Meloxicam - Indications, Contraindications, Dosage, and Side Effects

Overview

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) used to reduce various types of pain, including pain caused by arthritis (inflammation of joints). It is a long-acting drug that belongs to the oxicam class of medications. It also has antipyretic and anti-inflammatory properties. Meloxicam was approved by the United States Food and Drug Administration (USFDA) on 13th April 2000, and the oral suspension was approved in 2004.

How Does Meloxicam Work?

Meloxicam is a drug that acts by inhibiting the effect of enzymes called cyclooxygenase enzymes 1 and 2 (COX 1 and 2), which in turn prevents prostaglandin synthesis; responsible for mediating painful inflammatory symptoms. However, it is exactly unclear how the reduced synthesis of the compounds such as prostaglandins, prostacyclins, and thromboxanes results in therapeutic efficacy. Meloxicam mainly exhibits COX-2 inhibition but also exerts mild activity against COX-1, which may result in gastrointestinal irritation.

What Are the Indications of Meloxicam?

Indications of Meloxicam include;

• Signs and symptoms of osteoarthritis.

• Patients with rheumatoid arthritis.

• It is also indicated to provide relief for polyarticular course juvenile rheumatoid arthritis in patients above two years of age.

What Are the Contraindications of Meloxicam?

Contraindications of Meloxicam include;

• Meloxicam must not be administered to patients with asthma or who have experienced allergic reactions to Aspirin or other NSAIDs.

• Patients with known hypersensitivity, such as serious skin reactions or anaphylactoid reactions to Meloxicam.

• Meloxicam is contraindicated in the treatment of perioperative pain in coronary artery bypass graft (CABG) surgery.

What Is the Dosage of Meloxicam?

Meloxicam is available in the form of tablets and oral suspension, and it can be taken with or without food. The maximum recommended dose of Meloxicam in adults is 15 mg regardless of the formulation; however, for patients undergoing hemodialysis, a maximum daily of 7.5 mg is recommended. An oral suspension of 7.5 mg per 5 ml or 15 mg per 10 ml may be substituted respectively for 7.5 mg and 15 mg Meloxicam tablets.

What Are the Drug Warnings and Precautions?

• Cardiovascular Events: Clinical trials have shown that many COX-2 selective and nonselective NSAIDs used for up to three years have an increased risk of cardiovascular events such as myocardial infarction, stroke, etc., which can be fatal. Therefore patients with a history of cardiovascular diseases may be at greater risk; hence, the lowest effective dose must be used for a shorter duration to minimize the potential risk. Patients must be alert and inform the doctor in case of cardiovascular signs and symptoms.

• Hypertension: Meloxicam can cause an onset of hypertension or worsen pre-existing hypertension, hence blood pressure must be monitored before the treatment and during the course of therapy. NSAIDs can cause fluid retention and swelling, so Meloxicam must be used cautiously in patients with a history of cardiac failure or hypertension.

• Gastrointestinal Effects: NSAIDs can cause severe gastrointestinal side effects such as bleeding, ulceration, inflammation, and perforation of the stomach and the intestine, which can be fatal. Therefore these drugs must be used with caution in patients with diseases of the gastrointestinal tract, and the lowest effective dose and a short-term therapy are recommended. An alternate treatment that does not involve NSAIDs may be considered in very high-risk patients. Patients on long-term NSAID treatment must get a periodic checkup of their complete blood count and chemistry profile.

• Renal Effects: Long-term administration of Meloxicam can cause renal impairment such as acute renal failure, renal insufficiency, renal papillary necrosis, etc. Patients with renal impairment must be closely monitored, and Meloxicam is not recommended in patients with severe renal diseases or those under diuretics.

• Hepatic Effects: According to clinical trials, significant elevations in the alanine transaminase (ALT) and aspartate transaminase (AST) were seen in some patients with NSAIDs, and in some rare cases, severe hepatic reactions such as jaundice, liver necrosis, hepatic failure, etc. were reported. Therefore, patients with symptoms of liver dysfunction must be evaluated, and the treatment must be discontinued if evidence of systemic manifestations is observed.

• Hematological Effects: NSAIDs, including Meloxicam, can cause anemia which may be due to fluid retention, gastrointestinal blood loss, etc. Hence patients on long-term therapy with NSAIDs must get their hemoglobin levels checked in case any signs or symptoms of anemia are noticed. Patients with coagulation disorders or under anticoagulant therapy and treated with Meloxicam must be carefully monitored as NSAIDs cause platelet aggregation and may increase the bleeding time in some patients.

• Asthmatic Patients: Meloxicam must not be administered in patients with Aspirin-sensitive asthma and must be cautiously used in patients with a history of asthma as it can cause severe bronchospasm.

• Skin Reactions: Meloxicam can cause adverse effects on the skin, such as Stevens-Johnson syndrome, exfoliative dermatitis, etc., which can be fatal. Therefore patients must inform the doctor if any skin rash or other serious hypersensitivity reactions are observed.

• Pregnancy: Meloxicam must be avoided after 30 weeks of gestation, as it can cause premature closure of the ductus arteriosus.

What Are the Adverse Effects of Meloxicam?

Adverse effects of Meloxicam include;

• Constipation.

• Gastric problems.

• Dizziness.

• Sore throat.

• Diarrhea.

• Nausea and vomiting.

Some of the serious adverse effects include:

• Skin blisters and itching.

• Rash.

• Swelling of the face, eyes, lips, and throat.

• Swelling in the hands and feet.

• Abdominal pain.

• Excessive fatigue.

• Difficulty breathing.

• Dark urine or painful urination.

For Patients

What Is Arthritis?

Arthritis is characterized by pain, swelling, limited motion, and joint stiffness. Among the different types of arthritis and the common ones include; osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, etc. Symptoms vary among individuals from mild to severe. Severe arthritis can cause chronic pain and can affect daily activities. It is more common in elderly people, especially women, compared to younger adults.

What Is Meloxicam?

Meloxicam is a prescription medicine used to relieve pain, swelling, and stiffness in the joints in adults and also in children above two years. It works by preventing the production of enzymes (natural chemicals or proteins) responsible for causing pain, swelling, and fever. It is a long-acting medicine usually taken once a day. It can also be prescribed in cases of ankylosing spondylitis (arthritis that affects the spine). This medicine does not cure arthritis but reduces the symptoms and helps as long as it is taken.

What Is the Most Important Information About Meloxicam?

• Meloxicam may cause serious cardiac side effects; hence the patients must be alert and inform the doctor in case of symptoms such as chest pain, shortness of breath, weakness, etc.

• Meloxicam may cause stomach discomfort, gastric ulcers, and bleeding. Hence the patients must be alert and inform the doctor in case they experience symptoms such as pain, discomfort, indigestion, bleeding, etc.

• Patients must also inform the doctor in case of unexplained weight gain, jaundice, swelling of the face and throat, flu-like symptoms, or any skin side effects such as itching, rashes, etc., during the course of treatment with Meloxicam.

What Should the Patients Inform the Doctor About Before Taking Meloxicam?

• If the patient is allergic to Meloxicam, Aspirin, or other NSAIDs such as Ibuprofen, Naproxen, etc, the doctor must be informed.

• If the patient is taking any over-the-counter drugs, vitamins, or herbal supplements, the doctor must be informed.

• If the patient is under medications such as angiotensin-converting enzyme (ACE) inhibitors such as Enalapril, Captopril, etc.; angiotensin receptor blockers such as Azilsartan, Telmisartan, etc.; beta-blockers such as Atenolol, Metoprolol, or under diuretics, the doctor must be informed before the initiation of treatment with Meloxicam. The doctor may change the doses or monitor the patient frequently for any side effects.

• If the patient is suffering from kidney or liver disease, heart failure, asthma, ever had asthma, or has a frequent runny or stuffy nose, swelling in the hands or lower legs, etc., the doctor must be informed before taking the medication.

• Female patients must inform the doctor if they are pregnant, planning to become pregnant, or breastfeeding, as Meloxicam may harm the baby. Meloxicam must not be taken after 20 weeks of pregnancy as it can cause problems with the delivery.

• The patient must inform the doctor if having any dental or surgery appointments during the treatment with Meloxicam.

• The oral suspension of Meloxicam contains sorbitol; the doctor must be informed if the patient is prescribed this formulation and has fructose intolerance (a genetic condition in which the body lacks a protein required to break down fructose).

How Should Meloxicam Be Stored?

Meloxicam is available as tablets and oral suspension and must be stored at room temperature, in a dry place, at around 25 degrees Celsius. The tablets must be kept in a tight container away from moisture, and the oral suspension container must be closed tightly to prevent contamination. Medicines must be kept out of the reach of children.

How Should Meloxicam Be Taken?

Meloxicam must be taken exactly as prescribed by the doctor and must not be taken often or more or less than instructed. It is taken orally, once a day at the same time every day, and can be taken with or without food. If the suspension is prescribed, it must be shaken thoroughly before each use to mix the medication evenly. If the patient misses a dose, it must be taken as soon as remembered. If it is almost time for the next scheduled dose, the missed dose can be skipped, and the regular dosing schedule must be continued.

What Are the Side Effects of Meloxicam?

Some of the common side effects include;

• Nausea and vomiting.

• Constipation.

• Sore throat.

• Gastric problems.

• Diarrhea.

Some serious side effects which require medical attention include;

• Pain in the upper part of the stomach.

• Itching and rash.

• Blisters on the skin.

• Difficulty breathing.

• Excessive tiredness.

• Swelling of ankles and feet.

• Back pain.

• Difficulty or pain during urination.

For Doctors

Description

Meloxicam belongs to the enolic acid group of non-steroidal anti-inflammatory drugs (NSAIDs) and is an oxicam derivative drug. It is available as tablets and oral suspension. The drug is insoluble in water but highly soluble in strong acids and bases. Each tablet contains 7.5 mg or 15 mg of Meloxicam for oral administration, and each bottle contains 7.5 mg per 5 ml of Meloxicam for oral suspension. The inactive ingredients in Meloxicam tablets include;

• Colloidal silicon dioxide.

• Lactose monohydrate.

• Microcrystalline cellulose.

• Magnesium stearate.

• Crospovidone.

• Povidone.

• Sodium citrate dihydrate.

Clinical Pharmacology

Mechanism of Action

The enzymes COX 1 and 2 are responsible for converting arachidonic acid into prostaglandin H2. Prostaglandins sensitize neuronal pain receptors, and Meloxicam, similar to other NSAIDs, causes inhibition of prostaglandins. This leads to its decreased synthesis, thus reducing the pain and inflammatory symptoms.

Pharmacokinetics

• Absorption: The oral bioavailability of a single dose of Meloxicam is around 89 percent in comparison to intravenous bolus injection, which is around 100 percent. The maximum concentration of Meloxicam in plasma after an oral administration of a 7.5 mg tablet takes around four to five hours, and the steady state is attained after multiple dosing for about five days. Administering the drug after a high-fat meal showed an increase in the drug levels in the plasma (approximately 22 percent); however, the area under the curve remains the same. The administration of antacids does not have any pharmacokinetic interaction.

• Distribution: The volume of distribution after absorption of Meloxicam is approximately ten liters, with 99.4 percent of drugs getting bound to plasma proteins, especially albumin. In patients with renal diseases, the plasma protein binding is slightly decreased.

• Metabolism: Meloxicam gets metabolized extensively in the liver involving cytochrome P450 enzymes, and metabolites such as 5-carboxy Meloxicam are formed through oxidation. The peroxidase enzyme also leads to the formation of two or more metabolites.

• Excretion: The metabolites get excreted in the feces and urine with only the traces of the original drug. The half-life of Meloxicam after an oral administration is around 15 to 20 hours.

Pharmacodynamics

Meloxicam exhibits anti-inflammatory, antipyretic, and analgesic properties. It also demonstrated the ability to reduce the erythrocyte sedimentation rate (ESR) in patients with rheumatoid arthritis. Similar to other NSAIDs, prolonged use of Meloxicam can cause renal or cardiovascular problems or thrombotic events. The drug also possesses a risk of gastrointestinal symptoms; however, it is less severe compared to Diclofenac.

Drug Interactions

Meloxicam can interfere with the following drugs:

• Aspirin.

• NSAIDs such as Ibuprofen, Ketorolac, Celecoxib, etc.

• ACE inhibitors such as Captopril, Enalapril, Lisinopril, etc.

• Angiotensin II receptor blockers such as Losartan, Telmisartan, Valsartan, etc.

• Lithium.

• Sodium polystyrene sulfonate.

• Methotrexate.

• Diuretics such as Furosemide.

• Cyclosporine.

• Anti-platelet drugs such as Warfarin, Clopidogrel, Enoxaparin, etc.

Clinical Studies

• A 12-week double-blind controlled trial was conducted to evaluate the use of Meloxicam for the treatment of osteoarthritis. Patients on 7.5 mg and 15 mg of Meloxicam showed significant improvement in comparison to the placebo. A similar result was observed in clinical trials of patients suffering from rheumatoid arthritis in comparison to the placebo, and no incremental benefit was noted with a 22.5 mg dose when compared to the 15 mg dose.

• A 12-week double-blind active-controlled parallel-arm trial was conducted in patients above two years to evaluate the use of Meloxicam for the treatment of juvenile rheumatoid arthritis, and no significant change was observed between the different dose groups.

Nonclinical Toxicology

• Carcinogenesis: In the long-term carcinogenicity studies of rats and mice, there was no increase in tumor incidence up to 0.5 to 2.6 fold, respectively, more than the maximum recommended human daily dose of Meloxicam.

• Mutagenicity: Studies revealed that Meloxicam was not mutagenic in an Ames assay or clastogenic in a chromosome aberration assay with human lymphocytes.

• Fertility: Meloxicam did not cause any significant changes in male and female fertility in rats up to 5.8 and 3.2 folds, respectively, higher than the maximum recommended human daily dose.

Uses of Meloxicam in Specific Populations

• Pregnancy: No adequate well-controlled studies are performed on pregnant females to determine the safety of Meloxicam. However, Meloxicam is known to cross the placental barrier, and the use of Meloxicam during pregnancy must be avoided to prevent potential risk to the fetus.

• Nursing Mothers: It is unknown whether Meloxicam is excreted in human milk. Many drugs are excreted in human milk; therefore, due to the risk of serious adverse reactions, a decision should be made whether the drug is necessary for the mother or to discontinue feeding.

• Pediatric Use: The safety and effectiveness of the drug in pediatric patients between two to 17 years with juvenile rheumatoid arthritis have been evaluated in three clinical trials.

• Geriatric Use: Caution must be taken with Meloxicam, similar to other NSAIDs, in the treatment of elderly people above 65 years of age. However, no significant changes were observed with respect to the safety and effectiveness of Meloxicam in comparison to younger adults.

• Hepatic or Liver Impairment: Dose adjustment is not necessary for patients with mild to moderate liver or kidney impairment; however, the use of Meloxicam in patients suffering from severe renal or hepatic diseases has not been studied.