Paliperidone

Warnings and Precautions ( 5.3 , 5.5 , 5.11 , 5.12 ) 02/2021 Warnings and Precautions, Thrombotic Thrombocytopenic Purpura ( 5.16 ) Removed 02/2021 Warnings and Precautions, Antiemetic Effect (5.18) Removed 02/2021 Warnings and Precautions, Concomitant Illness (5.19) Removed 02/2021

1 INDICATIONS AND USAGE Paliperidone extended-release tablets are an atypical antipsychotic agent indicated for Treatment of schizophrenia (1.1) Adults: Efficacy was established in three 6-week trials and one maintenance trial. (14.1) Adolescents (ages 12 to 17): Efficacy was established in one 6-week trial. (14.1) Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants. (1.2) Efficacy was established in two 6-week trials in adult patients. (14.2) 1.1 Schizophrenia Paliperidone extended-release tablets are indicated for the treatment of schizophrenia [see Clinical Studies (14.1) ]. The efficacy of paliperidone extended-release tablets in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents, as well as one maintenance trial in adults. 1.2 Schizoaffective Disorder Paliperidone extended-release tablets are indicated for the treatment of schizoaffective disorder as monotherapy and an adjunct to mood stabilizers and/or antidepressant therapy [see Clinical Studies (14.2) ] . The efficacy of paliperidone in schizoaffective disorder was established in two 6-week trials in adults.

1.1 Schizophrenia Paliperidone extended-release tablets are indicated for the treatment of schizophrenia [see Clinical Studies (14.1) ]. The efficacy of paliperidone extended-release tablets in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents, as well as one maintenance trial in adults.

1.2 Schizoaffective Disorder Paliperidone extended-release tablets are indicated for the treatment of schizoaffective disorder as monotherapy and an adjunct to mood stabilizers and/or antidepressant therapy [see Clinical Studies (14.2) ] . The efficacy of paliperidone in schizoaffective disorder was established in two 6-week trials in adults.

2 DOSAGE AND ADMINISTRATION Initial Dose Recommended Dose Maximum Dose Schizophrenia - adults (2.1) 6 mg/day 3 to 12 mg/day 12 mg/day Schizophrenia-adolescents (2.1) Weight < 51 kg 3 mg/day 3 to 6 mg/day 6 mg/day Weight ≥ 51 kg 3 mg/day 3 to 12 mg/day 12 mg/day Schizoaffective disorder - adults (2.2) 6 mg/day 3 to 12 mg/day 12 mg/day Tablet should be swallowed whole and should not be chewed, divided, or crushed. (2.3) 2.1 Schizophrenia Adults The recommended dose of paliperidone extended-release tablets for the treatment of schizophrenia in adults is 6 mg administered once daily. Initial dose titration is not required. Although it has not been systematically established that doses above 6 mg have additional benefit, there was a general trend for greater effects with higher doses. This must be weighed against the dose-related increase in adverse reactions. Thus, some patients may benefit from higher doses, up to 12 mg/day, and for some patients, a lower dose of 3 mg/day may be sufficient. Dose increases above 6 mg/day should be made only after clinical reassessment and generally should occur at intervals of more than 5 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day. In a longer-term study, paliperidone extended-release tablets have been shown to be effective in delaying time to relapse in patients with schizophrenia who were stabilized on paliperidone extended-release tablets for 6 weeks [see Clinical Studies (14) ]. Paliperidone extended-release tablets should be prescribed at the lowest effective dose for maintaining clinical stability and the physician should periodically reevaluate the long-term usefulness of the drug in individual patients. Adolescents (12 to 17 years of age) The recommended starting dose of paliperidone extended-release tablets for the treatment of schizophrenia in adolescents 12 to 17 years of age is 3 mg administered once daily. Initial dose titration is not required. Dose increases, if considered necessary, should be made only after clinical reassessment and should occur at increments of 3 mg/day at intervals of more than 5 days. Prescribers should be mindful that, in the adolescent schizophrenia study, there was no clear enhancement to efficacy at the higher doses, i.e., 6 mg for subjects weighing less than 51 kg and 12 mg for subjects weighing 51 kg or greater, while adverse events were dose-related. 2.2 Schizoaffective Disorder The recommended dose of paliperidone extended-release tablets for the treatment of schizoaffective disorder in adults is 6 mg administered once daily. Initial dose titration is not required. Some patients may benefit from lower or higher doses within the recommended dose range of 3 to 12 mg once daily. A general trend for greater effects was seen with higher doses. This trend must be weighed against dose-related increase in adverse reactions. Dosage adjustment, if indicated, should occur only after clinical reassessment. Dose increases, if indicated, generally should occur at intervals of more than 4 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day. 2.3 Administration Instructions Paliperidone extended-release tablets can be taken with or without food. Paliperidone extended-release tablets must be swallowed whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet. 2.4 Use with Risperidone Concomitant use of paliperidone extended-release tablets with risperidone has not been studied. Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone …

3 DOSAGE FORMS AND STRENGTHS Paliperidone extended-release tablets are available in the following strengths and colors: 1.5 mg tablets are brown colored, round, biconvex, film-coated tablet with release portal on one side and ‘PL1’ imprinting with black ink on either side of the tablets. 3 mg tablets are white to off-white colored, round, biconvex, film-coated tablet with release portal on one side and ‘PL2’ imprinting with black ink on either side of the tablets. 6 mg tablets are yellow colored, round, biconvex, film-coated tablet with release portal on one side and ‘PL3’ imprinting with black ink on either side of the tablets. 9 mg tablets are pink colored, round, biconvex, film-coated tablet with release portal on one side and ‘PL4’ imprinting with black ink on either side of the tablets. Tablets: 1.5 mg, 3 mg, 6 mg, and 9 mg ( 3 )

4 CONTRAINDICATIONS Paliperidone extended-release tablets are contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the paliperidone extended-release tablets formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. Paliperidone is a metabolite of risperidone. Known hypersensitivity to paliperidone, risperidone, or to any excipients in paliperidone extended-release tablets. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Increased mortality in elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1) ] Cerebrovascular adverse reactions, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2) ] Neuroleptic malignant syndrome [see Warnings and Precautions (5.3) ] QT prolongation [see Warnings and Precautions (5.4) ] Tardive dyskinesia [see Warnings and Precautions (5.5) ] Metabolic changes [see Warnings and Precautions (5.6) ] Hyperprolactinemia [see Warnings and Precautions (5.7) ] Potential for gastrointestinal obstruction [see Warnings and Precautions (5.8) ] Orthostatic hypotension and syncope [see Warnings and Precautions (5.9) ] Falls [see Warnings and Precautions (5.10) ] Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions (5.11) ] Potential for cognitive and motor impairment [see Warnings and Precautions (5.12) ] Seizures [see Warnings and Precautions (5.13) ] Dysphagia [see Warnings and Precautions (5.14) ] Priapism [see Warnings and Precautions (5.15) ] Disruption of body temperature regulation [see Warnings and Precautions (5.16) ] Commonly observed adverse reactions (incidence ≥ 5% and at least twice that for placebo) were ( 6 ) Adults with schizophrenia: extrapyramidal symptoms, tachycardia, and akathisia. Adolescents with schizophrenia: somnolence, akathisia, tremor, dystonia, cogwheel rigidity, anxiety, weight increased, and tachycardia. Adults with schizoaffective disorder: extrapyramidal symptoms, somnolence, dyspepsia, constipation, weight increased, and nasopharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience The most common adverse reactions in clinical trials in adult subjects with schizophrenia (reported in 5% or more of subjects treated with paliperidone and at least twice the placebo rate in any of the dose groups) were extrapyramidal symptoms, tachycardia, and akathisia. The most common adverse reactions in clinical trials in adult patients with schizoaffective disorder (reported in 5% or more of subjects treated with paliperidone and at least twice the placebo rate) were extrapyramidal symptoms, somnolence, dyspepsia, constipation, weight increased, and nasopharyngitis. The most common adverse reactions that were associated with discontinuation from clinical trials in adult subjects with schizophrenia (causing discontinuation in 2% of paliperidone-treated subjects) were nervous system disorders. The most common adverse reactions that were associated with discontinuation from clinical trials in adult subjects with schizoaffective disorder were gastrointestinal disorders, which resulted in discontinuation in 1% of paliperidone-treated subjects. [see Adverse Reactions (6) ]. The safety of paliperidone was evaluated in 1205 adult subjects with schizophrenia who participated in three placebo-controlled, 6-week, double-blind trials, of whom 850 subjects received paliperidone at fixed doses ranging from 3 mg to 12 mg once daily. The information presented in this section was derived from pooled data from these three trials. Additional safety information from the placebo-controlled phase of the long-term maintenance study, in which subjects received paliperidone at daily doses within the range of 3 mg to 15 mg (n=104), is also included. The safety of paliperidone was evaluated in 150 adolescent subjects 12 to 17 years of age with schizophrenia who received paliperidone in the dose range of 1.5 mg to 12 mg/day in a 6-week, double-blind, placebo-controlled trial. The safety of paliperidone was also evaluated in 622 adult subjects with schizoaffective disorder who participated in two placebo-controlled, 6-week, double-blind trials. In one of these trials, 206 subj …

7 DRUG INTERACTIONS Centrally-acting drugs: Due to CNS effects, use caution in combination. Avoid alcohol. (7.1) Drugs that may cause orthostatic hypotension: An additive effect may be observed when co-administered with paliperidone. (7.1) Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of paliperidone when a strong inducer of both CYP3A4 and P-gp (e.g., carbamazepine) is co-administered. Conversely, on discontinuation of the strong inducer, it may be necessary to decrease the dose of paliperidone. (7.2) Co-administration of divalproex sodium increased C max and AUC of paliperidone by approximately 50%. Adjust dose of paliperidone if necessary based on clinical assessment. (7.2) 7.1 Potential for Paliperidone to Affect Other Drugs Given the primary CNS effects of paliperidone [see Adverse Reactions (6.1, 6.2) ] , paliperidone should be used with caution in combination with other centrally acting drugs and alcohol. Paliperidone may antagonize the effect of levodopa and other dopamine agonists. Because of its potential for inducing orthostatic hypotension, an additive effect may be observed when paliperidone is administered with other therapeutic agents that have this potential [see Warnings and Precautions (5.9) ]. Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P450 isozymes. In vitro studies in human liver microsomes showed that paliperidone does not substantially inhibit the metabolism of drugs metabolized by cytochrome P450 isozymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5. Therefore, paliperidone is not expected to inhibit clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner. Paliperidone is also not expected to have enzyme inducing properties. Paliperidone is a weak inhibitor of P-glycoprotein (P-gp) at high concentrations. No in vivo data are available and the clinical relevance is unknown. Pharmacokinetic interaction between lithium and paliperidone is unlikely. In a drug interaction study, co-administration of paliperidone (12 mg once daily for 5 days) with divalproex sodium extended-release tablets (500 mg to 2000 mg once daily) did not affect the steady-state pharmacokinetics (AUC 24h and C max,ss ) of valproate in 13 patients stabilized on valproate. In a clinical study, subjects on stable doses of valproate had comparable valproate average plasma concentrations when paliperidone 3 to 15 mg/day was added to their existing valproate treatment. 7.2 Potential for Other Drugs to Affect Paliperidone Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, and CYP2C19, so that an interaction with inhibitors or inducers of these isozymes is unlikely. While in vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone metabolism, in vivo studies do not show decreased elimination by these isozymes and they contribute to only a small fraction of total body clearance. In vitro studies have shown that paliperidone is a P-gp substrate. Co-administration of paliperidone 6 mg once daily with carbamazepine, a strong inducer of both CYP3A4 and P-glycoprotein (P-gp), at 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state C max and AUC of paliperidone. This decrease is caused, to a substantial degree, by a 35% increase in renal clearance of paliperidone. A minor decrease in the amount of drug excreted unchanged in the urine suggests that there was little effect on the CYP metabolism or bioavailability of paliperidone during carbamazepine co-administration. On initiation of carbamazepine, the dose of paliperidone should be re-evaluated and increased if necessary. Conversely, on discontinuation of carbamazepine, the dose of paliperidone should be re-evaluated and decreased if necessary. Paliperidone is metabolized to a limited extent by CYP2D6 [see Clinical Pharmacology (12 …

8 USE IN SPECIFIC POPULATIONS Renal impairment: Dosing must be individualized according to renal function status. (2.5) Elderly: Same as for younger adults (adjust dose according to renal function status). (2.4) Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. (8.1) Pediatric Use: Safety and effectiveness in the treatment of schizophrenia not established in patients less than 12 years of age. Safety and effectiveness in the treatment of schizoaffective disorder not established in patients less than 18 years of age. (8.4) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including paliperidone, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) . Overall, available data from published epidemiologic studies of pregnant women exposed to paliperidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ) . There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including paliperidone, during pregnancy (see Clinical Considerations ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. In animal reproduction studies, there were no increases in fetal abnormalities when pregnant rats and rabbits were treated with paliperidone during the period of organogenesis with up to 8 times the maximum recommended human dose (MRHD) based on mg/m 2 body surface area. Additional reproduction toxicity studies were conducted with orally administered risperidone, which is extensively converted to paliperidone (see Animal data ) . Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide. Schizophrenia are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including paliperidone, during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. A prospective observational study including 6 women treated with risperidone, the parent compound of paliperidone, demonstrated placental passage of risperidone and paliperidone. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth …

12.1 Mechanism of Action Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone in schizophrenia is unclear. However, the drug’s therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2A ) receptor antagonism.

11 DESCRIPTION Paliperidone Extended-Release Tablets contains paliperidone, an atypical antipsychotic belonging to the chemical class of benzisoxazole derivatives. Paliperidone Extended-Release Tablets contains a racemic mixture of (+)- and (-)-paliperidone. The chemical name is (±)-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a] pyrimidin-4-one. Its molecular formula is C 23 H 27 FN 4 O 3 and its molecular weight is 426.49. The structural formula is Paliperidone is sparingly soluble in 0.1N HCl and in methylene chloride; practically insoluble in water, in 0.1N NaOH and hexane; and slightly soluble in N, N-dimethyl formamide and in Tetrahydrofuran. Paliperidone Extended-Release Tablets are intended for oral administration and are available in 1.5 mg (blue), 3 mg (white), 6 mg (yellow), and 9 mg (beige) strengths. Paliperidone Extended-Release Tablets utilizes Osmotic Drug delivery (OROS, Push-Pull technology) system. Inactive ingredients are hydroxypropyl cellulose, butylated hydroxytoluene, polyethylene oxide, talc, sodium chloride, colloidal silicon dioxide, sodium stearyl fumarate, iron oxide red, cellulose acetate, polyethylene glycol, polyvinyl alcohol, and titanium dioxide. The 1.5 mg tablets also contain F D & C blue # 2 and the 6 mg, and 9 mg tablets also contain iron oxide yellow. The imprinting ink contains shellac, black iron oxide, propylene glycol, and ammonium hydroxide. Chemical Structure Delivery System Components and Performance Paliperidone Extended-Release Tablets uses osmotic pressure to deliver paliperidone at a controlled rate. The tablets contain an osmotically active bi-layer core tablet that consists of a drug layer containing the entire amount of active ingredient in a hydrophilic polymer matrix and a push layer that contains an osmotic agent in a hydrophilic, swell-able polymer matrix. The bi-layer core tablet is coated with a release-controlling semi-permeable membrane (SPM). The SPM allows water permeation into the core without allowing components to quickly dissipate from the core. A laser-drilled aperture is present on the drug layer side of the SPM-coated tablet and is necessary for delivery. The tablets contain a water-soluble cosmetic over-coating that is imprinted with an identifier. Once ingested, the cosmetic over-coating rapidly dissipates in the gastrointestinal tract. The SPM allows water to penetrate into the core as the osmotic agent in the push layer provides a driving force for water influx. Once hydrated, the swell-able polymer matrix in the push layer (high molecular weight polyethylene oxide) expands, exerting a pressure on the drug layer portion of the core tablet which forces it out of the laser-drilled aperture in a plug-flow fashion. As the release rate is controlled by the rate of water influx into the core (SPM permeability), the delivery is independent of pH or gastrointestinal motility. The biologically inert tablet core, containing residual push layer components, remains intact and is eliminated in the feces. Drug absorption is controlled by a combination of drug release from the tablet and subsequent dissolution in the gastrointestinal tract.

10 OVERDOSAGE 10.1 Human Experience While experience with paliperidone overdose is limited, among the few cases of overdose reported in pre-marketing trials, the highest estimated ingestion of paliperidone was 405 mg. Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and somnolence, tachycardia and hypotension, and QT prolongation. Torsade de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose. Paliperidone is the major active metabolite of risperidone. Overdose experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert. 10.2 Management of Overdosage There is no specific antidote to paliperidone, therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers. Consideration should be given to the extended-release nature of the product when assessing treatment needs and recovery. Multiple drug involvement should also be considered. In case of acute overdose, establish and maintain an airway and ensure adequate oxygenation and ventilation. Administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately, including continuous electrocardiographic monitoring for possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients with an acute overdose of paliperidone. Similarly, the alpha-blocking properties of bretylium might be additive to those of paliperidone, resulting in problematic hypotension. Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of paliperidone-induced alpha blockade). In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered.

10.1 Human Experience While experience with paliperidone overdose is limited, among the few cases of overdose reported in pre-marketing trials, the highest estimated ingestion of paliperidone was 405 mg. Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and somnolence, tachycardia and hypotension, and QT prolongation. Torsade de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose. Paliperidone is the major active metabolite of risperidone. Overdose experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert.

10.2 Management of Overdosage There is no specific antidote to paliperidone, therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers. Consideration should be given to the extended-release nature of the product when assessing treatment needs and recovery. Multiple drug involvement should also be considered. In case of acute overdose, establish and maintain an airway and ensure adequate oxygenation and ventilation. Administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should c …

16 HOW SUPPLIED/STORAGE AND HANDLING Paliperidone extended-release tablets are available in the following strengths and packages. All tablets are capsule-shaped. 1.5 mg tablets are brown, capsule-shaped, film-coated tablets, with a small orifice on one end, and imprinted with “A86” on the body. They are available in bottles of 30 with child-resistant closure (NDC 27808-222-01) and bottles of 500 (NDC 27808-222-02). 3 mg tablets are white, capsule-shaped, film-coated tablets, with a small orifice on one end, and imprinted with “A87” on the body. They are available in bottles of 30 with child-resistant closure (NDC 27808-223-01) and bottles of 500 (NDC 27808-223-02). 6 mg tablets are beige, capsule-shaped, film-coated tablets, with a small orifice on one end, and imprinted with “A88” on the body. They are available in bottles of 30 with child-resistant closure (NDC 27808-224-01) and bottles of 500 (NDC 27808-224-02). 9 mg tablets are pink, capsule-shaped, film-coated tablets, with a small orifice on one end, and imprinted with “A89” on the body. They are available in bottles of 30 with child-resistant closure (NDC 27808-225-01) and bottles of 500 (NDC 27808-225-02). Storage and Handling Store up to 25oC (77oF); excursions permitted from 15o to 30oC (59o to 86oF) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in tight (USP) containers. Keep out of reach of children.