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Ethotoin

Pronunciation

(ETH oh toyn)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Peganone: 250 mg [DSC]

Peganone: 250 mg [scored]

Brand Names: U.S.

  • Peganone

Pharmacologic Category

  • Anticonvulsant, Hydantoin

Pharmacology

Stabilizes the seizure threshold and prevents the spread of seizure activity

Absorption

Rapid

Metabolism

Saturable, hepatic; forms metabolites; the relationship between dose and ethotoin and metabolite concentrations is non-linear.

Excretion

Urine (Naestoft 1976)

Half-Life Elimination

3 to 9 hours

Use: Labeled Indications

Seizures: Control of generalized tonic-clonic (grand mal) and complex-partial (psychomotor) seizures

Contraindications

Hepatic abnormalities; hematologic disorders

Documentation of allergenic cross-reactivity for hydantoins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Seizures: Oral: Initial: ≤1 g/day, in 4 to 6 divided doses; increase dose over a period of several days; usual maintenance: 2 to 3 g/day

Dosing: Geriatric

Refer to adult dosing; use with caution.

Dosing: Pediatric

Seizures: Children ≥1 year and Adolescents: Oral: Initial: ≤750 mg/day, in 4 to 6 divided doses; usual maintenance: 0.5 to 1 g/day; maximum: 3 g/day

Dosing: Renal Impairment

There are no dosage adjustment provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

Use is contraindicated.

Administration

Administer after food to decrease GI distress.

Storage

Store at 20°C to 25˚C (68°F to 77˚F). Protect from light.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Ethotoin may enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Ethotoin. Management: Anticoagulant dose adjustment will likely be necessary when ethotoin is initiated or discontinued. Monitor patients extra closely (INR and signs/symptoms of bleeding) when using this combination. Consider therapy modification

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

Frequency not defined.

Cardiovascular: Chest pain

Central nervous system: Ataxia, dizziness, fatigue, headache, insomnia, numbness

Dermatologic: Skin rash, Stevens-Johnson syndrome

Gastrointestinal: Diarrhea, gingival hyperplasia, nausea, vomiting

Hematologic & oncologic: Hematologic disease, lymphadenopathy

Neuromuscular & skeletal: Lupus-like syndrome

Ophthalmic: Diplopia, nystagmus

Miscellaneous: Fever

Warnings/Precautions

Concerns related to adverse effects:

• Blood dyscrasias: Have been reported with use; patients with a previous history of adverse hematologic reaction to any drug may be at increased risk. Early detection of hematologic change is important; advise patients of early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy bruising, petechial or purpuric hemorrhage. Discontinue therapy in patients with decreased blood counts. Hydantoin-like compounds may interfere with folic acid metabolism precipitating megaloblastic anemia. Contraindicated in patients with hematologic disorders.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Withdrawal: Do not discontinue anticonvulsants abruptly because of the possibility of increasing seizure frequency; withdraw therapy gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Monitoring Parameters

CBC and urinalysis (initiation of therapy and monthly for several months); liver function tests if signs of dysfunction; suicidality (eg, suicidal thoughts, depression, behavioral changes)

Pregnancy Considerations

Adverse fetal effects may occur following maternal use of ethotoin. Cleft lip and cleft palate observed with other hydantoins has also been reported following in utero exposure to ethotoin (Zablen 1977). Maternal ingestion of antiepileptic agents has been associated with neonatal coagulation defects/bleeding usually within 24 hours of birth..

Patients exposed to ethotoin during pregnancy are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, diarrhea, headache, insomnia, vomiting, or nausea. Have patient report immediately to prescriber signs of infection, signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), change in balance, gingival pain or edema, angina, involuntary eye movements, diplopia, severe loss of strength and energy, burning or numbness feeling, enlarged lymph nodes, seizures, bruising, bleeding, agitation, irritability, panic attacks, mood changes, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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