Mycophenolate mofetil

RECENT MAJOR CHANGES Indications and Usage, Pediatric Heart or Liver Transplants (1)................................................ 6/2022 Dosage and Administration, Dosage Recommendations for Heart Transplant Patients (2.3) ............................................................................................................................ 6/2022 Dosage and Administration, Dosage Recommendations for Liver Transplant Patients (2.4) ............................................................................................................................. 6/2022 Warnings and Precautions, Serious Infections (5.3) ............................................................... 10/2021 Warnings and Precautions, Acute Inflammatory Syndrome Associated with Mycophenolate Products (5.7) ........................................................................................................................................... 10/2021

1 INDICATIONS AND USAGE Mycophenolate mofetil tablets are indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1) ], heart [see Clinical Studies (14.2) ] or liver transplants [see Clinical Studies (14.3) ] , in combination with other immunosuppressants. Mycophenolate mofetil tablets are an antimetabolite immunosuppressant indicated for the prophylaxis of organ rejection in adult and pediatric recipients 3 months of age and older of allogeneic kidney, heart or liver transplants, in combination with other immunosuppressants. ( 1 )

2 DOSAGE & ADMINISTRATION ADULTS DOSAGE Kidney Transplant 1g twice daily,orally or intravenously (IV) over no less than 2h (2.2) Heart Transplant 1.5 g twice daily orally or IV, over no less than 2 h (2.3) Liver Transplant 1.5 g twice daily orally or 1 g twice daily IV over no less than 2 h (2.4) PEDIATRICS Kidney Transplant 600mg/m 2 orally twice daily, up to maximum of 2 g daily (2.2) Heart Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (3 g or 15 mL of oral suspension) (2.3) Liver Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (3 g or 15 mL of oral suspension) (2.4) Mycophenolate mofetil intravenous is an alternative when patients cannot tolerate oral medication. Administer within 24 hours following transplantation, until patients can tolerate oral medication, up to 14 days. ( 2.1 ) Reduce or interrupt dosing in the event of neutropenia. ( 2.5 ) See full prescribing information (FPI) for: adjustments for renal impairment and neutropenia ( 2.5 ), preparation of oral suspension and IV solution. (2.6 ) 2.1 Important Administration Instructions Mycophenolate mofetil should not be used without the supervision of a physician with experience in immunosuppressive therapy. Mycophenolate Mofetil Capsules, Tablets and Oral Suspension Mycophenolate mofetil oral dosage forms (capsules, tablets or oral suspension) should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of mycophenolate mofetil oral dosage forms and mycophenolic acid delayed-release tablets are not equivalent. Mycophenolate mofetil tablets should not be crushed and mycophenolate mofetil capsules should not be opened or crushed. Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in mycophenolate mofetil capsules and oral suspension. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water. The initial oral dose of mycophenolate mofetil should be given as soon as possible following kidney, heart or liver transplant. It is recommended that mycophenolate mofetil be administered on an empty stomach. In stable transplant patients, however, mycophenolate mofetil may be administered with food if necessary [see Clinical Pharmacology ( 12.3 )]. Once reconstituted, mycophenolate mofetil for oral suspension must not be mixed with any liquids prior to dose administration. If needed, mycophenolate mofetil for oral suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter). Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take mycophenolate mofetil at the usual times. 2.2 Dosage Recommendations for Kidney Transplant Patients Adults The recommended dosage for adult kidney transplant patients is 1 g orally or intravenously infused over no less than 2 hours, twice daily (total daily dose of 2 g). Pediatrics (3 months and older) Pediatric dosing is based on body surface area (BSA). The recommended dosage of mycophenolate mofetil for oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m 2 , administered twice daily (maximum total daily dose of 2g or 10 mL of the oral suspension). Pediatric patients with BSA ≥ 1.25 m 2 may be dosed with capsules or tablets as follows: Table 1 Pediatric Kidney Transplant: Dosage Using Capsules or Tablets Body Surface Area Dosage 1.25 m 2 to less than 1.5 m 2 Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose) Greater than and equal to 1.5 m 2 Mycophenolate mofetil capsules or tablets 1 g twice daily (2 g total da …

3 DOSAGE FORMS AND STRENGTHS Mycophenolate mofetil for tablets and capsules are available in the following dosage forms and strengths: Capsules 250 mg mycophenolate mofetil, white to off-white blend of mycophenolate mofetil filled in size "1" hard gelatin capsule with Ivory Cap and Ivory Body, printed "SAL" on cap and "726" on body in black. Tablets 500 mg mycophenolate mofetil, pinkish brown colored, capsule shaped, film coated tablet with "SAL" engraved on one side and engraved "725" on other side. • Capsules: 250 mg • Tablets: 500 mg

4 CONTRAINDICATIONS Mycophenolate mofetil is contraindicated in patients with a history of hypersensitivity, including anaphylaxis, to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product [see Warnings and Precautions (5.8)]. Mycophenolate mofetil Intravenous is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN). History of hypersensitivity, including anaphylaxis, to mycophenolate mofetil, mycophenolic acid or any component of the drug product ( 4 ) Patients allergic to Polysorbate 80 (present in mycophenolate mofetil IV) ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Embryofetal Toxicity [see Warnings and Precautions ( 5.1 )] Lymphomas and Other Malignancies [see Warnings and Precautions ( 5.2 )] Serious Infections [see Warnings and Precautions ( 5.3 )] Blood Dyscrasias: Neutropenia, Pure Red Cell Aplasia [see Warnings and Precautions ( 5.4 )] Gastrointestinal Complications [see Warnings and Precautions ( 5.5 )] Acute Inflammatory Syndrome Associated with Mycophenolate Products [see Warnings and Precautions ( 5.7 )] The most common adverse reactions in clinical trials (20 percent or greater) include diarrhea, leukopenia, infection, vomiting, and there is evidence of a higher frequency of certain types of infections e.g. opportunistic infection (6.1). To report SUSPECTED ADVERSE REACTIONS contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.com 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. An estimated total of 1,557 adult patients received mycophenolate mofetil during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids. The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of mycophenolate mofetil in de novo kidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies ( 14.1 , 14.2 , and 14.3 )] . Mycophenolate Mofetil Oral The incidence of adverse reactions for mycophenolate mofetil was determined in five randomized, comparative, double-blind trials in the prevention of rejection in kidney, heart and liver transplant patients (two active-and one placebo-controlled trials, one active-controlled trial, and one active-controlled trial, respectively) [see Clinical Studies ( 14.1 , 14.2 and 14.3 )] . The three de novo kidney studies with 12-month duration compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune ® ) and corticosteroids to prevent acute rejection episodes. One study also included anti-thymocyte globulin (ATGAM ® ) induction therapy. In the de novo heart transplantation study with 12-month duration, patients received mycophenolate mofetil 1.5 g twice daily (n=289) or azathioprine 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ® or Neoral ® ) and corticosteroids as maintenance immunosuppressive therapy. In the de novo liver transplantation study with 12-month duration, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or azathioprine 1 to 2 mg/kg/day intravenously followed by azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ® ) and corticosteroids as maintenance immunosuppressive therapy. The total number of patients enrolled was 565. Approximately 53% of the kidney transplant patients, 65% of the heart transplant patients, and 48% of the liver transplant patients were treated for more than 1 year. Adverse reactions reported in ≥20% of patients in the mycophenolate mofetil treatment groups are presented below. The safety data of three kidney transplantation studies are pooled together. Table 5 Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in ≥20% of Patients in the Mycophenolate Mofetil Group Adverse drug reaction Kidney Studies Heart Study Liver …

Drug Interactions Drug interaction studies with mycophenolate mofetil have been conducted with acyclovir, antacids, cholestyramine, cyclosporine, ganciclovir, oral contraceptives, sevelamer, trimethoprim/sulfamethoxazole, norfloxacin, and metronidazole. Drug interaction studies have not been conducted with other drugs that may be commonly administered to renal, cardiac or hepatic transplant patients. Mycophenolate mofetil has not been administered concomitantly with azathioprine. Acyclovir Coadministration of mycophenolate mofetil (1 g) and acyclovir (800 mg) to 12 healthy volunteers resulted in no significant change in MPA AUC and C max . However, MPAG and acyclovir plasma AUCs were increased 10.6% and 21.9%, respectively. Because MPAG plasma concentrations are increased in the presence of renal impairment, as are acyclovir concentrations, the potential exists for mycophenolate and acyclovir or its prodrug (e.g., valacyclovir) to compete for tubular secretion, further increasing the concentrations of both drugs. Antacids with Magnesium and Aluminum Hydroxides Absorption of a single dose of mycophenolate mofetil (2 g) was decreased when administered to ten rheumatoid arthritis patients also taking Maalox ®† TC (10 mL qid). The C max and AUC (0-24h) for MPA were 33% and 17% lower, respectively, than when mycophenolate mofetil was administered alone under fasting conditions. Mycophenolate mofetil may be administered to patients who are also taking antacids containing magnesium and aluminum hydroxides; however, it is recommended that mycophenolate mofetil and the antacid not be administered simultaneously. Proton Pump Inhibitors (PPIs) Coadministration of PPIs (e.g., lansoprazole, pantoprazole) in single doses to healthy volunteers and multiple doses to transplant patients receiving mycophenolate mofetil has been reported to reduce the exposure to mycophenolic acid (MPA). An approximate reduction of 30% to 70% in the C max and 25% to 35% in the AUC of MPA has been observed, possibly due to a decrease in MPA solubility at an increased gastric pH. The clinical impact of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PPIs and mycophenolate mofetil. Because clinical relevance has not been established, PPIs should be used with caution when coadministered to transplant patients being treated with mycophenolate mofetil. Cholestyramine Following single-dose administration of 1.5 g mycophenolate mofetil to 12 healthy volunteers pretreated with 4 g tid of cholestyramine for 4 days, MPA AUC decreased approximately 40%. This decrease is consistent with interruption of enterohepatic recirculation which may be due to binding of recirculating MPAG with cholestyramine in the intestine. Therefore, mycophenolate mofetil is not recommended to be given with cholestyramine or other agents that may interfere with enterohepatic recirculation. Cyclosporine Cyclosporine (Sandimmune ®† ) pharmacokinetics (at doses of 275 to 415 mg/day) were unaffected by single and multiple doses of 1.5 g bid of mycophenolate mofetil in ten stable renal transplant patients. The mean (± SD) AUC (0-12h) and C max of cyclosporine after 14 days of multiple doses of mycophenolate mofetil were 3290 (± 822) ng•h/mL and 753 (± 161) ng/mL, respectively, compared to 3245 (± 1088) ng•h/mL and 700 (± 246) ng/mL, respectively, one week before administration of mycophenolate mofetil. Cyclosporine A interferes with MPA enterohepatic recirculation. In renal transplant patients, mean MPA exposure (AUC 0-12h ) was approximately 30% to 50% greater when mycophenolate mofetil is administered without cyclosporine compared with when mycophenolate mofetil is coadministered with cyclosporine. This interaction is due to cyclosporine inhibition of multidrug-resistance-associated protein 2 (MRP-2) transporter in the biliary tract, thereby preventing the excretion of MPAG into the bile that would lead to enterohepatic recirculation of MPA. This infor …

8 USE IN SPECIFIC POPULATIONS Male Patients: Sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment (8.3) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing mycophenolate mofetil treatment. To report a pregnancy or obtain information about the registry, visit www.mycophenolateREMS.com or call 1-800-617-8191. Risk Summary Use of mycophenolate mofetil (MMF) during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems [see Human Data] . Oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see Animal Data]. Consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of mycophenolate mofetil should be discussed with the pregnant woman. The estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. 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. Data Human Data A spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23 to 27% of live births in MMF exposed pregnancies, based on published data from pregnancy registries. Malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. Based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45 to 49% following MMF exposure. Animal Data In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Oral administration of MMF to pregnant rats from Gestational Day 7 to Day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of MMF to pregnant rabbits from Gestational Day 7 to Day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. 8.2 Lactation Risk Summary There are no data on the presence of mycophenolate in human milk, or the effects on milk production. There are limited data in the National Transplantation Pregnancy Registry on the effects of mycophenolate on a breastfed child [see Data] . Studies in rats treated with MMF have shown mycophenolic acid (MPA) to be present in milk. Because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mycophenolate mofetil and any potential adverse effects on the breastfed infant from mycophenolate mofetil or from the underlying maternal condition. Data Limited information is available from the National Transplantation Pregnancy Registry. Of seven infants reported by the N …

Mechanism of Action Mycophenolate mofetil has been demonstrated in experimental animal models to prolong the survival of allogeneic transplants (kidney, heart, liver, intestine, limb, small bowel, pancreatic islets, and bone marrow). Mycophenolate mofetil has also been shown to reverse ongoing acute rejection in the canine renal and rat cardiac allograft models. Mycophenolate mofetil also inhibited proliferative arteriopathy in experimental models of aortic and cardiac allografts in rats, as well as in primate cardiac xenografts. Mycophenolate mofetil was used alone or in combination with other immunosuppressive agents in these studies. Mycophenolate mofetil has been demonstrated to inhibit immunologically mediated inflammatory responses in animal models and to inhibit tumor development and prolong survival in murine tumor transplant models. Mycophenolate mofetil is rapidly absorbed following oral administration and hydrolyzed to form MPA, which is the active metabolite. MPA is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, MPA has potent cytostatic effects on lymphocytes. MPA inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody formation by B-lymphocytes. MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. Mycophenolate mofetil did not inhibit early events in the activation of human peripheral blood mononuclear cells, such as the production of interleukin-1 (IL-1) and interleukin-2 (IL-2), but did block the coupling of these events to DNA synthesis and proliferation.

DESCRIPTION Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor. The chemical name for mycophenolate mofetil is 2-Morpholinoethyl ( E )-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoate. It has a molecular formula of C 23 H 31 NO 7 , a molecular weight of 433.5, and the following structural formula: Mycophenolate mofetil, USP is a white to almost white crystalline powder. It is practically insoluble in water (43 mcg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in anhydrous ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for mycophenolate mofetil are 5.6 for the morpholino group and 8.5 for the phenolic group. Mycophenolate mofetil is available for oral administration as capsules containing 250 mg of mycophenolate mofetil and tablets containing 500 mg of mycophenolate mofetil. Mycophenolate Mofetil Capsules USP, 250 mg contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch (corn), and sodium lauryl sulfate. The empty gelatin capsule shells contain black iron oxide, FD&C Blue No. 2, gelatin, red iron oxide, titanium dioxide, and yellow iron oxide. In addition, the imprinting ink contains the following: ammonium hydroxide, black iron oxide, propylene glycol, and shellac glaze. Mycophenolate Mofetil Tablets USP, 500 mg contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, povidone, pregelatinized starch (corn), red iron oxide, sodium lauryl sulfate, talc, titanium dioxide and yellow iron oxide. Chemical Structure-Mycophenolate mofetil

OVERDOSAGE The experience with overdose of mycophenolate mofetil in humans is very limited. The events received from reports of overdose fall within the known safety profile of the drug. The highest dose administered to renal transplant patients in clinical trials has been 4 g/day. In limited experience with cardiac and hepatic transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, principally neutropenia, leading to a need to reduce or discontinue dosing. In acute oral toxicity studies, no deaths occurred in adult mice at doses up to 4000 mg/kg or in adult monkeys at doses up to 1000 mg/kg; these were the highest doses of mycophenolate mofetil tested in these species. These doses represent 11 times the recommended clinical dose in renal transplant patients and approximately 7 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In adult rats, deaths occurred after single-oral doses of 500 mg/kg of mycophenolate mofetil. The dose represents approximately 3 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. MPA and MPAG are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (> 100 mcg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine (see CLINICAL PHARMACOLOGY: Pharmacokinetics ).

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 Handling and Disposal Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)] . Mycophenolate mofetil tablets should not be crushed and mycophenolate mofetil capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in mycophenolate mofetil capsules [see Dosage and Administration (2.6)]. Follow applicable special handling and disposal procedures 1 . 16.2 Mycophenolate Mofetil Capsules, USP 250 mg Capsules White to off-white blend of mycophenolate mofetil filled in size "1" hard gelatin capsule with Ivory Cap and Ivory Body, printed "SAL" on cap and "726" on body in black. Sizes Bottles of 100 ................ NDC 73190-009-01 Bottles of 500 ................ NDC 73190-009-50 Storage • Store at 20° to 25°C (68° to 77°F), [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers. 16.3 Mycophenolate Mofetil Tablets, USP 500 mg Tablets Pinkish brown colored, capsule shaped, film coated tablet with "SAL" engraved on one side and engraved "725" on other side. Sizes Bottle of 100.................................... NDC 73190-010-01 Bottle of 500.................................... NDC 73190-010-50 Storage: • Store at 20° to 25°C (68° to 77°F). [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers.

16.2 Mycophenolate Mofetil Capsules, USP 250 mg Capsules White to off-white blend of mycophenolate mofetil filled in size "1" hard gelatin capsule with Ivory Cap and Ivory Body, printed "SAL" on cap and "726" on body in black. Sizes Bottles of 100 ................ NDC 73190-009-01 Bottles of 500 ................ NDC 73190-009-50 Storage • Store at 20° to 25°C (68° to 77°F), [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers.

16.3 Mycophenolate Mofetil Tablets, USP 500 mg Tablets Pinkish brown colored, capsule shaped, film coated tablet with "SAL" engraved on one side and engraved "725" on other side. Sizes Bottle of 100.................................... NDC 73190-010-01 Bottle of 500.................................... NDC 73190-010-50 Storage: • Store at 20° to 25°C (68° to 77°F). [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers.