Zepose

Contraindications

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What is the most important information I should know about Zepose?

You should not use this medication if you are allergic to Zepose or similar medicines (Ativan, Klonopin, Restoril, Xanax, and others), or if you have myasthenia gravis, severe liver disease, narrow-angle glaucoma, a severe breathing problem, or sleep apnea.

Do not use Zepose if you are pregnant. It could harm the unborn baby.

Do not start or stop taking Zepose during pregnancy without your doctor's advice. Zepose may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby. Tell your doctor right away if you become pregnant while taking Zepose for seizures.

Before you take Zepose, tell your doctor if you have glaucoma, asthma or other breathing problems, kidney or liver disease, seizures, or a history of drug or alcohol addiction, mental illness, depression, or suicidal thoughts.

Do not drink alcohol while taking Zepose. This medication can increase the effects of alcohol.

Never take more of this medication than your doctor has prescribed. An overdose of Zepose can be fatal.

Zepose may be habit forming. Never share Zepose with another person, especially someone with a history of drug abuse or addiction.

Undesirable effects

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What are the possible side effects of Zepose?

Zepose rectal gel adverse event data were collected from double-blind, placebo-controlled studies and open-label studies. The majority of adverse events were mild to moderate in severity and transient in nature.

Two patients who received Zepose rectal gel died seven to 15 weeks following treatment; neither of these deaths was deemed related to Zepose rectal gel.

The most frequent adverse event reported to be related to Zepose rectal gel in the two double-blind, placebo-controlled studies was somnolence (23%). Less frequent adverse events were dizziness, headache, pain, abdominal pain, nervousness, vasodilatation, diarrhea, ataxia, euphoria, incoordination, asthma, rhinitis, and rash, which occurred in approximately 2-5% of patients.

Approximately 1.4% of the 573 patients who received Zepose rectal gel in clinical trials of epilepsy discontinued treatment because of an adverse event. The adverse event most frequently associated with discontinuation (occurring in three patients) was somnolence. Other adverse events most commonly associated with discontinuation and occurring in two patients were hypoventilation and rash. Adverse events occurring in one patient were asthenia, hyperkinesia, incoordination, vasodilatation and urticaria. These events were judged to be related to Zepose rectal gel.

In the two domestic double-blind, placebo-controlled, parallel-group studies, the proportion of patients who discontinued treatment because of adverse events was 2% for the group treated with Zepose rectal gel, versus 2% for the placebo group. In the Zepose rectal gel group, the adverse events considered the primary reason for discontinuation were different in the two patients who discontinued treatment; one discontinued due to rash and one discontinued due to lethargy. The primary reason for discontinuation in the patients treated with placebo was lack of effect.

Table 1 lists treatment-emergent signs and symptoms that occurred in > 1% of patients enrolled in parallel-group, placebo-controlled trials and were numerically more common in the Zepose rectal gel group. Adverse events were usually mild or moderate in intensity.

The prescriber should be aware that these figures, obtained when Zepose rectal gel was added to concurrent antiepileptic drug therapy, cannot be used to predict the frequency of adverse events in the course of usual medical practice when patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescribing physician with one basis to estimate the relative contribution of drug and non-drug factors to the adverse event incidences in the population studied.

TABLE 1: Treatment-Emergent Signs And Symptoms That Occurred In > 1% Of Patients Enrolled In Parallel-Group, Placebo-Controlled Trials And Were Numerically More Common In The Zepose Rectal Gel Group

Other events reported by 1% or more of patients treated in controlled trials but equally or more frequent in the placebo group than in the Zepose rectal gel group were abdominal pain, pain, nervousness, and rhinitis. Other events reported by fewer than 1% of patients were infection, anorexia, vomiting, anemia, lymphadenopathy, grand mal convulsion, hyperkinesia, cough increased, pruritus, sweating, mydriasis, and urinary tract infection.

The pattern of adverse events was similar for different age, race and gender groups.

Zepose rectal gel has been administered to 573 patients with epilepsy during all clinical trials, only some of which were placebo-controlled. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. These categories are used in the listing below. All of the events listed below occurred in at least 1% of the 573 individuals exposed to Zepose rectal gel.

All reported events are included except those already listed above, events unlikely to be drug-related, and those too general to be informative. Events are included without regard to determination of a causal relationship to Zepose.

BODY AS A WHOLE: Asthenia

CARDIOVASCULAR: Hypotension, vasodilatation

NERVOUS: Agitation, confusion, convulsion, dysarthria, emotional lability, speech disorder, thinking abnormal, vertigo

RESPIRATORY: Hiccup

The following infrequent adverse events were not seen with Zepose rectal gel but have been reported previously with Zepose use: depression, slurred speech, syncope, constipation, 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 Zepose; should these occur, use of Zepose rectal gel should be discontinued.

Zepose is a Schedule IV controlled substance and can produce drug dependence. It is recommended that patients be treated with Zepose rectal gel no more frequently than every five days and no more than five times per month.

Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving Zepose or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

Abrupt discontinuation of Zepose following chronic regular use has resulted in withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating). The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuation of benzodiazepines taken continuously at therapeutic levels for several months.

Therapeutic indications

Zepose Rectal Gel is a gel formulation of Zepose intended for rectal administration in the management of selected, refractory, patients with epilepsy, on stable regimens of AEDs, who require intermittent use of Zepose to control bouts of increased seizure activity.

Evidence to support the use of Zepose Rectal Gel was adduced in two controlled trials that enrolled patients with partial onset or generalized convulsive seizures who were identified jointly by their caregivers and physicians as suffering intermittent and periodic episodes of markedly increased seizure activity, sometimes heralded by nonconvulsive symptoms, that for the individual patient were characteristic and were deemed by the prescriber to be of a kind for which a benzodiazepine would ordinarily be administered acutely. Although these clusters or bouts of seizures differed among patients, for any individual patient the clusters of seizure activity were not only stereotypic but were judged by those conducting and participating in these studies to be distinguishable from other seizures suffered by that patient. The conclusion that a patient experienced such unique episodes of seizure activity was based on historical information.

Zepose is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). Zepose affects chemicals in the brain that may be unbalanced in people with certain conditions.

Zepose injection is used to treat anxiety disorders, alcohol withdrawal symptoms, or muscle spasms. Zepose injection is also used to treat a seizure emergency called status epilepticus.

Zepose injection is sometimes used as a sedative to help you relax before having surgery or other medical procedure.

Zepose may also be used for purposes not listed in this medication guide.

Name of the medicinal product

Qualitative and quantitative composition

Each tablet contains Diazepam 2 mg, 5 mg and 10 mg, respectively. Each ampoule contain Zepose 10 mg/2 mL. It also contains the following excipients: Tablets: Lactose. Ampoules: Benzyl alcohol.

Special warnings and precautions for use

Use Zepose Rectal Gel as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Zepose Rectal Gel. Talk to your pharmacist if you have questions about this information.
• A health care provider will teach your caregiver how to use Zepose Rectal Gel. Be sure your caregiver understands how to use Zepose Rectal Gel. Contact your health care provider if you or your caregiver have any questions about using Zepose Rectal Gel.
• To use Zepose Rectal Gel, place the patient on their side where they cannot fall. Get the syringe. Push up with your thumb and remove the cap from the syringe. Be sure the seal pin is removed with the cap. Lubricate the rectal tip with the lubricating jelly provided.
• Turn the patient on their side facing you. Bend the upper leg forward and separate the buttocks to expose the rectum.
• Gently insert the syringe tip into the rectum. Slowly count to 3 while gently pushing the plunger in until it stops. Slowly count to 3 before removing the syringe from the rectum. Slowly count to 3 while holding the buttocks together to prevent leakage of the medicine.
• Keep the patient on their side facing you. Continue to observe the patient as directed by the patient's doctor.
• Do not reuse the syringe or other materials. Throw away all used materials in the trash can. Keep out of the reach of children and away from pets.
• Contact the patient's doctor at once if seizures continue for 15 minutes after using Zepose Rectal Gel, unless the patient's doctor tells you otherwise.
• Contact the doctor at once if you are alarmed by the frequency or severity of the seizures, or the color or breathing of the patient.
• Contact the doctor at once if the seizures are different from the patient's usual seizure episodes or if the patient is having unusual or serious problems.
• Do NOT use Zepose Rectal Gel more often than once every 5 days unless your doctor tells you otherwise.
• Do NOT use Zepose Rectal Gel more often than 5 times per month unless your doctor tells you otherwise.
• If you miss a dose of Zepose Rectal Gel, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Zepose Rectal Gel.

Zepose is used to treat anxiety, muscle spasms, and alcohol withdrawal. The injection form is used when prompt relief is desired or when the medication cannot be taken by mouth.

This medication is also used for the short-term treatment of serious seizures that do not stop (status epilepticus). It is not for ongoing daily use to prevent seizures.

Zepose is also used before a surgery or procedure to cause drowsiness, decrease anxiety, and to help the patient forget what happened during the surgery/procedure.

This medication works by calming the brain and nerves. Zepose belongs to a class of drugs known as benzodiazepines.

This medication is given by injection into a vein or deep into a muscle as directed by your doctor. You should be closely monitored for several hours after receiving this medication.

If you are using this medication at home, learn all preparation and usage instructions from your health care professional. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.

The dosage is based on your medical condition, age, and response to treatment. Giving the medication too fast into a vein can cause serious side effects. If giving this medication into a vein, inject it slowly into a large vein. Do not inject this medication into an artery or into the skin.

If you suddenly stop using this medication, you may have withdrawal symptoms (such as shaking, abdominal/muscle cramps, vomiting, sweating, anxiety, restlessness, seizures). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used Zepose for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.

When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.

Along with its benefits, this medication may rarely cause abnormal drug-seeking behavior (addiction). This risk may be increased if you have abused alcohol or drugs in the past. Use this medication exactly as prescribed to lessen the risk of addiction.

Dosage (Posology) and method of administration

This section is intended primarily for the prescriber; however, the prescriber should also be aware of the dosing information and directions for use provided in the patient package insert.

A decision to prescribe Zepose rectal gel involves more than the diagnosis and the selection of the correct dose for the patient.

First, the prescriber must be convinced from historical reports and/or personal observations that the patient exhibits the characteristic identifiable seizure cluster that can be distinguished from the patient's usual seizure activity by the caregiver who will be responsible for administering Zepose rectal gel.

Second, because Zepose rectal gel is only intended for adjunctive use, the prescriber must ensure that the patient is receiving an optimal regimen of standard anti-epileptic drug treatment and is, nevertheless, continuing to experience these characteristic episodes.

Third, because a non-health professional will be obliged to identify episodes suitable for treatment, make the decision to administer treatment upon that identification, administer the drug, monitor the patient, and assess the adequacy of the response to treatment, a major component of the prescribing process involves the necessary instruction of this individual.

Fourth, the prescriber and caregiver must have a common understanding of what is and is not an episode of seizures that is appropriate for treatment, the timing of administration in relation to the onset of the episode, the mechanics of administering the drug, how and what to observe following administration, and what would constitute an outcome requiring immediate and direct medical attention.

The Zepose rectal gel dose should be individualized for maximum beneficial effect. The recommended dose of Zepose rectal gel is 0.2-0.5 mg/kg depending on age. See the dosing table for specific recommendations.

Zepose Rectal Gel rectal delivery system is a non-sterile, prefilled, unit dose, rectal delivery system. The rectal delivery system includes a plastic applicator with a flexible, molded tip available in two lengths, designated for convenience as 10 mg delivery system and 20 mg delivery system. The available doses from 20 mg delivery system are 12.5 mg, 15 mg, 17.5 mg, and 20 mg. The available doses from 10 mg delivery system are 5 mg, 7.5 mg and 10 mg. The Zepose Rectal Gel delivery system is available in the following three presentations:

Each twin pack contains two Zepose Rectal Gel delivery systems, two packets of lubricating jelly, and administration and disposal Instructions available on the bottom of the package. Zepose Rectal Gel is also packed with Instructions for Caregivers upon receipt from pharmacy.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

Zepose Rectal Gel 10 mg delivery system and 20 mg delivery system

Distributed by: TEVA PHARMACEUTICALS USA, INC., North Wales, PA 19454. Manufactured By: DPT Laboratories, LTD., San Antonio, TX 78215, 9435000. Revised: Feb 2015

Interaction with other medicinal products and other forms of interaction

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What other drugs will affect Zepose?

If Zepose rectal gel is to be combined with other psychotropic agents or other CNS depressants, careful consideration should be given to the pharmacology of the agents to be employed particularly with known compounds which may potentiate the action of Zepose, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants.

The clearance of Zepose and certain other benzodiazepines can be delayed in association with cimetidine administration. The clinical significance of this is unclear.

Valproate may potentiate the CNS-depressant effects of Zepose.

There have been no clinical studies or reports in literature to evaluate the interaction of rectally administered Zepose with other drugs. As with all drugs, the potential for interaction by a variety of mechanisms is a possibility.

Effect of Other Drugs on Zepose Metabolism: In vitro studies using human liver preparations suggest that CYP2C19 and CYP3A4 are the principal isozymes involved in the initial oxidative metabolism of Zepose. Therefore, potential interactions may occur when Zepose is given concurrently with agents that affect CYP2C19 and CYP3A4 activity. Potential inhibitors of CYP2C19 (e.g., cimetidine, quinidine, and tranylcypromine) and CYP3A4 (e.g., ketoconazole, troleandomycin, and clotrimazole) could decrease the rate of Zepose elimination, while inducers of CYP2C19 (e.g., rifampin) and CYP3A4 (e.g., carbamazepine, phenytoin, dexamethasone and phenobarbital) could increase the rate of elimination of Zepose.

Effect of Zepose on the Metabolism of Other Drugs : There are no reports as to which isozymes could be inhibited or induced by Zepose. But, based on the fact that Zepose is a substrate for CYP2C19 and CYP3A4, it is possible that Zepose may interfere with the metabolism of drugs which are substrates for CYP2C19, (e.g. omeprazole, propranolol, and imipramine) and CYP3A4 (e.g. cyclosporine, paclitaxel, terfenadine, theophylline, and warfarin) leading to a potential drug-drug interaction.