Amoxapine is started as 50 mg, which can be taken two to three times a day (300 mg daily may be given).

  • The drug may be given for maintenance therapy at a dosage of 300 mg or less, in a single dose, preferably at bedtime. Amoxapine can make one sleepy and tired and should be taken at night.

  • The drug should never be doubled, as it may cause an overdose, requiring urgent medical care.

  • It may take up to three weeks for Amoxapine to show good results and improve the symptoms.

  • The drug should not be stopped abruptly. It may cause unpleasant withdrawal symptoms.

Things to Discuss With Doctor Before Beginning AmoxapineTherapy:

  • Allergies - Inform the physician if one has ever had an allergic reaction to Amoxapine or other ingredients in the formulation.

  • Medical History- The patient must always inform the treating doctor of his illnesses, such as diabetes, bronchospastic diseases, myocardial infarction, and impaired renal or hepatic function.

  • Drug History- Always give the treating doctor a complete list of the prescription and non-prescription medications that one may be taking, including any herbal supplements, nutritional supplements, and vitamins.

  • Pregnancy- If one is pregnant or planning to get pregnant any soon, it is important to inform the doctor. The use of Amoxapine may harm the fetus and the mother. Using Amoxapine during the third trimester of pregnancy may increase the risk of adverse events. If one gets pregnant while on Amoxapine, inform the doctor as soon as you find out.

  • Lactation- The doctor must know if one is breastfeeding. The possibility of Amoxapine passing into the breastmilk has been observed. Amoxapine should be avoided while breastfeeding.


Amoxapine has been associated with a low rate of minor serum aminotransferase elevations during the treatment. The usage of drugs has shown rare instances of clinically apparent acute liver injury. Long-term therapy with Amoxapine is found to have fewer liver test abnormalities.


  • Amoxapine is effective in both reactive and neurotic depression and major endogenous depressive disorders.

  • Amoxapine interrupts the transmission of norepinephrine but also blocks histamines and cholinergic receptors, accounting for mild sedative effects.

  • Amoxapine has effects that are similar to those of major tranquilizers. Therefore, it works better in patients who are agitated or have anxiety and depression.

What Side Effects Can the Patient Expect With Amoxapine?

The serious side effects that occur with the use of Amoxapine are as follows:

  • Irregular or rapid heartbeat.

  • Tremors.

  • Flu-like symptoms.

  • Rash.

  • Confusion.

  • Difficulties with speech.

  • Chest pain.

  • Hives.

  • Hostility.

  • Increased depression.

  • Serious blood problems include agranulocytosis (deficiency of granulocytes in the blood, causing an increased risk of infection), thrombocytopenia (low platelet level), or liver problems.

The common side effects may include,

  • Fatigue.

  • Dry mouth (xerostomia).

  • Weight gain.

  • Low blood pressure.

  • Stomach upset.

  • Increased sensitivity to sunlight.

  • Constipation.

  • Nightmares.

  • Excessive sweating.

  • Difficulty in urination.

  • Blurry vision.

  • Drowsiness.

  • Constipation.

  • Dizziness.

  • Flatulence.

  • Increase in prolactin.

  • Enlarged breast.

Overdose of Amoxapine:

The toxic manifestations of Amoxapine differ significantly from other tricyclic antidepressants. If a person overdoses, contact the doctor immediately and do not take another tablet until the doctor tells you to do so.

  • If you experience severe side effects like seizures or breathing difficulty, a bystander or family member should take you to the emergency room or contact local poison control services.

  • It can cause serious central nervous system effects such as grand mal convulsions, including loss of consciousness and violent muscle contractions). The drug may develop status epilepticus (a seizure that lasts longer than five minutes) and constitute a neurologic emergency. Coma and acidosis (build-up of acid in the bloodstream) are serious complications of Amoxapine overdose.

  • You should never stop taking Amoxapine without first talking to your doctor. Consult your physician or visit the emergency room if you experience any side effects that require immediate attention.

  • Do not skip the dose or stop taking Amoxapine suddenly. This can worsen the condition or cause serious problems, including worsening depression or cause withdrawal symptoms. The doctor will instruct you on how to taper the dose gradually.

  • Remember that you must continue taking Amoxapine, regardless of how well you respond to it, unless your doctor explicitly mentions otherwise. The drug is usually meant for long-term use and should not be stopped even if you respond well.

Dietary Restrictions to Consider When Taking Amoxapine:

You may continue to follow your regular diet unless your doctor asks you to change it. No dietary restrictions are needed. The drug may be taken with or without food.

  • Grapefruit Juice - Amoxapine can lose its effectiveness when taken with grapefruit juice.

  • Caffeine-Containing Foods - Avoid consuming chocolates and coffee while taking Amoxapine.

  • St. John's Wort - Avoid using St. John's wort with tricyclic antidepressants. It can increase the risk of serotonin syndromes, such as hypertension, hyperthermia, myoclonus (muscle jerks), and mental status changes.

  • Alcohol - Drinking alcohol while taking Amoxapine may result in enhanced drowsiness and impaired motor skills.

Storage of Amoxapine:

  • Store Amoxapine at room temperature in a closed container, away from heat, moisture, and direct light.

  • Amoxapine tablets should be stored in the original packaging or container with a tightly closed lid.

  • Keep this drug far from the reach of children and pets.

Disposal of Amoxapine:

  • Amoxapine should not be disposed of by flushing or throwing it out with regular garbage.

  • You may dispose of Amoxapine through your local medicine take-back program, which you can access or learn more about through your local pharmacist.

  • If you do not have access to a medicine take-back program, ask your local pharmacist about other drug disposal options.

For Doctors


Amoxapine is indicated for the following purposes:

  • Amoxapine is used to treat symptoms of depression as they cause an increase in serotonergic neurotransmission. It helps patients suffering from neurotic ( signs of mental disturbances) or symptoms in response to external problems or reactive depressive disorders. It can be used to treat endogenous and psychotic depression, which occurs without the presence of any stress or trauma.

  • It has shown efficacy as an atypical antipsychotic drug in open trials.

  • Amoxapine may also be used to treat depression associated with anxiety or agitation.

  • Amoxapine is an FDA-approved drug belonging to second-generation tricyclic dibenzoxazepine antidepressants used when selective serotonin-norepinephrine reuptake inhibitors fail to control depression.

  • Amoxapine has shown improvement in neuropathic pain.

Pharmacology of Amoxapine:


Amoxapine is designated chemically as 2-Chloro-11-(1-piperazinyl) dibenzo oxazepine. It has a tricyclic ring system with an alkyl amine substituent on the central ring.


1. Active Ingredients

  • Amoxapine - 25 mg.

2. Inactive Ingredients

  • Anhydrous dibasic calcium phosphate.

  • Magnesium stearate.

  • Starch.

  • Corn.

  • Stearic acid.

Clinical Pharmacology:

Mechanism of Action

Amoxapine's primary action mechanism is through inhibition of the presynaptic reuptake of norepinephrine. The drug is a selective inhibitor of noradrenaline uptake and produces a significant blockade of dopamine D2 receptors.


The mechanism of the clinical action of Amoxapine in man is not well understood. Clinical studies show that Amoxapine has a rapid onset of action compared to drugs like Amitriptyline or Imipramine.


  • Mean Cmax- Within four to seven days.

  • Median Tmax- 90 minutes.

[Cmax- Maximum concentration achieved by a drug in the blood, cerebrospinal fluid, or target organ after administration of a dose]

[Tmax- Time taken for a drug to reach maximum concentration after administration of a dose]

Pharmacokinetic Changes -The dose is to be adjusted to individual requirements due to variations in the rate of metabolism.


The drug is widely distributed in body tissues, with the highest concentration in the lungs, spleen, kidneys, heart, and brain. A lower concentration may be detected in the testes and muscles.

  • Steady-state Plasma Levels- It is absorbed rapidly within 90 minutes of ingestion. The concentration of serum may fall. It has a half-life of fewer than eight hours.

  • Time to Approach Steady-state Levels- In two weeks, over 80 %.

  • Binding to Plasma Proteins- Amoxapine binds to human plasma proteins is approximately 90 %.


Amoxapine is almost completely absorbed from the gastrointestinal tract

  • Active Metabolites - 8-hydroxy Amoxapine has a biological half-life of 30 hours.

  • Inactive Metabolites - Glucuronides as conjugated forms and minor metabolite is 7-hydroxy Amoxapine.


After One Week Of Administration -

  • Recovery of Anastrozole- 85 % recovered in feces and urine.

  • 60 % of the single oral dose is excreted in the urine.

  • 18 % is excreted in the feces, mainly as metabolites that are not chemically conjugated.

  • 5 % of the ingested drug dose is excreted unchanged in the urine.

Special Considerations

  • Cardiovascular Disease - Therapy with tricyclic antidepressants such as Amoxapine can cause orthostatic hypotension, which refers to a fall in the blood pressure when one stands up after sitting or lying down), syncope, tachycardia, and dizziness. This usually happens at the initiation of the treatment.

  • Seizure Disorders - Amoxapine can lower the seizure threshold and may trigger seizures. Therapy should be used cautiously in patients who have had episodes of seizures in the past or have experienced head trauma, central nervous system abnormalities, and alcoholism.

  • Diabetes - Tricyclic antidepressants have been reported to cause both elevation and lowering of blood sugar levels. Patients with a history of low blood sugar must be monitored closely for any spike in blood glucose levels when treated with these agents.

  • Renal Disease - Amoxapine undergoes metabolism in the liver. Therapy must be cautiously administered in patients with significantly impaired renal or hepatic function and may require adjusting the dose.

Drug Interactions:

  • Monoamine Oxidase Inhibitors (MAO) - These drugs act by inhibiting presynaptic reuptake of norepinephrine. Amoxapine, too, imparts similar effects and should not be given within 14 days of other antidepressants, such as MAO inhibitors. Sufficient time should be given to allow the previous antidepressant to leave the system before initiating treatment with Amoxapine.

  • Antihistamines - Medicines such as Diphenhydramine, Loratadine, and Fexofenadine. These drugs may exacerbate the symptoms such as drowsiness and dizziness.

  • Antacids - The use of antacids such as Famotidine can increase the risk of an irregular heart rhythm. This can be a serious and life-threatening condition.

  • Antifungals Drugs - Fluconazole and Itraconazole can interfere with the actions of Amoxapine. It can cause unwanted side effects such as dizziness, drowsiness, and rapid heartbeat.

  • Sleeping Pills - Drugs such as Temazepam, Triazolam, and Zolpidem can interact and cause dangerous side effects by suppressing the central nervous system.

  • Antipsychotics - Combining antipsychotics with antidepressants can have antimuscarinic effects (mediate the parasympathetic effects such as slow heart rate and increased smooth muscle activity) and worsen the side effects.

  • Vitamins - High intake of vitamins, St. John's wort, and garcinia Cambogia can increase the risk of serotonin syndrome.

  • Herbal Products - St. John's wort, Grapefruit juice can interfere with the effectiveness of the drug.

What Have Clinical Trials Shown About Amoxapine?

Aim of Trial 1:

To test the hypothesis that there may be no disadvantages and perhaps even an advantage of a once-a-day regimen of Amoxapine.

A six-week double-blind clinical trial was carried out on 35 hospitalized patients with major (18 patients) and minor (17 patients) depressive disorders.

Placebo Comparator - Inactive placebo and Amitriptyline 50 mg.

Primary Outcome - No statistically significant difference was found in overall therapeutic and adverse effects between the treated group with single or divided daily doses.

Results - The onset of the therapeutic effect appeared a bit faster in the group treated with a single daily dose.

Given the above findings, a second study was carried out with a Latin square design.

Results showed no significant difference from the placebo.

Aim of Trial 2:

The study's objective was to compare the antipsychotic and side effects profile of Amoxapine and Risperidone in a randomized, standard dosage, double-blind trial of patients with acute psychotic and schizophrenia.

Forty-eight schizophrenic patients were enrolled in the study and were randomized in a double-blind six-week trial to receive either Risperidone 5 mg daily or Amoxapine 250 mg daily.

Primary Outcome - Positive, negative, and affective symptoms and motor side effects were determined at baseline. Prolactin levels were also determined. 39 patients (Amoxapine, n=22, and Risperidone, n=21) completed the trial.

Mean Duration of Follow-up - Six weeks.

Results - Equivalent improvement in [positive, negative, and depressive symptoms were observed. Amoxapine was associated with fewer prolactin levels elevation.

Patient Counseling Information:

Administration Instructions

  • Take Amoxapine only as prescribed by the doctor.

  • Amoxapine can be taken with or on an empty stomach.

  • Swallow these tablets and do not crush, split, or chew them.

  • Do not stop taking Amoxapine abruptly.

Complications or Side Effects

  • Pregnancy- Studies have shown that Amoxapine therapy can cause heart defects, stillbirths, preterm birth, spina bifida, or cleft lip and should not be used unless necessary.

  • Hypersensitivity- Amoxapine is contraindicated in people allergic to the drug or its constituents.

  • Hyperthyroidism - Amoxapine can mask the signs and symptoms of an overactive thyroid gland, such as a fast heart rate. The condition may worsen if the drug is stopped suddenly.

  • Tardive Dyskinesia - Amoxapine causes neuroleptic activity and may precipitate symptoms of tardive dyskinesia (long-term neuroleptic drugs) following chronic use.

  • Hypertension - Amoxapine can cause fluctuations in blood pressure, arrhythmias, stroke, and tachycardia.

Frequently Asked Questions


What Are the Uses of Amoxapine?

Amoxapine treats symptoms of mental disorders, such as depression. The drug is used to treat symptoms of depression, like low mood, inability to function, sad feelings, anxiety, trouble sleeping, increased fatigue, changes in appetite, and loss of interest in activities once enjoyed.


Is Amoxapine a Tricyclic Antidepressant?

Amoxapine belongs to a class of medication known as tricyclic antidepressants. The second-generation tricyclic dibenzoxazepine antidepressants are Food and Drug Administration (FDA)-approved and act by increasing levels of certain natural substances in the brain to maintain mental balance.


Does Amoxapine Cause Sedation?

Amoxapine blocks the transmission of histamine (produced as a part of the immune response to inflammation), producing mild sedation with the most commonly reported as drowsiness and relaxation. The onset of sedative effects reduces negative emotions, stress, or anxiety that may gradually disappear.


What Are the After Effects Caused by Amoxapine?

Amoxapine can cause side effects, including:
- Nausea.
- Drowsiness.
- Tiredness.
- Dry mouth.
- Photosensitivity (sensitivity to sunlight).
- Weight changes.
- Constipation.
- Excessive sweating.
- Blurred vision.


Does Amoxapine Make a Person Feel More Sleepy?

Amoxapine can make some people feel sleepy or less alert than usual. The drug also makes one feel more lethargic and can cause drowsiness, especially at the beginning of the treatment.


What Is the Average Time Taken by Amoxapine to Act?

Amoxapine does not work immediately and may take up to two weeks to bring its full effects. However, some people may feel some effect in a week too. Therefore, medication should only be stopped after discussing it with the doctor.


Can a Person Abruptly Stop Taking Amoxapine?

Amoxapine should never be stopped abruptly. Reducing or stopping the dose without the doctor's consent can cause withdrawal symptoms, such as headache and nausea, or may worsen the symptoms.


Does Amoxapine Have an Antipsychotic Effect?

Amoxapine has shown its efficacy as an atypical antipsychotic drug used to treat psychosis (a condition of the mind when a person has difficulty determining reality and imagines or sees things that do not exist).


Does Amoxapine Affect the Release of Dopamine?

Dopamine helps to send messages between the nerve cells. The use of Amoxapine increases the number of dopamine transmitters throughout the body. This interference with the autonomic nervous system function results in side effects, like dryness of the mouth, blurred vision, and constipation.


Can Amoxapine Cause Extrapyramidal Effects?

The use of Amoxapine can induce extrapyramidal side effects (drug-induced movement disorders), including dyskinesias (involuntary muscle movement), tardive dyskinesia (caused due to long-term use of psychiatric drugs), Parkinsonism (neurological disorder), and neuroleptic malignant syndrome (a life-threatening neurologic emergency).


Does Amoxapine Cause Milky Discharge in Women?

Amoxapine can cause rare side effects, like galactorrhea, a milky nipple discharge in women. It is not related to normal milk production but is a sign of an underlying problem.


Can Treatment with Amoxapine increase weight?

Clinical trials have shown weight gain in people taking Amoxapine. The increased appetite caused by the drug makes one eat more, leading to weight gain.
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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

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