Toprophan

Drug overview for TOPROPHAN (melatonin/tryptophan/valerian/chamomile/niacin/inositol/b6):

Generic name: melatonin/tryptophan/valerian/chamomile/niacin/inositol/B6
Drug class: Antianxiety Agents
Therapeutic class: Central Nervous System Agents

No enhanced Introduction information available for this drug.

No enhanced Uses information available for this drug.

DRUG IMAGES

No Image Available

The following indications for TOPROPHAN (melatonin/tryptophan/valerian/chamomile/niacin/inositol/b6) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following drug interaction information is available for TOPROPHAN (melatonin/tryptophan/valerian/chamomile/niacin/inositol/b6):

Contraindicated
Severe
Moderate

There are 2 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
MAO Inhibitors/Tryptophan SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Concurrent use may result in additive effects on serotonin levels. MAOIs may potentiate the effects of tryptophan.(1) CLINICAL EFFECTS: Concurrent administration of tryptophan with a MAO Inhibitor may result in serotonin syndrome and/or hypertensive crisis.(1) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(15) In addition to these effects, disorientation, delirium, agitation, hypomania, shivering, ocular oscillation, and Babinski signs have been reported with concurrent tryptophan and phenelzine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving MAO Inhibitors should not take agents such as tryptophan. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: In a study in nine subjects, the administration of a single intravenous dose of tryptophan with tranylcypromine significantly increased the normal prolactin response to tryptophan. Four of the nine subjects developed a distinctive neuromotor syndrome characterized by hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea.(2) Another set of authors reported eight cases of delirium, ranging from mild to severe, in patients who received concurrent tranylcypromine and tryptophan. Symptoms developed within two days to 4 weeks of beginning concurrent therapy.(3) In a case report, the addition of tryptophan to a tranylcypromine regimen resulted in hypomania.(4) In another report, a patient developed hyperventilation, shivering, hyperthermia, increased muscle tone, and hyperreflexia when tryptophan was added to tranylcypromine therapy.(5) There are two reports of fatalities following the concurrent administration of tryptophan and tranylcypromine. In the first report, a a patient had been receiving chlorpromazine, lithium, and tryptophan when phenelzine was initiated. Four weeks later, the patient developed neuroleptic malignant syndrome and expired despite resuscitation efforts.(6) In the second report, a patient had been receiving fluoxetine, levothyroxine, propranolol, quinidine, and hydroxyzine. Fluoxetine was discontinued and tranylcypromine, thioridazine, and tryptophan were initiated. The patient developed neuroleptic malignant syndrome two and one-half hours after the first tryptophan dose and expired 24 hours later. (7) In a case report, the addition of tryptophan to a regimen that included phenelzine resulted in an acute behavioral and neurologic syndrome. The patient's symptoms resolved 24 hours after the discontinuation of both agents.(8) In another report, a patient developed hypomania following the addition of tryptophan to phenelzine therapy.(4) Another report describes the development of delirium following the addition of tryptophan to phenelzine.(9) One set of authors reported three cases of myoclonus, hyperreflexia, and diaphoresis following the addition of tryptophan to phenelzine therapy.(10) Some studies have shown that the addition of tryptophan to MAO Inhibitor therapy may have beneficial results, including greater improvement in depression and faster onset of effects.(11,12) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(13,14) Metaxalone is a weak inhibitor of MAO.(16,17)	AZILECT, EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR
Sodium Oxybate/Sedative Hypnotics; Alcohol SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Oxybate may be associated with respiratory depression. As oxybate is taken at bedtime, concurrent use with alcohol or hypnotics may increase the risk for respiratory depression or loss of consciousness.(1-3) Primidone is metabolized to phenobarbital. CLINICAL EFFECTS: Concurrent use of sodium oxybate and sedative hypnotics or alcohol may further increase the risk for respiratory depression and profound sedation or coma.(1,2) Fatalities have been reported.(3) PREDISPOSING FACTORS: Based upon FDA evaluation of deaths in patients taking sodium oxybate, risk factors may include: use of multiple drugs which depress the CNS, more rapid than recommended oxybate dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Note that in oxybate clinical trials for narcolepsy 78% - 85% of patients were also receiving concomitant CNS stimulants.(1-3) PATIENT MANAGEMENT: The FDA states that sodium oxybate is contraindicated in patients also taking hypnotics or alcohol.(1,2) Significant quantities of alcohol may be present in medicinal products. Alcohol is is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (4): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation DISCUSSION: The FDA evaluated sodium oxybate postmarket fatal adverse event reports from the FDA Adverse Event Reporting System(AERS)and from the manufacturer. Although report documentation was not always optimal or complete, useful information was obtained. Factors which may have contributed to fatal outcome: concomitant use of one or more drugs which depress the CNS, more rapid than recommended upward dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Many deaths occurred in patients with serious psychiatric disorders such as depression and substance abuse. Other concomitant diseases may have also contributed to respiratory and CNS depressant effects of oxybate.(3)	LUMRYZ, LUMRYZ STARTER PACK, SODIUM OXYBATE, XYREM, XYWAV

Drug Interaction

Drug Names

MAO Inhibitors/Tryptophan

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Concurrent use may result in additive effects on serotonin levels. MAOIs may potentiate the effects of tryptophan.(1)

CLINICAL EFFECTS: Concurrent administration of tryptophan with a MAO Inhibitor may result in serotonin syndrome and/or hypertensive crisis.(1) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(15) In addition to these effects, disorientation, delirium, agitation, hypomania, shivering, ocular oscillation, and Babinski signs have been reported with concurrent tryptophan and phenelzine.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving MAO Inhibitors should not take agents such as tryptophan. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea.

DISCUSSION: In a study in nine subjects, the administration of a single intravenous dose of tryptophan with tranylcypromine significantly increased the normal prolactin response to tryptophan. Four of the nine subjects developed a distinctive neuromotor syndrome characterized by hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea.(2) Another set of authors reported eight cases of delirium, ranging from mild to severe, in patients who received concurrent tranylcypromine and tryptophan.

Symptoms developed within two days to 4 weeks of beginning concurrent therapy.(3) In a case report, the addition of tryptophan to a tranylcypromine regimen resulted in hypomania.(4) In another report, a patient developed hyperventilation, shivering, hyperthermia, increased muscle tone, and hyperreflexia when tryptophan was added to tranylcypromine therapy.(5)

There are two reports of fatalities following the concurrent administration of tryptophan and tranylcypromine. In the first report, a a patient had been receiving chlorpromazine, lithium, and tryptophan when phenelzine was initiated. Four weeks later, the patient developed neuroleptic malignant syndrome and expired despite resuscitation efforts.(6)

In the second report, a patient had been receiving fluoxetine, levothyroxine, propranolol, quinidine, and hydroxyzine. Fluoxetine was discontinued and tranylcypromine, thioridazine, and tryptophan were initiated. The patient developed neuroleptic malignant syndrome two and one-half hours after the first tryptophan dose and expired 24 hours later.

(7) In a case report, the addition of tryptophan to a regimen that included phenelzine resulted in an acute behavioral and neurologic syndrome. The patient's symptoms resolved 24 hours after the discontinuation of both agents.(8) In another report, a patient developed hypomania following the addition of tryptophan to phenelzine therapy.(4)

Another report describes the development of delirium following the addition of tryptophan to phenelzine.(9) One set of authors reported three cases of myoclonus, hyperreflexia, and diaphoresis following the addition of tryptophan to phenelzine therapy.(10) Some studies have shown that the addition of tryptophan to MAO Inhibitor therapy may have beneficial results, including greater improvement in depression and faster onset of effects.(11,12)

Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(13,14) Metaxalone is a weak inhibitor of MAO.(16,17)

AZILECT, EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR

Sodium Oxybate/Sedative Hypnotics; Alcohol

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Oxybate may be associated with respiratory depression. As oxybate is taken at bedtime, concurrent use with alcohol or hypnotics may increase the risk for respiratory depression or loss of consciousness.(1-3) Primidone is metabolized to phenobarbital.

CLINICAL EFFECTS: Concurrent use of sodium oxybate and sedative hypnotics or alcohol may further increase the risk for respiratory depression and profound sedation or coma.(1,2) Fatalities have been reported.(3)

PREDISPOSING FACTORS: Based upon FDA evaluation of deaths in patients taking sodium oxybate, risk factors may include: use of multiple drugs which depress the CNS, more rapid than recommended oxybate dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Note that in oxybate clinical trials for narcolepsy 78% - 85% of patients were also receiving concomitant CNS stimulants.(1-3)

PATIENT MANAGEMENT: The FDA states that sodium oxybate is contraindicated in patients also taking hypnotics or alcohol.(1,2) Significant quantities of alcohol may be present in medicinal products. Alcohol is is used to improve docetaxel and paclitaxel solubility.

- The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer.

FDA data on alcohol content (4): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj.

Sandoz 5.5 grams Docetaxel Inj. Accord 4.0

grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7

grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: The FDA evaluated sodium oxybate postmarket fatal adverse event reports from the FDA Adverse Event Reporting System(AERS)and from the manufacturer. Although report documentation was not always optimal or complete, useful information was obtained. Factors which may have contributed to fatal outcome: concomitant use of one or more drugs which depress the CNS, more rapid than recommended upward dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine.

Many deaths occurred in patients with serious psychiatric disorders such as depression and substance abuse. Other concomitant diseases may have also contributed to respiratory and CNS depressant effects of oxybate.(3)

LUMRYZ, LUMRYZ STARTER PACK, SODIUM OXYBATE, XYREM, XYWAV

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Linezolid/Tryptophan SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use may result in additive effects on serotonin levels. MAOIs may potentiate the effects of tryptophan.(1) CLINICAL EFFECTS: Concurrent administration of tryptophan with a MAO Inhibitor may result in serotonin syndrome and/or hypertensive crisis.(1) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2) In addition to these effects, disorientation, delirium, agitation, hypomania, shivering, ocular oscillation, and Babinski signs have been reported with concurrent tryptophan and phenelzine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving linezolid should not be administered tryptophan unless they can be closely monitored for serotonin syndrome. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: In a case report, a patient receiving metoclopramide and a TPN containing tryptophan developed serotonin syndrome following the addition of linezolid to therapy.(3) In a study in nine subjects, the administration of a single intravenous dose of tryptophan with tranylcypromine significantly increased the normal prolactin response to tryptophan. Four of the nine subjects developed a distinctive neuromotor syndrome characterized by hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea.(4) Another set of authors reported eight cases of delirium, ranging from mild to severe, in patients who received concurrent tranylcypromine and tryptophan. Symptoms developed within two days to 4 weeks of beginning concurrent therapy.(5) In a case report, the addition of tryptophan to a tranylcypromine regimen resulted in hypomania.(6) In another report, a patient developed hyperventilation, shivering, hyperthermia, increased muscle tone, and hyperreflexia when tryptophan was added to tranylcypromine therapy.(7) There are two reports of fatalities following the concurrent administration of tryptophan and tranylcypromine. In the first report, a a patient had been receiving chlorpromazine, lithium, and tryptophan when phenelzine was initiated. Four weeks later, the patient developed neuroleptic malignant syndrome and expired despite resuscitation efforts.(8) In the second report, a patient had been receiving fluoxetine, levothyroxine, propranolol, quinidine, and hydroxyzine. Fluoxetine was discontinued and tranylcypromine, thioridazine, and tryptophan were initiated. The patient developed neuroleptic malignant syndrome two and one-half hours after the first tryptophan dose and expired 24 hours later. (9) In a case report, the addition of tryptophan to a regimen that included phenelzine resulted in an acute behavioral and neurologic syndrome. The patient's symptoms resolved 24 hours after the discontinuation of both agents.(10) In another report, a patient developed hypomania following the addition of tryptophan to phenelzine therapy.(6) Another report describes the development of delirium following the addition of tryptophan to phenelzine.(11) One set of authors reported three cases of myoclonus, hyperreflexia, and diaphoresis following the addition of tryptophan to phenelzine therapy.(12) Some studies have shown that the addition of tryptophan to MAO Inhibitor therapy may have beneficial results, including greater improvement in depression and faster onset of effects.(13,14)	LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, ZYVOX

Drug Interaction

Drug Names

Linezolid/Tryptophan

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use may result in additive effects on serotonin levels. MAOIs may potentiate the effects of tryptophan.(1)

CLINICAL EFFECTS: Concurrent administration of tryptophan with a MAO Inhibitor may result in serotonin syndrome and/or hypertensive crisis.(1) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2) In addition to these effects, disorientation, delirium, agitation, hypomania, shivering, ocular oscillation, and Babinski signs have been reported with concurrent tryptophan and phenelzine.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving linezolid should not be administered tryptophan unless they can be closely monitored for serotonin syndrome. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea.

DISCUSSION: In a case report, a patient receiving metoclopramide and a TPN containing tryptophan developed serotonin syndrome following the addition of linezolid to therapy.(3) In a study in nine subjects, the administration of a single intravenous dose of tryptophan with tranylcypromine significantly increased the normal prolactin response to tryptophan. Four of the nine subjects developed a distinctive neuromotor syndrome characterized by hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea.(4)

Another set of authors reported eight cases of delirium, ranging from mild to severe, in patients who received concurrent tranylcypromine and tryptophan. Symptoms developed within two days to 4 weeks of beginning concurrent therapy.(5) In a case report, the addition of tryptophan to a tranylcypromine regimen resulted in hypomania.(6)

In another report, a patient developed hyperventilation, shivering, hyperthermia, increased muscle tone, and hyperreflexia when tryptophan was added to tranylcypromine therapy.(7) There are two reports of fatalities following the concurrent administration of tryptophan and tranylcypromine. In the first report, a a patient had been receiving chlorpromazine, lithium, and tryptophan when phenelzine was initiated.

Four weeks later, the patient developed neuroleptic malignant syndrome and expired despite resuscitation efforts.(8) In the second report, a patient had been receiving fluoxetine, levothyroxine, propranolol, quinidine, and hydroxyzine. Fluoxetine was discontinued and tranylcypromine, thioridazine, and tryptophan were initiated.

The patient developed neuroleptic malignant syndrome two and one-half hours after the first tryptophan dose and expired 24 hours later. (9) In a case report, the addition of tryptophan to a regimen that included phenelzine resulted in an acute behavioral and neurologic syndrome. The patient's symptoms resolved 24 hours after the discontinuation of both agents.(10)

In another report, a patient developed hypomania following the addition of tryptophan to phenelzine therapy.(6) Another report describes the development of delirium following the addition of tryptophan to phenelzine.(11) One set of authors reported three cases of myoclonus, hyperreflexia, and diaphoresis following the addition of tryptophan to phenelzine therapy.(12) Some studies have shown that the addition of tryptophan to MAO Inhibitor therapy may have beneficial results, including greater improvement in depression and faster onset of effects.(13,14)

LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, ZYVOX

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Ziprasidone/Serotonergic Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ziprasidone is a 5-HT1A agonist and serotonin and norepinephrine reuptake inhibitor. Concurrent administration with one or more serotonergic agents may increase serotonin effects, resulting in serotonin toxicity.(1,2) CLINICAL EFFECTS: Concurrent use of ziprasidone and other serotonergic agents may result in serotonin syndrome, a potentially life-threatening condition with symptoms including altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor.(1) PREDISPOSING FACTORS: Serotonin syndrome risk is dose-related. Higher systemic concentrations of either drug would be predicted to increase risk for serotonin toxicity.(2) Concomitant therapy with multiple agents which increase brain serotonin concentrations may also increase risk for serotonin syndrome.(2) PATIENT MANAGEMENT: Caution patients about the risk of serotonin syndrome with the concomitant use of ziprasidone with other serotonergic drugs. Instruct patients to contact their healthcare provider, or report to the emergency room, should they experience signs or symptoms of serotonin syndrome.(1) DISCUSSION: Several cases of serotonin syndrome have been reported in patients receiving ziprasidone.(4-6)	GEODON, ZIPRASIDONE HCL, ZIPRASIDONE MESYLATE

Drug Interaction

Drug Names

Ziprasidone/Serotonergic Agents

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Ziprasidone is a 5-HT1A agonist and serotonin and norepinephrine reuptake inhibitor. Concurrent administration with one or more serotonergic agents may increase serotonin effects, resulting in serotonin toxicity.(1,2)

CLINICAL EFFECTS: Concurrent use of ziprasidone and other serotonergic agents may result in serotonin syndrome, a potentially life-threatening condition with symptoms including altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor.(1)

PREDISPOSING FACTORS: Serotonin syndrome risk is dose-related. Higher systemic concentrations of either drug would be predicted to increase risk for serotonin toxicity.(2) Concomitant therapy with multiple agents which increase brain serotonin concentrations may also increase risk for serotonin syndrome.(2)

PATIENT MANAGEMENT: Caution patients about the risk of serotonin syndrome with the concomitant use of ziprasidone with other serotonergic drugs. Instruct patients to contact their healthcare provider, or report to the emergency room, should they experience signs or symptoms of serotonin syndrome.(1)

DISCUSSION: Several cases of serotonin syndrome have been reported in patients receiving ziprasidone.(4-6)

GEODON, ZIPRASIDONE HCL, ZIPRASIDONE MESYLATE

The following contraindication information is available for TOPROPHAN (melatonin/tryptophan/valerian/chamomile/niacin/inositol/b6):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 1 contraindications. Absolute contraindication.

Contraindication List
Eosinophilia myalgia syndrome

There are 4 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Autoimmune disease
Invasive surgical procedure
Peptic ulcer
Systemic lupus erythematosus

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Diabetes mellitus
Disease of liver
Gout
Hypotension
Increased risk of bleeding due to coagulation disorder
Unstable angina pectoris

The following adverse reaction information is available for TOPROPHAN (melatonin/tryptophan/valerian/chamomile/niacin/inositol/b6):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 2 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Hallucinations Hepatitis

There are 37 less severe adverse reactions.

More Frequent	Less Frequent
Dizziness Headache disorder Sedation hangover effect	Abdominal pain with cramps Acute cognitive impairment CNS depression Concentration difficulty Depression Hypotension Irritability Nausea Symptoms of anxiety Tremor Vomiting

Rare/Very Rare
Accidental fall Agitation Ataxia Blurred vision Dizziness Dream disorder Drowsy Dyspepsia Excitement Fatigue Headache disorder Hypersensitivity drug reaction Hypothermia Insomnia Muscle relaxation Nausea Nervousness Palpitations Panic disorder Paresthesia Sedation Skin rash Xerostomia

The following precautions are available for TOPROPHAN (melatonin/tryptophan/valerian/chamomile/niacin/inositol/b6):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

No enhanced Pregnancy information available for this drug.

No enhanced Lactation information available for this drug.

No enhanced Geriatric Use information available for this drug.