Indomethacin Suppositories for Rheumatoid Arthritis - Exploring the Benefits

Overview:

Indomethacin is a highly productive pain reliever with many applications. Indomethacin suppositories are indicated for rheumatoid arthritis, where the joints develop soreness and impaired functions. The use of Indomethacin in suppository form was evaluated and authorized by the drug regulatory authority of the United States - the Food and Drug Administration (FDA). Indomethacin suppositories received FDA authorization in the year 1965. Currently, it is being marketed across the globe under various brand names.

Drug Group:

Indomethacin suppositories are categorized under the drug group of non-steroidal anti-inflammatory drugs (NSAIDs), which encompasses numerous subclasses of drugs. Being an NSAID, Indomethacin gears down the inflammatory process, alleviating pain and associated discomfort.

Available Doses and Dosage Forms:

Indomethacin suppositories are marketed and circulated in a single dose of 50 milligrams (mg). These are available in a suppository form indicated strictly for rectal use, in which the medicine should be introduced into the rectum. Indomethacin suppository is not manufactured to be taken by mouth. Capsule forms of Indomethacin are also marketed, which can be employed instead of suppository forms.

For Patients:

What Is Rheumatoid Arthritis?

Rheumatoid arthritis is demonstrated to be an immune disorder with noticeable inflammatory changes in the joint space and joint tissues. In rheumatoid arthritis, the immune cells are misguided and wrongly target their healthy cells. The cells and structures that line the joint cavity are more susceptible to these poorly directed immune cells. The knee, hand, and wrist joints are more vulnerable to rheumatoid arthritis.

The affected person may elicit manifestations like soreness and puffiness in and around the joint region. Often, the person experiences compromised joint movement in more than one joint and elicits pain on touching or while moving the joints. Drop in body weight, elevated body temperature, and general tiredness are other general manifestations elicited in rheumatoid arthritis. The joint structure and shape may even alter in more advanced stages, reflecting gross joint disfigurement. Patients may struggle to balance their bodies and perform routine day-to-day activities in such cases. It significantly hampers the patient’s quality of life. In the later stages, rheumatoid arthritis extends its effects on other organs like the heart, skin, eyes, and blood vessels.

Middle-aged women have a slight preference for rheumatoid arthritis when compared with other population groups. Rheumatoid arthritis is reported to have a strong familial association; hence, anybody with a family history of the condition is more likely to develop it. Smoking and being overweight are two other factors that can trigger the development of rheumatoid arthritis in susceptible persons.

How Does Indomethacin Suppository Work?

Indomethacin suppositories elicit their action by checking a specific enzyme called cyclooxygenase (COX), which is imperative for the formation of prostaglandins, by facilitating the transformations of a compound called arachidonic acid into prostaglandin H2. Prostaglandin is the metabolically active and reactive version of the prostaglandin H2 molecule. Prostaglandins are structurally lipid molecules capable of evoking inflammatory signs (soreness, redness, puffiness) in the event of any infection or destructive process in the body. As the prostaglandin formation is hindered by checking the enzyme needed for triggering its formation, Indomethacin succeeds in bringing down the inflammatory response.

What Is the Dosage of Indomethacin Suppository?

The dose is often kept minimal during the inception of the treatment using Indomethacin. Since Indomethacin has numerous indications, the concerned doctor often determines the dose after considering the condition for which it is prescribed and the prescribed drug form.

25 mg of rectal formulations is the routinely advised inceptive dose at a frequency of two to three times daily. Later, the dose will be titrated to 50 mg, keeping track of the total daily dose of Indomethacin. The daily dose should be restricted to 200 mg; hence, the dose will be modified accordingly. 50 mg of Indomethacin rectal formulation at a daily frequency of two to three times is estimated to be the standard dose of Indomethacin suppository for rheumatoid arthritis.

How Effective Is Indomethacin Suppository?

Various clinical trials and studies have been concluded to expose the efficacy of Indomethacin in tackling rheumatoid arthritis when administered in suppository form via rectum. It was concluded that the Indomethacin suppositories exhibited effectiveness comparable with their oral forms. No appreciable differences were reported in the safety aspect of both the drug forms. The effectiveness of Indomethacin for rheumatoid arthritis over other medicines was proven unequivocally. Its practical applicability has increased tremendously over the last decade.

What Are the Things to Inform the Doctor Before Taking the Drug?

Before proceeding with a new drug regimen, it is imperative to keep the doctor informed about things that can directly reflect on the patient's safety while on the therapy.

• Previous allergic encounters with Indomethacin or other medicines of the same or related drug group should be informed without fail, as subsequent exposure to allergic medicine can bring grave consequences to the body.

• The patient's detailed medical history is essential to assess the current health status. Hence, it is advised to keep the doctor updated about past and present ailments from which the person suffered or is suffering. Rectal disorders like bleeding rectum, proctitis (swollen rectum), heart disease, respiratory issues like asthma (troubled breathing), kidney diseases, and nasal polyp (tissue growth within the nose) are certain medical conditions that need attention while undergoing Indomethacin rectal therapy.

• A comprehensive drug history is another important thing the doctor should be aware of before commencing the treatment. Anticoagulants, selective serotonin reuptake inhibitors, oral steroid medicines, serotonin-norepinephrine reuptake inhibitors, and other NSAIDs are certain medications that can interfere with Indomethacin. Hence, the doctors should be informed about these drug intakes beforehand.

• The patient should disclose their pregnancy and lactation status to the concerned doctor. Pregnant women are not supposed to use Indomethacin suppositories unless under medical advice.

How Is the Indomethacin Suppository Administered?

Indomethacin suppository needs to be lodged into the patient's rectum. So, the patients are instructed to follow specific steps to ensure proper placement of the suppository. It is always advised to place the medicine at a specified time throughout the treatment regimen, which ensures consistency in the concentration of Indomethacin in the blood.

Indomethacin suppository is administered by following these techniques:

• Before issuing the Indomethacin suppository, ensure the hands are correctly cleaned and germ-free.

• Just like capsules, each suppository is enveloped inside its wrapper. The suppository should be removed from its wrapper only at the time of insertion. Wet the suppository’s tip to facilitate the placement of the suppository into the rectum.

• The wetted end should be directed toward the anus, and the suppository should be wedged into the rectum.

• The person should then lie down on their non-dominant side and elevate their dominant knee towards the chest. Further, a one-inch advancement of the suppository is achieved by driving it more and maintaining this position. The person should continue sleeping for another five minutes to check the expulsion of the suppository from the rectum.

• After administration, the person should wash their hands before returning to work.

What Are the Side Effects of Indomethacin Suppositories?

The most frequently encountered side effects associated with Indomethacin suppositories are dizziness, headache, indigestion, and a tendency to vomit. Sudden development of rashes over the skin, fluid-filled skin bumps, prickling sensations, facial puffiness, and troubled breathing are some of the critical side effects that demand immediate medical attention. Depression, vertigo, collapse in the blood cell counts, psychosis (unrealistic thoughts), altered liver functions, and cardiac issues are rarely reported during Indomethacin therapy.

Dietary Considerations:

No specific dietary instructions must be followed while undergoing therapy using Indomethacin suppositories. However, considering the simultaneous medicine intake and other underlying ailments, certain patients are advised to follow specific dietary considerations.

Missed Dose:

Indomethacin suppository is advised to be administered at a specified time, but the patient may sometimes forget to get the suppository on time. In such cases, the person can rectally introduce the suppository once aware of the missed dose. But if the person recalls a missing dose at the time of the subsequent dose, it is advised to ignore and disregard it. Administering double the prescribed dose is unacceptable as it can bring in overdose issues and other potential adverse effects.

Overdose:

Overdosage may potentiate the side effects and often require immediate medical assistance. Dizziness, stomach pain, extreme tiredness, vomiting, troubled breathing, and collapse are reported with the overdose administration of Indomethacin suppository.

Storage:

Indomethacin suppositories come with individual wrapping, like capsules. It is advised to store the suppositories along with the wrapping in the refrigerator. Only unwrap the suppositories at the time of administration. However, keeping the medicine below 30 degrees Celsius (86 degrees Fahrenheit) is safe. Temperature over 40 degrees Celsius (104 degrees Fahrenheit) can dramatically impair the composition of Indomethacin suppositories and thereby impact their effectiveness.

For Doctors:

Indication:

• Rheumatoid arthritis (moderate to severe grades with periods of acute flare-ups).

• Osteoarthritis (moderate to severe degree).

• Ankylosing spondylitis (moderate to severe grades).

• Acute gouty arthritis.

• Bursitis.

• Tendinitis.

Dose:

The dosage of Indomethacin is primarily formulated considering the condition for which it is advised.

• Rheumatoid Arthritis, Osteoarthritis, and Ankylosing Spondylitis: The Indomethacin dosage remains more or less the same with an inceptive dose of 25 mg at a daily frequency of two to three times. The dose can then be modified after evaluating the response from the patient. The utmost dose of Indomethacin, proven safe, is 200 mg. Hence, the dose should be adjusted without overriding the safer limit.

• Tendinitis and Bursitis: It is often elicited as an acute painful shoulder. A 75 to 150 mg daily dose is advised for acute painful shoulders. The daily dose should be divided into three or four smaller doses.

• Acute Gouty Arthritis: 150 mg of Indomethacin is the recommended daily dosage for acute gouty arthritis, which should be given in three doses of 50 mg.

Dosing Considerations:

The rectal formulations can be given as an alternative to the capsule form of Indomethacin. Administration of the same doses of rectal and oral forms of Indomethacin precipitated slight variations in the utmost blood concentration achieved; hence, switching between rectal and oral formulations is not appreciated without a doctor’s advice, as it needs medical guidance for the dose confirmation.

What Are the Pharmacological Aspects of Indomethacin Suppositories?

• Mechanism: Indomethacin suppositories, being an NSAID, elicit its actions in the body by primarily checking the cyclooxygenase (COX) enzymes. It blocks both the cyclooxygenase enzymes, COX 1 and COX 2. It bears anti-inflammatory, antipyretic, and analgesic properties. All the effects that Indomethacin contributes are brought in by COX inhibition. By hampering the functions of COX, Indomethacin can bring down prostaglandin production, which is identified to be a potent inflammatory mediator. It can evoke inflammatory responses in the event of an infection, injury, or trauma, inflicting pain and other associated inflammatory reactions in the body. In addition, recent studies have concluded the efficacy of Indomethacin in gearing down viral growth and is identified as an antiviral agent. However, practical applicability is not extended to viral therapy, as the literature studies are not backed up with clinical evidence.

• Pharmacodynamics: Indomethacin has various other effects on the body by hampering the COX enzymes. COX-1 enzyme inhibition interrupts the platelet aggregation process by checking thromboxane A2 production. It predisposes the patient to anti-platelet effects, which can harm individuals with known cardiac complications. Indomethacin also adversely impacts the intestinal mucosa due to the down-regulation of the COX-1 enzyme.

• Pharmacokinetics: The rectal formulations of Indomethacin elicited an enhanced absorption rate when compared with the capsule form. However, despite enhanced absorption, a slight reduction in the total uptaken drug is reported in suppository form. It is because of the poor retention of the suppository at the rectum. Once the Indomethacin is uptaken into the circulation, it is distributed with the plasma protein's help. Around 99 percent of the distribution happens through plasma proteins. Certain liver enzymes are responsible for the breakdown or metabolic transformation of Indomethacin. Deacylation and demethylation of Indomethacin give rise to metabolites like desbenzoyl and desmethyl indomethacin. The medicine was eliminated through urinary and fecal routes as either metabolites or in the parent form.

Toxicity:

Non-clinical studies on animals, particularly rats and mice, substantiated that Indomethacin is not associated with any potential for carcinogenesis and mutagenesis. The non-clinical studies were conducted at a daily dose of one milligram per kilogram of body weight, much higher than the normally advised human dosage. Animal studies were also conducted to expose the impact of Indomethacin on fertility. A daily dose of 0.5 milligrams per kilogram of body weight was tested on animals to assess fertility impairment, and it could not reflect any apparent influences on fertility.

Clinical Studies:

Clinical studies have successfully demonstrated the potency of Indomethacin in tackling the inflammatory manifestations associated with rheumatoid arthritis. In addition to rheumatoid arthritis, patients with osteoarthritis and ankylosing spondylitis also showed appreciable alleviation in soreness and other manifestations.

Randomized control trials were conducted to evaluate the potency and safety of Indomethacin against standard drugs for rheumatoid arthritis. However, it was found that Indomethacin could not create a check on disease advancement. It only works to comfort the patient by diminishing their symptoms and discomfort. Hence, Indomethacin is proven to enhance the quality of life of patients detected with moderate to severe forms of rheumatoid arthritis. Indomethacin works well for diminishing joint stiffness, typically in the morning.

Subjects who were studied with the suppository form of Indomethacin precipitated outcomes on par with the oral forms of Indomethacin. None of the studies could reflect any demonstrable variations in their outcomes. Indomethacin suppository forms were also studied against the corticosteroids routinely advised for tackling rheumatoid arthritis.

What Are the Contraindications of Indomethacin Suppositories?

All the patients do not well tolerate indomethacin suppositories. Certain conditions contraindicate the use of Indomethacin suppositories.

Some of the absolute contraindications include the following:

• Previous allergic encounters with Indomethacin or other medicines in the same class are advised not to use Indomethacin suppositories as they risk anaphylactic reactions. Reported hyperreactivity to any of the ingredients present in the Indomethacin suppository is also identified to be another contraindication for the Indomethacin suppository.

• Patients undergoing coronary artery bypass graft surgery should not take Indomethacin suppositories. All the medicines that come under the category of NSAIDs are reported to evoke cardiac complications like myocardial infarction and stroke in patients with a history of coronary artery bypass graft surgery.

• Indomethacin suppositories are strictly not advised for patients with severe skin reactions in response to NSAID intake. The skin reactions can be urticaria, toxic epidermal necrolysis, exfoliative dermatitis, and Stevens-Johnson syndrome.

• Aspirin-sensitive asthma is considered an absolute contraindication for advising Indomethacin rectal formulation. Patients who have precipitated asthma or aggravated asthmatic attack following NSAID intake are not advised to use Indomethacin suppositories. Reports suggested the possibility of grave reactions in such patients while undergoing treatment using Indomethacin suppositories.

• Patients with a prior experience of salicylate-induced hyperreactivity are another category contraindicated to use Indomethacin suppositories.

• Rectal conditions like rectal bleeding and proctitis are also recognized as absolute contraindications for rectal formulations of Indomethacin. In addition, it can make the placement painful and uneasy for patients with rectal pathology.

• Indomethacin rectal formulations are not to be used by pregnant women approaching the final trimester of pregnancy, as they can trigger early closure of the baby’s ductus arteriosus.

Warnings and Precautions:

• Cardiovascular Risks: Indomethacin, being an NSAID, bears the risk of triggering thrombotic events, which can endanger the patient’s life. Incidences of myocardial infarction and strokes were reported during treatment using NSAIDs. The risk will be enhanced in the case of patients with active cardiac ailments like heart failure.

• Gastrointestinal Issues: NSAIDs can detrimentally impact the mucosa that lines the gastrointestinal (GI) tract. It can give rise to gastrointestinal issues like gastric or intestinal ulcers, gastrointestinal bleeding, and rupture of the intestinal mucosa. Though it can develop in any patient while undergoing therapy using NSAIDs, those with pre-existing gastrointestinal issues are more susceptible to developing GI complications.

• Hepatotoxicity: Long-term exposure to NSAIDs can progressively disrupt the functions of the liver. Hence, keeping the patients aware of the risk for toxic liver disease aids in the early detection of symptoms.

• Nephrotoxicity: It is one of the potent warnings concerning NSAIDs. It is often the deep-rooted result of prolonged therapy using NSAIDs like Indomethacin. Patients advised with Indomethacin for a remarkably more extended period should be periodically assessed for kidney function. Renal papillary necrosis is the frequently encountered manifestation of nephrotoxicity triggered by Indomethacin.

• Aggravation of Asthma: Caution should be exercised while advising Indomethacin rectal formulations for patients with asthmatic attacks. It is associated with an enhanced probability of aggravating asthma, so thorough monitoring is employed.

• Hypertension: Periodic blood pressure evaluation is dictated as Indomethacin can modify one’s blood pressure.

• Grave Skin Reactions: Indomethacin can trigger grave skin reactions like toxic epidermal necrolysis. In the event of skin reaction, the Indomethacin therapy should be withdrawn immediately to check for further worsening of the hypersensitivity reactions.

• Hematological Issues: NSAIDs impact the blood profile and may precipitate anemia. Hence, throughout the treatment period, periodic evaluation of the blood picture is necessary to keep track of hematological disparities.

• Anaphylactic Reactions: Indomethacin can also precipitate anaphylactic reactions, threatening one’s life. It entails immediate medical assistance to safeguard life.

• Ocular Defects: Prolonged administration of Indomethacin can bring changes in the eyes and thereby fade the vision. Disturbances in the retina and corneal deposits may develop in response to long-term Indomethacin usage. Periodic ocular evaluation is hence warranted; therapy withdrawal is preferred in the event of visual troubles.

• Suppress the Manifestations of Other Inflammatory Conditions: Being an anti-inflammatory, the manifestations of other infections will also get suppressed during Indomethacin therapy, which makes it difficult to identify other underlying infectious conditions.

• Induce Sleepiness: The patient should be warned about the sedative effects of Indomethacin as it compromises mental alertness. It can impact the activities that demand fine motor skills and concentration; hence, patients should be informed beforehand.

What Are the Drug Interactions of Indomethacin Suppositories?

• Simultaneous use of Indomethacin, a potent anticoagulant, can aggravate bleeding issues.

• Indomethacin interferes with diuretics and can gear down the efficacy of diuretics by compromising the natriuretic effects.

• Indomethacin potentiates the blood proportion of Digoxin when both medicines are advised simultaneously. The potential risk for an upsurge in the Digoxin concentration exposes one to toxicity issues.

• Indomethacin interferes with the efficacy of certain antihypertensive medicines like beta-blockers and angiotensin-converting enzyme inhibitors. When coupled with Indomethacin, the compromised effectiveness of these drugs reflects an escalation in blood pressure.

• Concomitant exposure to Indomethacin and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors can enhance the deterioration of kidney functions.

Specific Considerations:

• Pregnancy: FDA recognizes Indomethacin under category C of pregnancy medicine. Pregnant women over 30 weeks of gestation are advised not to use Indomethacin rectal formulations as it can impact the baby in the womb. It is proven that Indomethacin could prematurely trigger the baby’s ductus arteriosus closure.

• Lactation: Clinical studies have demonstrated that Indomethacin will be reflected in the breast milk when used by a lactating mother. So, using Indomethacin rectal formulations by a lactating mother exposes the breastfed baby to the risk of the medicine. Hence, generally, it is not preferred for lactating women unless the medical need of the lactating mother mandates it. The concerned doctor will assess the case and evaluate its benefits and risks.

• Pediatric Use: No clinical reports are available concerning Indomethacin rectal formulations in the pediatric population below 14.

• Geriatric Use: In aged patients, the probability of underlying other health conditions is higher, and therefore, it is associated with an enhanced risk of adverse side effects.