Meloxicam Capsules: A Safe and Effective Alternative to Opioids for Arthritis Pain

Overview

Meloxicam, an NSAID (Non-steroidal anti-inflammatory drug) approved by the FDA (Food and Drug Administration) in 2000, effectively treats pain and inflammation associated with conditions like arthritis. By inhibiting enzymes that produce inflammatory compounds, it reduces pain symptoms. It is prescribed for various forms of arthritis, usually taken once daily at 5 to 7.5 milligrams (mg).

Meloxicam is considered an alternative to opioids for pain management due to its effectiveness and tolerability. While not addictive like opioids, caution is advised to prevent misuse or dependence. Patients should consult doctors to manage their Meloxicam consumption and avoid unnecessary risks.

Meloxicam and other NSAIDs offer a non-addictive option for pain relief, but careful consideration of patient history and health risks is essential. Vigilance is necessary to ensure patient safety and well-being.

How Do Meloxicam Capsules Work?

Meloxicam capsules work by reducing pain, stiffness, and swelling in muscles and joints affected by conditions such as arthritis, enhancing the quality of life for individuals experiencing these discomforts. The active ingredient in Meloxicam capsules is Meloxicam itself, which functions by inhibiting the action of the cyclo-oxygenase (COX) enzyme in the body. This enzyme is responsible for producing certain chemicals called prostaglandins that contribute to pain and swelling.

Clinical Efficacy and Safety of Meloxicam: Meloxicam has been proven effective and safe in treating rheumatoid arthritis (RA). Short-term trials demonstrated efficacy at different doses, with both 7.5 mg and 15 mg doses improving RA symptoms. Long-term use (18 months) showed significant improvement compared to baseline, with an 11.4 % discontinuation rate due to efficacy, similar to other NSAIDs. In addition, Meloxicam (7.5 mg/d and 15 mg/d) is effective, safe, and well-tolerated for treating osteoarthritis (OA). They outperformed the placebo and showed similar efficacy to diclofenac.

For Patients:

What Is an Analgesic?

An analgesic, commonly known as a painkiller, is a medication designed to alleviate various types of pain, ranging from headaches and injuries to conditions like arthritis. These drugs can be available over-the-counter or require a prescription, and they come in different forms.

There are distinct categories of analgesics, including:

• Opioids (Narcotics): Examples include Morphine, Oxycodone, Codeine, and Fentanyl. These medications alter the brain's perception of pain.

• Acetaminophen: Also known as Tylenol, it is used for pain relief and reducing fever.

• Combination Medicines: These combine Acetaminophen with opioids.

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Ibuprofen, Naproxen, and Celecoxib are examples. They reduce pain and inflammation.

• Aspirin: Sometimes considered an NSAID, it is used for pain relief and anti-inflammatory purposes.

Analgesics finds application in various scenarios, such as treating pain resulting from injuries, surgery, arthritis, toothaches, headaches, menstrual cramps, and sore muscles. They play a vital role in providing relief and improving the quality of life for individuals experiencing pain.

What Are Meloxicam Capsules?

Meloxicam capsules are a type of medication classified as a nonsteroidal anti-inflammatory drug (NSAID). They are primarily used to alleviate pain and inflammation associated with various conditions such as osteoarthritis, rheumatoid arthritis, and sometimes ankylosing spondylitis. The medication helps manage pain and swelling over extended periods of time in chronic conditions like rheumatoid arthritis and ankylosing spondylitis. Additionally, it may also be used for shorter durations to address inflammation and discomfort associated with osteoarthritis.

How Should the Patient Take Meloxicam?

For effective use of Meloxicam tablets:

• Swallowing With Water: Ingest the complete tablet using a drink of water.

• Taking With Food: Consume each dose alongside a snack or shortly after eating a meal. Also, ensure ample consumption of ample water while on meloxicam.

• Maintaining Consistency in Timing: Establish a routine to take doses at the same time daily. This practice aids in remembering to take them.

• Handling Missed Dose: If a dose is forgotten, take it promptly with food when remembered. If the next day is when it is remembered, skip the missed dose. Avoid taking two doses together to compensate for the missed one.

What Are the Things to Inform the Doctor Before Taking Meloxicam Capsules?

Certain conditions might render Meloxicam unsuitable for individuals. Due to these factors, prior to commencing Meloxicam intake, it is crucial for an individual to inform their doctor or pharmacist about:

• Any history of asthma or other allergic disorders.

• Past instances of stomach or duodenal ulcers or any inflammatory bowel disorders such as Crohn's disease or ulcerative colitis.

• Pregnancy attempts at conception or current breastfeeding status.

• Existing liver or kidney complications.

• Pre-existing heart conditions, blood vessel issues, or circulatory problems.

• High blood pressure.

• Elevated blood sugar or cholesterol levels.

• Smoking habits.

• Previous experiences with blood clotting disorders.

• Presence of systemic lupus erythematosus, an inflammatory condition also referred to as lupus or SLE.

• Concurrent usage of other medications, encompassing both over-the-counter and herbal or complementary varieties.

• Past allergic reactions to other NSAIDs (like Aspirin, Ibuprofen, Diclofenac, and Indomethacin) or any other medications.

What Are the Side Effects of Meloxicam Capsules?

• Swelling (edema).

• Headache.

• Feeling lightheaded (dizziness).

• Skin rash.

• Upset stomach (diarrhea).

• Indigestion (dyspepsia).

• Nausea.

• Excess gas (flatulence).

• Abdominal discomfort.

• Sore throat (pharyngitis).

• Symptoms resembling the flu.

• Tiredness (fatigue).

• Sudden waves of heat (hot flashes).

• Episodes of abnormal brain activity (seizures).

• Shaking or quivering (tremor).

• A sensation of spinning (vertigo).

Overdose:

Regarding Meloxicam overdose, there is limited experience. Recovery was reported in cases where patients took Meloxicam tablets at six to 11 times the maximum recommended dose of 15 mg. Cholestyramine can hasten Meloxicam clearance.

How Should the Patient Store Meloxicam?

Proper storage for Meloxicam involves:

• Safeguarding all medications from children by keeping them out of their reach and visibility.

• Storing in a cool, dry location, distant from direct sunlight and excessive heat.

• Retaining the tablets within their original packaging.

For Doctors:

Indication and Usage: Meloxicam capsules are indicated for the management of pain associated with osteoarthritis.

Dosage and Administration: Use the lowest effective dose, short duration.

For osteoarthritis, start with 5 mg orally daily. Increase to 10 mg if needed. Maximum daily dose: 10 mg. In hemodialysis patients, the maximum daily dose is 5 mg. Even though the milligrams are the same, Meloxicam capsules and other oral forms cannot be substituted. Do not substitute other Meloxicam products.

What Are the Clinical Pharmacological Aspects?

1. Mechanism of Action: Meloxicam possesses properties of analgesia, anti-inflammation, and antipyresis. Although the complete mechanism of action for Meloxicam, like other NSAIDs, is not entirely elucidated, it involves the inhibition of cyclooxygenase (COX-1 and COX-2). It acts as a potent suppressor of prostaglandin synthesis in laboratory studies, which has shown corresponding in vivo effects. Prostaglandins heighten pain sensations through nerve sensitization and enhance the impact of bradykinin in pain induction in animal models. Meloxicam's action as a prostaglandin synthesis inhibitor could stem from its capacity to diminish prostaglandins in peripheral tissues.

2. Pharmacokinetics:

• Absorption: In a study with healthy subjects, Meloxicam 10 mg capsules resulted in lower systemic exposure compared to 15 mg tablets. Under fasting conditions, Meloxicam capsules with 33 % less dose had similar peak plasma concentration (Cmax) but 33 % lower overall systemic exposure (AUCinf) compared to Meloxicam 15 mg tablets.

• Distribution: Meloxicam has a mean volume of distribution (Vss) of approximately 10 L. About 99.4 % binds to human plasma proteins, primarily albumin. This binding remains constant across drug concentrations but decreases to ~99 % in renal disease patients. Meloxicam's penetration into human red blood cells post-oral dosing is minimal, less than 10 %.

• Metabolism: Meloxicam undergoes extensive liver metabolism, generating metabolites including 5'-carboxy Meloxicam (60 % of dose) through P-450 mediated oxidation of an intermediate 5'-hydroxymethyl Meloxicam (9 % of dose). CYP2C9 and CYP3A4 are involved. Patients' peroxidase activity likely contributes to two other metabolites (16 % and 4 % of dose) with no known in vivo pharmacological activity.

• Excretion: Mostly excreted as metabolites equally through urine and feces. Minor amounts of unchanged parent compound in urine (0.2 %) and feces (1.6 %). The urine contained Meloxicam, 5'-hydroxymethyl, and 5'-carboxy metabolites at 0.5 %, 6 %, and 13 % of the dose, respectively. Biliary and/or enteral secretion is significant.

Specific Populations:

• Pediatric: No explored data.

• Hepatic Impairment: Mild to moderate impairment did not significantly alter Meloxicam plasma concentrations or binding. Severe hepatic impairment lacks study.

• Renal Impairment: Mild to moderate renal impairment led to increased clearance and decreased total drug plasma concentrations. For severe renal impairment, the use of Meloxicam capsules is not recommended.

What Are the Contraindications of Meloxicam Capsules?

Meloxicam capsules are contraindicated in certain patient populations due to potential hypersensitivity reactions and allergic-type responses. These contraindications include:

• Known Hypersensitivity: Meloxicam capsules should not be used in patients with a known hypersensitivity to Meloxicam itself or any components present in the drug product. This includes individuals who have experienced anaphylactic reactions and serious skin reactions as a result of Meloxicam use.

• History of Allergic Reactions: Patients with a history of asthma, urticaria (hives), or other allergic-type reactions after taking Aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) should avoid Meloxicam. This is important because severe and potentially fatal anaphylactic reactions to NSAIDs, like Meloxicam, have been reported in individuals with such a history.

What Are the Adverse Effects of Meloxicam Capsules?

The adverse effects of Meloxicam capsules, as reported in clinical trials, have been discussed below.

Clinical Trials Experience:

Adverse reactions observed during clinical trials of Meloxicam capsules are detailed below. It is important to consider that these rates might not accurately reflect real-world occurrences due to varying conditions.

1. Adverse Reactions in Patients with Osteoarthritis Pain:

In phase 3 clinical trials involving 868 patients aged 40 to 87 with osteoarthritis pain who received Meloxicam capsules of 5 mg or 10 mg daily, the following adverse reactions were noted:

• Diarrhea: 3 %.

• Nausea: 2 %.

• Abdominal discomfort: 2 %

In a 52-week open-label trial with 600 patients receiving Meloxicam capsules 10 mg daily, the most prevalent adverse reactions were:

• Arthralgia: 6 %.

• Urinary tract infection: 6 %.

• Osteoarthritis: 5 %

• Hypertension: 4 %

• Diarrhea: 4 %

• Headache: 4 %

• Upper respiratory tract infection: 4 %

• Back pain: 4 %

• Nasopharyngitis: 4 %

• Bronchitis: 3 %

• Sinusitis: 3 %

• Constipation: 3 %

• Dyspepsia: 3 %

• Nausea: 2 %

• Edema peripheral: 2 %

• Pain in extremity: 2 %

2. Additional Adverse Reactions:

• Apart from the aforementioned reactions, other adverse effects reported for Meloxicam include allergic reaction, face edema, fatigue, fever, hot flashes, malaise, syncope, weight decrease, and weight increase.

• Cardiovascular: Angina pectoris, cardiac failure, hypertension, hypotension, myocardial infarction, vasculitis.

• Central and Peripheral Nervous System: Convulsions, paresthesia, tremors, and vertigo were reported.

• Gastrointestinal: Dry mouth, duodenal ulcer, eructation, esophagitis, gastric ulcer, gastroesophageal reflux, gastrointestinal hemorrhage, hematemesis, hemorrhagic duodenal ulcer, colitis, hemorrhagic gastric ulcer, gastritis, intestinal perforation, melena, pancreatitis, perforated duodenal ulcer, perforated gastric ulcer, and stomatitis ulcerative.

• Heart Rate and Rhythm: Arrhythmia, palpitation, and tachycardia.

• Hematologic: Agranulocytosis, leukopenia, purpura, and thrombocytopenia.

• Immune System: Anaphylactoid reactions (including shock).

• Liver and Biliary System: Elevated ALT, elevated AST, bilirubinemia, elevated GGT, hepatitis, jaundice, and liver failure.

• Metabolic and Nutritional: Dehydration.

• Psychiatric: Abnormal dreams, anxiety, increased appetite, confusion, depression, agitation, nervousness, and somnolence.

• Respiratory: Asthma, bronchospasm, and dyspnea.

• Skin and Appendages: Alopecia, angioedema, bullous eruption, erythema multiforme, photosensitivity reaction, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, increased sweating, and urticaria.

• Special Senses: Abnormal vision, conjunctivitis, perverted taste, and tinnitus.

• Urinary System: Albuminuria, acute urinary retention, increased BUN, increased creatinine, hematuria, interstitial nephritis, and renal failure.

Short-Term and Long-Term Trials:

In clinical trials involving around 10,500 patients treated with MOBIC, the most common adverse events were related to the gastrointestinal system, followed by various other systems:

• Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, nausea, vomiting.

• Body as a Whole: Edema, pain.

• Central and Peripheral Nervous System: Dizziness, headache.

• Hematologic: Anemia.

• Musculoskeletal: Arthralgia, back pain.

• Psychiatric: Insomnia.

• Respiratory: Coughing, upper respiratory tract infection.

• Skin: Pruritus, rash.

• Urinary: Micturition frequency, urinary tract infection.

Higher doses of Meloxicam were linked to a heightened risk of serious gastrointestinal events, and the daily dose should not exceed 15 mg.

Less Common Adverse Reactions:

Additional, less common adverse reactions were reported, including the cardiovascular, central, and peripheral nervous system, metabolic and nutritional, and respiratory issues, among others.

Warnings and Precautions:

• Cardiovascular Thrombotic Events:

Clinical trials have indicated an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, associated with the use of NSAIDs, including Meloxicam. The risk appears to be higher at higher doses and in patients with known CV disease or risk factors. Physicians should use the lowest effective dose for the shortest duration possible and be vigilant for symptoms of CV events.

• Gastrointestinal Bleeding, Ulceration, and Perforation:

Serious gastrointestinal adverse events, such as bleeding, ulceration, and perforation, can occur without warning symptoms in patients treated with Meloxicam capsules. Special caution is advised for patients with a history of peptic ulcer disease, gastrointestinal (GI) bleeding, or other risk factors. Physicians should consider the lowest effective dose for the shortest duration, avoid concomitant use of multiple NSAIDs, and monitor for signs of GI ulceration and bleeding.

• Hepatotoxicity:

Elevated liver enzymes, including rare severe hepatic injury, have been reported in NSAID-treated patients. Patients should be informed about signs of hepatotoxicity, and if clinical signs occur, Meloxicam capsules should be discontinued and the patient evaluated.

• Hypertension:

NSAIDs, such as Meloxicam, can cause the onset of hypertension or a worsening of the condition. Blood pressure should be monitored during treatment.

• Heart Failure and Edema:

The use of NSAIDs has been linked to an increased risk of heart failure and edema. Caution is advised, especially in patients with heart failure. Monitoring for signs of worsening heart failure is recommended.

• Renal Toxicity and Hyperkalemia:

NSAIDs, including Meloxicam, can cause renal toxicity, especially in patients with impaired renal function, dehydration, or other risk factors. Monitoring of renal function and electrolytes is advised. Hyperkalemia may occur, even in patients without renal impairment.

• Anaphylactic Reactions:

Meloxicam has been linked to anaphylactic reactions in patients with and without meloxicam-specific hypersensitivity, including those with aspirin-sensitive asthma.

• Exacerbation of Asthma Related to Aspirin Sensitivity:

Meloxicam is contraindicated in patients with aspirin-sensitive asthma. Caution is advised in patients with pre-existing asthma.

• Serious Skin Reactions:

NSAID use has been linked to serious skin side effects, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN). Patients should be informed about signs of serious skin reactions, and Meloxicam capsules should be discontinued if such reactions occur.

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS):

DRESS has been reported with NSAID use. Patients should be monitored for fever, rash, lymphadenopathy, and other systemic symptoms. Meloxicam should be discontinued if signs of DRESS are present.

• Fetal Toxicity:

Use of NSAIDs, including Meloxicam, in late pregnancy can lead to premature closure of the fetal ductus arteriosus and fetal renal dysfunction. Its use in pregnant women at about 30 weeks of gestation and later should be avoided.

• Hematologic Toxicity:

Anemia and bleeding events have been reported with NSAID use. Patients should be monitored for signs of anemia and bleeding, especially those on anticoagulants.

• Masking of Inflammation and Fever:

NSAID use can mask symptoms of infections or other conditions.

• Laboratory Monitoring:

Consider periodic laboratory monitoring for patients on long-term NSAID treatment, including CBC and chemistry profiles.

What Are the Drug Interactions of Meloxicam Capsules?

1. Hemostasis-Interfering Drugs:

• Concomitant use of Meloxicam and anticoagulants (Like Warfarin) increases bleeding risk.

• Combination with drugs affecting serotonin reuptake (SSRIs, SNRIs) may potentiate bleeding risk.

2. Aspirin:

• Using Meloxicam and analgesic doses of aspirin together does not enhance therapeutic effects and increases GI adverse reactions.

3. ACE Inhibitors, ARBs, and Beta-blockers:

• NSAIDs may reduce the antihypertensive effect of these drugs.

• Elderly, volume-depleted, or renal-impaired patients might experience renal function deterioration.

4. Diuretics:

• NSAIDs can reduce the effectiveness of loop and thiazide diuretics.

5. Digoxin:

• Combining Meloxicam with Digoxin increases Digoxin concentration and prolongs its half-life.

6. Methotrexate:

• Concomitant use of NSAIDs and methotrexate increases the risk of methotrexate toxicity.

7. Cyclosporine:

• Co-administration of Meloxicam and cyclosporine may worsen cyclosporine's nephrotoxicity.

8. NSAIDs and Salicylates:

• Using Meloxicam with other NSAIDs or salicylates increases GI toxicity risk without added efficacy.

9. Pemetrexed:

• Pemetrexed-related myelosuppression, renal, and GI toxicity are all more likely when Meloxicam and pemetrexed are taken together.

10. Other Interaction Considerations:

Monitor for interactions with other medications like cholestyramine, corticosteroids, hydralazine, lithium, loop diuretics, thiazide diuretics, and Warfarin.

Doctors should carefully assess potential interactions and adjust treatment accordingly to ensure patient safety and treatment efficacy.

Clinical Studies:

Study 1: Osteoarthritis Pain:

The efficacy of Meloxicam capsules in managing osteoarthritis pain was demonstrated in a randomized, double-blind, multicenter, parallel-arm, placebo-controlled study. This study compared Meloxicam capsules of 5 mg or 10 mg taken once daily with a placebo. The participants included patients with pain due to osteoarthritis of the knee or hip. The study involved 402 patients with a mean age of 61, ranging from 40 to 87 years. Osteoarthritis pain was assessed using the Western Ontario and McMaster University Arthritis Index (WOMAC) pain subscale. The mean baseline WOMAC pain subscale score across treatment groups was 73 mm on a 0 to 100 mm visual analog scale.

Study 2: U.S. Controlled Trial:

A double-blind controlled trial was conducted in the United States, involving 464 patients treated with Meloxicam for 12 weeks. Meloxicam was administered at doses of 3.75 mg, 7.5 mg, and 15 mg daily and was compared to placebo. The trial's primary endpoints included the investigator’s global assessment, the patient's global assessment, the patient's pain assessment, and the total WOMAC score. Patients who received daily doses of Meloxicam 7.5 mg and Meloxicam 15 mg demonstrated significant improvements in each of these endpoints compared to those who received a placebo.

Study 3: International Active-Controlled Trials:

In six double-blind, active-controlled studies conducted outside of the United States, the efficacy of Meloxicam in managing the signs and symptoms of osteoarthritis was determined. These trials involved a total of 9589 patients and spanned four weeks to six months. Meloxicam was administered at doses of 7.5 milligrams per day (mg/day) and 15 mg/day. The efficacy of Meloxicam at these doses was found to be comparable to Piroxicam 20 mg/day and Diclofenac 100 mg/day. The results of these international trials were consistent with the findings from the U.S. trial.

Across these studies, the primary measure of efficacy was the change from baseline to Week 12 in the WOMAC pain subscale score. Both doses of Meloxicam capsules (5 mg and 10 mg) taken once daily demonstrated a significant reduction in osteoarthritis pain compared to placebo. The changes in WOMAC pain subscale scores indicated this reduction. The proportion of patients achieving various percentage reductions in pain intensity from baseline to Week 12 was similar for both the 5 mg and 10 mg once-daily doses.