Medical Editor: John P. Cunha, DO, FACOEP
What Is Diastat Acudial?
Diastat Acudial (diazepam) Rectal Gel is a benzodiazepine used for rectal administration in the management of selected, refractory, patients with epilepsy, on stable regimens of AEDs, who require intermittent use of diazepam to control bouts of increased seizure activity.
What Are Side Effects of Diastat Acudial?
Common side effects of Diastat Acudial Rectal Gel include:
- stomach or abdominal pain
- dilated blood vessels (vasodilatation
- loss of balance or coordination
- nasal irritation
- blurred vision
- sleep problems (insomnia),
- or slurred speech.
Tell your doctor if you have serious side effects of Diastat Acudial Rectal Gel including:
- worsening seizures, or seizures that seem different from your other seizures;
- pale or discolored skin;
- confusion, hallucinations, unusual thoughts or behavior, unusual risk-taking behavior, decreased inhibitions, no fear of danger;
- hyperactivity, agitation, hostility, depression, thoughts of suicide or hurting yourself;
- feeling like you might pass out; or
- pain or burning when you urinate.
Dosage for Diastat Acudial
The recommended dose of Diastat Acudial rectal gel is 0.2-0.5 mg/kg depending on age.
What Drugs, Substances, or Supplements Interact with Diastat Acudial?
Diastat Acudial may interact with other psychotropic agents or other CNS depressants, phenothiazines, narcotics, barbiturates, MAO inhibitors, antidepressants, cimetidine, quinidine, tranylcypromine, ketoconazole, troleandomycin, clotrimazole, rifampin, carbamazepine, phenytoin, dexamethasone, phenobarbital, omeprazole, propranolol, imipramine, cyclosporine, paclitaxel, terfenadine, theophylline, and warfarin. Tell your doctor all medications and supplements you use.
Diastat Acudial During Pregnancy and Breastfeeding
Tell your doctor If you are pregnant or plan to become pregnant before using Diastat Acudial. Some anticonvulsant drugs cause birth defects. This drug passes into breast milk. Do not breastfeed for an appropriate period of time after receiving treatment with Diastat Acudial rectal gel. Withdrawal symptoms may occur if you suddenly stop taking this medication.
Our Diastat Acudial (diazepam) Rectal Gel Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Diazepam can slow or stop your breathing, especially if you have recently used an opioid medication, alcohol, or other drugs that can slow your breathing. A person caring for you should seek emergency medical attention if you have weak or shallow breathing, if you are hard to wake up, or if you stop breathing.
Call your doctor at once if the person receiving this medicine has:
- new or worsening seizures;
- unusual changes in mood or behavior;
- thoughts of suicide or hurting yourself;
- confusion, hallucinations;
- sleep problems; or
- anxiety, excitement, anger, or feeling restless.
The sedative effects of diazepam rectal may last longer in older adults. Accidental falls are common in elderly patients who take benzodiazepines. Use caution to avoid falling or accidental injury while you are using diazepam rectal.
Common side effects may include:
- drowsiness, dizziness, headache, feeling nervous;
- problems with coordination or muscle movement;
- flushing (sudden warmth, redness, or tingly feeling);
- stomach pain, diarrhea; or
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Diastat Acudial (Diazepam Rectal Gel)
Diazepam 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 diazepam rectal gel died seven to 15 weeks following treatment; neither of these deaths was deemed related to diazepam rectal gel.
The most frequent adverse event reported to be related to diazepam 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 diazepam 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 diazepam 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 diazepam rectal gel, versus 2% for the placebo group. In the diazepam 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.
Adverse Event Incidence In Controlled Clinical Trials
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 diazepam rectal gel group. Adverse events were usually mild or moderate in intensity.
The prescriber should be aware that these figures, obtained when diazepam 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 Diazepam Rectal Gel Group
|Body System||COSTART Term||DIASTAT
N = 101 %
N = 104 %
|Body As A Whole||Headache||5%||4%|
|Skin and Appendages||Rash||3%||0%|
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 diazepam 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.
Other Adverse Events Observed During All Clinical Trials
Diazepam 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 diazepam 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 diazepam.
BODY AS A WHOLE: Asthenia
CARDIOVASCULAR: Hypotension, vasodilatation
NERVOUS: Agitation, confusion, convulsion, dysarthria, emotional lability, speech disorder, thinking abnormal, vertigo
The following infrequent adverse events were not seen with diazepam rectal gel but have been reported previously with diazepam 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 diazepam; should these occur, use of diazepam rectal gel should be discontinued.
To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Abuse And Dependence
DIASTAT contains diazepam, a Schedule IV controlled substance.
DIASTAT 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, Abuse, Misuse, and Addiction).
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).
Physical Dependence After Use Of DIASTAT More Frequently Than Recommended
DIASTAT may produce physical dependence if used more frequently than recommended. 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. Although DIASTAT is indicated only for intermittent use (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION), if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction 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, Dependence and Withdrawal Reactions).
For patients using DIASTAT more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue DIASTAT (see WARNINGS, Dependence and Withdrawal Reactions).
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 reemergence or continuation of symptoms for which the benzodiazepine was being used.
Tolerance to DIASTAT may develop after use more frequently than recommended. 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 benzodiazepines may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.
There have been no clinical studies or reports in literature to evaluate the interaction of rectally administered diazepam with other drugs. As with all drugs, the potential for interaction by a variety of mechanisms is a possibility.
Effect Of Concomitant Use Of Benzodiazepines And Opioids
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 GABAA 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. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation.
Other Psychotropic Agents Or Other CNS Depressants
If diazepam 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 diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants.
The clearance of diazepam 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 diazepam.
Effect Of Other Drugs On Diazepam Metabolism
In vitro studies using human liver preparations suggest that CYP2C19 and CYP3A4 are the principal isozymes involved in the initial oxidative metabolism of diazepam. Therefore, potential interactions may occur when diazepam 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 diazepam elimination, while inducers of CYP2C19 (e.g., rifampin) and CYP3A4 (e.g., carbamazepine, phenytoin, dexamethasone, and phenobarbital) could increase the rate of elimination of diazepam.
Effect Of Diazepam On The Metabolism Of Other Drugs
There are no reports as to which isozymes could be inhibited or induced by diazepam. But, based on the fact that diazepam is a substrate for CYP2C19 and CYP3A4, it is possible that diazepam 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.
Read the entire FDA prescribing information for Diastat Acudial (Diazepam Rectal Gel)
© Diastat Acudial Patient Information is supplied by Cerner Multum, Inc. and Diastat Acudial Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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