MEPERIDINE HYDROCHLORIDE

Meperidine hydrochloride tablets are opioid agonists. Meperidine hydrochloride tablets are available as 50 mg for oral administration. The chemical name is 4-Piperidinecarboxylic acid, 1-methyl-4-phenyl-,ethyl ester, hydrochloride. The molecular weight is 283.80. Its molecular formula is C 15 H 21 NO 2 ∙HCl, and it has the following chemical structure. Meperidine hydrochloride is a white crystalline substance with a melting point of 186°C to 189°C. It is readily soluble in water and has a neutral reaction and a slightly bitter taste. The solution is not decomposed by a short period of boiling. The tablets contain 50 mg of meperidine hydrochloride. The Inactive Ingredients in meperidine hydrochloride tablets include: hypromellose, microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and stearic acid. Meperidine hydrochloride tablets 50 mg, are white, round, scored, and convex debossed with "214" on one side and "G" bisect "L"on the other side. Chemical Structure

Meperidine hydrochloride tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Meperidine hydrochloride tablets are opioid agonists indicated for the management of pain, severe enough to require an opioid analgesic and for which alternative treatments are inadequate. ( 1 ) Limitations of Use ( 1 ) Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, reserve meperidine hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated, or are not expected to be tolerated, ( 1 ) Have not provided adequate analgesia, or are not expected to provide adequate analgesia ( 1 ). Meperidine Hydrochloride Tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. Meperidine Hydrochloride Tablets should not be used for the treatment of chronic pain. Use of Meperidine Hydrochloride Tablets for an extended period of time may increase the risk of toxicity (e.g., seizures) from the accumulation of the meperidine metabolite, normeperidine. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see Warnings and Precautions (5.2) ] , reserve meperidine hydrochloride tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): Have not been tolerated, or are not expected to be tolerated, Have not provided adequate analgesia, or are not expected to provide adequate analgesia. Meperidine Hydrochloride Tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. Meperidine hydrochloride tablets should not be used for treatment of chronic pain. Use of meperidine hydrochloride tablets for an extended period of time may increase the risk of toxicity (e.g., seizures) from the accumulation of the meperidine metabolite, normeperidine.

Meperidine Hydrochloride Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of Meperidine Hydrochloride Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. ( 2.1 ) Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. ( 2.1 , 5.2 ) Respiratory depressi on can occur at any time during opioid therapy, especially when initiating and following dosage increases with Meperidine Hydrochloride Tablets. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.3 ) Discuss availability of naloxone with the patient and caregiver and assess each patient's need for access to naloxone, both when initiating and renewing treatment with meperidine hydrochloride tablets. Consider prescribing naloxone based in the patient's risk factors for overdose. ( 2.2 , 5.2 , 5.3 , 5.4 ) Adult Patients: Initiate treatment in adults with 50 mg to 150 mg every 3 to 4 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia ( 2.3 ). Titrate the dose based upon the individual patient's response to their initial dose of Meperidine Hydrochloride Tablets. Pediatric Patients: Initiate treatment in pediatric patients with 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as needed at the lowest dose necessary to achieve adequate analgesia ( 2.3 ). Titrate the dose based upon the individual patient's response to their initial dose of Meperidine Hydrochloride Tablets. Do not abruptly discontinue meperidine hydrochloride tablets in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.6 ). 2.1 Important Dosage and Administration Instructions Meperidine hydrochloride tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions (5) ] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of meperidine hydrochloride tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.2) ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Meperidine Hydrochloride Tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions (5) ] . 2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with meperidine hydrochloride tablets [see Warnings and Precautions (5.3) , Patient Counseling Information (17) ] . Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see Warnings and Precautions (5.2 , 5.3 , 5.4) ]. Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. 2.3 Initial Dosage Adults Initiate treatment with meperidine hydrochloride tablets in a dosing range of 50 mg to 150 mg orally, every 3 or 4 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose of meperidine hydrochloride tablets. Pediatric Patients Initiate treatment with meperidine hydrochloride tablets in a dosing range of 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as needed, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose of meperidine hydrochloride tablets. 2.4 Dosage Modification with Concomitant Use with Phenothiazines The dose of meperidine hydrochloride tablets should be reduced by 25 to 50% when administered concomitantly with phenothiazines and other tranquilizers. 2.5 Titration and Maintenance of Therapy Individually titrate meperidine hydrochloride tablets to a dose that provides adequate analgesia and minimizes adverse reactions. If adequate pain management cannot be achieved with a total daily dosage of 600 mg or less, discontinue treatment with meperidine hydrochloride tablets by tapering the dose and select an alternate analgesic. Continually reevaluate patients receiving meperidine hydrochloride tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.2) ] . Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the meperidine hydrochloride tablets dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage [see Warnings and Precautions (5) ] . Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. 2.6 Safe Reduction or Discontinuation of Meperidine Hydrochloride Tablets Do not abruptly discontinue meperidine hydrochloride tablets in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking meperidine hydrochloride tablets, there are a variety of factors that should be considered, including the total daily dose of opioid (including meperidine hydrochloride tablets) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on meperidine hydrochloride tablets who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.17) , Drug Abuse and Dependence (9.3) ].

Meperidine hydrochloride tablets are contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.3) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.11) ] Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of having taken an MAOI [see Drug Interactions (7) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.15) ] Hypersensitivity to meperidine or to any of other ingredients of the product (e.g., anaphylaxis) [see Adverse Reactions (6) ] Significant respiratory depression. ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. ( 4 ) Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of having taken an MAOI. ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) Hypersensitivity to meperidine or to any other ingredients of the product. ( 4 )

The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.2) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3) ] Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.4) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.5) ] Opioid-Induced Hyperalgesia and Allodynia [See Warnings and Precautions (5.9) ] Serotonin Syndrome [see Warnings and Precautions (5.10) ] Adrenal Insufficiency [see Warnings and Precautions (5.12) ] Severe Hypotension [see Warnings and Precautions (5.13) ] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.15) ] Seizures [see Warnings and Precautions (5.16) ] Withdrawal [see Warnings and Precautions (5.17) ] The following adverse reactions associated with the use of meperidine were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The major hazards of meperidine, as with other opioid analgesics, are respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest. The most frequently observed adverse reactions included lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. These effects seem to be more prominent in ambulatory patients and in those who are not experiencing severe pain. In such individuals, lower doses are advisable. Some adverse reactions in ambulatory patients may be alleviated if the patient lies down. Other adverse reactions include: Nervous System : Mood changes (e.g., euphoria, dysphoria), weakness, headache, agitation, tremor, involuntary muscle movements (e.g., muscle twitches, myoclonus), severe convulsions, transient hallucinations and disorientation, confusion, delirium, visual disturbances. Gastrointestinal : Dry mouth, constipation, biliary tract spasm. Cardiovascular : Flushing of the face, tachycardia, bradycardia, palpitation, hypotension [see Warnings and Precautions (5.4) ] , syncope. Genitourinary : Urinary retention. Allergic : Pruritus, urticaria, other skin rashes, wheal and flare over the vein with intravenous injection. Hypersensitivity reactions, anaphylaxis. Histamine release leading to hypotension and/or tachycardia, flushing, sweating, and pruritus. Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Androgen deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology (12.2) ] . Hyperalgesia and Allodynia : Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions (5.9) ] Hypoglycemia : Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g. diabetes). To report SUSPECTED ADVERSE REACTIONS, contact Allucent at 1-866-511-6754 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Most common adverse reactions were lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Allucent at 1-866-511-6754 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Table 1 includes clinically significant drug interactions with meperidine hydrochloride tablets. Table 1: Clinically Significant Drug Interactions with Meperidine Hydrochloride Tablets Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: Meperidine is contraindicated in patients who are receiving monoamine oxidase (MAOIs) or those who have recently received such agents. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received such agents within 14 days. The mechanism of these reactions is unclear, but may be related to a preexisting hyperphenylalaninemia. Some have been characterized by coma, severe respiratory depression, cyanosis, and hypotension, and have resembled the syndrome of acute narcotic overdose. Serotonin syndrome with agitation, hyperthermia, diarrhea, tachycardia, sweating, tremors and impaired consciousness may also occur. In other reactions the predominant manifestations have been hyperexcitability, convulsions, tachycardia, hyperpyrexia, and hypertension. Intervention: Do not use meperidine hydrochloride tablets in patients taking MAOIs or within 14 days of stopping such treatment. Intravenous hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of intravenous chlorpromazine in those cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of narcotic antagonists in the treatment of these reactions is unknown.) Examples: phenelzine, tranylcypromine, linezolid Inhibitors of CYP3A4 and CYP2B6 Clinical Impact: The concomitant use of meperidine hydrochloride tablets and CYP3A4 or CYP2B6 inhibitors can increase the plasma concentration of meperidine, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of meperidine hydrochloride tablets and CYP2B6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of meperidine hydrochloride tablets is achieved [see Warnings and Precautions (5.7) ] . After stopping a CYP3A4 or CYP2B6 inhibitor, as the effects of the inhibitor decline, the meperidine plasma concentration will decrease [see Clinical Pharmacology (12.3) ] , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to meperidine. Intervention: If concomitant use is necessary, consider dosage reduction of meperidine hydrochloride tablets until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 or CYP2B6 inhibitor is discontinued, consider increasing the meperidine hydrochloride tablets dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents(e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 and CYP2B6 Inducers Clinical Impact: The concomitant use of meperidine hydrochloride tablets and CYP3A4 or CYP2B6 inducers can decrease the plasma concentration of meperidine [see Clinical Pharmacology (12.3) ] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to meperidine [see Warnings and Precautions (5.7) ] . After stopping a CYP3A4 or CYP2B6 inducer, as the effects of the inducer decline, the meperidine plasma concentration will increase [see Clinical Pharmacology (12.3) ] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the meperidine hydrochloride tablets dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. If a CYP3A4 or CYP2B6 inducer is discontinued, consider meperidine hydrochloride tablets dosage reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation. Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) , Warnings and Precautions (5.2 , 5.3 , 5.4) ] . Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions (5.10) ]. Intervention: If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue meperidine hydrochloride tablets immediately if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase inhibitors (MAOIs) (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of meperidine hydrochloride tablets and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Meperidine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Because respiratory depression may be greater than otherwise expected, evaluate patients for signs of respiratory depression, decrease the dosage of meperidine hydrochloride tablets and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) , Warnings and Precautions (5.3 , 5.4) ]. Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Evaluate patients for signs of urinary retention or reduced gastric motility when meperidine hydrochloride tablets are used concomitantly with anticholinergic drugs. Acyclovir Clinical Impact: The concomitant use of acyclovir may increase the plasma concentrations of meperidine and its metabolite, normeperidine. Intervention: If concomitant use of acyclovir and meperidine hydrochloride tablets is necessary, evaluate patients for respiratory depression and sedation at frequent intervals. Cimetidine Clinical Impact: The concomitant use of cimetidine may reduce the clearance and volume of distribution of meperidine also the formation of the metabolite, normeperidine, in healthy subjects. Intervention: If concomitant use cimetidine and meperidine hydrochloride tablets is necessary, evaluate patients for respiratory depression and sedation at frequent intervals. Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics : Avoid use with meperidine hydrochloride tablets because they may reduce analgesic effect of meperidine hydrochloride tablets or precipitate withdrawal symptoms. ( 7 )

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