How Long Does Morphine Stay In Your System

Contents

1 How many hours does morphine effect last?
2 How long does it take for 10mg of morphine to wear off?
3 How long is morphine detection?
4 How long does extended-release morphine last?
5 Does morphine make you drowsy the next day?
6 What do you check when giving morphine?
7 Does morphine make you tired and sleepy?
- 7.1 Are mood changes a side effect of morphine?
8 What is the strongest pain killer?
- 8.1 What is morphine sulfate 10 mg mL?

How many hours does morphine effect last?

Morphine Sulfate – IV Formulation Pronounced: MORE-feen SUL-fate This type of morphine is given intravenously (into a vein). Your care provider will determine the exact dosage and dosing schedule. When morphine is injected, it is immediately absorbed into the body.

It will begin working to relieve pain almost instantly, although it reaches its peak effect in 5 to 10 minutes. It will continue to work for 2 to 4 hours. This medication can interact with other medications that depress the central nervous system like barbituates (including phenobarbital), tranquilizers (including Haldol®, Librium®, and Xanax ®), other narcotics, MAOI’s, cimetidine, and general anesthetic.

Be sure to tell your healthcare provider about all medications and supplements you take. This medication can cause dizziness, sleepiness, and confusion. You should not drive or operate machinery while taking this medication until you know how it will affect you.

How long does it take for 10mg of morphine to wear off?

Morphine tablets and liquid work in 30 to 60 minutes but wear off after 4 to 6 hours.

How long is morphine detection?

What does the test measure? – Opioid testing detects the presence of opioids or opioid metabolites in a test sample. Opioid metabolites are substances created when the body is processing and breaking down an opioid. Opioids include both natural and manufactured substances:

Natural opioids are derived from the seeds of the opium poppy plant. Also called opiates, natural opioids include morphine, codeine, and opium. Heroin, which can be made from morphine easily, is often grouped with natural opioids. Synthetic opioids are created in the laboratory and act on the same receptors in the brain as natural opioids. They may not look chemically similar to natural opioids. Synthetic opioids include tramadol and fentanyl. Semi-synthetic opioids are chemically similar to natural opioids but are also manufactured in the laboratory and act on the same receptors in the brain as natural opioids. Semi-synthetic opioids include oxycodone, hydrocodone, hydromorphone, and oxymorphone.

Any individual opioid test may not detect all opioids and their metabolites. The types of opioids included in an opioid test varies by medical facility, laboratory, and geographical region. A routine drug screening panel often detects only natural opioids like heroin, morphine, and codeine.

While opioid tests can be ordered on their own, testing is often conducted as part of a broad screening panel.
A drug screening panel, such as a 10-panel drug test, may be used to find evidence of a variety of illegal and prescription drugs.
If a patient tests positive on an initial drug screening panel, results may be confirmed by a second, more specific test.

Common drug screening panels may not detect widely-used synthetic and semi-synthetic opioids, such as tramadol, methadone, and fentanyl. Testing for these opioids often requires a more extensive panel or a more targeted drug test. For example, the Department of Defense uses an expanded drug panel that includes several semi-synthetic opioids.

Opioids and their metabolites can only be detected in the body for a limited amount of time after use, called the detection window.
This varies based on many factors, including the type of opioid used, the amount and frequency of use, the type of test sample and factors specific to the patient such as body weight, ability to process the drug, nutrition and other medications.

The detection window can also vary based on the cutoff values used by an individual laboratory to determine a positive result. The table below provides examples of detection windows for a urine sample:


URINE DETECTION WINDOWS AFTER OPIOID USE
OPIOID AND EXAMPLE TRADE NAMES	ESTIMATED DETECTION WINDOW
Buprenorphine (Buprenex, Suboxone)	Up to 14 days
Codeine	Up to 3 days
Fentanyl (Duragesic, Fentora)	Up to 3 days
Heroin	Less than 1 day
Hydrocodone (Lorcet, Vicodin)	Up to 3 days
Hydromorphone (Dilaudid, Exalgo)	Up to 3 days
Meperidine (Demerol, Mepergan)	Up to 4 days
Methadone (Dolophine, Methadose)	Up to 14 days
Morphine (Avinza, Duramorph)	Up to 3 days
Oxycodone (Oxycontin, Percocet)	Up to 3 days
Oxymorphone (Numorphan, Opana)	Up to 3 days
Propoxyphene (Darvon, Darvocet)	Up to 4 days
Tapentadol (Nucynta)	Up to 3 days
Tramadol (Ultram)	Up to 4 days

The following table provides examples of detection windows in other types of test samples:


OTHER ESTIMATED DETECTION WINDOWS
OPIOID	HAIR	SALIVA	SWEAT
Codeine	Up to 90 days	Up to 36 hours	Up to 14 days
Morphine	Up to 90 days	Up to 36 hours	Up to 14 days
Heroin	Up to 90 days	Up to 36 hours	Up to 14 days

How long does extended-release morphine last?

Morphine Sulfate (MS Contin, Morphine Sulfate – Long Acting Pill) Morphine sulfate long-acting pills are available in both tablet and capsule form. The medication is released slowly over the course of the day (called extended-release) and comes in a variety of doses.

Your care provider will determine the exact dosage and dosing schedule. This form of morphine can be taken with or without food. The tablets should be swallowed whole. Do not break, chew or crush the tablets as this could cause an overdose of the medication. Kadian and Avinza, the capsule formulations, can be opened and sprinkled into applesauce or pudding, but the beads should not be crushed or chewed.

These medications begin working in 2 to 4 hours and reach peak effect in 15 to 30 hours (depending on the preparation). It can continue to work for a few days. This type of medication is designed to produce a long-acting, steady amount of pain relief. It is important to make sure you are taking the correct amount of medication every time.

Before every dose, check that what you are taking matches what you have been prescribed.
This medication can interact with other medications that depress the central nervous system like barbituates (including phenobarbital), tranquilizers (including Haldol®, Librium® and Xanax ®), other narcotics, MAOI’s, cimetidine, and general anesthetic.

Be sure to tell your healthcare provider about all medications and supplements you take. DO NOT share this medication or give it to someone else, as severe breathing problems and death can occur. This medication can cause dizziness, sleepiness, and confusion.

Does morphine make you drowsy the next day?

Tolerance and addiction – People taking morphine for weeks or months can develop a physical dependence. This causes withdrawal symptoms if morphine is stopped. Your doctor or nurse will advise you how to reduce the morphine dose gradually if necessary.

What does morphine do?

How does morphine work? – Morphine works directly on opioid receptors in the central nervous system, It reduces feelings of pain by interrupting the way nerves signal pain between the brain and the body.

How often can you ask for morphine?

Dosing – The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

For oral dosage form (extended-release capsules):

For moderate to severe pain:

Adults—

The total amount of milligrams (mg) per day is determined by your doctor. Your doctor may adjust your dose as needed. Avinza®: The capsule is given every 24 hours. Kadian®: The capsule is given every 12 or 24 hours.

Children—Use and dose must be determined by your doctor.

For oral dosage form (extended-release tablets):

For moderate to severe pain:

Adults—The total amount of milligrams (mg) per day is determined by your doctor. Your doctor may adjust your dose as needed. The tablet is usually given every 8 or 12 hours. Children—Use and dose must be determined by your doctor.

For oral dosage form (solution):

For moderate to severe pain:

Adults—10 to 20 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed. Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets):

For moderate to severe pain:

Adults—15 to 30 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed. Children—Use and dose must be determined by your doctor.

Does morphine show up on a standard drug test?

Response & Analysis: – It depends. Heroin, along with several other legal and illegal substances, falls under the “opiate” drug classification 1, The standard five-panel urine test will test for opiate use but cannot tell the employer which specific drug is responsible for the positive result.

This uncertainty could potentially allow applicants or employees to mask heroin use with other legally prescribed or obtained opiates.
Furthermore, a person may use heroin but still test negative for opiates due to the cut-off level used by laboratories—which is typically set at 2,000 ng/mL.
The first issue for employers is that a positive opiate result using the standard five-panel drug test still does not allow an employer to definitively confirm that heroin was used.

Because heroin is quickly metabolized and not excreted in urine to any appreciable extent, tests to identify heroin use typically look for one of its metabolites—morphine or 6-acetylmorphine (6-AM) 2, The standard five-panel urine test will only detect the first metabolite—morphine—which may be problematic for employers because morphine is also a metabolite of a number of other legal and illegal drugs.

Because of this, a positive result for morphine will not necessarily allow an employer to confirm heroin use. It may be important for the employer to differentiate between those individuals who test positive due to heroin use and those individuals who test positive due to some other legally prescribed or over-the-counter opiate because heroin is a Schedule I drug in the United States with no legitimate medical use.

This leads to the second potential issue when using the standard five-panel drug test to screen for heroin—heroin users may be able to explain a positive opiate result by providing a valid opiate prescription, thus leaving the heroin use undetected. If morphine is detected in a specimen provided by an applicant or employee, that individual could produce a valid codeine or morphine prescription to explain the positive result.

Thus, if the individual is using heroin, this use would go undetected since the morphine prescription is an acceptable explanation for the positive result and can, therefore, be used to mask any heroin use.
The final issue with using the standard five-panel test to screen for heroin is that the applicant or employee’s heroin use may not be significant enough to clear the typical confirmation cut-off level of 2,000 ng/mL for opiates, producing a false-negative result.

When testing specimens for potential drug use, labs use “cut-off levels” to determine whether the concentration is significant enough to report a positive result. Ideally, the chosen cut-off level will optimize drug detection and minimize the number of false-positive results.

Federally mandated screening and confirmation cut-off levels for opiates were recently increased from 300 ng/mL to 2,000 ng/mL. While this increase makes it less likely that specimens will produce false positives due to things like poppy seed ingestion, it also makes it more likely that some heroin use will not be significant enough to clear the higher cut-off level, thus producing a false-negative result for heroin.

In order to address these issues, employers are starting to follow U.S. Department of Transportation (DOT) guidelines by adding a 6-AM test to the standard five-panel urine-based drug test.6-AM is a metabolite that is unique to heroin and is only produced by the body after heroin use.

Recognizing the benefits of testing for this unique metabolite, the DOT adopted a rule in October 2010 that made 6-AM testing a required part of the standard initial DOT drug screen.6-AM is rapidly created in the body following heroin use and then is either metabolized into morphine or excreted in the urine.

Since 6-AM is a unique metabolite to heroin, its presence in the urine confirms that heroin was the opiate used (or at least one of the opiates used), and thus allows the laboratory to verify the result as positive for heroin, even if the donor has an opiate prescription or another plausible explanation for a positive opiate result 3,

Thus, by testing for 6-AM, employers can make it more difficult for applicants to mask heroin use with other legally-prescribed opiates. Another benefit to screening for 6-AM is the previously discussed issue of heroin use not being significant enough to clear the typical confirmation cut-off level of 2,000 ng/mL for morphine, resulting in a false negative on a standard five-panel drug screen.

According to the DOT, data shows that 6-AM-positive tests almost always have morphine levels that are above this confirmation cut-off or the laboratory’s level of detection, however, there are cases where a specimen is positive for 6-AM but no morphine is detected 4,

Thus, testing for 6-AM may allow employers to confirm an applicant’s heroin use even if the applicant tests negative for opiates.
However, please note that the absence of 6-AM does not rule out heroin use because trace amounts of 6-AM are only excreted for approximately 2 to 8 hours following heroin use (or slightly longer for heavy or chronic usage) 5, requiring a urine specimen to be collected soon after the last heroin use in order for it to be detected.

Thus, it is a best practice for employers to continue to use the standard five-panel urine-based drug test—which includes screening for opiate use—but to also add a 6-AM metabolite test to more specifically screen for heroin.1 Please note, the standard five-panel drug screen only tests for “natural opiates” and does not test for synthetic and semisynthetic opiates—such as hydrocodone (e.g.

Vicodin), hydromorphone (e.g. Dilaudid), oxycodone (e.g. OxyContin, Percocet), and oxymorphone—because they do not metabolize to codeine, morphine, or 6-AM. However, employers can add on additional testing for these specific synthetic and semisynthetic drugs. See Robert B. Swotinsky, M.D., M.P.H., The Medical Review Officer’s Manual 253 (5th ed.2015).2 Id.3 Id.

at 257.4 6-AM CG/MS analysis has a 10 ng/mL cutoff level, significantly lower than for morphine, making it a very sensitive and specific test to detect heroin use. See Id.5 Id. at 255. All Rights Reserved © 2017 Truescreen, Inc.This document and/or presentation is provided as a service to our customers.

Its contents are designed solely for informational purposes, and should not be inferred or understood as legal advice or binding case law, nor shared with any third parties.
Persons in need of legal assistance should seek the advice of competent legal counsel.
Although care has been taken in preparation of these materials, we cannot guarantee the accuracy, currency or completeness of the information contained within it.

Anyone using this information does so at his or her own risk. : Resource Center

What do you check when giving morphine?

Monitoring – The efficacy and therapeutic index of morphine are assessable with a combination of subjective and objective findings. Controlling pain, which is usually the first symptom evaluated in patients, is the ultimate goal of morphine use. Other essential parameters requiring monitoring include mental status, blood pressure, respiratory drive, and misuse/overuse.

Although it may seem intuitive, it is also important to monitor what other medications a patient is taking. This list includes but is not limited to prescription medications. All patients taking morphine should understand the need to avoid any other substances that could lead to respiratory depression.

These medications include but are not limited to alcohol, additional opioids, benzodiazepines, and barbiturates. Patients can become apneic at lower doses if combining morphine with any of these substances.

Does morphine make you tired and sleepy?

Precautions – It is very important that your doctor check your progress while you are using this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

Do not use this medicine if you have used an MAO inhibitor (MAOI) (eg, isocarboxazid, linezolid, phenelzine, selegiline, tranylcypromine ) within the past 14 days.
This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants.
CNS depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert.

Some examples of CNS depressants are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicine, other prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.

This effect may last for a few days after you stop using this medicine.
Check with your doctor before taking any of these medicines while you are using this medicine.
This medicine may be habit-forming.
If you feel that the medicine is not working as well, do not use more than your prescribed dose.
Dizziness, lightheadedness, or fainting may occur when you get up suddenly from a lying or sitting position.

Getting up slowly may help lessen this problem. Also, lying down for a while may relieve the dizziness or lightheadedness. This medicine may make you dizzy, drowsy, confused, or disoriented. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

This medicine may cause a serious allergic reaction called anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing or swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

If you have been using this medicine regularly for several weeks or longer, do not change your dose or suddenly stop using it without checking with your doctor.
Your doctor may want you to gradually reduce the amount you are using before stopping it completely.
This may help prevent worsening of your condition and reduce the possibility of withdrawal symptoms, such as abdominal or stomach cramps, anxiety, fever, nausea, runny nose, sweating, tremors, or trouble sleeping.

Do not take too much of this medicine or take it more often than your doctor tells you to. This can be life-threatening. Symptoms of an overdose include: extreme dizziness or weakness, slow heartbeat or breathing, seizures, trouble breathing, and cold, clammy skin.

Call your doctor right away if you notice these symptoms. Using this medicine while you are pregnant may cause serious unwanted effects, including neonatal opioid withdrawal syndrome in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.

Using too much of this medicine may cause reduced infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children. Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there.

Are mood changes a side effect of morphine?

Recognizing A Morphine Addiction – As with many prescription drugs, it can be hard to tell if someone is addicted to Morphine or simply keeping their pain at bay. Although Morphine has been considered a godsend for people in extreme chronic pain, it is also a drug that is often and easily abused.

People addicted to Morphine have developed a high tolerance to it. Sometimes, a Morphine addiction is so advanced that its users need more of the drug just to feel normal. Some common side effects of Morphine addiction are anxiety, depression, and negative personal and professional impacts. Some of the outward signs of a Morphine addiction may include dramatic changes in behavior or spending time around people outside of normal social circles who are also Morphine abusers.

Clinically, there are 11 criteria for diagnosing a Morphine addiction. A few examples of the criteria include using more Morphine than intended or prioritizing Morphine use over personal and professional obligations. Learn more about how addictions are clinically diagnosed.

What is the strongest pain killer?

Scientists Take Another Step Toward Creating Better Pain Medications Led by graduate student Jeff DiBerto, the UNC School of Medicine lab of Bryan Roth teamed with scientists in China to publish detailed structures of the entire human opioid receptor family to guide the creation of more targeted pain medications.

A detailed look into the amino acid bonds of opioid receptors bound to peptides.
CHAPEL HILL, NC – In the continuing effort to improve upon opioid pain relievers, American and Chinese scientists used cryoEM technology to solve the detailed structures of the entire family of opioid receptors bound to their naturally occurring peptides.

Subsequent structure-guided biochemical studies were then performed to better understand the mechanisms of peptide-receptor selectivity and signaling drugs. This work,, provides a comprehensive structural framework that should help drug developers rationally design safer drugs to relieve severe pain.

This work was spearheaded by the lab of Eric Xu, PhD, at the CAS Key Lab of Receptor Research in China, in collaboration with the lab of Bryan L.
Roth, MD, PhD, at the UNC School of Medicine, where graduate student Jeff DiBerto led the pharmacological experiments to understand the receptors’ signaling mechanisms.

Opioid drugs relieve pain by mimicking a naturally occurring pain-relief function within our nervous symptoms. They are the best, strongest pain relievers we have. Unfortunately, they come with side effects, some severe such as numbness, addiction, and respiratory depression, leading to overdose deaths.

Scientists have been trying for many years to overcome the side-effect problem in various ways, all involving one or more of four opioid receptors to no avail.
One way scientists continue to explore is the creation of peptide or peptide-inspired small molecule drugs.
Peptides are short chains of amino acids; think of them as short proteins.

Certain naturally occurring, or endogenous, peptides bind to opioid receptors on the surface of cells to create an analgesic effect, also known as pain relief. Think of an analgesic like an anesthetic, except that analgesics do not “turn off” the nerves to numb the body or alter consciousness. Bryan Roth, MD, PhD “The problem in the field is we’ve lacked the molecular understanding of the interplay between opioid peptides and their receptors,” said Roth, co-senior author and the Michael Hooker Distinguished Professor of Pharmacology. “We’ve needed this understanding in order to try to rationally design potent and safe peptide or peptide-inspired drugs.” Using cryogenic electron microscopy, or cryoEM, and a battery of biomechanistic experiments in cells, the Xu and Roth labs systematically solved the detailed structures of endogenous peptides bound to all four opioid receptors.

These structures revealed details and insights into how specific naturally occurring opioid peptides selectively recognize and activate opioid receptors.
The researchers also used exogenous peptides, or drug-like compounds, in some of their experiments to learn how they activate the receptors.
The cryoEM structures of agonist-bound receptors in complex with their G protein effectors (called their “active state”) represents what these receptors look like when they are signaling in cells, giving a detailed view of peptide-receptor interactions.

The Roth lab used the structures solved by the Xu lab to guide the design of mutant receptors, and then tested these receptors in biochemical assays in cells to determine how they alter receptor signaling. Understanding these interactions can then be used to design drugs that are selective for opioid receptor subtypes, as well as to produce certain signaling outcomes that may be more beneficial than those of conventional opioids. Jeff DiBerto creating subtype-selective drugs,” said DiBerto, first author and PhD candidate in the Roth lab. “We provide more needed information to keep pushing the field forward, to answer basic science questions we hadn’t been able to answer before now.” Previous research showed the structure of opioid receptors in their inactive or active-like states, with active state structures only existing for the mu-opioid receptor subtype, the primary target of drugs like fentanyl and morphine.

In the Cell paper, the authors show agonist-bound receptors in in complex with their G protein effectors, made possible through cryoEM technology that did not exist when currently used medications were being developed.
Drugs such as oxycontin, oxycodone, and morphine cause various effects inside cells and throughout the nervous symptom, including pain relief.

But they have effects in the digestive and respiratory systems, too, and interact with cells to lead to addiction. Fentanyl, meanwhile, is another powerful pain reliever, but it binds to opioid receptors in such a way as to cause severe side effects, including the shutdown of the respiratory system.

The thrust behind such research led by Xu and Roth is to home in on the mechanistic reasons for pain relief potency without triggering the cellular mechanisms that lead to severe side effects and overdosing.
We are attempting to build a better kind of opioid,” Roth says, “We’re never going to get there without these kind of basic molecular insights, wherein we can see why pain is relieved and why side effects occur.” Co-first authors of the Cell paper are Yue Wang and Youwen Zhuang of the CAS Key Laboratory of Receptor Research and the State Key Laboratory of Drug Research at the Shanghai Institute of Materia Medica in the Chinese Academy of Sciences.

Other authors are Edward Zhou and Karsten Melcher of the Van Andel Research Institute in Grand Rapids, MI, Gavin Schmitz and Manish Jain at the UNC School of Medicine, and Qingning Yuan, Weiyi Liu, and Yi Jiant at the CAS Key Laboratory. UNC School of Medicine contact: : Scientists Take Another Step Toward Creating Better Pain Medications

What causes end of life pain?

What causes pain? – Pain is a physical sensation. It happens when damaged areas of the body send signals to the brain. Pain can be caused by the person’s illness itself, or by a treatment or operation they’ve had. It could also be caused by a condition they’ve had for a while, such as arthritis.

People who have experienced pain during their illness or who have certain conditions, such as cancer that has spread around their body, may need more support to manage their pain.
Although pain is a physical sensation, we also know that lots of other things can affect how people experience pain.
Feeling stressed, anxious, worried, tired, or alone can all make pain worse.

Towards the end of life, pain can sometimes be worse if someone is finding it difficult to accept that they are dying or they are worried about how others will cope when they are gone. Read more about different types of pain that people may experience.

Is it safe to take 10mg of morphine?

For oral dosage form (extended-release capsules):

For moderate to severe pain:

Adults—

Children—Use and dose must be determined by your doctor.

For oral dosage form (extended-release tablets):

For moderate to severe pain:

For oral dosage form (solution):

For moderate to severe pain:

Adults—10 to 20 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed. Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets):

For moderate to severe pain:

Adults—15 to 30 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed. Children—Use and dose must be determined by your doctor.

How often to take 10mg morphine?

2.2 Initiation of Therapy in Opioid-Naïve Patients Start patients who have not been receiving opioid analgesics on morphine sulfate in the following dosing range using Oral Solution, 10 mg per 5 mL or 20 mg per 5 mL strengths: Morphine Sulfate Oral Solution: 10 to 20 mg every 4 hours as needed for pain.

How many 10mg morphine can you take?

Expand All

Posology
Adults:	Recommended dose: 10-20 mg (5-10 ml) every 4 hours. Maximum daily dose: 120 mg per day
Children 1-5 years:	Recommended dose 5 mg (2.5 ml) every 4 hours. Maximum daily dose: 30 mg per day
Children under 1 year:	Not recommended.

What is morphine sulfate 10 mg mL?

My Account Area – 1. Name of the medicinal product Morphine sulfate 10 mg/ml solution for injection 2. Qualitative and quantitative composition 1 ml of solution contains 10 mg of morphine sulfate. Excipient with known effect: Also contains 3.11 mg of sodium per ml. For the full list of excipients, see section 6.1.3. Pharmaceutical form Solution for injection. Clear colourless or almost colourless solution.4. Clinical particulars 4.1 Therapeutic indications Morphine is used for the symptomatic relief of severe pain; relief of dyspnoea of left ventricular failure and pulmonary oedema of cardiogenic origin; pre-operative use in adults.4.2 Posology and method of administration Posology Adults The dosage should be based on the severity of the pain and the response and tolerance of the patient. The usual adult subcutaneous or intramuscular dose is 10 mg every 4 hours if necessary, but may range from 5 mg to 20 mg. The usual adult intravenous dose is 2.5 mg to 15 mg not more than 4 hourly, where necessary, but dosage and dosing interval must be titrated against the patient’s response and adjustments made until analgesia is achieved. Elderly Because of the depressant effect on respiration, caution is necessary when giving morphine to the elderly and reduced doses may be required. Paediatric population Use in children is not recommended. Hepatic impairment A reduction in dosage should be considered in hepatic impairment. Renal impairment The dosage should be reduced in moderate to severe renal impairment. For concomitant illnesses/conditions where dose reduction may be appropriate see 4.4 Special warnings and precautions for use. Discontinuation of therapy An abstinence syndrome may be precipitated if opioid administration is suddenly discontinued. Therefore the dose should be gradually reduced prior to discontinuation. Method of administration The injection may be given by the intravenous, intramuscular or subcutaneous route. The subcutaneous route is not suitable for oedematous patients.4.3 Contraindications – Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. – Acute respiratory depression – Obstructive airways disease – Concurrent treatment with monoamine oxidase inhibitors or within two weeks of their discontinuation of treatment with them – Cerebral oedema – Head injuries – Coma – Convulsive disorders – Raised intracranial pressure – Biliary colic – Acute alcoholism – Antibiotic induced pseudomembranous colitis – Ulcerative colitis because of the risk of toxic megacolon – Phaeochromocytoma – Paralytic ileus – Acute diarrhoea caused by poisoning or invasive pathogens.4.4 Special warnings and precautions for use Morphine is a potent medicine but with considerable potential for harmful effect, including addiction. It should be used only if other drugs with fewer hazards are inadequate, and with the recognition that it may possibly mask significant manifestations of disease which should be identified for proper diagnosis and treatment. Use with caution or reduced doses Morphine should be given in reduced doses or with caution to patients with asthma or a reduced respiratory reserve (including emphysema, chronic cor pulmonale, kyphoscoliosis, excessive obesity and sleep apnoea). Avoid use during an acute asthma attack (see 4.3 Contraindications). Opioid analgesics in general should be administered with caution or in reduced doses to patients with hypotension, hypothyroidism, adrenocortical insufficiency, impaired kidney or liver function, prostatic hypertrophy, urethral stricture, shock, inflammatory or obstructive bowel disorders, or convulsive disorders. Caution is advised when giving morphine to patients with impaired liver function due to its hepatic metabolism (see 4.2 Posology). Severe and prolonged respiratory depression has occurred in patients with renal impairment who have been given morphine (see 4.2 Posology). Dosage should be reduced in elderly and debilitated patients. Plasma concentrations of morphine may be reduced by rifampicin. The analgesic effect of morphine should be monitored and doses of morphine adjusted during and after treatment with rifampicin. Biliary disorders Opioids such as morphine should either be avoided in patients with biliary disorders or they should be given with an antispasmodic. Morphine can cause an increase in intrabiliary pressure as a result of effects on the sphincter of Oddi. Therefore in patients with biliary tract disorders morphine may exacerbate pain (use in biliary colic is a contraindication, see 4.3). In patients given morphine after cholecystectomy, biliary pain has been induced. Drug abuse Morphine has an abuse potential similar to other strong agonist opioids, and should be used with special caution in patients with a history of alcohol or drug abuse. Dependence and withdrawal (abstinence) syndrome Use of opioid analgesics may be associated with the development of physical and/or psychological dependence or tolerance. The risk increases with the time the drug is used, and with higher doses. Symptoms can be minimised with adjustments of dose or dosage form, and gradual withdrawal of morphine. For individual symptoms, see section 4.8. Hyperalgesia that does not respond to a further dose increase of morphine may occur in particular in high doses. A morphine dose reduction or change in opioid may be required. An unexplained increase in abdominal pain associated with disturbed intestinal motility, symptoms of constipation, bloating, abdominal distension and increased gastroesophageal reflux during treatment with morphine sulfate, may indicate the development of opioid-induced bowel dysfunction or narcotic bowel syndrome. In such situations consider the use of alternative analgesics and a morphine detoxification. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Morphine sulfate and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Morphine sulfate concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5). Oral P2Y12 inhibitor antiplatelet therapy Within the first day of concomitant P2Y12 inhibitor and morphine treatment, reduced efficacy of P2Y12 inhibitor treatment has been observed (see section 4.5). Palliative care In the control of pain in terminal illness, these conditions should not necessarily be a deterrent to use. Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) Due to a possible association between ACS and morphine use in SCD patients treated with morphine during a vaso-occlusive crisis, close monitoring for ACS symptoms is warranted. Adrenal insufficiency Opioid analgesics may cause reversible adrenal insufficiency requiring monitoring and glucocorticoid replacement therapy. Symptoms of adrenal insufficiency may include e.g. nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or low blood pressure. Decreased Sex Hormones and increased prolactin Long-term use of opioid analgesics may be associated with decreased sex hormone levels and increased prolactin. Symptoms include decreased libido, impotence or amenorrhea.4.5 Interaction with other medicinal products and other forms of interaction Alcohol: enhanced sedative and hypotensive effects. Anti-arrhythmics: There may be delayed absorption of mexiletine. Antibacterials: The opioid analgesic papaveretum has been shown to reduce plasma ciprofloxacin concentration. The manufacturer of ciprofloxacin advises that premedication with opioid analgesics be avoided. Antidepressants, anxiolytics, hypnotics: Severe CNS excitation or depression (hypertension or hypotension) has been reported with the concurrent use of pethidine and monoamine oxidase inhibitors (MAOIs) including selegiline, moclobemide and linezolid. As it is possible that a similar interaction may occur with other opioid analgesics, morphine should be used with caution and consideration given to a reduction in dosage in patients receiving MAOIs. The sedative effects of morphine (opioid analgesics) are enhanced when used with depressants of the central nervous system such as hypnotics, anxiolytics, tricyclic antidepressants and sedating antihistamines. Antipsychotics: possible enhanced sedative and hypotensive effect. Antidiarrhoeal and antiperistaltic agents (such as loperamide and kaolin): concurrent use may increase the risk of severe constipation. Antimuscarinics: agents such as atropine antagonise morphine-induced respiratory depression and can partially reverse biliary spasm but are additive to the gastrointestinal and urinary tract effects. Consequently, severe constipation and urinary retention may occur during intensive antimuscarinicanalgesic therapy. Metoclopramide and domperidone: There may be antagonism of the gastrointestinal effects of metoclopramide and domperidone. Sedative medicines such as benzodiazepines or related drugs: The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4). Cimetidine: inhibits the metabolism of morphine. Rifampicin: Plasma concentrations of morphine may be reduced by rifampicin. Ritonavir: Although there are no pharmacokinetic data available for concomitant use of ritonavir with morphine, ritonavir induces the hepatic enzymes responsible for the glucuronidation of morphine, and may possiblu decrease plasma concentrations of morphine. Oral P2Y12 inhibitors : A delayed and decreased exposure to oral P2Y12 inhibitor antiplatelet therapy has been observed in patients with acute coronary syndrome treated with morphine. This interaction may be related to reduced gastrointestinal motility and apply to other opioids. The clinical relevance is unknown, but data indicate the potential for reduced P2Y12 inhibitor efficacy in patients co administered morphine and a P2Y12 inhibitor (see section 4.4). In patients with acute coronary syndrome, in whom morphine cannot be withheld and fast P2Y12 inhibition is deemed crucial, the use of a parenteral P2Y12 inhibitor may be considered.4.6 Fertility, pregnancy and lactation Pregnancy Since morphine rapidly crosses the placental barrier, it is not advised to administer morphine during pregnancy and labour. It may reduce uterine contractions, cause respiratory depression in the foetus and new born infant, and may have significant effects on foetal heart rate. Newborns whose mothers received opioid analgesics during pregnancy should be monitored for signs of neonatal withdrawal (abstinence) syndrome. Treatment may include an opioid and supportive care. As with all drugs it is not advisable to administer morphine during pregnancy. Breastfeeding The amount of morphine secreted in breast milk after a single-dose administration seems to be compatible with breast feeding and insufficient to cause major problems or dependence. However long-term treatment with morphine in high doses may cause significant plasma concentration. That is why caution is advised on the use of morphine in breast-feeding patient and the benefit must outweigh the risk to the infant. If breast feeding is continued, the infant should be observed for possible adverse effects. Fertility Animal studies have shown that morphine may reduce fertility (see section 5.3 Preclinical safety data).4.7 Effects on ability to drive and use machines Morphine has major influence on the ability to drive and use machines. It may cause drowsiness so patients should avoid driving or operating machinery. This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told: • The medicine is likely to affect your ability to drive • Do not drive until you know how the medicine affects you • It is an offence to drive while under the influence of this medicine • However, you would not be committing an offence (called ‘statutory defence’) if: o The medicine has been prescribed to treat a medical or dental problem and o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely 4.8 Undesirable effects Adverse effects can be listed in terms of their frequency of occurrence: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), not known (cannot be estimated from the available data). Morphine may cause the following adverse events: Nervous system disorders:

Very common:	Drowsiness, hyperhidrosis.
Common:	Convulsion, headache, increased intracranial pressure, myoclonus; opioid-induced hyperalgesia (or hyperaesthesia) (see section 4.4), vertigo.
Not known:	Allodynia (see section 4.4), coma.

Psychiatric disorders:

Very common:	Confusional state, hallucinations, physical and psychological dependence.
Common:	Decreased libido, mood swings, restlessness.

Eye disorders:

Common:

Blurred vision, miosis, nystagmus.

Respiratory, thoracic and mediastinal disorders:

Very common:	Respiratory depression.
Common:	Bronchospasm, pulmonary oedema, which can lead to death.
Not known:	Respiratory failure, which also can lead to death.

Cardiac disorders:

Common:	Bradycardia, circulatory failure, tachycardia.
Uncommon:	Palpitations.

Vascular disorders:

Common:

Hypotension, orthostatic hypotension.

Gastrointestinal disorders:

Very common:	Constipation, nausea, vomiting.
Common:	Dry mouth, paralytic ileus.
Not known:	Intestinal functional disorder, narcotic bowel syndrome.

Hepatobiliary disorders:

Common:	Biliary spasm.
Uncommon:	Hepatic enzyme increase.
Not known:	Spasm of the sphincter of Oddi.

Reproductive system and breast disorders:

Common:

Erectile dysfunction.

Renal and urinary disorders:

Common:	Urinary retention.
Uncommon:	Urethral spasm.
Not known:	Renal failure.

Immune system disorders:

Uncommon:	Anaphylactic reaction, hypersensitivity.
Not known:	Anaphylactoid reactions

Musculoskeletal and connective tissue disorders:

Not known:

Muscle rigidity, rhabdomyolysis.

Skin and subcutaneous tissue disorders:

Very common:	Pruritus.
Common:	Angioedema, contact dermatitis, rash, urticaria.

General disorders and administration site conditions:

Very common:	Drug tolerance
Common:	Fatigue, facial flushing, hypothermia, injection site pain, injection site irritation, drug withdrawal (abstinence) syndrome (babies born to opioid-dependent mothers also at risk to present withdrawal syndrome).

Drug dependence and withdrawal (abstinence) syndrome Use of opioid analgesics may be associated with the development of physical and/or psychological dependence or tolerance. An abstinence syndrome may be precipitated when opioid administration is suddenly discontinued or opioid antagonists administered, or can sometimes be experienced between doses.

For management, see 4.4.
Physiological withdrawal symptoms include: Body aches, tremors, restless legs syndrome, diarrhoea, abdominal colic, nausea, flu-like symptoms, tachycardia and mydriasis.
Psychological symptoms include dysphoric mood, anxiety and irritability.
In drug dependence, “drug craving” is often involved.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose Symptoms: respiratory depression, pin-point pupils, pneumonia aspiration and coma.

In addition, shock, reduced body temperature and hypotension may occur. In mild overdose, symptoms include nausea and vomiting, tremor, miosis, dysphoria, hypothermia, hypotension, confusion and sedation. In cases of severe poisoning, hypotension with circulatory failure, rhabdomyolosis progressing to renal failure, respiratory collapse may occur.

Death may occur from respiratory failure. Treatment: the patient must be given both respiratory and cardiovascular support and the specific antagonist, naloxone, should be administered using one of the recommended dosage regimens. Fluid and electrolyte levels should be maintained.5.

Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Natural opium alkaloids, ATC code: N02AA01.
Morphine is a narcotic analgesic obtained from opium, which acts mainly on the central nervous system and smooth muscle.5.2 Pharmacokinetic properties Absorption Variably absorbed after oral administration; rapidly absorbed after subcutaneous or intramuscular administration.

Blood concentration After an oral dose of 10 mg as the sulfate, peak serum concentrations of free morphine of about 10 ng/ml are attained in 15 to 60 minutes. After an intramuscular dose of 10 mg, peak serum concentrations of 70 to 80 ng/ml are attained in 10 to 20 minutes.

After an intravenous dose of 10 mg, serum concentrations of about 60 ng/ml are obtained in 15 minutes falling to 30 ng/ml after 30 minutes and to 10 ng/ml after three hours. Subcutaneous doses give similar concentrations to intramuscular doses at 15 minutes but remain slightly higher during the following 3 hours; serum concentrations measured soon after administration correlate closely with the ages of the subjects studied and are increased in the elderly.

Half-life Serum half-life in the period 10 minutes to 6 hours following intravenous administration, 2 to 3 hours; serum half-life in the period 6 hours onwards, 10 to 44 hours. Distribution Widely distributed throughout the body, mainly in the kidneys, liver, lungs and spleen; lower concentrations appear in the brain and muscles.

Morphine crosses the placenta and traces are secreted in sweat and milk. Protein binding, about 35% bound to albumin and to immunoglobulins at concentrations within the therapeutic range. Biotransformation Mainly glucuronic acid conjugation to form morphine-3 and 6-glucuronides, with sulfate conjugation.

N-demethylation, O-methylation and N-oxide glucuronide formation occurs in the intestinal mucosa and liver; N-demethylation occurs to a greater extent after oral than parental administration; the O-methylation pathway to form codeine has been challenged and codeine and norcodeine metabolites in urine may be formed from codeine impurities in the morphine sample studied.

Elimination After an oral dose, about 60% is excreted in the urine in 24 hours, with about 3% excreted as free morphine in 48 hours.
After a parental dose, about 90% is excreted in 24 hours, with about 10% as free morphine, 65 to 70% as conjugated morphine, 1% as normorphine and 3% as normorphine glucuronide.

After administration of large doses to addicts about 0.1% of a dose is excreted as norcodeine. Urinary excretion of morphine appears to be pH dependent to some extent; as the urine becomes more acidic more free morphine is excreted and as the urine becomes more alkaline more of the glucuronide conjugate is excreted; up to 10% of a dose may be excreted in the bile.5.3 Preclinical safety data Non-clinical data based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential reveal no special hazard additional to the known safety profile of morphine in humans.

In male rats, reduced fertility and chromosomal damage in gametes have been reported.6.
Pharmaceutical particulars 6.1 List of excipients Sodium chloride Hydrochloric acid (for pH adjustment) Water for injections 6.2 Incompatibilities Morphine salts may be precipitated in alkaline solution.
Morphine sulfate is incompatible with oxidizing agents.

Physicochemical incompatibility (formation of precipitates) has been demonstrated between solutions of morphine sulfate and 5-fluorouracil.6.3 Shelf life 2 years.6.4 Special precautions for storage Keep the ampoules in the outer carton in order to protect from light.6.5 Nature and contents of container Type I amber glass ampoules of 1 ml with white open point cut.

The ampoules are packed in transparent polyvinylchloride film liners.
The liners together with leaflets are packed in cartons.
Pack size: 5 or 10 ampoules.
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling The medicinal product is for single use only; discard any remaining contents after use.

Instruction of ampoule opening: 1) Hold the ampoule upright. If there is any solution in the upper part of the ampoule, gently tap with your finger to get all the solution to the lower part of the ampoule.2) Use both hands to open; while holding the lower part of the ampoule in one hand, use the other hand to break off the upper part of the ampoule in the direction away from the coloured point (see the pictures below). The required volume should be calculated based on the prescribed dose. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.7. Marketing authorisation holder AS KALCEKS Krustpils iela 53, Rīga, LV-1057, Latvia Tel.: +371 67083320 E-mail: 8.

Skye Skinner