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Norpramin

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Overview

What is Norpramin?

NORPRAMIN (desipramine hydrochloride USP) is an antidepressant drug of the tricyclic type, and is chemically: 5-Dibenz[]azepine-5-propanamine,10,11-dihydro--methyl-, monohydrochloride.

Inactive Ingredients



What does Norpramin look like?



What are the available doses of Norpramin?

Sorry No records found.

What should I talk to my health care provider before I take Norpramin?

Sorry No records found

How should I use Norpramin?

NORPRAMIN is indicated for the treatment of depression.

Not recommended for use in children (see ).

Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients compared to hospitalized patients, who are closely supervised. Dosage should be initiated at a low level and increased according to clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a period of time and should be at the lowest dose that will maintain remission.


What interacts with Norpramin?

Sorry No Records found


What are the warnings of Norpramin?

Sorry No Records found


What are the precautions of Norpramin?

Sorry No Records found


What are the side effects of Norpramin?

Sorry No records found


What should I look out for while using Norpramin?

The use of MAOIs intended to treat psychiatric disorders with NORPRAMIN or within 14 days of stopping treatment with NORPRAMIN is contraindicated because of an increased risk of serotonin syndrome. The use of NORPRAMIN within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see and ).

Starting NORPRAMIN in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see and ).

NORPRAMIN is contraindicated in the acute recovery period following myocardial infarction. It should not be used in those who have shown prior hypersensitivity to the drug. Cross-sensitivity between this and other dibenzazepines is a possibility.


What might happen if I take too much Norpramin?

Deaths may occur from overdosage with this class of drugs. Overdose of desipramine has resulted in a higher death rate compared to overdoses of other tricyclic antidepressants. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible. There is no specific antidote for desipramine overdosage.


How should I store and handle Norpramin?

Store olanzapine tablets at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect olanzapine tablets from light and moisture. Store olanzapine tablets at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect olanzapine tablets from light and moisture. 10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)10 mg blue coated tablets imprinted 68-7       NDC 30698-007-01: bottles of 10025 mg yellow coated tablets imprinted NORPRAMIN 25       NDC 30698-011-01: bottles of 10050 mg green coated tablets imprinted NORPRAMIN 50       NDC 30698-015-01: bottles of 10075 mg orange coated tablets imprinted NORPRAMIN 75       NDC 30698-019-01: bottles of 100100 mg peach coated tablets imprinted NORPRAMIN 100       NDC 30698-020-01: bottles of 100150 mg white coated tablets imprinted NORPRAMIN 150       NDC 30698-021-05-: bottles of 50Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container.Rx OnlyDistributed by:Validus Pharmaceuticals LLCParsippany, New Jersey 07054info@validuspharma.comwww.validuspharma.com1-866-9VALIDUS (1-866-982-5438)© 2016 Validus Pharmaceuticals LLC60040-00                         (Rev January 2016)


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Clinical Information

Chemical Structure

No Image found
Clinical Pharmacology

Available evidence suggests that many depressions have a biochemical basis in the form of a relative deficiency of neurotransmitters such as norepinephrine and serotonin. Norepinephrine deficiency may be associated with relatively low urinary 3-methoxy-4-hydroxyphenyl glycol (MHPG) levels, while serotonin deficiencies may be associated with low spinal fluid levels of 5-hydroxyindoleacetic acid.

While the precise mechanism of action of the tricyclic antidepressants is unknown, a leading theory suggests that they restore normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system. Evidence indicates that the secondary amine tricyclic antidepressants, including NORPRAMIN, may have greater activity in blocking the re-uptake of norepinephrine. Tertiary amine tricyclic antidepressants, such as amitriptyline, may have greater effect on serotonin re-uptake.

NORPRAMIN is not a monoamine oxidase inhibitor (MAOI) and does not act primarily as a central nervous system stimulant. It has been found in some studies to have a more rapid onset of action than imipramine. Earliest therapeutic effects may occasionally be seen in 2 to 5 days, but full treatment benefit usually requires 2 to 3 weeks to obtain.

Non-Clinical Toxicology
The use of MAOIs intended to treat psychiatric disorders with NORPRAMIN or within 14 days of stopping treatment with NORPRAMIN is contraindicated because of an increased risk of serotonin syndrome. The use of NORPRAMIN within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see and ).

Starting NORPRAMIN in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see and ).

NORPRAMIN is contraindicated in the acute recovery period following myocardial infarction. It should not be used in those who have shown prior hypersensitivity to the drug. Cross-sensitivity between this and other dibenzazepines is a possibility.

Drugs Metabolized by P450 2D6.

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type IC antiarrhythmics propafenone and flecainide). While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

Close supervision and careful adjustment of dosage are required when this drug is given concomitantly with anticholinergic or sympathomimetic drugs.

Patients should be warned that while taking this drug their response to alcoholic beverages may be exaggerated.

If NORPRAMIN is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of NORPRAMIN and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive. Both the sedative and anticholinergic effects of the major tranquilizers are also additive to those of NORPRAMIN.

Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) and serotonergic drugs may potentially cause life threatening adverse events (See , , and ).

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with NORPRAMIN and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions” is available for NORPRAMIN. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking NORPRAMIN.

Clinical Worsening and Suicide Risk

Patients should be advised that taking Norpramin can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.

Included in the following listing are a few adverse reactions that have not been reported with this specific drug. However, the pharmacologic similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when NORPRAMIN is given.

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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Professional

Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72
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Interactions

Interactions

A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).