Morphine Sulfate Solution, Concentrate

Each mL of clear/colorless Morphine Sulfate Oral Solution contains 20 mg of morphine sulfate, USP.  The concentration of this solution is 100 mg per 5 mL (20 mg per mL).

CNS Depressants

Other central nervous system (CNS) depressants including sedatives, hypnotics, general anesthetics, antiemetics, phenothiazines, or other tranquilizers or alcohol increases the risk of respiratory depression, hypotension, profound sedation, or coma. Use morphine sulfate with caution and in reduced dosages in patients taking these agents.

Muscle Relaxants

Morphine sulfate may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

Mixed Agonist/Antagonist Opioid Analgesics

Do not administer mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) to patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic such as morphine sulfate. In these patients, mixed agonist/antagonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

Cimetidine or cimetidine hydrochloride

Concomitant administration of morphine sulfate and cimetidine or cimetidine hydrochloride has been reported to precipitate apnea, confusion, and muscle twitching in an isolated report. Monitor patients for increased respiratory and CNS depression when receiving cimetidine or cimetidine hydrochloride concomitantly with morphine sulfate.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs markedly potentiate the action of morphine sulfate. Allow at least 14 days after stopping treatment with MAOIs before initiating treatment with morphine sulfate.

Anticholinergics

Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

P-Glycoprotein (P-gp) Inhibitors

Based on published reports, P-gp inhibitors (e.g. quinidine) may increase the absorption/exposure of morphine sulfate by about two fold. Therefore, exercise caution when morphine sulfate is co-administered with P-gp inhibitors.

Chemically, morphine sulfate is 7,8-didehydro-4,5 alpha-epoxy-17 methyl-morphinan-3,6 alpha-diol sulfate (2:1) (salt) pentahydrate with a molecular mass of 758. Morphine sulfate occurs as white, feathery, silky crystals; cubical masses of crystal; or white crystalline powder. It is soluble in water and slightly soluble in alcohol, but is practically insoluble in chloroform or ether. The octanol:water partition coefficient of morphine is 1.42 at physiologic pH and the pKa is 7.9 for the tertiary nitrogen (the majority is ionized at pH 7.4).

Each mL of oral solution contains 20 mg of morphine sulfate, USP and the following inactive ingredients: anhydrous citric acid, edetate disodium dihydrate, glycerin, methylparaben, propylparaben, sodium benzoate, sorbitol and purified water.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals to evaluate the carcinogenic potential of morphine sulfate have not been conducted. No formal studies to assess the mutagenic potential of morphine sulfate have been conducted. In the published literature, the results of in vitro studies showed that morphine sulfate is non-mutagenic in the Drosophila melanogaster lethal mutation assay and produced no evidence of chromosomal aberrations when incubated with murine splenocytes. Contrary to these results, morphine sulfate was found to increase DNA fragmentation when incubated in vitro with a human lymphoma line. In vivo, morphine sulfate has been reported to produce an increase in the frequency of micronuclei in bone marrow cells and immature red blood cells in the mouse micronucleus test and to induce chromosomal aberrations in murine lymphocytes and spermatids. Some of the in vivo clastogenic effects reported with morphine sulfate in mice may be directly related to increases in glucocorticoid levels produced by morphine sulfate in this species.

A literature report indicated that morphine sulfate impairs fertility in rats. In a fertility study in which male rats were administered morphine sulfate subcutaneous prior to mating (up to 30 mg/kg twice daily) and during mating (20 mg/kg twice daily) with untreated females, a number of adverse reproductive effects were observed. These included reduction in total pregnancies, higher incidence of pseudopregnancies, and reduction in implantation sites.

See Medication Guide 

Provide the following information to patients receiving morphine sulfate or their caregivers:

• Advise patients that morphine sulfate is a narcotic pain medication, and should be taken only as directed.
• Advise patients that Morphine Sulfate Oral Solution is marketed in multiple concentrations including concentrations lower than 100 mg per 5 mL (20 mg per mL). Carefully instruct patients about which concentration they have been prescribed and how to measure and take the correct dose of Morphine Sulfate Oral Solution. Advise patients whenever the prescribed concentration is changed to avoid dosing errors, which could result in accidental overdose and death.
• Instruct patients to always use the enclosed calibrated oral syringe when administering Morphine Sulfate Oral Solution 100 mg per 5 mL (20 mg per mL) to ensure the dose is measured and administered accurately.
• Instruct patients that Morphine Sulfate Oral Solution 100 mg per 5 mL (20 mg per mL) is only for patients who are already receiving opioid-therapy and have demonstrated opioid-tolerance. Use of this formulation may cause fatal respiratory depression when administered to patients who have not had previous exposure to opioids.
• Instruct patients NEVER to share their Morphine Sulfate Oral Solution 100 mg per 5 mL (20 mg per mL), even if they have the same symptoms, because doing so could result in death.
• Instruct patients not to adjust the dose of morphine sulfate without consulting with a physician or other healthcare professional.
• Instruct patients that if they miss one dose of Morphine Sulfate Oral Solution 100 mg per 5 mL (20 mg per mL), they can take the dose when they remember it if they have pain, or they can wait for the next dose.
• Advise patients that morphine sulfate may cause drowsiness, dizziness, or lightheadedness and may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery). Advise patients started on morphine sulfate or patients whose dose has been adjusted to refrain from any potentially dangerous activity until it is established that they are not adversely affected.
• Advise patients that morphine sulfate will add to the effect of alcohol and other CNS depressants (such as antihistamines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and monoamine oxidase [MAO] inhibitors).
• Instruct patients not to combine morphine sulfate with central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, and not to combine with alcohol because dangerous additive effects may occur, resulting in serious injury or death.
• Instruct women of childbearing potential who become or are planning to become pregnant to consult a physician prior to initiating or continuing therapy with morphine sulfate.
• Advise patients that safe use in pregnancy has not been established and that prolonged use of opioid analgesics during pregnancy may cause fetal-neonatal physical dependence, and neonatal withdrawal may occur.
• If patients have been receiving treatment with morphine sulfate for more than a few weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose and that abruptly discontinuing the medication could precipitate withdrawal symptoms. Provide a dose schedule to accomplish a gradual discontinuation of the medication.
• Advise patients that morphine sulfate is a potential drug of abuse. They must protect it from theft. It should never be given to anyone other than the individual for whom it was prescribed.
• Instruct patients to keep morphine sulfate in a secure place out of the reach of children. When morphine sulfate is no longer needed, the unused oral solution should be destroyed by flushing down the toilet.
• Advise patients taking morphine sulfate of the potential for severe constipation; appropriate laxatives and/or stool softeners as well as other appropriate treatments should be initiated from the onset of opioid therapy.
• Advise patients of the most common adverse events that may occur while taking morphine sulfate: constipation, nausea, somnolence, lightheadedness, dizziness, sedation, vomiting, and sweating.

Manufactured by:
Cody Laboratories, Inc.
Cody, WY 82414

Manufactured for:
Lannett Company, Inc.
Philadelphia, PA 19136

Made in the USA

Revised 07/2013; Revision 4

11-138