Estazolam, a triazolobenzodiazepine derivative, is an oral hypnotic agent. Estazolam occurs as a fine, white, odorless powder that is soluble in alcohol and practically insoluble in water. The chemical name for estazolam is 8-chloro-6-phenyl-4H-s-triazolo[4,3-α][1,4]benzodiazepine. The structural formula is represented as follows:

Each tablet, for oral administration, contains either 1 mg or 2 mg of estazolam, USP. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, corn starch, lactose monohydrate and magnesium stearate. In addition, the 2 mg tablet contains yellow iron oxide and red iron oxide.

Pharmacokinetics

Absorption

Estazolam tablets have been found to be equivalent in absorption to an orally administered solution of estazolam. In healthy subjects who received up to three times the recommended dose of estazolam, peak estazolam plasma concentrations occurred within two hours after dosing (range 0.5 to 6.0 hours) and were proportional to the administered dose, suggesting linear pharmacokinetics over the dosage range tested.

Distribution

Independent of concentration, estazolam in plasma is 93% protein bound.

Metabolism

Estazolam is extensively metabolized. Only two metabolites (1-oxo-estazolam & 4-hydroxy-estazolam) were detected in human plasma up to 18 hrs.

The pharmacologic activity of estazolam is primarily from the parent drug. The elimination of the parent drug takes place via hepatic metabolism of estazolam to hydroxylated and other metabolites that are eliminated largely in the urine both free and conjugated. In humans, greater than 70% of a single dose of estazolam was recovered in the urine as metabolites. Less than 5% of a 2 mg dose of estazolam was excreted unchanged in the urine, with only 4% of the dose appearing in the feces. The principal urinary excretion product is an unidentified metabolite, presumed to be a metabolic product of 4-hydroxyestazolam, accounting for at least 27% of the administered dose. 4-hydroxy-estazolam is the major metabolite in plasma, with concentrations approaching 12% of those of the parent eight hours after administration. Urinary 4-hydroxy-estazolam and 1-oxo-estazolam account for 11.9% and 4.4% of the dose respectively. In vitro studies with human liver microsomes indicate that the biotransformation of estazolam to the major circulating metabolite 4-hydroxy-estazolam is mediated by cytochrome P450 3A (CYP3A). While 4-hydroxy-estazolam and the lesser metabolite, 1-oxo-estazolam, have some pharmacologic activity, their low potencies and low concentrations preclude any significant contribution to the hypnotic effect of estazolam.

Elimination

The range of estimates for the mean elimination half-life of estazolam varied from 10 to 24 hours. Radiolabel mass balance studies indicate that the main route of excretion is via the kidneys. After 5 days, 87% of the administered radioactivity was excreted in human urine. Less than 4% of the dose was excreted unchanged. Eleven metabolites were found in urine. Four metabolites were identified as 1-oxo-estazolam, 4'-hydroxy-estazolam, 4-hydroxy-estazolam, and benzophenone, as free metabolites and glucuronides. The predominant metabolite in urine (17% of the administered dose) has not been identified, but is likely to be a metabolite of 4-hydroxy-estazolam.

Special Populations

In a small study (N = 8) using various doses in older subjects (59 to 68 years), peak estazolam concentrations were found to be similar to those observed in younger subjects with a mean elimination half-life of 18.4 hours (range 13.5 to 34.6 hours). The influence of hepatic or renal impairment on the pharmacokinetics of estazolam has not been studied.

Pediatrics

The pharmacokinetics of estazolam have not been studied in pediatric patients.

Race

The influence of race on the pharmacokinetics of estazolam has not been studied.

Gender

The gender-effect on the pharmacokinetics of estazolam has not been investigated.

Cigarette smoking

The clearance of benzodiazepines is accelerated in smokers compared to nonsmokers, and there is evidence that this occurs with estazolam. This decrease in half-life, presumably due to enzyme induction by smoking, is consistent with other drugs with similar hepatic clearance characteristics. In all subjects and at all doses, the mean elimination half-life appeared to be independent of the dose.

Drug-drug interaction

The metabolism of estazolam to the major circulating metabolite 4-hydroxy-estazolam is catalyzed by CYP3A. While no in vivo drug-drug interaction studies were conducted between estazolam and inhibitors/inducers of CYP3A, compounds that are potent CYP3A inhibitors (such as ketoconazole, itraconazole, nefazodone, fluvoxamine, and erythromycin) would be expected to increase plasma estazolam concentrations and CYP3A inducers (such as carbamazepine, phenytoin, rifampin and barbiturates) would be expected to decrease estazolam concentrations.

Drug interaction with fluoxetine

A multiple-dose study was conducted to assess the effect of fluoxetine 20 mg BID on the pharmacokinetics of estazolam 2 mg QHS after seven days. The pharmacokinetics of estazolam (Cmax and AUC) were not affected during multiple-dose fluoxetine, suggesting no clinically significant pharmacokinetic interaction.

The ability of estazolam to induce or inhibit human enzyme systems

The results from in vitro human liver microsomal studies suggest that at therapeutic concentrations, estazolam has no significant inhibitory effect on the major human cytochrome P450 enzyme activities (i.e., CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A). The ability of estazolam to induce human hepatic enzyme systems has not been determined.

Pharmacodynamics

Postulated relationship between elimination rate of benzodiazepine hypnotics and their profile of common untoward effects: The type and duration of hypnotic effects and the profile of unwanted effects during administration of benzodiazepine drugs may be influenced by the biologic half-life of administered drug and any active metabolites formed. If half-lives are long, drug or metabolites may accumulate during periods of nightly administration and may be associated with impairments of cognitive and/or motor performance during waking hours; the possibility of interaction with other psychoactive drugs or alcohol will be increased. In contrast, if half-lives are short, drug and metabolites will be cleared before the next dose is ingested, and carry-over effects related to excessive sedation or CNS depression should be minimal or absent. However, during nightly use for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop. If the drug has a short elimination half-life, it is possible that a relative deficiency of the drug or its active metabolites (i.e., in relationship to the receptor site) may occur at some point in the interval between each night's use. This sequence of events may account for two clinical findings reported to occur after several weeks of max nightly use of rapidly eliminated benzodiazepine hypnotics, namely, increased wakefulness during the last third of the night and increased daytime anxiety in selected patients.

Controlled Trials Supporting Efficacy

In three 7 night, double-blind, parallel-group trials comparing estazolam 1 mg and/or 2 mg with placebo in adult outpatients with chronic insomnia, estazolam 2 mg was consistently superior to placebo in subjective measures of sleep induction (latency) and sleep maintenance (duration, number of awakenings, depth and quality of sleep); estazolam 1 mg was similarly superior to placebo on all measures of sleep maintenance, however, it significantly improved sleep induction in only one of two studies. In a similarly designed trial comparing estazolam 0.5 mg and 1 mg with placebo in geriatric outpatients with chronic insomnia, only the 1 mg estazolam dose was consistently superior to placebo in sleep induction (latency) and in only one measure of sleep maintenance (i.e., duration of sleep).

In a single-night, double-blind, parallel-group trial comparing estazolam 2 mg and placebo in patients admitted for elective surgery and requiring sleep medications, estazolam was superior to placebo in subjective measures of sleep induction and maintenance.

In a 12 week, double-blind, parallel-group trial including a comparison of estazolam 2 mg and placebo in adult outpatients with chronic insomnia, estazolam was superior to placebo in subjective measures of sleep induction (latency) and maintenance (duration, number of awakenings, total wake time during sleep) at week 2, but produced consistent improvement over 12 weeks only for sleep duration and total wake time during sleep. Following withdrawal at week 12, rebound insomnia was seen at the first withdrawal week, but there was no difference between drug and placebo by the second withdrawal week in all parameters except latency, for which normalization did not occur until the fourth withdrawal week.

Adult outpatients with chronic insomnia were evaluated in a sleep laboratory trial comparing four doses of estazolam (0.25, 0.5, 1 and 2 mg) and placebo, each administered for 2 nights in a crossover design. The higher estazolam doses were superior to placebo in most EEG measures of sleep induction and maintenance, especially at the 2 mg dose, but only for sleep duration in subjective measures of sleep.

Estazolam is indicated for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Both outpatient studies and a sleep laboratory study have shown that estazolam administered at bedtime improved sleep induction and sleep maintenance (see CLINICAL PHARMACOLOGY).

Because insomnia is often transient and intermittent, the prolonged administration of estazolam is generally neither necessary nor recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered.

There is evidence to support the ability of estazolam to enhance the duration and quality of sleep for intervals up to 12 weeks (see CLINICAL PHARMACOLOGY).

Estazolam is contraindicated with ketoconazole and itraconazole, since these medications significantly impair oxidative metabolism mediated by CYP3A (see WARNINGS and PRECAUTIONS, Drug Interactions).

Risks from Concomitant Use with Opioids

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

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe estazolam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of estazolam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking estazolam, prescribe a lower initial dose of the opioid and titrate based upon clinical response.

Advise both patients and caregivers about the risks of respiratory depression and sedation when estazolam is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see PRECAUTIONS, Drug Interactions).

Abuse, Misuse, and Addiction

The use of benzodiazepines, including estazolam, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. 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 (see DRUG ABUSE AND DEPENDENCE, Abuse).

Before prescribing estazolam and throughout treatment, assess each patient's risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of estazolam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of estazolam along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.

Dependence and Withdrawal Reactions

To reduce the risk of withdrawal reactions, use a gradual taper to discontinue estazolam or reduce the dosage (a patient-specific plan should be used to taper the dose) (see DOSAGE AND ADMINISTRATION, Discontinuation or Dosage Reduction of Estazolam).

Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use.

Acute Withdrawal Reactions

The continued use of benzodiazepines, including estazolam, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of estazolam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see DRUG ABUSE AND DEPENDENCE, Dependence).

Protracted Withdrawal Syndrome

In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE, Dependence).

Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative-hypnotic drugs. Because some of the important adverse effects of sedative-hypnotics appear to be dose-related (see PRECAUTIONS and DOSAGE AND ADMINISTRATION), it is important to use the smallest possible effective dose, especially in the elderly.

Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported. These events can occur in sedative hypnotic-naïve as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep driving may occur with sedative-hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with sedative-hypnotics appears to increase the risk of such behaviors, as does the use of sedative-hypnotics at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of sedative-hypnotics should be strongly considered for patients who report a "sleep-driving" episode.

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.

Because sedative-hypnotics can cause drowsiness and a decreased level of consciousness, patients, particularly the elderly, are at higher risk of falls.

Severe Anaphylactic and Anaphylactoid Reactions

Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including estazolam. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with estazolam should not be rechallenged with the drug.

Estazolam, like other benzodiazepines, has CNS depressant effects. For this reason, patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle, after ingesting the drug, including potential impairment of the performance of such activities that may occur the day following ingestion of estazolam. Patients should also be cautioned about possible combined effects with alcohol and other CNS depressant drugs.

As with all benzodiazepines, amnesia, paradoxical reactions (e.g., excitement, agitation, etc.), and other adverse behavioral effects may occur unpredictably.

Estazolam Interaction with Drugs That Inhibit Metabolism via Cytochrome P450 3A (CYP3A)

The metabolism of estazolam to the major circulating metabolite 4-hydroxy-estazolam and the metabolism of other triazolobenzodiazepines is catalyzed by CYP3A. Consequently, estazolam should be avoided in patients receiving ketoconazole and itraconazole, which are very potent inhibitors of CYP3A (see CONTRAINDICATIONS). With drugs inhibiting CYP3A to a lesser, but still significant degree, estazolam should be used only with caution and consideration of appropriate dosage reduction. The following are examples of drugs known to inhibit the metabolism of other related benzodiazepines, presumably through inhibition of CYP3A: nefazodone, fluvoxamine, cimetidine, diltiazem, isoniazide, and some macrolide antibiotics.

While no in vivo drug-drug interaction studies were conducted between estazolam and inducers of CYP3A, compounds that are potent CYP3A inducers (such as carbamazepine, phenytoin, rifampin, and barbiturates) would be expected to decrease estazolam concentrations.

Neonatal Sedation and Withdrawal Syndrome

Use of estazolam late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate (seePRECAUTIONS, Pregnancy) . Monitor neonates exposed to estazolam during pregnancy or labor for signs of sedation and monitor neonates exposed to estazolam during pregnancy for signs of withdrawal; manage these neonates accordingly.

Commonly Observed

The most commonly observed adverse events associated with the use of estazolam, not seen at an equivalent incidence among placebo-treated patients were somnolence, hypokinesia, dizziness, and abnormal coordination.

Associated with Discontinuation of Treatment

Approximately 3% of 1277 patients who received estazolam in U.S. premarketing clinical trials discontinued treatment because of an adverse clinical event. The only event commonly associated with discontinuation, accounting for 1.3% of the total, was somnolence.

Incidence in Controlled Clinical Trials

The table below enumerates adverse events that occurred at an incidence of 1% or greater among patients with insomnia who received estazolam in 7-night, placebo-controlled trials. Events reported by investigators were classified into standard dictionary (COSTART) terms to establish event frequencies. Event frequencies reported were not corrected for the occurrence of these events at baseline. The frequencies were obtained from data pooled across six studies: estazolam, N = 685; placebo, N = 433. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice in which patient characteristics and other factors differ from those that prevailed in these six clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigators involving related drug products and uses, since each group of drug trials was conducted under a different set of conditions. However, the cited figures provide the physician with a basis of estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the population studied.

INCIDENCE OF ADVERSE EXPERIENCES IN PLACEBO-CONTROLLED CLINICAL TRIALS (Percentage of Patients Reporting)

*Events reported by at least 1% of estazolam patients.

Other Adverse Events

During clinical trials, some of which were not placebo-controlled, estazolam was administered to approximately 1300 patients. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals experiencing adverse events, similar types of untoward events must be grouped into a smaller number of standardized event categories. In the tabulations that follow, a standard COSTART dictionary terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the 1277 individuals exposed to estazolam who experienced an event of the type cited on at least one occasion while receiving estazolam. All reported events are included except those already listed in the previous table, those COSTART terms too general to be informative, and those events where a drug cause was remote. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in less than 1/1000 patients. It is important to emphasize that, although the events reported did occur during treatment with estazolam, they were not necessarily caused by it.

Body as a Whole - Infrequent: allergic reaction, chills, fever, neck pain, upper extremity pain; Rare: edema, jaw pain, swollen breast.

Cardiovascular System - Infrequent: flushing, palpitation; Rare: arrhythmia, syncope.

Digestive System - Frequent: constipation, dry mouth; Infrequent: decreased appetite, flatulence, gastritis, increased appetite, vomiting; Rare: enterocolitis, melena, ulceration of the mouth.

Endocrine System - Rare: thyroid nodule.

Hematologic and Lymphatic System - Rare: leukopenia, purpura, swollen lymph nodes.

Metabolic/Nutritional Disorders - Infrequent: thirst; Rare: increased SGOT, weight gain, weight loss.

Musculoskeletal System - Infrequent: arthritis, muscle spasm, myalgia; Rare: arthralgia.

Nervous System - Frequent: anxiety; Infrequent: agitation, amnesia, apathy, emotional lability, euphoria, hostility, paresthesia, seizure, sleep disorder, stupor, twitch; Rare: ataxia, circumoral paresthesia, decreased libido, decreased reflexes, hallucinations, neuritis, nystagmus, tremor.

Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during estazolam therapy or withdrawal and are of no known clinical significance.

Respiratory System - Infrequent: asthma, cough, dyspnea, rhinitis, sinusitis; Rare: epistaxis, hyperventilation, laryngitis.

Skin and Appendages - Infrequent: rash, sweating, urticaria; Rare: acne, dry skin.

Special Senses - Infrequent: abnormal vision, ear pain, eye irritation, eye pain, eye swelling, perverse taste, photophobia, tinnitus; Rare: decreased hearing, diplopia, scotomata.

Urogenital System - Infrequent: frequent urination, menstrual cramps, urinary hesitancy, urinary urgency, vaginal discharge/itching; Rare: hematuria, nocturia, oliguria, penile discharge, urinary incontinence.

Postintroduction Reports - Voluntary reports of non-U.S. postmarketing experience with estazolam have included rare occurrences of photosensitivity, Stevens-Johnson syndrome, and agranulocytosis.

Because of the uncontrolled nature of these spontaneous reports, a causal relationship to estazolam treatment has not been determined.

Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal (see WARNINGS, Dependence and Withdrawal Reactions). Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage.

In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information.

Consider contacting a poison center (1-800-222-1222), poisoncontrol.org, or a medical toxicologist for additional overdosage management recommendations.

The recommended initial dose for adults is 1 mg at bedtime; however, some patients may need a 2 mg dose. In healthy elderly patients, 1 mg is also the appropriate starting dose, but increases should be initiated with particular care. In small or debilitated older patients, a starting dose of 0.5 mg, while only marginally effective in the overall elderly population, should be considered.

Discontinuation or Dosage Reduction of Estazolam

To reduce the risk of withdrawal reactions, use a gradual taper to discontinue estazolam 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, Dependence and Withdrawal Reactions and DRUG ABUSE AND DEPENDENCE, Dependence).

Estazolam Tablets, USP 1 mg are available as white, square, flat-faced, beveled edge, scored tablets debossed “N” above the bisect and “480” below the bisect on one side and bisected on the other side packaged in bottles of 100 (NDC 70954-480-10).

Estazolam Tablets, USP 2 mg are available as salmon colored, square, flat-faced, beveled edge, scored tablets debossed “N” above the bisect and “481” below the bisect on one side and bisected on the other side packaged in bottles of 100 (NDC 70954-481-10).

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

All trademarks are the property of their respective owners.

Manufactured by:

Novitium Pharma LLC

70 Lake Drive, East Windsor

New Jersey 08520.

Issued: 11/2022

LB4282-03

Estazolam Tablets, USP 1 mg - NDC 70954-480-10

Estazolam Tablets, USP 2 mg - NDC 70954-481-10