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| Product NDC Code | 50090-4733 | ||||||
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| Drug Name | Triazolam |
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| Type | Generic | ||||||
| Pharm Class | Benzodiazepine [EPC], Benzodiazepines [CS] |
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| Active Ingredients |
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| Route | ORAL | ||||||
| Dosage Form | TABLET | ||||||
| RxCUI drug identifier | 198318 | ||||||
| Application Number | ANDA074224 | ||||||
| Labeler Name | A-S Medication Solutions | ||||||
| Packages |
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| Check if available Online | Get Medication Prices online with Discount |
Abuse
Information about the types of abuse that can occur with the drug and adverse reactions pertinent to those types of abuse, primarily based on human data. May include descriptions of particularly susceptible patient populations.9.2 Abuse Triazolam is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see Warnings and Precautions ( 5.2 )] . The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol).
Controlled substance
Information about the schedule in which the drug is controlled by the Drug Enforcement Administration, if applicable.9.1 Controlled Substance Triazolam tablets contain triazolam, a Schedule IV controlled substance.
Dependence
Information about characteristic effects resulting from both psychological and physical dependence that occur with the drug, the quantity of drug over a period of time that may lead to tolerance or dependence, details of adverse effects related to chronic abuse and the effects of abrupt withdrawl, procedures necessary to diagnose the dependent state, and principles of treating the effects of abrupt withdrawal.9.3 Dependence Physical Dependence Triazolam may produce physical dependence from continued therapy. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see Warnings and Precautions ( 5.3 )] . To reduce the risk of withdrawal reactions, use a gradual taper to discontinue triazolam or reduce the dosage [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.3 )] . Acute Withdrawal Signs and Symptoms Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. Protracted Withdrawal Syndrome Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. Tolerance Tolerance to triazolam may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to the therapeutic effect of triazolam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.
Drug abuse and dependence
Information about whether the drug is a controlled substance, the types of abuse that can occur with the drug, and adverse reactions pertinent to those types of abuse.9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Triazolam tablets contain triazolam, a Schedule IV controlled substance. 9.2 Abuse Triazolam is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see Warnings and Precautions ( 5.2 )] . The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol). 9.3 Dependence Physical Dependence Triazolam may produce physical dependence from continued therapy. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see Warnings and Precautions ( 5.3 )] . To reduce the risk of withdrawal reactions, use a gradual taper to discontinue triazolam or reduce the dosage [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.3 )] . Acute Withdrawal Signs and Symptoms Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. Protracted Withdrawal Syndrome Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. Tolerance Tolerance to triazolam may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to the therapeutic effect of triazolam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.
Overdosage of Triazolam
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE Manifestations of overdosage with triazolam include somnolence, confusion, impaired coordination, slurred speech, and ultimately, coma. Respiratory depression and apnea have been reported with overdosages of triazolam. Seizures have been reported after overdosages. Death has been reported in association with overdoses of triazolam. In addition, fatalities have been reported in patients who have overdosed with a combination of a single benzodiazepine, including triazolam, and alcohol; benzodiazepine and alcohol levels seen in some of these cases have been lower than those usually associated with reports of fatality with either substance alone. Respiration, pulse, and blood pressure should be monitored and supported by general measures when necessary. Immediate gastric lavage should be performed. An adequate airway should be maintained. Intravenous fluids may be administered. Flumazenil may be useful in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression, and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including Contraindications and Warnings and Precautions should be consulted prior to use. Hemodialysis and forced diuresis are probably of little value. As with the management of intentional overdosage with any drug, the physician should bear in mind that multiple agents may have been ingested by the patient. In case of an overdosage, consult a Certified Poison Control Center at 1-800-222-1222 for latest recommendations.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections: • Risks from Concomitant Use with Opioids [see Warnings and Precautions ( 5.1 )] • Abuse, Misuse, and Addiction [see Warnings and Precautions ( 5.2 )] • Dependence and Withdrawal Reactions [see Warnings and Precautions ( 5.3 )] • Persistent or Worsening Insomnia [see Warnings and Precautions ( 5. 4)] • “Sleep-driving” and Other Complex Behaviors [see Warnings and Precautions ( 5. 5)] • Central Nervous System Manifestations [see Warnings and Precautions ( 5. 6)] • Effects on Driving and Operating Heavy Machinery [see Warnings and Precautions ( 5. 7)] • Patients with Depression [see Warnings and Precautions ( 5. 9)] • Compromised Respiratory Function [see Warnings and Precautions ( 5.1 1)] Most common adverse reactions (incidence ≥4% and twice placebo) are drowsiness, dizziness, light-headedness, and coordination disorder/ataxia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The incidences cited below are estimates of clinical reactions among 1003 subjects who participated in the short term (duration of 1 to 42 days) placebo-controlled clinical trials of triazolam. Adverse reactions leading to discontinuation in two multi-dose placebo controlled clinical trials include coordination disorders, drowsiness, grogginess, somnolence, depression, restlessness, dizziness, lightheadedness, headache, nausea, visual disturbance, nervousness, abdominal distress, bladder trouble, aching limbs, backache, and blepharitis. Table 1: Common Adverse Drug Reactions in 1% or More of Triazolam-Treated Subjects (and Greater than Placebo) Reported in Placebo-Controlled Clinical Trials Event Triazolam (N=1003) % Patients Reporting Placebo (N=997) % Patients Reporting Central Nervous System Drowsiness 14.0 6.4 Headache 9.7 8.4 Dizziness 7.8 3.1 Nervousness 5.2 4.5 Light-headedness 4.9 0.9 Coordination disorders/ataxia 4.6 0.8 Gastrointestinal Nausea/vomiting 4.6 3.7 In addition to the common reactions enumerated above in Table 1, the following adverse reactions have been reported at an incidence of 0.9% to 0.5%: euphoria, tachycardia, tiredness, confusional states/memory impairment, cramps/pain, depression, and visual disturbances. Adverse reactions reported at an incidence less than 0.5% include: constipation, taste alterations, diarrhea, dry mouth, dermatitis/allergy, dreaming/nightmares, insomnia, paresthesia, tinnitus, dysesthesia, weakness, congestion, and death from hepatic failure in a patient also receiving diuretic drugs. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of triazolam. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General Disorders and Administration Site Conditions: Paradoxical drug reaction, chest pain and fatigue Gastrointestinal Disorders: Tongue discomfort, glossitis, stomatitis Hepatobiliary Disorders: Jaundice Injury, Poisoning and Procedural Complications: Fall Metabolism and Nutrition Disorders: Anorexia Nervous System Disorders: Anterograde amnesia, altered state of consciousness, dystonia, sedation, syncope, dysarthria and muscle spasticity Psychiatric Disorders: Confusional state (disorientation, derealisation, depersonalization), mania, agitation, restlessness, irritability, sleep disorder and libido disorder, hallucination, delusion, aggression, somnambulism, and abnormal behavior Renal and Urinary Disorders : Urinary retention and urinary incontinence Reproductive System and Breast Disorders: Menstruation irregular Skin and Subcutaneous Tissue Disorders: Pruritis
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Triazolam Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS • Use with Opioids : Increase the risk of respiratory depression ( 7.1 ) • Use with Other CNS Depressants : Produces additive CNS depressant effects ( 7.1 ) • Use with CYP 3A4 Inhibitors : Increased risk of adverse reactions ( 4 , 5. 8, 7.1 ) 7.1 Drugs Having Clinically Important Interactions With Triazolam Table 2 includes clinically significant drug interactions with triazolam [see Clinical Pharmacology ( 12.3 )]. Table 2: Clinically Important Drug Interactions with Triazolam Opioids Clinical implication The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Prevention or management Limit dosage and duration of concomitant use of triazolam and opioids, and monitor patients closely for respiratory depression and sedation [see Warnings and Precautions ( 5.1 )]. CNS Depressants Clinical implication Triazolam produces additive CNS depressant effects when co-administered with other CNS depressants. Prevention or management Limit dosage and duration of triazolam during concomitant use with CNS depressants. Strong Inhibitors of CYP 3A Clinical implication Concomitant use of triazolam with strong CYP3A inhibitors has a profound effect on the clearance of triazolam, resulting in increased concentrations of triazolam and increased risk of adverse reactions [see Clinical Pharmacology ( 12.3 )]. Prevention or management Do not administer triazolam with a strong CYP3A4 inhibitor [see Contraindications ( 4 ), Warnings and Precautions ( 5. 8)]. Moderate and Weak Inhibitors of CYP 3A Clinical implication Concomitant use of triazolam with moderate or weak inhibitors of CYP3A inhibitors may increase the concentrations of triazolam, resulting in increased risk of adverse reactions [see Clinical Pharmacology ( 12.3 )]. Prevention or management Use with caution and consider appropriate dose reduction of triazolam when coadministered with moderate and weak CYP3A inhibitors [see Warnings and Precautions ( 5. 8)]. Strong Inducers of CYP 3A Clinical implication Coadministration of triazolam with strong inducers of CYP3A4 can significantly decrease the plasma concentration of triazolam and may decrease effectiveness of triazolam. Prevention or management Caution is recommended during coadministration of triazolam with strong inducers of CYP3A4. Interactions Based on Experience with Other Benzodiazepines or in vitro Studies with Triazolam Clinical implication Available data from clinical studies of benzodiazepines other than triazolam, from in vitro studies with triazolam, or from in vitro studies with benzodiazepines other than triazolam suggest a possible drug interaction with triazolam [see Clinical Pharmacology ( 12.3 )]. Prevention or management Caution is recommended during coadministration of triazolam with any of these drugs. [see Warnings and Precautions ( 5. 8)].
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Triazolam is a benzodiazepine. Triazolam exerts its effect for the short-term treatment of insomnia through binding to the benzodiazepine site of the gamma-aminobutyric acid-A (GABA A ) receptors in the brain and enhances GABA-mediated synaptic inhibition. 12.3 Pharmacokinetics Absorption Peak plasma levels of triazolam are reached within 2 hours following oral administration. Following recommended doses of triazolam tablets, triazolam peak plasma levels in the range of 1 to 6 ng/mL are seen. The plasma levels achieved are proportional to the dose given. In normal subjects treated for 7 days with four times the recommended dosage, there was no evidence of altered systemic bioavailability, rate of elimination, or accumulation. Distribution Extremely high concentrations of triazolam do not displace bilirubin bound to human serum albumin in vitro. Elimination Triazolam has a mean plasma elimination half-life in the range of 1.5 to 5.5 hours. Metabolism The initial step in triazolam metabolism is cytochrome P450 3A (CYP 3A)-mediated hydroxylation to form 1- hydroxytriazolam and 4-hydroxytriazolam, which are subsequently conjugated to form glucuronides. Excretion Triazolam and its metabolites, principally as conjugated glucuronides which are presumably inactive, are excreted primarily in the urine. Only small amounts of unmetabolized triazolam appear in the urine. The two primary metabolites accounted for 79.9% of urinary excretion. Urinary excretion appeared to be biphasic in its time course. Specific Populations Geriatric Patients In a study of elderly (62 to 83 years old) versus younger subjects (21 to 41 years old) who received triazolam at the same dose levels (0.125 mg and 0.25 mg), the elderly experienced both greater sedation and impairment of psychomotor performance. These effects resulted largely from higher plasma concentrations of triazolam in the elderly. Drug Interaction Studies The effect of other drugs on triazolam: Macrolide Antibiotics Coadministration of erythromycin increased the maximum plasma concentration of triazolam by 46%, decreased clearance by 53%, and increased half-life by 35%. Cimetidine Coadministration of cimetidine increased the maximum plasma concentration of triazolam by 51%, decreased clearance by 55%, and increased half-life by 68%. Isoniazid Coadministration of isoniazid increased the maximum plasma concentration of triazolam by 20%, decreased clearance by 42%, and increased half-life by 31%. Oral Contraceptives Coadministration of oral contraceptives increased maximum plasma concentration by 6%, decreased clearance by 32%, and increased half-life by 16%. Grapefruit Juice Coadministration of grapefruit juice increased the maximum plasma concentration of triazolam by 25%, increased the area under the concentration curve by 48%, and increased half-life by 18%. Ranitidine Coadministration of ranitidine increased the maximum plasma concentration of triazolam by 30%, increased the area under the concentration curve by 27%, and increased half-life by 3.3%. Caution is recommended during coadministration with triazolam. Available data from clinical studies of benzodiazepines other than triazolam suggest a possible drug interaction with triazolam for the following: fluvoxamine, diltiazem, and verapamil. Data from in vitro studies of triazolam suggest a possible drug interaction with triazolam for the following: sertraline and paroxetine. Data from in vitro studies of benzodiazepines other than triazolam suggest a possible drug interaction with triazolam for the following: ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine. The effect of triazolam on other drugs: Warfarin Triazolam tablets 0.5 mg, in two separate studies, did not affect the prothrombin times or plasma warfarin levels in male volunteers administered sodium warfarin orally.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action Triazolam is a benzodiazepine. Triazolam exerts its effect for the short-term treatment of insomnia through binding to the benzodiazepine site of the gamma-aminobutyric acid-A (GABA A ) receptors in the brain and enhances GABA-mediated synaptic inhibition.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Absorption Peak plasma levels of triazolam are reached within 2 hours following oral administration. Following recommended doses of triazolam tablets, triazolam peak plasma levels in the range of 1 to 6 ng/mL are seen. The plasma levels achieved are proportional to the dose given. In normal subjects treated for 7 days with four times the recommended dosage, there was no evidence of altered systemic bioavailability, rate of elimination, or accumulation. Distribution Extremely high concentrations of triazolam do not displace bilirubin bound to human serum albumin in vitro. Elimination Triazolam has a mean plasma elimination half-life in the range of 1.5 to 5.5 hours. Metabolism The initial step in triazolam metabolism is cytochrome P450 3A (CYP 3A)-mediated hydroxylation to form 1- hydroxytriazolam and 4-hydroxytriazolam, which are subsequently conjugated to form glucuronides. Excretion Triazolam and its metabolites, principally as conjugated glucuronides which are presumably inactive, are excreted primarily in the urine. Only small amounts of unmetabolized triazolam appear in the urine. The two primary metabolites accounted for 79.9% of urinary excretion. Urinary excretion appeared to be biphasic in its time course. Specific Populations Geriatric Patients In a study of elderly (62 to 83 years old) versus younger subjects (21 to 41 years old) who received triazolam at the same dose levels (0.125 mg and 0.25 mg), the elderly experienced both greater sedation and impairment of psychomotor performance. These effects resulted largely from higher plasma concentrations of triazolam in the elderly. Drug Interaction Studies The effect of other drugs on triazolam: Macrolide Antibiotics Coadministration of erythromycin increased the maximum plasma concentration of triazolam by 46%, decreased clearance by 53%, and increased half-life by 35%. Cimetidine Coadministration of cimetidine increased the maximum plasma concentration of triazolam by 51%, decreased clearance by 55%, and increased half-life by 68%. Isoniazid Coadministration of isoniazid increased the maximum plasma concentration of triazolam by 20%, decreased clearance by 42%, and increased half-life by 31%. Oral Contraceptives Coadministration of oral contraceptives increased maximum plasma concentration by 6%, decreased clearance by 32%, and increased half-life by 16%. Grapefruit Juice Coadministration of grapefruit juice increased the maximum plasma concentration of triazolam by 25%, increased the area under the concentration curve by 48%, and increased half-life by 18%. Ranitidine Coadministration of ranitidine increased the maximum plasma concentration of triazolam by 30%, increased the area under the concentration curve by 27%, and increased half-life by 3.3%. Caution is recommended during coadministration with triazolam. Available data from clinical studies of benzodiazepines other than triazolam suggest a possible drug interaction with triazolam for the following: fluvoxamine, diltiazem, and verapamil. Data from in vitro studies of triazolam suggest a possible drug interaction with triazolam for the following: sertraline and paroxetine. Data from in vitro studies of benzodiazepines other than triazolam suggest a possible drug interaction with triazolam for the following: ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine. The effect of triazolam on other drugs: Warfarin Triazolam tablets 0.5 mg, in two separate studies, did not affect the prothrombin times or plasma warfarin levels in male volunteers administered sodium warfarin orally.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS Triazolam is contraindicated in: • Patients with known hypersensitivity to triazolam, any of component of triazolam tablets, or other benzodiazepines. Reactions consistent with angioedema (involving the tongue, glottis, or larynx), dyspnea, and throat closing have been reported and may be fatal. • Concomitant administration of strong cytochrome P450 (CYP 3A) enzyme inhibitors (e.g., ketoconazole, itraconazole, nefazodone, lopinavir, ritonavir) [see Warnings and Precautions ( 5.8 ), Drug Interactions ( 7.1 )]. • Known hypersensitivity to triazolam or other benzodiazepines ( 4 ) • Concomitant use with medications that significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP 3A) including ketoconazole, itraconazole, nefazodone, and several human immunodeficiency virus (HIV) protease inhibitors ( 4 , 5. 8, 17 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION Triazolam Tablets, USP contain triazolam, a triazolobenzodiazepine. Triazolam, USP is a white to off-white powder, soluble in chloroform; slightly soluble in alcohol; and practically insoluble in ether and in water. It has a molecular weight of 343.2. The chemical name for triazolam is 8-chloro-6-( o -chlorophenyl)-1-methyl-4 H -s-triazolo-[4,3- α ][1,4]benzodiazepine. The structural formula is represented below: Each triazolam tablet for oral administration, contains 0.125 mg or 0.25 mg of triazolam, USP. Inactive ingredients: 0.125 mg - docusate sodium with sodium benzoate, lactose (anhydrous), magnesium stearate, microcrystalline cellulose, and pregelatinized starch; 0.25 mg - docusate sodium with sodium benzoate, FD&C Blue No. 1, lactose (anhydrous), magnesium stearate, microcrystalline cellulose, and pregelatinized starch. triazo-black.jpg
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION • Adults: Recommended dosage is 0.25 mg once daily before bedtime. Maximum recommended dosage is 0.5 mg once daily ( 2.1 ) • Geriatric patients: Reduce starting dosage to 0.125 mg once daily. May increase to 0.25 mg if no response. Geriatric patients should not exceed 0.25 mg once daily ( 2.2 , 8.5 ) • Triazolam tablets should not be prescribed in quantities exceeding a 1-month supply ( 2.1 ) 2.1 Dosing Information The recommended dosage is 0.25 mg once daily before bedtime. A dosage of 0.125 mg once daily may be sufficient for some patients (e.g., patients with low body weight). A dosage of 0.5 mg should be used only for patients who do not respond adequately to a trial of a lower dose. The maximum recommended dosage is 0.5 mg once daily. Use the lowest effective dose for the patient as there are significant dose related adverse reactions. Use of triazolam tablets for more than 3 weeks requires evaluation of the patient for a primary psychiatric or medical condition [see Warnings and Precautions ( 5.4 , 5. 6)]. Prescriptions for triazolam tablets should be written for short-term use (7 to 10 days) and it should not be prescribed in quantities exceeding a 1-month supply. 2.2 Use in Geriatric Patients In geriatric patients, the recommended dosage is 0.125 mg to 0.25 mg once daily. Initiate therapy at 0.125 mg once daily. The 0.25 mg dose should be used only for patients who do not respond to a trial of the lower dose. The maximum recommended dosage is 0.25 mg once daily. Elderly patients have an increased risk of dose related adverse reactions [see Use in Specific Populations ( 8.5 )]. 2.3 Discontinuation or Dosage Reduction of Triazolam To reduce the risk of withdrawal reactions, use a gradual taper to discontinue triazolam or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly [see Warnings and Precautions ( 5.3 ), Drug Abuse and Dependence ( 9.3 )].
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS Triazolam Tablets, USP are available as a 0.125 mg and 0.25 mg tablet. • 0.125 mg tablet is supplied as a white, oval-shaped tablet with tablet identification “54 519” debossed on one side and plain on the other side. • 0.25 mg tablet is supplied as a light blue, oval-shaped tablet, scored on one side with tablet identification “54 620” debossed on the other side. Unscored tablets: 0.125 mg and Scored tablets: 0.25 mg ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE Triazolam is indicated for the short-term treatment of insomnia (generally 7 to 10 days) in adults. Triazolam is a benzodiazepine indicated for the short-term treatment of insomnia (generally 7 to 10 days) in adults.
Spl product data elements
Usually a list of ingredients in a drug product.Triazolam Triazolam TRIAZOLAM TRIAZOLAM DOCUSATE SODIUM/SODIUM BENZOATE FD&C BLUE NO. 1 ANHYDROUS LACTOSE MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE STARCH, CORN light 54;620
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No evidence of carcinogenic potential was observed in rats or mice administered triazolam in the diet for 24-months at doses greater than or equal to 900 times the MRHD of 0.5 mg, based on mg/m 2 body surface area. Mutagenesis Triazolam was not mutagenic in the in vitro Ames bacterial reverse mutation assay, and no DNA damage was observed in an in vitro alkaline elution assay in Chinese hamster lung fibroblast cells. Impairment of Fertility Female rats were administered triazolam in the diet for 14 days before cohabitation, during gestation, and until 21 days post parturition, and male rats for 60 days before cohabitation. No effects on mating or fertility were observed in rats up to 5 mg/kg/day which is approximately 100 times the MRHD of 0.5 mg/day, based on mg/m 2 body surface area.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No evidence of carcinogenic potential was observed in rats or mice administered triazolam in the diet for 24-months at doses greater than or equal to 900 times the MRHD of 0.5 mg, based on mg/m 2 body surface area. Mutagenesis Triazolam was not mutagenic in the in vitro Ames bacterial reverse mutation assay, and no DNA damage was observed in an in vitro alkaline elution assay in Chinese hamster lung fibroblast cells. Impairment of Fertility Female rats were administered triazolam in the diet for 14 days before cohabitation, during gestation, and until 21 days post parturition, and male rats for 60 days before cohabitation. No effects on mating or fertility were observed in rats up to 5 mg/kg/day which is approximately 100 times the MRHD of 0.5 mg/day, based on mg/m 2 body surface area.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.Triazolam Label Image
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.Boxed Warning 2/2021 Dosage and Administration ( 2.3 ) 2/2021 Warnings and Precautions ( 5.2 , 5.3 ) 2/2021
Triazolam: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Risks from Concomitant Use with Opioids Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when triazolam is used with opioids and not to use such drugs concomitantly unless supervised by a healthcare provider. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.1 )]. Abuse, Misuse, and Addiction Inform patients that the use of triazolam, even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug [see Warnings and Precautions ( 5.2 ), Drug Abuse and Dependence ( 9.2 )] . Withdrawal Reactions Inform patients that the continued use of triazolam may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of triazolam may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of triazolam may require a slow taper [see Warnings and Precautions ( 5.3 ), Drug Abuse and Dependence ( 9.3 )] . “Sleep-driving” and Other Complex Behaviors There have been reports of people getting out of bed after taking a sedative-hypnotic and driving their cars while not fully awake, often with no memory of the event. Advise patients to report similar experiences to their healthcare provider immediately, since “sleep-driving” can be dangerous. This behavior is more likely to occur when sedative-hypnotics are taken with alcohol or other CNS depressants [see Warnings and Precautions ( 5. 5)]. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative hypnotic. As with sleep-driving, patients usually do not remember these events. Advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients. Effects on Driving and Operating Heavy Machinery Caution patients against driving a motor vehicle or operating heavy machinery until the effects of taking triazolam are determined due to its CNS depressant effects. Also advise patients to avoid the use of alcohol or other CNS depressants while taking triazolam [see Warnings and Precautions ( 5. 7)]. Patients with Depression Advise patients, their families and caregivers to look out for any signs of suicidality or worsening depression, and to inform the patient’s prescriber or healthcare provider immediately [see Warnings and Precautions ( 5.9 )]. Concomitant Medications Advise patients to inform their healthcare provider of all medicines they take, including prescription and nonprescription medicines, vitamins and herbal supplements [see Drug Interactions ( 7.1 )]. Grapefruit Juice Advise patients to avoid eating grapefruit or drinking grapefruit juice while taking triazolam [see Drug Interactions ( 7.1 )]. Pregnancy Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Advise mothers using triazolam to monitor neonates for signs of sedation, respiratory depression, withdrawal, and feeding problems [see Warnings and Precautions ( 5.10 ), Use in Specific Populations ( 8.1 )]. Lactation Advise mothers using benzodiazepines to monitor neonates for signs of sedation, respiratory depression, withdrawal symptoms, and feeding problems. A lactating woman may consider pumping and discarding breastmilk during treatment and for 28 hours after triazolam administration to minimize drug exposure to a breastfed infant [see Use in Specific Populations ( 8.2 )]. Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 C50000773/01 Revised November 2021
Spl medguide
Information about the patient medication guide that accompanies the drug product. Certain drugs must be dispensed with an accompanying medication guide. This field may contain information about when to consult the medication guide and the contents of the medication guide.MEDICATION GUIDE Triazolam Tablets, USP CIV (trye az’ oh lam) Rx only What is the most important information I should know about Triazolam Tablets? • Triazolam is a benzodiazepine medicine. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system (CNS) depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death. Get emergency help right away if any of the following happens: o shallow or slowed breathing o breathing stops (which may lead to the heart stopping) o excessive sleepiness (sedation) Do not drive or operate heavy machinery until you know how taking triazolam tablets with opioids affects you. • Risk of abuse, misuse, and addiction. There is a risk of abuse, misuse, and addiction with benzodiazepines, including triazolam tablets which can lead to overdose and serious side effects including coma and death. o Serious side effects including coma and death have happened in people who have abused or misused benzodiazepines, including triazolam tablets. These serious side effects may also include delirium, paranoia, suicidal thoughts or actions, seizures, and difficulty breathing. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these serious side effects. o You can develop an addiction even if you take triazolam tablets as prescribed by your healthcare provider. o Take triazolam tablets exactly as your healthcare provider prescribed. o Do not share your triazolam tablets with other people. o Keep triazolam tablets in a safe place and away from children. • Physical dependence and withdrawal reactions. Triazolam tablets can cause physical dependence and withdrawal reactions. o Do not suddenly stop taking triazolam tablets. Stopping triazolam tablets suddenly can cause serious and life-threatening side effects, including unusual movements, responses, or expressions, seizures, sudden and severe mental or nervous system changes, depression, seeing or hearing things that others do not see or hear, an extreme increase in activity or talking, losing touch with reality, and suicidal thoughts or actions. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these symptoms. o Some people who suddenly stop benzodiazepines, have symptoms that can last for several weeks to more than 12 months, including, anxiety, trouble remembering, learning, or concentrating, depression, problems sleeping feeling like insects are crawling under your skin, weakness, shaking, muscle twitching, burning or prickling feeling in your hands, arms, legs or feet, and ringing in your ears. o Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction. o Do not take more triazolam tablets than prescribed or take triazolam tablets for longer than prescribed. • After taking triazolam tablets, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. You have a higher chance for doing these activities if you drink alcohol or take other medicines that make you sleepy with triazolam tablets. Reported activities include: o driving a car (“sleep-driving”) o making and eating food o talking on the phone o having sex o sleep-walking Call your healthcare provider right away if you find out that you have done any of the above activities after taking triazolam tablets. What are Triazolam Tablets? Triazolam is a prescription medicine used in adults for the short-term treatment of a sleep problem called insomnia. Triazolam tablets are usually taken for 7 to 10 days. • Triazolam is a federal controlled substance (CIV) because it can be abused or lead to dependence. Keep triazolam tablets in a safe place to prevent misuse and abuse. Selling or giving away triazolam tablets may harm others, and is against the law. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription medicines or street drugs. • It is not known if triazolam is safe and effective in children. • It is not known if triazolam is safe and effective for use longer than 2 to 3 weeks. Do not take triazolam tablets if you: • are allergic to triazolam, other benzodiazepines, or any of the ingredients in triazolam tablets. Severe allergic reactions including swelling of the tongue or throat, trouble breathing and throat closing have happened and may lead to death. Get medical help right away if you have an allergic reaction to triazolam tablets. See the end of this Medication Guide for a complete list of ingredients in triazolam tablets. • take antifungal medicines including ketoconazole and itraconazole • take a medicine to treat depression called nefazodone • take medicines to treat human immunodeficiency virus (HIV)-1 infection called protease inhibitors. Before you take triazolam tablets, tell your healthcare provider about all of your medical conditions, including if you: • have a history of depression, mood problems, mental illness, suicidal thoughts or behavior • have a history of drug or alcohol abuse or addiction • have lung problems, breathing problems, or sleep apnea • are pregnant or plan to become pregnant. o If you become pregnant while taking triazolam tablets, talk to your healthcare provider about registering with the National Pregnancy Registry for psychiatric medicines during pregnancy. You can register by calling 1-866-961-2388 or visit https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/ . o Babies born to mothers who take benzodiazepine medicines, including triazolam tablets, late in pregnancy may have symptoms of sedation, such as breathing problems, sluggishness, and low muscle tone (floppy baby syndrome), feeding problems and withdrawal symptoms. • are breastfeeding or plan to breastfeed. It is not known if triazolam can pass through your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take triazolam tablets. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking triazolam tablets with certain other medicines can cause side effects or affect how well triazolam or the other medicines work. Do not start or stop other medicines without talking to your healthcare provider. How should I take triazolam tablets? • Take triazolam tablets exactly as your healthcare provider tells you to take them. • Take triazolam tablets right before you get into bed. • Do not eat grapefruit or drink grapefruit juice during treatment with triazolam tablets. • Call your healthcare provider if your insomnia worsens or is not better within 7 to 10 days of treatment with triazolam tablets. This may mean that there is another condition causing your sleep problem. • If you take too many triazolam tablets, call your healthcare provider or have somebody drive you to the nearest hospital emergency room right away. What are the possible side effects of triazolam tablets? Triazolam Tablets may cause serious side effects, including: • See “What is the most important information I should know about triazolam tablets?” • Increased daytime anxiety. • Abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions. • Memory loss • Triazolam Tablets can make you sleepy or dizzy and can slow your thinking and motor skills. o Do not drive, operate heavy machinery, or do other dangerous activities until you know how triazolam tablets affect you. o Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking triazolam tablets without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, triazolam tablets may make your sleepiness or dizziness much worse. • Worsening depression. Call your healthcare provider right away if you have any thoughts of suicide or dying or worsening depression. The most common side effects of triazolam tablets include: • drowsiness • dizziness • light-headedness • difficulty with coordination Elderly people have an increased risk of dose related side effects during treatment with triazolam tablets. These are not all the possible side effects of triazolam tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store Triazolam Tablets, USP? • Store at 20º to 25°C (68º to 77°F). [See USP Controlled Room Temperature.] • Keep Triazolam Tablets, USP and all medicines out of the reach of children General information about the safe and effective use of triazolam tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use triazolam tablets for a condition for which they were not prescribed. Do not give triazolam tablets to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about triazolam tablets that is written for healthcare professionals. What are the ingredients in Triazolam Tablets, USP? Active ingredient: triazolam, USP Inactive ingredients: 0.125 mg: docusate sodium with sodium benzoate, lactose (anhydrous), magnesium stearate, microcrystalline cellulose and pregelatinized starch; 0.25 mg: docusate sodium with sodium benzoate, FD&C Blue No. 1, lactose (anhydrous), magnesium stearate, microcrystalline cellulose and pregelatinized starch. Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 For information, please call 1-800-962-8364. This Medication Guide has been approved by the U.S. Food and Drug Administration. C50000773/01 Revised November 2021
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Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use Elderly patients exhibit higher plasma triazolam concentrations due to reduced clearance as compared with younger subjects at the same dose. Because elderly patients are especially susceptible to dose related adverse reactions and to minimize oversedation, the smallest effective dose should be used [see Dosage and Administration ( 2.2 ), Clinical Pharmacology ( 12.3 )].
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use Safety and effectiveness of triazolam have not been established in pediatric patients.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to triazolam during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Other Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/ . Risk Summary Infants born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and neonatal withdrawal (see Clinical Considerations) [see Warnings and Precautions ( 5.10 )]. At this time, there is no clear evidence that triazolam exposure in early pregnancy can cause major birth defects (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to triazolam during pregnancy and labor for signs of sedation, respiratory depression, withdrawal, and feeding problems and manage accordingly [see Warnings and Precautions ( 5.10 )]. Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings. At this time, there is no clear evidence that triazolam exposure in early pregnancy can cause major birth defects. Infants exposed to benzodiazepines during the late third trimester of pregnancy or during labor have been reported to exhibit sedation and neonatal withdrawal symptoms. Animal Data Oral administration of triazolam to pregnant rats and rabbits during the period of organogenesis caused skeletal developmental changes (variations and malformations) at maternally toxic doses in rats and at doses in rats and rabbits which are approximately equal to or greater than 200 times the maximum recommended human dose (MRHD) of 0.5 mg/day based on mg/m 2 body surface area. Oral administration of triazolam to male and female rats before mating, and continuing during gestation and lactation did not result in embryotoxicity at doses up to approximately 100 times the MRHD based on mg/m 2 body surface area, but did cause an increase in the number of stillbirths and postnatal pup mortalities at doses greater than or equal to approximately 40 times the MRHD based mg/m 2 body surface area. 14 C-triazolam was administered orally to pregnant mice. Drug-related material appeared uniformly distributed in the fetus with 14 C concentrations approximately the same as in the brain of the mother.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS Lactation: A lactating woman may pump and discard breast milk during treatment and for 28 hours after triazolam administration ( 8.2 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to triazolam during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Other Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/ . Risk Summary Infants born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and neonatal withdrawal (see Clinical Considerations) [see Warnings and Precautions ( 5.10 )]. At this time, there is no clear evidence that triazolam exposure in early pregnancy can cause major birth defects (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to triazolam during pregnancy and labor for signs of sedation, respiratory depression, withdrawal, and feeding problems and manage accordingly [see Warnings and Precautions ( 5.10 )]. Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings. At this time, there is no clear evidence that triazolam exposure in early pregnancy can cause major birth defects. Infants exposed to benzodiazepines during the late third trimester of pregnancy or during labor have been reported to exhibit sedation and neonatal withdrawal symptoms. Animal Data Oral administration of triazolam to pregnant rats and rabbits during the period of organogenesis caused skeletal developmental changes (variations and malformations) at maternally toxic doses in rats and at doses in rats and rabbits which are approximately equal to or greater than 200 times the maximum recommended human dose (MRHD) of 0.5 mg/day based on mg/m 2 body surface area. Oral administration of triazolam to male and female rats before mating, and continuing during gestation and lactation did not result in embryotoxicity at doses up to approximately 100 times the MRHD based on mg/m 2 body surface area, but did cause an increase in the number of stillbirths and postnatal pup mortalities at doses greater than or equal to approximately 40 times the MRHD based mg/m 2 body surface area. 14 C-triazolam was administered orally to pregnant mice. Drug-related material appeared uniformly distributed in the fetus with 14 C concentrations approximately the same as in the brain of the mother. 8.2 Lactation Risk Summary There are no data on the presence of triazolam in human milk or the effects on milk production. There are reports of central nervous system depression (sedation, respiratory depression), withdrawal symptoms, and feeding problems in infants who are breastfed by mothers taking benzodiazepines (see Clinical Considerations). Triazolam and its metabolites are present in the milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for triazolam and any potential adverse effects on the breastfed infant from triazolam or from the underlying maternal condition. Clinical Considerations Infants exposed to triazolam through breast milk should be monitored for sedation, respiratory depression, withdrawal symptoms, and feeding problems. A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 28 hours (approximately 5 elimination half-lives) after triazolam administration in order to minimize drug exposure to a breast fed infant. Data Both triazolam and triazolam metabolites were detected in milk of rats. Lactating rats were orally administered 0.3 mg/kg 14 C-triazolam; drug and metabolite levels were determined in milk collected at 6 and 24 hours after administration. 8.4 Pediatric Use Safety and effectiveness of triazolam have not been established in pediatric patients. 8.5 Geriatric Use Elderly patients exhibit higher plasma triazolam concentrations due to reduced clearance as compared with younger subjects at the same dose. Because elderly patients are especially susceptible to dose related adverse reactions and to minimize oversedation, the smallest effective dose should be used [see Dosage and Administration ( 2.2 ), Clinical Pharmacology ( 12.3 )].
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-4733 NDC: 50090-4733-0 30 TABLET in a BOTTLE NDC: 50090-4733-1 100 TABLET in a BOTTLE
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS See full prescribing information for complete boxed warning. • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death . Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation ( 5.1 , 7.1 ). • The use of benzodiazepines, including triazolam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing triazolam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction ( 5.2 ). • Abrupt discontinuation or rapid dosage reduction of triazolam after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue triazolam or reduce the dosage ( 2.3 , 5.3 ).
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API