diazepam intranasal (Rx)

Brand and Other Names:Valtoco
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

intranasal spray: Schedule IV

  • 5mg/0.1mL
  • 7.5mg/0.1mL
  • 10mg/0.1mL

Epilepsy

Indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy

Adolescent or adult dose (0.2 mg/kg)

  • 14-27 kg: 5 mg (one 5-mg device); 1 spray in 1 nostril
  • 28-50 kg: 10 mg (one 10-mg device); 1 spray in 1 nostril
  • 51-75 kg: 15 mg (two 7.5-mg devices); 1 spray in each nostril
  • ≥76 kg: 20 mg (two 10-mg devices); 1 spray in each nostril

Second dose and maximum dose

  • Second dose: When required, may be administered after at least 4 hr after initial dose; if the second dose is to be administered, use a new blister pack of diazepam intranasal
  • Maximum dosage: Not to exceed 2 doses to treat a single episode
  • Treatment frequency: Do not use for more than 1 episode q5days and no more than 5 episodes/month

Dosage Modifications

Renal impairment

  • Not studied

Hepatic impairment

  • Not studied
  • Prescribing information describes literature review showing diazepam 0.1-0.15 mg/kg IV had prolonged half-life by 2- to 5-fold in patients with alcoholic cirrhosis

Dosage Forms & Strengths

intranasal spray: Schedule IV

  • 5mg/0.1mL
  • 7.5mg/0.1mL
  • 10mg/0.1mL

Epilepsy

Indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy aged ≥6 years

<6 years: Safety and efficacy not established

6-11 years (0.3 mg/kg)

  • 10-18 kg: 5 mg (one 5-mg device); 1 spray in 1 nostril
  • 19-37 kg: 10 mg (one 10-mg device); 1 spray in 1 nostril
  • 38-55 kg: 15 mg (two 7.5-mg devices); 1 spray in each nostril
  • 56-74 kg: 20 mg (two 10-mg devices); 1 spray in each nostril

12 years or older (0.2 mg/kg)

  • 14-27 kg: 5 mg (one 5-mg device); 1 spray in 1 nostril
  • 28-50 kg: 10 mg (one 10-mg device); 1 spray in 1 nostril
  • 51-75 kg: 15 mg (two 7.5-mg devices); 1 spray in each nostril
  • ≥76 kg: 20 mg (two 10-mg devices); 1 spray in each nostril

Second dose and maximum dose

  • Second dose: When required, may be administered after at least 4 hr after initial dose; if the second dose is to be administered, use a new blister pack of diazepam intranasal
  • Maximum dosage: Not to exceed 2 doses to treat a single episode
  • Treatment frequency: Do not use for more than 1 episode q5days and no more than 5 episodes/month

Dosage Modifications

Renal impairment

  • Not studied

Hepatic impairment

  • Not studied
  • Prescribing information describes literature review showing diazepam 0.1-0.15 mg/kg IV had prolonged half-life by 2- to 5-fold in patients with alcoholic cirrhosis

Dosing Considerations

Not approved for use in neonates or infants

Prolonged CNS depression observed with neonates treated with diazepam

Serious adverse reactions including fatal reactions and gasping syndrome occurred in premature neonates and low-birth-weight infants who received drugs containing benzyl alcohol as a preservative (diazepam intranasal contains benzyl alcohol 10.5 mg/0.1mL)

Epilepsy

Indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy

Clinical studies did not include sufficient numbers of individuals aged ≥65 yr to determine whether they respond differently from younger patients

Caution in geriatric patients owing to increased half-life that corresponds to decreased clearance of free diazepam

Decreased dose recommended in older patients to reduce likelihood of ataxia or over sedation

Use with caution in patients with compromised respiratory function related to a concurrent disease process (eg, asthma, pneumonia) or neurologic damage

Adult dose (0.2 mg/kg)

  • 14-27 kg: 5 mg (one 5-mg device); 1 spray in 1 nostril
  • 28-50 kg: 10 mg (one 10-mg device); 1 spray in 1 nostril
  • 51-75 kg: 15 mg (two 7.5-mg devices); 1 spray in each nostril
  • ≥76 kg: 20 mg (two 10-mg devices); 1 spray in each nostril

Second dose and maximum dose

  • Second dose: When required, may be administered after at least 4 hr after initial dose; if the second dose is to be administered, use a new blister pack of diazepam intranasal
  • Maximum dosage: Not to exceed 2 doses to treat a single episode
  • Treatment frequency: Do not use for more than 1 episode q5days and no more than 5 episodes/month

Dosage Modifications

Renal impairment

  • Not studied

Hepatic impairment

  • Not studied
  • Prescribing information describes literature review showing diazepam 0.1-0.15 mg/kg IV had prolonged half-life by 2- to 5-fold in patients with alcoholic cirrhosis
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Interactions

Interaction Checker

and diazepam intranasal

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            Adverse Effects

            Adverse effects reported in prescribing information based on data from diazepam rectal gel unless otherwise specified

            >10%

            Somnolence (23%)

            1-10%

            Headache (5%)

            Diarrhea (4%)

            Ataxia (3%)

            Dizziness (3%)

            Euphoria (3%)

            Incoordination (3%)

            Rash (3%)

            Asthma (2%)

            Vasodilation (2%)

            Asthenia (≥1%)

            Hypotension, vasodilatation (≥1%)

            Agitation, confusion, convulsion, dysarthria, emotional lability, speech disorder, thinking abnormal, vertigo (≥1%)

            Hiccup (≥1%)

            Diazepam intranasal

            • Nasal discomfort (6%)
            • Nasal congestion (3%)
            • Epistaxis (3%)
            • Dysgeusia (2%)

            Frequency Not Defined

            The following infrequent adverse events have been reported previously with diazepam use: Depression, slurred speech, syncope, changes in libido, urinary retention, bradycardia, cardiovascular collapse, nystagmus, urticaria, neutropenia, and jaundice

            Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances, and stimulation have been reported with other diazepam products

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            Warnings

            Black Box Warnings

            Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death

            Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate

            Limit dosages and durations to minimum requirement

            Monitor for signs and symptoms of respiratory depression and sedation

            Contraindications

            Hypersensitivity

            Acute narrow angle glaucoma

            Cautions

            Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death; because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for use in patients for whom alternative treatment options are inadequate

            May produce CNS depression; caution patients against engaging in hazardous activities requiring mental alertness until effects of the drug, such as drowsiness, have subsided, and as their medical condition permits

            Caution in patients with compromised respiratory function related to a concurrent disease process (eg, asthma, pneumonia) or neurologic damage

            Antiepileptic drugs (AEDs) increase risk of suicidal thoughts or behavior in patients taking these drugs for any indication; monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior

            Benzodiazepines can increase intraocular pressure in patients with glaucoma; may be used in patients with open-angle glaucoma only if they are receiving appropriate therapy; diazepam is contraindicated in patients with narrow-angle glaucoma

            Not approved for use in neonates or infants; diazepam intranasal contains benzyl alcohol, which can cause serious and fatal adverse reactions, including gasping syndrome, in neonates and low-birth-weight infants

            Drug interaction overview

            • Diazepam is a CYP2C19 and CYP3A4 substrate
            • Coadministration of benzodiazepines and opioids increases risk of respiratory depression; limit dosage and duration if concomitantly used; monitor closely for respiratory depression and sedation
            • Coadministration of other CNS depressants or alcohol consumption may potentiate CNS-depressant effects of diazepam
            • CYP2C19 or CYP3A4 inhibitors: May decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam
            • CYP2C19 or CYP3A4 inducers: May increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased
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            Pregnancy & Lactation

            Pregnancy

            North American Antiepileptic Drug (NAAED) Pregnancy Registry: 1-888-233-2334; http://www.aedpregnancyregistry.org

            There are no adequate data on the use of diazepam intranasal in pregnant women

            Available data suggest that the class of benzodiazepines is not associated with marked increases in risk for congenital anomalies

            Although some early epidemiological studies suggested a relationship between benzodiazepine use in pregnancy and congenital anomalies such as cleft lip and or palate, these studies had considerable limitations

            More recently completed studies of benzodiazepine use in pregnancy have not consistently documented elevated risks for specific congenital anomalies

            There is insufficient evidence to assess the effect of benzodiazepine pregnancy exposure on neurodevelopment

            Neonatal withdrawal and floppy infant syndrome

            • Neonatal withdrawal syndrome and symptoms suggestive of floppy infant syndrome associated with administration of benzodiazepines during the later stages of pregnancy and peripartum period have been reported

            Animal data

            • Increased incidences of fetal malformations in mice and hamsters when given PO at single doses of ≥100 mg/kg or greater (∼13 times the maximum recommended human dose [MRHD = 0.6mg/kg/day] or greater on a mg/m2 basis)
            • Cleft palate and exencephaly are the most common and consistently reported malformations produced in these species by administration of high, maternally toxic doses of diazepam during organogenesis

            Lactation

            Diazepam is excreted in human milk

            There are no data specifically for diazepam intranasal

            Postmarketing experience suggests that breastfed infants of mothers taking benzodiazepines may have effects of lethargy, somnolence, and poor sucking

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            The exact mechanism of action for diazepam is not fully understood, but it is thought to involve potentiation of gamma aminobutyric acid (GABA) neurotransmission resulting from binding at the benzodiazepine site of the GABA-A receptor

            Absorption

            Peak plasma concentration: 1.5 hr

            Absolute bioavailability: 97%

            Distribution

            Protein bound: 95-98% (including active desmethyldiazepam metabolite)

            Vd: 0.8-1 L/kg

            Metabolism

            Metabolism of diazepam is primarily hepatic and involves demethylation (primarily by CYP2C19 and CYP3A4) and 3-hydroxylation (primarily by CYP3A4), followed by glucuronidation

            Elimination

            Half-life: 49.2 hr (10-mg intranasal dose)

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            Administration

            Intranasal Administration

            For intranasal use only

            No device assembly required; ready-to-use nasal spray device; do not open individual blister packs or test nasal spray devices before use

            Do not use if nasal spray unit appears damaged

            Each single-dose nasal spray device sprays 1 time and cannot be reused

            Nasal spray delivers its entire contents upon activation

            Before use, instruct individual administering diazepam intranasal on how to identify seizure clusters and how to appropriately administer the product

            Storage

            Store at 20-25ºC (68-77ºF); excursions permitted from 15-30ºC (59-86ºF)

            Do not freeze

            Protect from light

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            Formulary

            FormularyPatient Discounts

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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.