Venlafaxine Hydrochloride

RECENT MAJOR CHANGES Warning and Precautions ( 5.18 ) 10/2021

1 INDICATIONS AND USAGE Venlafaxine Hydrochloride Extended-Release Tablets are a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for: • Major Depressive Disorder (MDD) ( 1.1 ) • Social Anxiety Disorder (SAD) ( 1.2 ) 1.1 Major Depressive Disorder Venlafaxine Hydrochloride Extended-Release Tablets are indicated for the treatment of major depressive disorder (MDD). Efficacy of venlafaxine in MDD was shown in both short-term trials and a longer-term trial in MDD [ see Clinical Studies ( 14.1 ) ]. A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed mood or the loss of interest or pleasure in nearly all activities, representing a change from previous functioning, and includes the presence of at least five of the following nine symptoms during the same two-week period: depressed mood, markedly diminished interest or pleasure in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. 1.2 Social Anxiety Disorder Venlafaxine Hydrochloride Extended-Release Tablets are indicated for the treatment of Social Anxiety Disorder (SAD), also known as Social Phobia, as defined in DSM-IV. Social Anxiety Disorder (DSM-IV) is characterized by a marked and persistent fear of 1 or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others. Exposure to the feared situation almost invariably provokes anxiety, which may approach the intensity of a panic attack. The feared situations are avoided or endured with intense anxiety or distress. The avoidance, anxious anticipation, or distress in the feared situation(s) interferes significantly with the person's normal routine, occupational or academic functioning, or social activities or relationships, or there is a marked distress about having the phobias. Lesser degrees of performance anxiety or shyness generally do not require psychopharmacological treatment. Efficacy of venlafaxine extended release in the treatment of SAD was established in short-term SAD trials [ see Clinical Studies ( 14.2 ) ].

2 DOSAGE AND ADMINISTRATION Venlafaxine Hydrochloride Extended-Release Tablets should be administered in a single dose with food either in the morning or in the evening at approximately the same time each day. Each tablet should be swallowed whole with fluid and not divided, crushed, chewed, or placed in water. Initial Treatment ( 2.1 ) Indication Starting Dose Dose Increase Maximum Dose Major Depressive Disorder 75 mg/day (in some patients, 37.5 mg/day for 4-7 days) 75 mg/day increments at intervals of 4 days or longer 225 mg/day Social Anxiety Disorder 75 mg/day No benefit at higher doses 75 mg/day Venlafaxine Hydrochloride Extended-Release Tablets should be taken as a single daily dose with food in either the morning or evening at the same time each day. ( 2 ) Discontinuation: Gradual; individualized as necessary. ( 2.4 ) 2.1 Initial Treatment Major Depressive Disorder For most patients, the recommended starting dose for Venlafaxine Hydrochloride Extended-Release Tablets is 75 mg/day, administered in a single dose. In the clinical trials establishing the efficacy of venlafaxine hydrochloride extended-release capsules in moderately depressed outpatients, the initial dose of venlafaxine was 75 mg/day. For some patients, it may be desirable to start at 37.5 mg/day for 4 to 7 days, to allow new patients to adjust to the medication before increasing to 75 mg/day. While the relationship between dose and antidepressant response for venlafaxine hydrochloride extended-release capsules has not been adequately explored, patients not responding to the initial 75 mg/day dose may benefit from dose increases to a maximum of approximately 225 mg/day. Dose increases should be in increments of up to 75 mg/day, as needed, and should be made at intervals of not less than 4 days, since steady state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4. In the clinical trials establishing efficacy, upward titration was permitted at intervals of 2 weeks or more; the average doses were about 140 to 180 mg/day [ see Clinical Studies ( 14 ) ]. It should be noted that, while the maximum recommended dose for moderately depressed outpatients is also 225 mg/day for venlafaxine hydrochloride immediate-release tablets, more severely depressed inpatients in one study of the development program for that product responded to a mean dose of 350 mg/day (range of 150 to 375 mg/day). Whether or not higher doses of Venlafaxine Hydrochloride Extended-Release Tablets are needed for more severely depressed patients is unknown; however, the experience with venlafaxine hydrochloride extended-release capsule doses higher than 225 mg/day is very limited [ see Warnings and Precautions ( 5.17 ) ]. Social Anxiety Disorder (Social Phobia) The recommended dose is 75 mg/day, administered in a single dose. There was no evidence that higher doses confer any additional benefit [s ee Warnings and Precautions ( 5.17 ) ]. 2.2 Maintenance Treatment There is no body of evidence available from controlled trials to indicate how long patients with major depressive disorder should be treated with Venlafaxine Hydrochloride Extended-Release Tablets. It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine hydrochloride extended-release capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine hydrochloride immediate-release tablets in maintaining a response in patients with recurrent major depressive disorder who had responded and continued t …

3 DOSAGE FORMS AND STRENGTHS Venlafaxine Hydrochloride Extended-Release Tablets are available as 225 mg tablets (white to off-white mottled round coated tablets imprinted in blue with "225mg" on one side). 225 mg tablets ( 3 )

4 CONTRAINDICATIONS Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with Venlafaxine Hydrochloride Extended-Release Tablets or within 7 days of stopping treatment with Venlafaxine Hydrochloride Extended-Release Tablets. Do not use Venlafaxine Hydrochloride Extended-Release Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start Venlafaxine Hydrochloride Extended-Release Tablets in a patient who is being treated with linezolid or intravenous methylene blue. ( 4.1 ) 4.1 Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with Venlafaxine Hydrochloride Extended-Release Tablets or within 7 days of stopping treatment with Venlafaxine Hydrochloride Extended-Release Tablets is contraindicated because of an increased risk of serotonin syndrome. The use of Venlafaxine Hydrochloride Extended-Release Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [ see Dosage and Administration ( 2.6 ) and Warnings and Precautions ( 5.2 ) ]. Starting Venlafaxine Hydrochloride Extended-Release Tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [ see Dosage and Administration ( 2.7 ) and Warnings and Precautions ( 5.2 ) ].

ADVERSE REACTIONS Associated With Discontinuation of Treatment Nineteen percent (537/2897) of venlafaxine patients in Phase 2 and Phase 3 depression studies discontinued treatment due to an adverse event. The more common events (≥ 1%) associated with discontinuation and considered to be drug-related (i.e., those events associated with dropout at a rate approximately twice or greater for venlafaxine compared to placebo) included: CNS Venlafaxine Placebo Somnolence 3% 1% Insomnia 3% 1% Dizziness 3% — Nervousness 2% — Dry mouth 2% — Anxiety 2% 1% Gastrointestinal Nausea 6% 1% Urogenital Abnormal ejaculation 1 3% — Other Headache 3% 1% Asthenia 2% — Sweating 2% — — Less than 1% 1. Percentages based on the number of males. Incidence in Controlled Trials Commonly Observed Adverse Events in Controlled Clinical Trials The most commonly observed adverse events associated with the use of venlafaxine hydrochloride (incidence of 5% or greater) and not seen at an equivalent incidence among placebo-treated patients (i.e., incidence for venlafaxine hydrochloride at least twice that for placebo), derived from the 1% incidence table below, were asthenia, sweating, nausea, constipation, anorexia, vomiting, somnolence, dry mouth, dizziness, nervousness, anxiety, tremor, and blurred vision as well as abnormal ejaculation/orgasm and impotence in men. Adverse Events Occurring at an Incidence of 1% or More Among Venlafaxine Hydrochloride-Treated Patients The table that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among venlafaxine hydrochloride-treated patients who participated in short-term (4 to 8 week) placebo-controlled trials in which patients were administered doses in a range of 75 to 375 mg/day. This table shows the percentage of patients in each group who had at least one episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based Dictionary terminology. 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 where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied. TABLE 2: Treatment-Emergent Adverse Experience Incidence in 4 to 8 Week Placebo-Controlled Clinical Trials 1 — Incidence less than 1%. 1. Events reported by at least 1% of patients treated with venlafaxine hydrochloride are included, and are rounded to the nearest %. Events for which the venlafaxine hydrochloride incidence was equal to or less than placebo are not listed in the table, but included the following: abdominal pain, pain, back pain, flu syndrome, fever, palpitation, increased appetite, myalgia, arthralgia, amnesia, hypesthesia, rhinitis, pharyngitis, sinusitis, cough increased, and dysmenorrhea 3 . 2. Incidence based on number of male patients. 3. Incidence based on number of female patients. Body System Preferred Term Venlafaxine Hydrochloride (n = 1033) Placebo (n = 609) Body as a Whole Headache 25% 24% Asthenia 12% 6% Infection 6% 5% Chills 3% — Chest pain 2% 1% Trauma 2% 1% Cardiovascular Vasodilatation 4% 3% Increased blood pressure/hypertension 2% — Tachycardia 2% — Postural hypotension 1% — Dermatological Sweating 12% 3% Rash 3% 2% Pruritus 1% — Gastrointestinal Nausea 37% 11% Constipation 15% 7% Anorexia 11% 2% Diarrhea 8% 7% Vomiting 6% 2% Dyspepsia 5% 4% Flatulence 3% 2% Metabolic Weight loss 1% — Nervous System Somnolence 23% 9% Dry mouth 22% 11% Dizziness 19% 7% Insomnia 18% 10% Nervousness 13% 6% Anxi …

7 DRUG INTERACTIONS MAOIs: concomitant use contraindicated. ( 4 ) Avoid MAOIs 14 days before starting venlafaxine and 7 days after stopping venlafaxine. ( 5.2 ) Cimetidine: Caution in patients with pre-existing hypertension, in elderly patients and patients with hepatic dysfunction. ( 7.2 ) Haloperidol: Increase in haloperidol AUC and C max . ( 7.4 ) Ketoconazole: Increase in venlafaxine and O-desmethylvenlafaxine AUC and C max . Caution when using venlafaxine with substances that inhibit both CYP2D6 and CYP3A4. ( 7.7 ) Metoprolol: Possibly reduced blood pressure lowering effect despite increased metoprolol plasma levels. Caution should be exercised with co-administration of venlafaxine and metoprolol. ( 7.8 ) CNS-active drugs: Caution when using venlafaxine with such drugs. ( 7.10 ) Serotonergic drugs (e.g., triptans, SSRIs, other SNRIs, linezolid, lithium, tramadol, or St. John's Wort): Potential for serotonin syndrome. Careful patient observation advised. ( 7.10 ) Tryptophan supplements: Concomitant use not recommended. ( 7.10 ) 7.1 Alcohol A single dose of ethanol (0.5 g/kg) had no effect on the pharmacokinetics of venlafaxine or O‐desmethylvenlafaxine (ODV) when venlafaxine was administered at 150 mg/day in 15 healthy male subjects. Additionally, administration of venlafaxine in a stable regimen did not exaggerate the psychomotor and psychometric effects induced by ethanol in these same subjects when they were not receiving venlafaxine. 7.2 Cimetidine Concomitant administration of cimetidine and venlafaxine in a steady-state study for both drugs resulted in inhibition of first-pass metabolism of venlafaxine in 18 healthy subjects. The oral clearance of venlafaxine was reduced by about 43%, and the exposure (AUC) and maximum concentration (C max ) of the drug were increased by about 60%. However, coadministration of cimetidine had no apparent effect on the pharmacokinetics of ODV, which is present in much greater quantity in the circulation than venlafaxine. The overall pharmacological activity of venlafaxine plus ODV is expected to increase only slightly, and no dosage adjustment should be necessary for most normal adults. However, for patients with pre-existing hypertension, and for elderly patients or patients with hepatic dysfunction, the interaction associated with the concomitant use of venlafaxine and cimetidine is not known and potentially could be more pronounced. Therefore, caution is advised with such patients. 7.3 Diazepam Under steady-state conditions for venlafaxine administered at 150 mg/day, a single 10 mg dose of diazepam did not appear to affect the pharmacokinetics of either venlafaxine or ODV in 18 healthy male subjects. Venlafaxine also did not have any effect on the pharmacokinetics of diazepam or its active metabolite, desmethyldiazepam, or affect the psychomotor and psychometric effects induced by diazepam. 7.4 Haloperidol Venlafaxine administered under steady-state conditions at 150 mg/day in 24 healthy subjects decreased total oral-dose clearance (Cl/F) of a single 2 mg dose of haloperidol by 42%, which resulted in a 70% increase in haloperidol AUC. In addition, the haloperidol C max increased 88% when coadministered with venlafaxine, but the haloperidol elimination half-life (t 1/2 ) was unchanged. The mechanism explaining this finding is unknown. 7.5 Lithium The steady-state pharmacokinetics of venlafaxine administered at 150 mg/day were not affected when a single 600 mg oral dose of lithium was administered to 12 healthy male subjects. ODV also was unaffected. Venlafaxine had no effect on the pharmacokinetics of lithium (see also CNS-Active Drugs, below). 7.6 Drugs Highly Bound to Plasma Proteins Venlafaxine is not highly bound to plasma proteins; therefore, administration of Venlafaxine Hydrochloride Extended-Release Tablets to a patient taking another drug that is highly protein bound should not cause increased free concentrations of the other drug. 7.7 Drugs that Inhibit Cytochrome P450 Isoe …

8 USE IN SPECIFIC POPULATIONS Pregnancy: Use during pregnancy only if clearly needed. Neonates exposed to venlafaxine in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Benefits and risk of venlafaxine use in the third trimester should be carefully considered. ( 2.3 ; 8.1 ) Nursing: Potential for serious adverse reactions in the infant. Discontinue nursing or drug, considering the importance of the drug to the mother. ( 8.3 ) Pediatric use: Not approved for use in pediatric patients. When considering use in a child or adolescent, balance potential risks with clinical need. ( 8.4 ) Hepatic impairment: Reduction of total daily dose by 50% recommended in patients with mild to moderate impairment. In patients with cirrhosis, further reduction may be necessary and dosing individualization may be desirable. ( 2.3 ; 8.6 ) Renal impairment: Reduction of daily dose by 25-50% recommended. Dosing individualization may be necessary. ( 2.3 ; 8.7 ) Hemodialysis: Reduction of daily dose by 50%. ( 2.3 ; 8.7 ) 8.1 Pregnancy Teratogenic Effects Pregnancy Category C Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m 2 basis. However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known. These effects occurred at 2.5 times (mg/m 2 ) the maximum human daily dose. The no effect dose for rat pup mortality was 0.25 times the human dose on a mg/m 2 basis. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Non-Teratogenic Effects Neonates exposed to venlafaxine hydrochloride extended-release capsules, other SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors) late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [ see Warnings and Precautions ( 5.2 ) ]. When treating a pregnant woman with Venlafaxine Hydrochloride Extended-Release Tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment [ see Dosage and Administration ( 2 ) ]. 8.2 Labor and Delivery The effect of venlafaxine on labor and delivery in humans is unknown. 8.3 Nursing Mothers Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Venlafaxine Hydrochloride Extended-Release Tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness in the pediatric population have not been established [ see BOXED WARNING and Warnings and Precautions ( 5.1 ) ]. Two placebo-controlled trials in 766 pediatric patients with MDD and two placebo-controlled trials in another disorder in 793 pediatric patients have been conducted with venlafaxine hydrochloride extended-release capsules, and the data were not suffi …

11 DESCRIPTION Venlafaxine Hydrochloride Extended-Release Tablets are extended-release tablets for oral administration that contain venlafaxine hydrochloride, a structurally novel antidepressant. Venlafaxine hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SNRI). It is designated (R/S)-1-[2-(dimethylamino)-1-(4‐methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[α- [(dimethylamino) methyl]-p-methoxybenzyl] cyclohexanol hydrochloride and has the empirical formula of C 17 H 27 NO 2 HCl. Its molecular weight is 313.87. The structural formula is shown below. Venlafaxine hydrochloride is a white to off-white crystalline solid with a solubility of 572 mg/mL in water (adjusted to ionic strength of 0.2 M with sodium chloride). Its octanol:water (0.2 M sodium chloride) partition coefficient is 0.43. Venlafaxine Hydrochloride Extended-Release Tablets are formulated as extended-release tablet for once-a-day oral administration. Venlafaxine Hydrochloride Extended-Release Tablets use matrix core and extended-release coating to deliver venlafaxine hydrochloride at a controlled rate over approximately 24 hours. The unitary tablet core is composed of the drug and excipients (including the matrix forming components). In an aqueous environment, such as the gastrointestinal tract, water permeates slowly through the coating into the tablet core, causing the hydrophilic matrix polymer to expand and to form a gel layer on the surface of the tablet. This gel acts as a barrier to the drug release, the drug is dissolved and is released by slow diffusion and erosion of the gel. The extended-release coating layer controls the rate at which water permeates into the tablet core, which in turn controls also the rate of drug delivery. The controlled rate of drug delivery into the gastrointestinal lumen is thus independent of pH or gastrointestinal motility. Tablets contain venlafaxine hydrochloride equivalent to 225 mg venlafaxine. Inactive ingredients consist of dibasic calcium phosphate dihydrate, hypromellose, methacrylic acid copolymer, colloidal silicon dioxide, magnesium stearate, polyvinyl acetate dispersion, talc, polyethylene glycol, polyvinyl alcohol, povidone, triethyl citrate, macrogol stearyl ether, sodium lauryl sulfate, carnauba wax, titanium dioxide, propylene glycol and FD&C blue #1. velafaxine-structure

10 OVERDOSAGE 10.1 Human Experience Among the patients included in the premarketing evaluation of venlafaxine hydrochloride extended-release capsules, there were 2 reports of acute overdosage with venlafaxine hydrochloride extended-release capsules in major depressive disorder trials, either alone or in combination with other drugs. One patient took a combination of 6 g of venlafaxine hydrochloride extended-release capsules and 2.5 mg of lorazepam. This patient was hospitalized, treated symptomatically, and recovered without any untoward effects. The other patient took 2.85 g of venlafaxine hydrochloride extended-release capsules. This patient reported paresthesia of all four limbs but recovered without sequelae. There were no reports of acute overdose with venlafaxine hydrochloride extended-release capsules in Social Anxiety Disorder trials. Among the patients included in the premarketing evaluation with venlafaxine hydrochloride immediate-release tablets, there were 14 reports of acute overdose with venlafaxine, either alone or in combination with other drugs and/or alcohol. The majority of the reports involved ingestion in which the total dose of venlafaxine taken was estimated to be no more than several-fold higher than the usual therapeutic dose. The 3 patients who took the highest doses were estimated to have ingested approximately 6.75 g, 2.75 g, and 2.5 g. The resultant peak plasma levels of venlafaxine for the latter 2 patients were 6.24 and 2.35 μg/mL, respectively, and the peak plasma levels of O‐desmethylvenlafaxine were 3.37 and 1.30 μg/mL, respectively. Plasma venlafaxine levels were not obtained for the patient who ingested 6.75 g of venlafaxine. All 14 patients recovered without sequelae. Most patients reported no symptoms. Among the remaining patients, somnolence was the most commonly reported symptom. The patient who ingested 2.75 g of venlafaxine was observed to have 2 generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Mild sinus tachycardia was reported in 2 of the other patients. In postmarketing experience, overdose with venlafaxine has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported reactions in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported. Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher pre-existing burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage as opposed to some characteristic(s) of venlafaxine-treated patients is not clear. Prescriptions for Venlafaxine Hydrochloride Extended-Release Tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. 10.2 Management of Overdosage Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal should …

HOW SUPPLIED Venlafaxine Tablets USP are available containing 25 mg, 37.5 mg, 50 mg, 75 mg or 100 mg of venlafaxine. The 25 mg are peach colored, round biconvex, uncoated tablets debossed with R and DY separated with a breakline on one side and “545” on the other side. They are supplied in bottles of 30, 60, 90, 100, 500 and unit dose package of 10 (1 x 10). Bottles of 30 NDC 55111-545-30 Bottles of 60 NDC 55111-545-60 Bottles of 90 NDC 55111-545-90 Bottles of 100 NDC 55111-545-01 Bottles of 500 NDC 55111-545-05 Unit dose package of 10 (1 × 10) NDC 55111-545-79 The 37.5 mg are peach colored, round biconvex, uncoated tablets debossed with R and DY separated with a breakline on one side and “546” on the other side. They are supplied in bottles of 30, 60, 90, 100, 500 and unit dose package of 10 (1 x 10). Bottles of 30 NDC 55111-546-30 Bottles of 60 NDC 55111-546-60 Bottles of 90 NDC 55111-546-90 Bottles of 100 NDC 55111-546-01 Bottles of 500 NDC 55111-546-05 Unit dose package of 10 (1 × 10) NDC 55111-546-79 The 50 mg are peach colored, round biconvex, uncoated tablets debossed with R and DY separated with a breakline on one side and “547” on the other side. They are supplied in bottles of 30, 60, 90, 100, 500 and unit dose package of 10 (1 x 10). Bottles of 30 NDC 55111-547-30 Bottles of 60 NDC 55111-547-60 Bottles of 90 NDC 55111-547-90 Bottles of 100 NDC 55111-547-01 Bottles of 500 NDC 55111-547-05 Unit dose package of 10 (1 × 10) NDC 55111-547-79 The 75 mg are peach colored, round biconvex, uncoated tablets debossed with R and DY separated with a breakline on one side and “548” on the other side. They are supplied in bottles of 30, 60, 90, 100, 500 and unit dose package of 10 (1 x 10). Bottles of 30 NDC 55111-548-30 Bottles of 60 NDC 55111-548-60 Bottles of 90 NDC 55111-548-90 Bottles of 100 NDC 55111-548-01 Bottles of 500 NDC 55111-548-05 Unit dose package of 10 (1 × 10) NDC 55111-548-79 The 100 mg are peach colored, round, flat bevel edged, uncoated tablets debossed with R and DY separated with a breakline on one side and “549” on the other side. They are supplied in bottles of 30, 60, 90, 100, 500 and unit dose package of 10 (1 x 10). Bottles of 30 NDC 55111-549-30 Bottles of 60 NDC 55111-549-60 Bottles of 90 NDC 55111-549-90 Bottles of 100 NDC 55111-549-01 Bottles of 500 NDC 55111-549-05 Unit dose package of 10 (1 × 10) NDC 55111-549-79 Store at 20° to 25°C (68° to 77°F); in a dry place; excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a well-closed container as defined in the USP. The unit of use package is intended to be dispensed as a unit.