Metaxalone 400 mg. Metaxalone 400mg: Comprehensive Guide to Uses, Side Effects, and Dosing
What are the primary uses of Metaxalone 400mg. How should Metaxalone be taken for optimal effectiveness. What are the potential side effects and drug interactions of Metaxalone. When should caution be exercised while using Metaxalone.
Understanding Metaxalone: A Powerful Muscle Relaxant
Metaxalone, commonly prescribed in 400mg doses, is a potent muscle relaxant used to alleviate discomfort associated with acute musculoskeletal conditions. This medication works by affecting the central nervous system to reduce muscle spasms and associated pain. While its exact mechanism of action is not fully understood, Metaxalone has proven effective in providing relief when used as part of a comprehensive treatment plan.
Key Features of Metaxalone 400mg
- Prescription-only medication
- Available in tablet form
- Typically prescribed for short-term use
- Used in conjunction with rest and physical therapy
Primary Uses and Indications for Metaxalone
Metaxalone is primarily prescribed for the treatment of acute, painful musculoskeletal conditions. These conditions often involve muscle spasms that can cause significant discomfort and limit mobility. The medication is most effective when used as part of a comprehensive treatment approach that includes rest, physical therapy, and other supportive measures.
Common Conditions Treated with Metaxalone
- Acute lower back pain
- Neck pain associated with muscle spasms
- Sprains and strains
- Post-traumatic muscle pain
Can Metaxalone be used for chronic pain conditions. While Metaxalone is primarily intended for short-term use in acute conditions, some healthcare providers may prescribe it for chronic pain management in certain cases. However, long-term use should be closely monitored by a medical professional due to the potential for side effects and dependency.
Proper Dosage and Administration of Metaxalone 400mg
The appropriate dosage of Metaxalone can vary depending on the individual patient and the specific condition being treated. However, the typical starting dose for adults is 800mg (two 400mg tablets) taken three to four times daily. It’s crucial to follow your healthcare provider’s instructions precisely and never exceed the recommended dosage.
Guidelines for Taking Metaxalone
- Take Metaxalone with or without food, but be consistent
- Swallow tablets whole with a full glass of water
- Space doses evenly throughout the day
- Do not crush, chew, or break the tablets
- Avoid alcohol while taking Metaxalone
How long should Metaxalone be taken. The duration of treatment with Metaxalone is typically short-term, often ranging from a few days to a couple of weeks. Prolonged use may lead to dependency or reduced effectiveness. Always consult with your healthcare provider before discontinuing or extending the use of this medication.
Potential Side Effects and Adverse Reactions
Like all medications, Metaxalone can cause side effects in some patients. While many people tolerate the medication well, it’s essential to be aware of potential adverse reactions and report any concerning symptoms to your healthcare provider promptly.
Common Side Effects of Metaxalone
- Drowsiness or dizziness
- Headache
- Nausea or vomiting
- Gastrointestinal discomfort
- Nervousness or irritability
Are there any serious side effects associated with Metaxalone. While rare, serious side effects can occur. These may include severe allergic reactions, liver problems, or changes in blood cell counts. Seek immediate medical attention if you experience symptoms such as rash, itching, swelling, severe dizziness, or difficulty breathing.
Drug Interactions and Precautions
Metaxalone can interact with various medications and substances, potentially altering its effectiveness or increasing the risk of side effects. It’s crucial to inform your healthcare provider about all medications, supplements, and herbal products you’re taking before starting Metaxalone.
Notable Drug Interactions
- MAO inhibitors
- Serotonergic drugs (e.g., SSRIs, SNRIs)
- CNS depressants (e.g., benzodiazepines, opioids)
- Alcohol
How does Metaxalone interact with alcohol. Combining Metaxalone with alcohol can intensify the sedative effects of both substances, leading to excessive drowsiness, dizziness, and impaired coordination. It’s strongly advised to avoid alcohol consumption while taking Metaxalone.
Special Populations and Considerations
Certain groups of patients may require special consideration when using Metaxalone. These include pregnant or breastfeeding women, elderly patients, and individuals with pre-existing liver or kidney conditions. Always consult with your healthcare provider about any specific concerns related to your health status.
Pregnancy and Breastfeeding
The safety of Metaxalone during pregnancy and breastfeeding has not been conclusively established. Pregnant or nursing mothers should discuss the potential risks and benefits with their healthcare provider before using this medication.
Elderly Patients
Older adults may be more sensitive to the effects of Metaxalone, particularly the sedative properties. Dosage adjustments may be necessary, and close monitoring for side effects is recommended.
Liver and Kidney Impairment
Patients with liver or kidney problems may require dosage adjustments or alternative treatments. Regular monitoring of liver function may be necessary for patients taking Metaxalone long-term.
Monitoring and Follow-up During Metaxalone Treatment
While taking Metaxalone, it’s important to maintain regular communication with your healthcare provider. This allows for proper monitoring of the medication’s effectiveness and any potential side effects or complications.
Key Aspects of Monitoring
- Regular assessment of pain and muscle spasm relief
- Evaluation of side effects and tolerability
- Periodic liver function tests for long-term users
- Adjustment of treatment plan as needed
How often should follow-up appointments be scheduled while taking Metaxalone. The frequency of follow-up appointments may vary depending on individual circumstances. Typically, patients should have at least one follow-up within the first few weeks of starting treatment, with additional appointments as needed based on response and side effects.
Alternatives and Complementary Therapies to Metaxalone
While Metaxalone can be effective for many patients, it’s not the only option for managing musculoskeletal pain and muscle spasms. Depending on the specific condition and individual patient factors, healthcare providers may recommend alternative or complementary treatments.
Alternative Medications
- Cyclobenzaprine
- Carisoprodol
- Baclofen
- Tizanidine
Non-Pharmacological Approaches
- Physical therapy
- Massage therapy
- Acupuncture
- Heat or cold therapy
- Stretching and exercise programs
Can lifestyle modifications help reduce the need for muscle relaxants like Metaxalone. Adopting healthy lifestyle habits such as maintaining good posture, practicing stress-reduction techniques, and engaging in regular exercise can often help manage musculoskeletal pain and reduce the need for medication. However, always consult with your healthcare provider before making significant changes to your treatment plan.
In conclusion, Metaxalone 400mg is a valuable tool in the management of acute musculoskeletal conditions. When used appropriately and under medical supervision, it can provide significant relief from muscle spasms and associated pain. However, like all medications, it comes with potential risks and side effects that must be carefully considered. By working closely with your healthcare provider and following prescribed guidelines, you can maximize the benefits of Metaxalone while minimizing potential drawbacks. Remember that this medication is just one component of a comprehensive treatment approach that may include physical therapy, rest, and other supportive measures. Always prioritize open communication with your healthcare team to ensure the best possible outcomes in your journey towards pain relief and improved mobility.
Metaxalone Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing
See also How to Use section.
Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.
Some products that may interact with this drug include: diet pills/appetite suppressants (such as diethylpropion), drugs for attention deficit disorder (such as atomoxetine, methylphenidate), apraclonidine, bupropion, buspirone, carbamazepine, cyclobenzaprine, deutetrabenazine, a certain combination product (dextromethorphan/quinidine), levodopa, maprotiline, methyldopa, metoclopramide, certain opioid pain relievers (such as fentanyl, meperidine, methadone, tapentadol), certain drugs for Parkinson’s disease (such as entacapone, tolcapone), certain supplements (such as tryptophan, tyramine), tetrabenazine, tricyclic antidepressants (such as amitriptyline, doxepin), valbenazine.
The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/”ecstasy,” St. John’s wort, certain antidepressants (including mirtazapine, SSRIs such as fluoxetine/paroxetine, SNRIs such as duloxetine/venlafaxine), tramadol, certain “triptans” used to treat migraine headaches (such as rizatriptan, sumatriptan, zolmitriptan), among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.
Some products can interact with metaxalone if you take them together, or even if you take them weeks before or after taking metaxalone. Tell your doctor or pharmacist if you take anything in the list of products that may interact with this drug, or any of the products that increase serotonin, within 2 weeks before or after taking metaxalone. Also tell them if you have taken fluoxetine within 5 weeks before starting metaxalone. Ask your doctor how much time to wait between starting or stopping any of these drugs and starting metaxalone.
Taking other MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Do not take any other MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.
Before using metaxalone, report the use of drugs that may increase the risk of extremely high blood pressure (hypertensive crisis) when combined with metaxalone, including herbal products (such as ephedra/ma huang), nasal decongestants (such as phenylephrine, pseudoephedrine), and stimulants (such as amphetamines, ephedrine, epinephrine, phenylalanine). Metaxalone should not be used with any of these medications. Talk to your doctor or pharmacist for more details.
Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), other muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).
Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.
This medication may interfere with certain lab tests (such as certain urine glucose tests), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.
Does Metaxalone interact with other drugs you are taking?
Enter your medication into the WebMD interaction checker
Metaxalone: MedlinePlus Drug Information
pronounced as (me tax’ a lone)
To use the sharing features on this page, please enable JavaScript.
Metaxalone, a muscle relaxant, is used with rest, physical therapy, and other measures to relax muscles and relieve pain and discomfort caused by strains, sprains, and other muscle injuries.
Metaxalone comes as a tablet to take by mouth. It usually is taken three or four times a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take metaxalone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
Before taking metaxalone,
- tell your doctor and pharmacist if you are allergic to metaxalone, any other medications, or any of the ingredients in metaxalone tablets. Ask your pharmacist for a list of the ingredients.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take while taking metaxolone. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have or have ever had kidney disease, liver disease, seizures, or a blood disorder.
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking metaxalone, call your doctor immediately.
- talk to your doctor about the risks and benefits of taking metaxalone if you are 65 years of age or older. Older adults should not usually take metaxalone because it is not as safe or effective as other medications that can be used to treat the same condition.
- you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how metaxalone affects you.
- remember that alcohol can add to the drowsiness caused by this drug.
Take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
Metaxalone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- drowsiness
- dizziness
- headache
- nervousness
If you experience any of the following symptoms, call your doctor immediately:
- agitation, hallucinations, coma
- fast heart rate, high body temperature
- muscle twitching, loss of muscle control
- nausea, vomiting, diarrhea
- severe skin rash
- difficulty breathing
- yellowing of the skin or eyes
- unusual bruising or bleeding
- unusual tiredness or weakness
- seizures
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature, away from excess heat and moisture (not in the bathroom).
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo. gl/c4Rm4p) for more information if you do not have access to a take-back program.
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.
- Skelaxin®
Last Revised – 07/15/2022
Browse Drugs and Medicines
instructions for use, dosage, composition, analogues, side effects / Pillintrip
and PATIENT INFORMATION ).
Carcinogenesis, mutagenesis, impaired fertility
The carcinogenic potential of metaxalone has not been determined.
Pregnancy
Reproduction studies in rats showed no evidence of impaired fertility or fetal harm due to metaxalone. Post-marketing experience has not shown any evidence of fetal injury, but such experience cannot rule out the possibility of rare or subtle injury to the human fetus. The safe use of metaxalone has not been demonstrated in relation to possible adverse effects on fetal development. Therefore, metaxalone tablets should not be used in women who are or may be pregnant, especially during early pregnancy, unless the physician considers that the potential benefits outweigh the potential hazards.
Nursing mothers
It is not known if this drug is excreted in breast milk. As a general rule, caution should not be exercised when taking medications, as many medications are excreted in breast milk.
Pediatric use
Safety and efficacy in children over 12 years of age have not been established.
Overdose and Contraindications
Intentional or accidental overdose deaths have occurred with metaxalone, especially when combined with antidepressants, and this class of drug has been reported in combination with alcohol.
Serotonin syndrome has been reported when metaxalone was used at doses above the recommended dose layers (see WARNINGS ).
When determining LD 50 progressive sedation, hypnosis and finally respiratory failure were found in rats and mice with increasing dosage. No LD can be found in dogs 50 is determined because higher doses were emetic after 15-30 minutes.
Treatment
Gastric lavage and supportive care. It is recommended that you consult with your regional gift management center.
PRICE
Hypersensitivity to components of this product is known.
Known tendency to drug-induced, hemolytic or other anemia.
Significantly impaired renal or hepatic function.
Clinical pharmacology
CLINICAL PHARMACOLOGY
Mechanism of action
The mechanism of action of metaxalone in humans has not been established, but it can be attributed to a general depression of the central nervous system.
Metaxalone has no direct effect on the contractile mechanism of the striated muscle, motor end plate or nerve fiber.
Pharmacokinetics
The pharmacokinetics of metaxalone was studied in healthy adult volunteers after a single dose of metaxalone in sober and well-fed conditions at doses ranging from 400 to 800 mg.
Absorption
Peak plasma concentrations of metaxalone occur approximately 3 hours after an oral dose of 400 mg under sober conditions. The logarithmic concentrations of metaxalone then decrease with a finite half-life of 9.0 ± 4.8 hours. Doubling the dose of Metaxalone from 400 mg to 800 mg results in an approximately proportional increase in Metaxalone exposure as evidenced by peak plasma concentrations (Cmax) and area under the curve (AUC). Dose proportionality at doses above 800 mg has not been studied. The absolute bioavailability of metaxalone is not known.
Pharmacokinetic parameters of single dose metaxalone in two groups of healthy volunteers are shown in Table 1.
Table 1: Mean (% CV) pharmacokinetic parameters of Metaxalone
Dose (mg) | Cmax (ng/ml) | Tmax (h) | AUC∞ (ng & ml; h/ml) | t½ (h) | CL / F ( L / h) |
400 1 | 983 (53) | 3. 3 (35) | 7479 (51) | 9, 0 (53) | 68 (50) |
800 2 | 1816 (43) | 3.0 (39) | 15044 (46) | 8.0 (58) | 66 (51) |
1 Subjects received 1x400mg tablet sober (N = 42) 2 Subjects received 2x400mg tablets sober conditions (N = 59) |
Food Effects
A randomized, bi-directional, crossover study was conducted in 42 healthy volunteers (31 males, 11 females) who administered a Metaxalone 400 mg tablet while sober and after a standard high-fat breakfast. Subjects ranged from 18 to 48 years (mean age = 23.5 ± 5.7 years). Compared to sober states, the presence of a high-fat meal increased by 177.5% during drug C administration and increased AUC (AUC0-t, AUC∞) by 123.5% and 115.4%, respectively. Time to peak concentration (Tmax) was also delayed (4.3 hours vs. 3.3 hours) and the terminal half-life was reduced (2. 4 hours vs. 9.0 hours) under feeding conditions compared with fasting.
In a second study with a similar effect, healthy volunteers (N = 59, 37 males, 22 females) were given two tablets of metaxalone 400 mg (800 mg) aged 18-50 years (mean age = 25). 6 ± 8.7 years). Compared to sober states, the presence of a high-fat meal increased by 193.6% during drug C administration and increased AUC (AUC0-t, AUC, ∞) by 146.4% and 142.2%, respectively. Time to Peak concentration (Tmax) was also delayed (4.9h versus 3.0 h), and the terminal half-life was shortened (4.2 h compared to 8.0 h) under fed versus fasting conditions. Similar nutritional effects were observed in the aforementioned study when a Metaxalone tablet was administered instead of two 400 mg Metaxalone tablets. An increase in metaxalone exposure, which coincides with a decrease in half-life, may be due to more complete absorption of metaxalone in the presence of a high-fat meal (Figure 1).
Figure 1: Mean (SD) concentrations of metaxalone after a dose of 800 mg under fasting and feeding conditions
Distribution, metabolism and elimination
Although plasma protein binding and absolute bioavailability of metaxalone are unknown, the apparent volume of distribution (V/F 800 L) and lipophilia (log P = 2. 42) of metaxalone indicate that the drug is mainly distributed in tissues. Metaxalone is metabolized in the liver and excreted in the urine as unidentified metabolites. Hepatic cytochrome P450 enzymes play a role in the metabolism of metaxalone. In particular, CYP1A2, CYP2D6, CYP2E1 and CYP3A4 and to a lesser extent CYP2C8, CYP2C9and CYP2C19 metabolize metaxalone.
Metaxalone does not significantly inhibit major CYP enzymes such as CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Metaxalone does not cause significant induction of important CYP enzymes such as CYP1A2, CYP2B6 and CYP3A4 in vitro .
Pharmacokinetics in special populations
Age
The effect of age on the pharmacokinetics of metaxalone was determined after a single administration of two 400 mg (800 mg) tablets under fasting and feeding conditions. The results were evaluated separately, as well as in combination with the results of three other studies. Using the combined data, the results show that the pharmacokinetics of metaxalone under sober conditions is significantly more dependent on age than under feeding, with bioavailability increasing with age under sober conditions.
The fasting and feeding bioavailability of metaxalone in three groups of healthy volunteers of different ages is shown in Table 2.
Table 2: Mean pharmacokinetic parameters (% CV) feeding
Age (years) | Junior volunteers | Elderly volunteers | |||||
25.6 ± 8.7 9007 9 | 39.3 ± 10.8 | 71.5 ± 5.0 | |||||
N | |||||||
Food | Tasty | Fed | Tasty | Fed | Delicious | Fed | |
Cmax (ng/ml) | 1816 (43) | 3510 (41) | 2719 (4 6) | 2915 (55) | 3168 (43) | 3680 ( 59) | |
TMAX (h) | 3.0 (39) | 4.9 (48) | 3.0 (40) | 8.7 (91) | 2 ,6 (30) | 6.5 (67) | |
AUC0-t (ng·h/ml) | 14531 (47) | 20683 (41) | 19836 (40) | 20482 (37) | 23797 (45) | 24340 (48) | |
AUC∞ (ng·h/mL) | 15045 (46) | 20833 (41) 9) | 20815 (37) | 24194 (44) | 24704 (47) |
Gender
in which 48 healthy adult subjects (24 men, 24 women) were administered, two tablets of metaxalone 400 mg (800 mg) in sober conditions. The bioavailability of metaxalone was significantly higher in women than in men than Cmax (2115 ng/ml vs 1335 ng/ml) and AUC∞ (17884 ng h/ml vs 10328 ng h/ml). The mean half-life was 11.1 hours for women and 7.6 hours for men. The apparent volume of distribution of metaxalone was approximately 22% higher in men than in women, but the difference was not significant when adjusted for body weight. Similar results were also seen when the previously described combined data set was used in the analysis.
Liver/renal failure
The effect of liver and kidney disease on the pharmacokinetics of metaxalone has not been determined. In the absence of such information, Metaxalone should be used with caution in patients with hepatic and/or renal insufficiency.
Skelaxin (Metaxalone): Uses, Dosage, Side Effects, Interactions, Warning0294 Product Description
Product description
What is skelaxin and how is it used?
Skelaxin is a prescription medicine used to treat the symptoms of musculoskeletal pain. Skelaxin can be used alone or with other medicines.
Skelaxin belongs to a class of drugs called skeletal muscle relaxants.
It is not known whether Skelaxin is safe and effective in children under 12 years of age.
What are the possible side effects of Skelaxin?
Skelaxin can cause serious side effects, including:
- weak or shallow breathing,
- lightheadedness,
- pale or yellow skin,
- dark urine0289
- high fever,
- confusion,
- weak spot,
- upper stomach pain,
- loss of appetite and
- yellowing of the skin or eyes (jaundice)
900 08 Seek immediate medical attention if you have any – any of the above symptoms.
The most common side effects of Skelaxin include:
- dizziness,
- drowsiness,
- nausea,0289
- upset stomach,
- headache, and
- feeling nervous or irritable
Tell your doctor if you have any side effects that bother you or that don’t go away.
These are not all possible side effects of Skelaxin. For more information, contact your doctor or pharmacist.
Ask your doctor about side effects. You can report side effects to the FDA at 1-800-FDA-1088.
DESCRIPTION
SKELAXIN (metaxalone) is available in the form of pink oval tablets with a score of 800 mg.
Chemically, metaxalone is 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone. Empirical formula: C 12 H fifteen HE 3 , which corresponds to a molecular weight of 221.25. Structural formula:
Metaxalone is a white or almost white odorless crystalline powder, easily soluble in chloroform, soluble in methanol and6% ethanol, but practically insoluble in ether or water.
Each tablet contains 800 mg of metaxalone and the following inactive ingredients: alginic acid, ammonium calcium alginate, B-Rose liquid, corn starch and magnesium stearate.
INDICATIONS AND DOSAGE
INDICATIONS
SKELAXIN (metaxalone) is indicated as an adjunct to rest, physical therapy and other measures to relieve discomfort associated with acute, painful musculoskeletal problems. The mechanism of action of this drug has not been precisely established, but may be related to its sedative properties. Metaxalone does not directly relax tense human skeletal muscles.
DOSAGE AND ADMINISTRATION
The recommended dose for adults and children over 12 years of age is one 800 mg tablet three to four times daily.
HOW SUPPLIED
SKELAXIN (Metaxalone) Available as an 800 mg scored oval pink tablet, debossed with 8667 on the grooved side and an ‘S’ on the other side. Available in vials of 100 ( NDC 60793-136-01) and in vials of 500 ( NDC 60793-136-05).
Store at controlled room temperature between 15°C and 30°C (59°F and 86 °F).
SKELAXIN is a registered trademark of King Pharmaceuticals Research and Development, Inc.
Distributed by: Pfizer Inc., New York, NY 10017 Revised: November 2015
Side effects and drug interactions
SIDE EFFECTS
The most common reactions to metaxalone include:
9 0008 CNS: drowsiness, dizziness headache and nervousness or “irritability”;
Digestive: nausea, vomiting, gastrointestinal upset.
Other adverse reactions:
Immune system: hypersensitivity reaction, rash with or without itching;
Hematological: leukopenia; hemolytic anemia;
Hepatobiliary: jaundice.
side effects of Kenalog 40 injection
Anaphylactoid reactions have been reported with metaxalone, although rare.
DRUG INTERACTIONS
No information provided.
Warnings and Precautions
WARNINGS
Potentially life-threatening serotonin syndrome (SS) has been reported with the use of metaxalone. These reports have usually occurred when metaxalone was used concomitantly with serotonergic drugs (such as tramadol or selective serotonin reuptake inhibitors (SSRIs)) or when metaxalone was used at higher than recommended doses (see DRUG INTERACTIONS and OVERDOSE ). Signs of SS may include clonus, agitation, sweating, tremors, hyperreflexia, hypertonicity, and fever.
SKELAXIN may potentiate the effects of alcohol and other CNS depressants.
PRECAUTIONS
Metaxalone should be used with great caution in patients with pre-existing liver disease. In such patients, serial liver function tests should be performed.
Benedict’s false positive tests have been noted due to an unknown reducing agent. A specific glucose test will differentiate the results.
Dietary intake of SKELaxin may increase overall CNS depression; Elderly patients may be particularly sensitive to such CNS effects. (See CLINICAL PHARMACOLOGY : Pharmacokinetics and PATIENT INFORMATION ).
Carcinogenesis, mutagenesis, impaired fertility
The carcinogenic potential of metaxalone has not been determined.
Pregnancy
Reproduction studies in rats showed no evidence of impaired fertility or harm to the fetus due to metaxalone. Post-marketing experience has not shown evidence of fetal injury, but such experience cannot rule out the possibility of infrequent or minor injury to the human fetus. The safe use of metaxalone has not been established with regard to possible adverse effects on fetal development. Therefore, metaxalone tablets should not be used by women who are pregnant or planning pregnancy, especially in early pregnancy, unless, in the opinion of the physician, the potential benefits outweigh the possible risks.
Nursing mothers
It is not known if this drug is secreted in breast milk. As a general rule, breastfeeding should not be done while the patient is taking medication, as many medications are excreted in breast milk.
Pediatric use
Safety and efficacy in children under 12 years of age have not been established.
Overdose and contraindications
OVERDOSAGE
Deaths due to intentional or accidental overdose have occurred with the use of metaxalone, especially in combination with antidepressants, and cases of this class of drugs in combination with alcohol have been reported.
Serotonin syndrome has been reported when higher than recommended doses of metaxalone have been reported (see WARNINGS ).
When determining the LD 50 in rats and mice with increasing dosage, progressive sedation, hypnosis and, finally, respiratory failure were noted. In dogs no LD 50 could be determined because higher doses caused emesis after 15-30 minutes.
Care
Gastric lavage and supportive care. It is recommended to consult with the regional poison control center.
CONTRAINDICATIONS
Known hypersensitivity to any component of this product.
Known tendency to drug-induced, hemolytic or other anemia.
Significant impairment of kidney or liver function.
Clinical pharmacology
CLINICAL PHARMACOLOGY
Mechanism of action
The mechanism of action of metaxalone in humans has not been established, but it may be associated with general depression of the central nervous system.
Metaxalone has no direct action on the contractile mechanism of the striated muscle, motor end plate or nerve fiber.
Pharmacokinetics.
The pharmacokinetics of metaxalone was evaluated in healthy adult volunteers after administration of a single dose of SCELaxin on an empty stomach and after meals at doses of 400 to 800 mg.
Absorption
Peak plasma concentrations of metaxalone occur approximately 3 hours after oral administration of 400 mg on an empty stomach. Thereafter, metaxalone concentrations decrease logarithmically with a terminal half-life of 9.0 ± 4.8 hours. Doubling the dose of SKELaxin from 400 mg to 800 mg results in an approximately proportional increase in metaxalone exposure, as evidenced by peak plasma concentrations (Cmax) and area under the curve (AUC). Dose proportionality at doses above 800 mg has not been studied. The absolute bioavailability of metaxalone is unknown.
Pharmacokinetic parameters of a single dose of metaxalone in two groups of healthy volunteers are presented in Table 1.
Table 1: Mean (% CV) pharmacokinetic parameters of metaxalone
Dose (mg) | Cmax (ng/ml) | Tmax (h) | AUC & infin; (ng & bull; h / ml) | t & frac12; | CL / F (51) | 9.0 (53) | 68 (50) |
800 two0079 8.0 (58) | 66 (51) | | |||||
one Subjects received 1 tablet of 400 mg on an empty stomach (N = 42). two Subjects received 2 x 400 mg tablets on an empty stomach (N = 59). |
Nutritional effects
A randomized, two-way crossover study was conducted in 42 healthy volunteers (31 males, 11 females) who were administered one tablet of SKELAXIN 400 mg on an empty stomach and after a standard high-fat breakfast. The age of the subjects ranged from 18 to 48 years (mean age = 23. 5 ± 5.7 years). Compared to fasting conditions, the presence of a high-fat meal during drug administration increased Cmax by 177.5% and increased AUC (AUC0-t, AUC.infin.) by 123.5% and 115.4%, respectively. The time to reach maximum concentration (Tmax) was also delayed (4.3 hours compared to 3.3 hours) and the terminal half-life was reduced (2.4 hours compared to 90 hours) under eating conditions compared with fasting.
In a similarly designed food impact study, two 400 mg (800 mg) SKELAXIN tablets were administered to healthy volunteers (N = 59, 37 males, 22 females) aged 18 to 50 years (mean age = 25.6 ± 8.7 years). Compared to fasting conditions, the presence of a high-fat meal during drug administration increased Cmax by 193.6% and increased AUC (AUC0-t, AUC & infin;) by 146.4% and 142.2%, respectively. The time to reach maximum concentration (Tmax) was also delayed (4.9hours compared to 3.0 hours), and the terminal elimination half-life decreased (4.2 hours compared to 8.0 hours) under conditions of food intake compared with conditions on an empty stomach. Similar nutritional effects results were observed in the aforementioned study when one SKELAXIN 800 mg tablet was administered instead of two SKELAXIN 400 mg tablets. An increase in metaxalone exposure, coinciding with a decrease in half-life, may be due to more complete absorption of metaxalone in the presence of a high-fat meal (Fig. 1).
Figure 1: Mean (SD) concentrations of metaxalone after a dose of 800 mg under fasting and feeding conditions
Distribution, metabolism and excretion
Although plasma protein binding and absolute bioavailability of metaxalone are unknown, it appears the volume of distribution (V/F ~ 800 L) and lipophilicity (log P = 2.42) of metaxalone suggest that the drug is widely distributed in tissues. Metaxalone is metabolized in the liver and excreted in the urine as unidentified metabolites. Liver cytochrome P450 enzymes play a role in the metabolism of metaxalone. In particular, CYP1A2, CYP2D6, CYP2E1 and CYP3A4 and, to a lesser extent, CYP2C8, CYP2C9and CYP2C19 appear to metabolize metaxalone.
Metaxalone slightly inhibits major CYP enzymes such as CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Metaxalone slightly induces major CYP enzymes such as CYP1A2, CYP2B6 and CYP3A4. in vitro .
Pharmacokinetics in special populations
Age
The effect of age on the pharmacokinetics of metaxalone was determined after a single dose of two 400 mg (800 mg) tablets on an empty stomach and after a meal. The results were analyzed separately and also in combination with the results of three other studies. Using the pooled data, the results show that the pharmacokinetics of metaxalone are significantly more dependent on age under fasted conditions than under food conditions, with fasting bioavailability increasing with age.
The fasting and postprandial bioavailability of metaxalone in three groups of healthy volunteers of different ages is shown in Table 2. feeding
Age (years) | Young volunteers | Older volunteers | ||||
25.6 ± 8.7 | 71.5 ± 5.0 | |||||
N | 59 | 21 | 2. 3 | |||
Food | Hungry | fed | Hungry | fed | Hungry | fed |
Cmax (ng/mL) | 1816 (43) | 3510 (41) | 2719 (46) | 3168 (43) | 3680 (59) | |
Tmax (h) | 3.0 (39) | 4.9 (48) | 3.0 (40) | 8.7 (91) | 2.6 (30) | 6.5 (67) 90 079 |
AUC0-t (ng and steer / ml) | 14531 (47) | 20683 (41) | 19836 (40) | 20482 (37) | 24340 (48) | |
AUC & infin; (ng & bull; h / ml) | 15045 (46) | 20833 (41) | 20490 (39) | 20815 (37) | 24194 (44) | 24704 (47) |
Gender women) were administered two SKELAXIN 400 mg tablets ( 800 mg) on an empty stomach.
Bioavailability of metaxalone was significantly higher in women compared to men as evidenced by Cmax (2115 ng/mL vs 1335 ng/mL) and AUC∞ (17884 ng-middot; h/ml compared to 10328 ng-middot; h/ml). The mean elimination half-life was 11.1 hours in women and 7.6 hours in men. The apparent volume of distribution of metaxalone was approximately 22% higher in men than in women, but differed slightly when adjusted for body weight. Similar results were also obtained when the previously described combined dataset was used in the analysis.
Hepatic / renal failure
The effect of liver and kidney disease on the pharmacokinetics of metaxalone has not been determined. In the absence of such information, SKELaxin should be used with caution in patients with hepatic and/or renal impairment.
Medication Guide
PATIENT INFORMATION
SKELAXIN may impair the mental and/or physical abilities required to perform hazardous tasks such as operating machinery or driving a car, especially when used with alcohol or other CNS depressants.