Infumorph 200

Dosage for morphine must be highly individualized based on the patient's age, weight, medical history, and previous exposure to opioid medications. Healthcare providers usually follow the principle of 'start low and go slow.'

• Opioid-Naive Patients: For those not currently taking opioids, a typical starting dose of immediate-release morphine might be 10 mg to 30 mg every 4 hours as needed for pain.
• Chronic Pain (Extended-Release): For around-the-clock management, doses may range from 15 mg to 60 mg once or twice daily, depending on the specific brand (e.g., MS Contin is usually every 12 hours, while Kadian may be once daily).
• Intravenous (IV) Administration: In a hospital setting, 2 mg to 10 mg every 4 hours is common for acute pain, often delivered via a Patient-Controlled Analgesia (PCA) pump.

Morphine is used in children, but dosing is strictly weight-based and must be managed by a pediatric specialist.

• Standard Pediatric Dose: Typically 0.1 mg/kg to 0.2 mg/kg every 4 hours for oral IR solution.
• Neonatal Use: Extreme caution is required due to immature renal and hepatic function; doses are significantly lower and monitoring is continuous.

Renal Impairment

Because morphine's active metabolites (M6G) are cleared by the kidneys, patients with a reduced Glomerular Filtration Rate (GFR) require significant dose reductions. If the GFR is between 10-50 mL/min, providers typically give 75% of the normal dose. If GFR is below 10 mL/min, the dose is often reduced to 50% or avoided entirely in favor of opioids not cleared renally (like hydromorphone or fentanyl).

Hepatic Impairment

Since the liver is the primary site of glucuronidation, patients with cirrhosis or hepatic failure may experience delayed clearance. Healthcare providers may increase the dosing interval (e.g., giving the drug every 8 hours instead of every 4) to prevent accumulation.

Elderly Patients

Older adults often have decreased renal function and increased sensitivity to CNS effects. Providers generally start elderly patients at 50% of the standard adult dose to minimize the risk of confusion, falls, and respiratory depression.

• Consistency: Extended-release tablets should be taken at the same time each day to maintain steady blood levels.
• Swallow Whole: ER formulations (like MS Contin) must be swallowed whole. Crushing, chewing, or dissolving them can lead to 'dose dumping,' where the entire 12-to-24-hour dose is released at once, which can be fatal.
• With or Without Food: Morphine can be taken with food if it causes stomach upset, though food does not significantly change the total amount of drug absorbed.
• Storage: Store at room temperature (68°F to 77°F) in a secure, locked location. Morphine is a Schedule II controlled substance and is a target for theft and misuse.

If you miss a dose of an around-the-clock morphine medication, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular schedule. Never double the dose to catch up, as this increases the risk of dangerous respiratory depression.

A morphine overdose is a medical emergency. Signs include:

• Pinpoint Pupils: Extreme constriction of the pupils.
• Respiratory Depression: Slow, shallow, or stopped breathing.
• Extreme Somnolence: Inability to wake up or stay conscious.
• Cold/Clammy Skin: Often accompanied by a bluish tint to the lips or fingernails (cyanosis).
• Bradycardia: Dangerously slow heart rate.

In the event of a suspected overdose, call emergency services immediately. Naloxone (Narcan) is the standard reversal agent and should be administered if available.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as sudden discontinuation can lead to severe withdrawal symptoms.

Most patients taking morphine will experience at least one side effect, particularly during the first few days of treatment or following a dose increase.

• Constipation: This is the most common side effect and, unlike other symptoms, patients do not develop a tolerance to it. Morphine slows down the movement of the muscles in the digestive system (peristalsis). Healthcare providers often recommend a 'mush and push' approach (a stool softener plus a stimulant laxative) from the start of therapy.
• Nausea and Vomiting: This occurs because morphine stimulates the chemoreceptor trigger zone in the brain. It often improves after a few days as the body adjusts.
• Drowsiness (Somnolence): A feeling of being sleepy or 'foggy.' This can impair the ability to drive or operate machinery.
• Pruritus (Itching): Morphine causes the release of histamine from mast cells, which can lead to itching or redness, even without an actual allergy.

• Dizziness and Orthostatic Hypotension: A drop in blood pressure when standing up, which can lead to fainting.
• Urinary Retention: Difficulty starting urination or fully emptying the bladder, more common in older men with enlarged prostates.
• Dry Mouth (Xerostomia): Reduced saliva production, which can increase the risk of dental cavities over time.
• Sweating (Diaphoresis): Sudden bouts of warmth or perspiration.

• Euphoria or Dysphoria: Intense feelings of happiness or, conversely, unexplained anxiety and sadness.
• Biliary Spasm: Morphine can cause the Sphincter of Oddi to spasm, potentially causing severe abdominal pain similar to a gallbladder attack.
• Myoclonus: Involuntary muscle twitching or jerking, often a sign of metabolite accumulation.

> Warning: Stop taking Morphine and call your doctor or emergency services immediately if you experience any of these:

• Severe Respiratory Depression: Breathing that is very slow (less than 8-10 breaths per minute) or shallow.
• Chest Pain: Could indicate a cardiac event or severe pulmonary issues.
• Anaphylaxis: Signs include swelling of the face, tongue, or throat, hives, and difficulty breathing.
• Serotonin Syndrome: If taken with other serotonergic drugs, symptoms include agitation, hallucinations, rapid heart rate, and muscle stiffness.
• Adrenal Insufficiency: Long-term use can cause the adrenal glands to stop producing enough cortisol. Symptoms include nausea, vomiting, loss of appetite, and worsening tiredness.

• Opioid-Induced Hyperalgesia (OIH): Paradoxically, long-term use can make a person more sensitive to pain.
• Hormonal Changes: Chronic use can lower levels of testosterone and estrogen, leading to decreased libido, infertility, or osteoporosis (brittle bones).
• Immune System Suppression: Some evidence suggests long-term opioids may weaken the immune response.
• Tolerance and Dependence: Over time, higher doses may be needed for the same effect, and the body becomes physically dependent on the drug.

The FDA has issued several 'Black Box Warnings' for morphine, the highest level of alert:

1. 1Addiction, Abuse, and Misuse: Morphine carries a high risk for opioid use disorder, which can lead to overdose and death.
2. 2Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur.
3. 3Neonatal Opioid Withdrawal Syndrome (NOWS): Prolonged use during pregnancy can result in life-threatening withdrawal in the newborn.
4. 4Interactions with Benzodiazepines: Using morphine with Valium, Xanax, or alcohol can result in profound sedation, respiratory depression, coma, and death.
5. 5Accidental Ingestion: Even one accidental dose, especially by a child, can be fatal.

Report any unusual symptoms to your healthcare provider immediately to ensure safe management of your therapy.

Morphine is a high-alert medication. It must only be used by the person for whom it was prescribed. Sharing morphine is illegal and dangerous. Patients should be screened for a personal or family history of substance abuse before starting therapy. It is vital to keep this medication in a locked cabinet, away from children and pets.

The FDA-approved labeling for morphine contains several critical warnings. These include the risk of Addiction, Abuse, and Misuse, which can occur even at recommended doses. Life-threatening Respiratory Depression is a constant risk, particularly during the initiation of therapy or after a dose increase. There is also a warning regarding Accidental Ingestion, noting that a single dose of morphine, especially by a child, can result in a fatal overdose. Furthermore, the Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants (including alcohol) are highlighted, as these combinations significantly increase the risk of fatal respiratory failure.

• Allergic Reactions: While true IgE-mediated allergies to morphine are rare, they can occur. Most 'reactions' are histamine-related (itching), but anaphylaxis is possible. Patients with a known allergy to codeine may also be allergic to morphine due to structural similarities.
• Gastrointestinal Risks: Morphine is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus (where the bowel stops moving).
• Head Injury and Increased Intracranial Pressure: Morphine can mask the clinical course of patients with head injuries and may further increase pressure within the skull by causing CO2 retention, which dilates cerebral blood vessels.
• Seizure Disorders: Morphine may lower the seizure threshold in patients with a history of epilepsy.
• Hypotension: Morphine can cause severe low blood pressure, especially in patients whose ability to maintain blood pressure is already compromised by reduced blood volume or certain medications.

Patients on long-term morphine therapy require regular monitoring by their healthcare provider:

• Pain Assessment: Regular evaluation of the efficacy of the treatment and whether the goals of therapy are being met.
• Respiratory Status: Monitoring for signs of slowed breathing, especially in those with underlying lung disease like COPD or sleep apnea.
• Liver and Kidney Function: Periodic blood tests (BUN, Creatinine, LFTs) to ensure the body is still processing the drug safely.
• Signs of Misuse: Providers may use urine drug screenings (UDS) and Prescription Drug Monitoring Programs (PDMP) to ensure the medication is being used as intended.

Morphine significantly impairs the mental and physical abilities required for potentially hazardous tasks. Do not drive a car or operate heavy machinery until you know how morphine affects you. Drowsiness and delayed reaction times are common, especially when starting the drug or increasing the dose.

Do not consume alcohol while taking morphine. Alcohol can increase the sedative effects of morphine and, in the case of some extended-release formulations, can cause the drug to be released into the bloodstream all at once ('dose dumping'), which can be fatal.

Do not stop taking morphine abruptly if you have been taking it for more than a few days. Sudden discontinuation can lead to a severe withdrawal syndrome, characterized by anxiety, sweating, insomnia, rigors (shaking), pain, nausea, and diarrhea. Your healthcare provider will provide a tapering schedule to slowly reduce the dose and minimize these symptoms.

> Important: Discuss all your medical conditions, especially any history of lung disease, kidney disease, or substance abuse, with your healthcare provider before starting Morphine.

Certain medications should never be combined with morphine due to the risk of extreme toxicity:

• MAO Inhibitors (MAOIs): Drugs like phenelzine or selegiline (used for depression or Parkinson's) can cause unpredictable and severe reactions when combined with opioids. Morphine should not be used within 14 days of taking an MAOI.
• Mixed Agonist/Antagonist Opioids: Medications like buprenorphine, nalbuphine, or pentazocine can trigger withdrawal symptoms and reduce the pain-relieving effectiveness of morphine if used together.

• Benzodiazepines and CNS Depressants: This includes medications like alprazolam (Xanax), diazepam (Valium), and sleep aids like zolpidem (Ambien). These drugs multiply the respiratory-depressant effects of morphine, significantly increasing the risk of death.
• Anticholinergic Drugs: Medications for overactive bladder or certain antihistamines can increase the risk of severe constipation and urinary retention when taken with morphine.
• Serotonergic Drugs: SSRIs (like fluoxetine) or SNRIs (like venlafaxine) can rarely contribute to Serotonin Syndrome when combined with high-dose opioids.

• Diuretics: Morphine can reduce the efficacy of diuretics (water pills) by stimulating the release of antidiuretic hormone (ADH). It may also lead to more significant drops in blood pressure.
• Muscle Relaxants: Drugs like cyclobenzaprine can increase the sedative effect of morphine, leading to increased fall risk and respiratory depression.

• High-Fat Meals: For certain extended-release brands, a high-fat meal can increase the peak concentration of the drug in the blood, potentially increasing side effects. Check the specific patient insert for your brand.
• Alcohol: As noted previously, alcohol is strictly contraindicated. It can lead to 'dose dumping' of extended-release products and fatal respiratory depression.

• St. John's Wort: May potentially decrease the plasma concentration of morphine by inducing certain metabolic pathways, though the effect is less pronounced than with other opioids.
• Kava, Valerian, and Melatonin: These supplements have sedative properties and can increase the drowsiness caused by morphine.

• Amylase/Lipase: Morphine can cause a rise in these enzymes due to spasms of the Sphincter of Oddi, which might be misinterpreted as pancreatitis.
• Urine Drug Screens: Morphine will result in a positive test for 'opiates.' Specialized testing is required to distinguish it from other opioids like codeine or heroin.

For each major interaction, the mechanism usually involves either pharmacodynamic synergy (two drugs doing the same thing to the body, like slowing breathing) or pharmacokinetic interference (one drug changing how the other is absorbed or excreted). The management strategy is typically to avoid the combination, reduce the dose, or increase monitoring.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. A complete list is the best way to prevent dangerous interactions.

There are several conditions where morphine must never be used because the risks far outweigh any potential benefit:

• Significant Respiratory Depression: Patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.
• Gastrointestinal Obstruction: Specifically known or suspected paralytic ileus, where the drug's effect on gut motility could cause a bowel rupture.
• Hypersensitivity: A known true allergy to morphine sulfate or any of the inactive ingredients in the formulation.
• Acute or Severe Bronchial Asthma: In unmonitored settings, the respiratory-depressant effect of morphine can be fatal for an asthma patient.

In these situations, a healthcare provider must perform a careful risk-benefit analysis:

• Chronic Obstructive Pulmonary Disease (COPD): Morphine can decrease the respiratory drive and increase airway resistance.
• Biliary Tract Disease: Due to the risk of Sphincter of Oddi spasm, morphine may worsen the pain of gallstones.
• Severe Renal or Hepatic Impairment: While not an absolute contraindication, the risk of metabolite toxicity (M6G) is extremely high, and alternative opioids are often preferred.
• Head Injury: Morphine can obscure the neurological signs used to monitor a patient's recovery from a brain injury.
• Hypovolemia or Shock: Morphine's ability to cause vasodilation can lead to a catastrophic drop in blood pressure in patients who are already hemodynamically unstable.

Patients who have had a severe allergic reaction to other phenanthrene-type opioids (such as codeine, hydrocodone, or hydromorphone) may also react to morphine. However, they may be able to tolerate opioids from different chemical classes, such as phenylpiperidines (fentanyl) or diphenylheptanes (methadone), under strict medical supervision.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of lung, kidney, or liver disease, before prescribing Morphine.

Morphine is generally classified as Pregnancy Category C (under the older system). Prolonged use of morphine during pregnancy can result in Neonatal Opioid Withdrawal Syndrome (NOWS), which can be life-threatening if not recognized and treated. Symptoms in the newborn include irritability, hyperactivity, abnormal sleep patterns, high-pitched cry, tremor, vomiting, and failure to gain weight. Morphine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Use during labor and delivery can lead to respiratory depression in the newborn.

Morphine is excreted in human milk. While the amounts are often small, there is a risk of sedation and respiratory depression in the nursing infant. If a breastfeeding mother requires morphine, the infant must be closely monitored for increased sleepiness, difficulty breastfeeding, or breathing problems. Many experts recommend using the lowest effective dose for the shortest duration or considering alternative pain management strategies.

Morphine is approved for use in children for the management of severe pain. However, the safety and effectiveness of extended-release formulations in pediatric patients under the age of 18 have not been well-established. Pediatric dosing is strictly weight-based, and children are more susceptible to the respiratory-depressant effects of opioids.

Elderly patients (65 years and older) are at an increased risk for adverse reactions. They often have reduced renal clearance, which leads to the accumulation of active metabolites. Furthermore, the elderly are more prone to morphine-induced confusion, delirium, and falls. Healthcare providers typically start with very low doses and monitor renal function closely.

As previously noted, the kidneys are responsible for clearing the active metabolite morphine-6-glucuronide (M6G). In patients with a GFR < 60 mL/min, M6G can accumulate to toxic levels, leading to unexpected respiratory depression even at 'standard' doses. Dose reductions of 25-50% are typically required for patients with moderate to severe renal disease.

While the liver's capacity to glucuronidate morphine is quite large, patients with severe hepatic impairment (Child-Pugh Class C) may have reduced clearance of the parent drug. This can lead to a longer duration of action and a higher risk of sedation. Monitoring for CNS depression is critical in these patients.

> Important: Special populations require individualized medical assessment. Always inform your doctor if you are pregnant, planning to become pregnant, or have any organ impairment.

Morphine is a pure opioid agonist whose principal therapeutic action is analgesia. It binds with high affinity to mu-opioid receptors in the CNS. At the cellular level, this binding stimulates G-proteins, which in turn inhibits adenylate cyclase, closes voltage-gated calcium channels, and opens potassium channels. This results in hyperpolarization of the neuron and a reduction in neuronal excitability, effectively 'turning down' the volume on pain signals. While it also binds to kappa and delta receptors, its effects at the mu-receptor are responsible for its most significant clinical actions: pain relief, respiratory depression, and euphoria.

The onset of action for IV morphine is nearly immediate, with peak effects occurring within 20 minutes. For oral immediate-release morphine, the onset is 30 to 60 minutes, with a duration of 4 to 6 hours. Tolerance—the need for increasing doses to maintain the same level of analgesia—can develop with chronic use. This is thought to occur due to receptor desensitization and down-regulation.

| Parameter | Value |

|---|---|

| Bioavailability | 20% - 40% (Oral) |

| Protein Binding | 35% |

| Half-life | 2 - 4 hours (Parent drug) |

| Tmax | 1 hour (IR), 3-4 hours (ER) |

| Metabolism | Hepatic (Glucuronidation to M3G and M6G) |

| Excretion | Renal (90%), Fecal (10%) |

• Molecular Formula: C17H19NO3 (Base), (C17H19NO3)2·H2SO4·5H2O (Sulfate salt)
• Molecular Weight: 285.34 g/mol (Base), 758.83 g/mol (Sulfate pentahydrate)
• Solubility: Soluble in water (1 in 21) and slightly soluble in alcohol.
• Structure: A complex pentacyclic structure containing a benzene ring, a cyclohexane ring, a cyclohexene ring, a piperidine ring, and a tetrahydrofuran ring.

Morphine is the primary member of the Opioid Agonist [EPC] class. It is a Schedule II controlled substance under the Controlled Substances Act, reflecting its high potential for abuse but also its accepted medical utility.