Roxanol
Roxanol Uses, Dosage, Side Effects, Food Interaction and all others data.
Roxanol is a phenanthrene derivative which acts mainly on the CNS and smooth muscles. It binds to opiate receptors in the CNS altering pain perception and response. Analgesia, euphoria and dependence are thought to be due to its action at the mu-1 receptors while resp depression and inhibition of intestinal movements are due to action at the mu-2 receptors. Spinal analgesia is mediated by morphine agonist action at the K receptor.
Roxanol binding to opioid receptors blocks transmission of nociceptive signals, signals pain-modulating neurons in the spinal cord, and inhibits primary afferent nociceptors to the dorsal horn sensory projection cells.
Roxanol has a time to onset of 6-30 minutes. Excess consumption of morphine and other opioids can lead to changes in synaptic neuroplasticity, including changes in neuron density, changes at postsynaptic sites, and changes at dendritic terminals.
Intravenous morphine's analgesic effect is sex dependent. The EC50 in men is 76ng/mL and in women is 22ng/mL.
| Trade Name | Roxanol |
| Availability | Prescription only |
| Generic | Morphine |
| Morphine Other Names | Morfina, Morphia, Morphin, Morphine, Morphinum, Morphium |
| Related Drugs | Buprenex, Subutex, aspirin, acetaminophen, tramadol, duloxetine, naproxen, Tylenol, oxycodone, Cymbalta |
| Type | Oral |
| Formula | C17H19NO3 |
| Weight | Average: 285.3377 Monoisotopic: 285.136493479 |
| Protein binding | Morphine is 35% protein bound, the metabolite morphine-3-glucuronide is 10% protein bound, and morphine-6-glucuronide is 15% protein bound. |
| Groups | Approved, Investigational |
| Therapeutic Class | Opioid analgesics |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
This medication is used to help relieve moderate to severe pain. Roxanol belongs to a class of drugs known as opioid (narcotic) analgesics. It works in the brain to change how your body feels and responds to pain.
Roxanol is also used to associated treatment for these conditions: Pain, Chronic, Severe Pain
How Roxanol works
Roxanol-6-glucuronide is responsible for approximately 85% of the response observed by morphine administration. Roxanol and its metabolites act as agonists of the mu and kappa opioid receptors. The mu-opioid receptor is integral to morphine's effects on the ventral tegmental area of the brain. Roxanol's activation of the reward pathway is mediated by agonism of the delta-opioid receptor in the nucleus accumbens, while modification of the respiratory system and addiction disorder are mediated by agonism of the mu-opioid receptor.
Dosage
Roxanol dosage
Oral-Moderate to severe pain:5-20 mg 4 hrly. Extended-release: 5-20 mg 12 hrly. Dosage is dependent on the severity of pain.
Intraspinal-Moderate to severe pain:Initially, 5 mg epidural inj; after 1 hr, additional doses of 1-2 mg may be given up to a total dose of 10 mg/24 hr if pain relief is unsatisfactory. A dose of 20-30 mg daily may be required in some patients. Liposomal inj: 10-20 mg depending on the type of surgery.
Intrathecal-Moderate to severe pain: 0.2-1 mg once daily or 1-10 mg daily for patients with opioid tolerance. Some patients may require a dose of up to 20 mg daily.
Intravenous-Acute pulmonary oedema:
- Adult: 5-10 mg via slow inj at 2 mg/min.
- Elderly: Half of the usual adult dose.
Intravenous-
Pain associated with myocardial infarction:
- Adult: 5-10 mg at 1-2 mg/min followed by a further 5-10 mg as necessary.
- Elderly: Half of the usual adult dose.
Parenteral-
- Moderate to severe pain:5-20 mg; 2.5-10 mg via slow IV inj over 4-5 min with patient in recumbent position or a starting dose of 1-2 mg/hr via continuous IV infusion (max: 100 mg/day; 4 g/day in cancer patients). Doses may be adjusted according to severity of pain and patient's response.
- Premedication in surgery:Up to 10 mg, given 60-90 min before operation.
May be taken with or without food. May be taken with meals to reduce GI discomfort.
Side Effects
Nausea, vomiting, constipation, abdominal pain, dry mouth, anorexia, taste disturbance, dyspepsia, resp depression, sedation, dizziness, confusion, insomnia, headache, somnolence, involuntary muscle contractions, hyperhidrosis, rash, pruritus, asthenic conditions, HTN, bronchospasm, seizures, amenorrhoea, rhabdomyolysis, nystagmus.
Toxicity
The LD50 is 0.78µg/mL in males and 0.98µg/mL in females.
Patients experiencing an overdose present with respiratory depression, somnolence, skeletal muscle flaccidity, cold and clammy skin, miosis, and mydriasis. Symptoms of overdose can progress to pulmonary edema, bradycardia, hypotension, cardiac arrest, and death. Treat overdose with symptomatic and supportive treatment which may include the use of oxygen, vasopressors, and naloxone.
Precaution
Patient with impaired resp function, severe bronchial asthma, convulsive disorders, acute alcoholism, delirium tremens, raised intracranial pressure, hypotension with hypovolaemia, cardiac arrhythmias, severe cor pulmonale, history of substance abuse, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency, toxic psychoses. Opioid dependent patients. Renal and hepatic impairment. Pregnancy and lactation.
Interaction
Additive depressant effects with other CNS depressants (e.g. sedatives, hypnotics, general anaesth, phenothiazines, other tranquilisers). May enhance the neuromuscular blocking action of skeletal muscle relaxants. Reduced analgesic effect with mixed agonist/antagonist opioid analgesics (e.g. pentazocine, nalbuphine, buprenorphine). Increased plasma concentrations with cimetidine. May reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. May delay the absorption of mexiletine. May antagonise the GI effect of cisapride, domperidone and metoclopramide. May produce hyperpyrexia and CNS toxicity with dopaminergics.
Food Interaction
- Avoid alcohol. Concomitant use may lead to profound sedation, respiratory depression, coma, and death.
- Take with or without food. There is no significant different in the AUC or Cmax of oral extended release tablets when taken with or without food.
[Major] GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including morphine and diamorphine.
Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills.
In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.
GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of morphine may cause rapid release of the drug, resulting in high systemic levels of morphine that may be potentially lethal.
Alcohol apparently can disrupt the release mechanism of some sustained-release formulations.
The interaction was observed in in vitro studies using a 24-hour morphine formulation (Avinza 30 mg capsule, available in the U.S. from Ligand Pharmaceuticals).
When the capsule was mixed with 900 mL of buffer solutions containing ethanol 20% and 40%, the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine.
Although the clinical relevance of this finding is unknown, 'dose-dumping' into the bloodstream is conceivable.
MANAGEMENT: Until more information is available, patients taking sustained-release formulations of morphine should not consume alcohol or use medications that contain alcohol.
In general, potent narcotics such as morphine or diamorphine should not be combined with alcohol.
Roxanol Drug Interaction
Major: lorazepam, hydromorphone, cyclobenzaprine, pregabalin, acetaminophen / hydrocodone, acetaminophen / oxycodone, diazepam, alprazolamModerate: diphenhydramine, duloxetine, furosemide, promethazine, ondansetron, sertralineUnknown: docusate, polyethylene glycol 3350, acetaminophen, acetaminophen, cyanocobalamin, cholecalciferol
Roxanol Disease Interaction
Major: impaired GI motility, infectious diarrhea, liver disease, prematurity, acute alcohol intoxication, drug dependence, gastrointestinal obstruction, hypotension, intracranial pressure, respiratory depressionModerate: adrenal insufficiency, biliary spasm, hypothyroidism, renal dysfunction, seizure disorders, urinary retention, arrhythmias
Volume of Distribution
The volume of distribution of morphine is 5.31L/kg. Roxanol-6-glucuronide has a volume of distribution of 3.61L/kg.
Elimination Route
Roxanol is absorbed in the alkaline environments of the upper intestine and rectal mucosa. The bioavailability of morphine is 80-100%. There is significant first-pass metabolism, therefore oral doses are 6 times larger than parenteral doses to achieve the same effect. Roxanol reaches steady-state concentrations after 24-48 hours. Parenteral morphine has a Tmax of 15 minutes and oral morphine has a Tmax of 90 minutes, with a Cmax of 283nmol/L. The AUC of morphine is 225-290nmol*h/L.
Half Life
Roxanol has a half life of 2-3 hours.
Clearance
The apparent clearance of intravenous or subcutaneous morphine is 1600 mL/min.
Elimination Route
70-80% of an administered dose is excreted within 48 hours. Roxanol is predominantly eliminated in the urine with 2-10% of a dose recovered as the unchanged parent drug. 7-10% of a dose of morphine is eliminated in the feces.
Pregnancy & Breastfeeding use
Parenteral or oral: C, D (if prolonged use/high doses at term)
Contraindication
Resp depression, obstructive airway disease, delayed gastric emptying, acute abdomen, heart failure secondary to chronic lung disease, known or suspected paralytic ileus, phaeochromocytoma. Concurrent admin with MAOIs or within 2 wk after treatment.
Special Warning
Renal Impairment: Dosage may need to be reduced.
Hepatic Impairment: Dosage may need to be reduced.
Acute Overdose
Symptoms: Resp depression, pinpoint pupils, extreme somnolence progressing to stupor and coma, skeletal muscle flaccidity, cold and clammy skin and sometimes bradycardia and hypotension. Apnoea, circulatory collapse, and cardiac arrest may occur in severe cases.
Management: Re-establish adequate resp exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, IV fluid, vasopressors and other supportive measures may be employed as necessary. Naloxone may be given as antidote.
Storage Condition
Inj/oral preparations: Store between 15-30°C. Liposomal inj: Store between 2-8°C. Supp: Store below 25°C. Protect from light.
Innovators Monograph
You find simplified version here Roxanol
Roxanol contains Morphine see full prescribing information from innovator Roxanol Monograph, Roxanol MSDS, Roxanol FDA label
FAQ
What is Roxanol used for?
Roxanol is used to treat severe pain, for example after an operation or a serious injury, or pain from cancer or a heart attack. It's also used for other types of long-standing pain when weaker painkillers no longer work.
How safe is Roxanol?
Roxanol has a risk for abuse and addiction, which can lead to overdose and death. Roxanol may also cause severe, possibly fatal, breathing problems. To lower your risk, your doctor should have you take the smallest dose of Roxanol that works, and take it for the shortest possible time.
How does Roxanol work?
Roxanol works by blocking pain signals from travelling along the nerves to the brain. The most common side effects of Roxanol are constipation, feeling sick and sleepiness.
What are the common side effects of Roxanol?
The most common side effects of Roxanol are constipation, feeling sick and sleepiness. It's possible to become addicted to Roxanol, but this is rare if you're taking it to relieve pain and your doctor is reviewing your treatment regularly.
Is Roxanol safe during pregnancy?
If you take opioids during pregnancy, they can cause serious problems for your baby, like premature birth and drug withdrawal called NAS. Even if you use an opioid exactly like your health care provider says to, it still may cause NAS in your baby.
Is Roxanol safe during breastfeeding?
Moderately safe for breastfeeding women. However, Roxanol is the preferred opiate to use by a breastfeeding mother due to its poor oral bioavailability.
Can I drive after taking Roxanol?
Do not drive a car or ride a bike if Roxanol makes you sleepy, gives you blurred vision or makes you feel dizzy, clumsy or unable to concentrate or make decisions.
How do I take Roxanol?
Roxanol comes as a solution (liquid), an extended-release (long-acting) tablet, and as an extended-release (long-acting) capsule to take by mouth.
How often can I take Roxanol?
The oral solution is usually taken every 4 hours as needed for pain.
Can I take Roxanol on an empty stomach?
Roxanol can be taken with food or on an empty stomach (but always with a full glass of water). Sometimes taking it with food can lessen stomach upset that may occur.
How long does Roxanol take to work?
Fast-acting Roxanol taken by mouth works in 30 to 60 minutes but it wears off after 4 to 6 hours. Slow-acting Roxanol taken by mouth can take a day or 2 to start working but the pain relief will last for longer.
Who should not take Roxanol?
You should not take Roxanol if you have severe asthma or breathing problems, a blockage in your stomach or intestines, or a bowel obstruction called paralytic ileus. You should not take this medicine if you have ever had an allergic reaction to morphine or other narcotic medicines, or if you have: severe asthma or breathing problems; a stomach or bowel obstruction (including paralytic ileus); or if you have taken an MAO inhibitor in the past 14 days, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, or tranylcypromine.
What happens if I overdose?
Seek emergency medical attention. An overdose can be fatal, especially in a child or person using opioid medicine without a prescription. Overdose symptoms may include severe drowsiness, pinpoint pupils, slow breathing, or no breathing.
What happen If I miss Roxanol?
If you do miss a dose, take the medicine as soon as you remember. Then take your next dose as follows: If you take Roxanol 3 times per day: Take your next dose 8 hours after taking the missed dose. If you take Roxanol 2 times per day: Take your next dose 12 hours after taking the missed dose.
Can Roxanol affects my heart ?
Roxanol may cause central nervous system suppression and depression of ventilation, in addition to hypotension, especially in the presence of co-existing volume depletion or when a significantly reduced decrease filling pressure reduces the preload and thereby affects the cardiac output.
Can Roxanol affect my kidneys?
Roxanol and codeine are contraindicated in advanced kidney failure because of the toxic accumulation of active me- tabolites in kidney failure.
Can Roxanol affects my liver?
Roxanol is rapidly metabolized in the liver which induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects, and oncogenic effects. Roxanol causes liver cell injury and exerts genotoxic effect in rat liver.
Can Roxanol gain my weight?
Roxanol is not a drug people turn to when they want to gain or lose weight; however, the Roxanol can affect a wide range of the body's systems. Roxanol is known to change the way the body uses food and resulting in changes to a user's eating and exercise habits. Bodyweight may go up or down as a result.
