Morphine Sulfate (Page 5 of 6)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals to evaluate the carcinogenic potential of morphine have not been conducted.

Mutagenesis

No formal studies to assess the mutagenic potential of morphine have been conducted. In the published literature, morphine was found to be mutagenic in vitro increasing DNA fragmentation in human T-cells. Morphine was reported to be mutagenic in the in vivo mouse micronucleus assay and positive for the induction of chromosomal aberrations in mouse spermatids and murine lymphocytes. Mechanistic studies suggest that the in vivo clastogenic effects reported with morphine in mice may be related to increases in glucocorticoid levels produced by morphine in this species. In contrast to the above positive findings, in vitro studies in the literature have also shown that morphine did not induce chromosomal aberrations in human leukocytes or translocations or lethal mutations in Drosophila.

Impairment of Fertility

No formal nonclinical studies to assess the potential of morphine to impair fertility have been conducted.

Several nonclinical studies from the literature have demonstrated adverse effects on male fertility in the rat from exposure to morphine. One study in which male rats were administered morphine sulfate subcutaneously 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 including reduction in total pregnancies and higher incidence of pseudopregnancies at 20 mg/kg/day (3.2 times the HDD) were reported.

Studies from the literature have also reported changes in hormonal levels in male rats (i.e. testosterone, luteinizing hormone) following treatment with morphine at 10 mg/kg/day or greater (1.6 times the HDD).

Female rats that were administered morphine sulfate intraperitoneally prior to mating exhibited prolonged estrous cycles at 10 mg/kg/day (1.6 times the HDD).

Exposure of adolescent male rats to morphine has been associated with delayed sexual maturation and following mating to untreated females, smaller litters, increased pup mortality, and/or changes in reproductive endocrine status in adult male offspring have been reported (estimated 5 times the plasma levels at the HDD).

16 HOW SUPPLIED/STORAGE AND HANDLING

Morphine Sulfate Tablets

15 mg tablet: white, biconvex tablets scored on one side and product identification “54 733” debossed on the other side.

NDC 0054-0235-24: 100 (4 x 25) Unit-Dose Tablets

NDC 0054-0235-25: Bottle of 100 Tablets

30 mg tablets: white, biconvex tablets scored on one side and product identification “54 262” debossed on the other side.

NDC 0054-0236-24: 100 (4 x 25) Unit-Dose Tablets

NDC 0054-0236-25: Bottle of 100 Tablets

Storage

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

Protect from moisture.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Addiction, Abuse, and Misuse

Inform patients that the use of Morphine Sulfate Tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1)]. Instruct patients not to share Morphine Sulfate Tablets with others and to take steps to protect morphine sulfate from theft or misuse.

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Morphine Sulfate Tablets or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.2)]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.

Accidental Ingestion

Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.2)]. Instruct patients to take steps to store Morphine Sulfate Tablets securely and to dispose of unused Morphine Sulfate Tablets by flushing the unused tablets down the toilet.

Interactions with Benzodiazepines and Other CNS Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if Morphine Sulfate Tablets are used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.4), Drug Interactions (7)].

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see Drug Interactions (7)].

MAOI Interaction

Inform patients not to take Morphine Sulfate Tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Morphine Sulfate Tablets [see Warnings and Precautions (5.6), Drug Interactions (7)].

Adrenal Insufficiency

Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions (5.7)].

Important Administration Instructions

Instruct patients how to properly take Morphine Sulfate Tablets. Advise patients not to adjust the dose of morphine sulfate without consulting with a physician or other healthcare professional.

If patients have been receiving treatment with Morphine Sulfate Tablets for more than a few weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose as abrupt discontinuation of the medication could precipitate withdrawal symptoms. Provide a dose schedule to accomplish a gradual discontinuation of the medication [see Dosage and Administration (2.4)].

Hypotension

Inform patients that Morphine Sulfate Tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.8)].

Anaphylaxis

Inform patients that anaphylaxis have been reported with ingredients contained in Morphine Sulfate Tablets. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4), Adverse Reactions (6)].

Pregnancy

Neonatal Opioid Withdrawal Syndrome: Inform patients of reproductive potential that prolonged use of Morphine Sulfate Tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see Warnings and Precautions (5.3), Use in Specific Populations (8.1)].

Embryo-Fetal Toxicity: Inform female patients of reproductive potential that Morphine Sulfate Tablets can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

Lactation

Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see Use in Specific Populations (8.2)].

Infertility

Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6)].

Driving or Operating Heavy Machinery

Inform patients that Morphine Sulfate Tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.13)].

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6)].

Disposal of Unused Morphine Sulfate Tablets

Advise patients to dispose of unused Morphine Sulfate Tablets by flushing down the toilet.

Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724

10004596/07

Revised December 2016

MEDICATION GUIDE

Morphine Sulfate (mor-pheen) Tablets CII

Rx only

Morphine Sulfate Tablets are:

•
A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage short term (acute) and long term (chronic) pain severe enough to require an opioid pain medicine, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.
•
An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.

Important information about Morphine Sulfate Tablets:

•
Get emergency help right away if you take too much Morphine Sulfate Tablets (overdose). When you first start taking Morphine Sulfate Tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur.
•
Taking Morphine Sulfate Tablets with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.
•
Never give anyone else your Morphine Sulfate Tablets. They could die from taking it. Store Morphine Sulfate Tablets away from children and in a safe place to prevent stealing or abuse. Selling or giving away Morphine Sulfate Tablets is against the law.

Do not take Morphine Sulfate Tablets if you have:

•
Severe asthma, trouble breathing, or other lung problems.
•
A bowel blockage or have narrowing of the stomach or intestines.
•
An allergy to morphine.

Before taking Morphine Sulfate Tablets, tell your healthcare provider if you have a history of:

•
Head injury, seizures.

•
Liver, kidney, thyroid problems.

•
Problems urinating.

•
Pancreas or gallbladder problems.

•
Abuse of street or prescription drugs, alcohol addiction, or mental health problems.

Tell your healthcare provider if you are:

•
Pregnant or planning to become pregnant. Prolonged use of morphine sulfate during pregnancy can cause withdrawal.
•
Breastfeeding. Morphine sulfate passes into breast milk and may harm your baby.
•
Taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking Morphine Sulfate Tablets with certain other medicines can cause serious side effects that could lead to death.

When taking Morphine Sulfate Tablets:

•
Do not change your dose. Take Morphine Sulfate Tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
•
Take your prescribed dose every 4 hours as needed for pain. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.
•
Call your healthcare provider if the dose you are taking does not control your pain.
•
If you have been taking Morphine Sulfate Tablets regularly, do not stop taking morphine sulfate without talking to your healthcare provider.
•
After you stop taking Morphine Sulfate Tablets, flush unused Morphine Sulfate Tablets down the toilet.

While taking Morphine Sulfate Tablets DO NOT:

•
Drive or operate heavy machinery, until you know how morphine sulfate affects you. Morphine Sulfate Tablets can make you sleepy, dizzy, or lightheaded.
•
Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with Morphine Sulfate Tablets may cause you to overdose and die.

The possible side effects of Morphine Sulfate Tablets:

•
Constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

• Trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.

These are not all the possible side effects of Morphine Sulfate Tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown NJ 07724

For more information, please call 1-800-962-8364.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

10004596/07

Revised December 2016