Arthotec

Artotek

Each modified-release tablet consists of a gastric-resistant core containing Artotec 75 mg, surrounded by an outer shell containing Misoprostol (Artotec) 200 mcg.

It also contains the following excipients: Tablet Core: Lactose monohydrate, microcrystalline cellulose, corn starch, povidone and magnesium stearate. Tablet coating: Methacrylic acid copolymer, sodium hydroxide, talc, microcrystalline cellulose, triethyl citrate, methylhydroxylpropylcellulose, crospovidone, colloidal silicon dioxide, and hydrogenated castor oil.

An indication is a term used to refer to a list of conditions, symptoms, or diseases for which a medication is prescribed or used by a patient. For example, acetaminophen or paracetamol is used by the patient for fever, or the doctor prescribes it for headaches or body aches. Now fever, headache, and body aches are all signs of paracetamol. The patient should be aware of the indications of medications used for common conditions, because they can be taken without a prescription at the pharmacy.

Acute and chronic treatment of signs and symptoms of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and acute diseases of the musculoskeletal system.

For patients who require a nonsteroidal anti-inflammatory drug (NSAID) together with Misoprostol (Artotec).

Diclofenac (Artotec) a component of Artotec is indicated for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute diseases of the musculoskeletal system. Misoprostol (Artotec) a component of Artotec is indicated for the prevention of NSAID-induced gastric and duodenal ulcers.

Artotek contains a combination of Diclofenac (Artotec) and Misoprostol (Artotek) Diclofenac (Artotec) is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing the amount of substances in the body that cause pain and inflammation.

Misoprostol (Artotec) reduces the level of gastric acid and replaces the protective substances in the stomach that are reduced when taking NSAIDs.

Artotec is used to treat osteoarthritis and rheumatoid arthritis in people at high risk of developing stomach or intestinal ulcers.

Artotec may also be used for purposes not listed in this medication guide.

​Carefully consider the potential benefits and risks of Artotec and other treatment options before deciding to use Artotec. Use the lowest effective dosage for the shortest period of time, according to the individual treatment goals of the patient.

​After monitoring the response to initial Artotec therapy, the dose and frequency should be adjusted according to the individual needs of the patient.

​For the relief of rheumatoid arthritis and osteoarthritis, the dosage is given below.

​Artotek is administered as Artotek 50 (50 mg Artotek/200 mcg Misoprostol (Artotek)) or as Artotek (75 mg Artotek/200 mcg Misoprostol (Artotek)).

​Note: See the special section below for dosing considerations.

​In osteoarthritis, the dosage for maximum protection of the gastrointestinal mucosa is Artotek 50 three times a day. For patients who experience intolerance, you can use Artotec twice a day or Artotec 50 twice a day, but they are less effective in preventing ulcers. This fixed combination product, Artotec, is not recommended for patients who do not receive an appropriate dose of both ingredients. The dosages of the components supplied with these regimens are as follows:

​In rheumatoid arthritis, the dosage is Artotec 50 three to four times a day. For patients who experience intolerance, you can use Artotec twice a day or Artotec 50 twice a day, but they are less effective in preventing ulcers. This fixed combination product, Artotec, is not recommended for patients who do not receive an appropriate dose of both ingredients. The dosages of the components supplied with these regimens are as follows:

​Special Recommendations For Dosing:

​Artotec contains Misoprostol (Artotec), which provides protection against stomach and duodenal ulcers. For the prevention of gastric ulcer disease, 200 mcg four and three times a day are therapeutically equivalent, but more protective than twice a day. For the prevention of duodenal ulcer disease, a four-times-a-day regimen is more protective than a three-or two-times-a-day regimen. However, the four-times-a-day regimen is less well tolerated than the three-times-a-day regimen, due to the usually self-limiting diarrhea associated with the Misoprostol dose (Artoteca), and the twice-a-day regimen may be better tolerated than the three-times-a-day regimen in some patients

​Dosages can be individualized using separate drugs (Misoprostol (Artotec) and Diclofenac (Artotec)), after which the patient can be changed to the appropriate dose of Artotec. In the presence of clinical indications, it may be advisable to co-treat Misoprostol (Artoteca) with Artotec or use separate components to optimize the dose and / or frequency of administration of Misoprostol (Artoteca). The total dose of Misoprostol (Artoteca) should not exceed 800 mcg / day, and no more than 200 mcg of Misoprostol (Artoteca) should be administered simultaneously. Doses of Diclofenac (Artotec) above 150 mg / day for osteoarthritis or above 225 mg / day for rheumatoid arthritis are not recommended

​If simultaneous use of CYP2C9 inhibitors is necessary, the total daily dose of Diclofenac (Artotec) should not exceed the lowest recommended dose of Artotec 50 twice a day.

​For more information, it may be useful to refer to the packaging inserts for Misoprostol (Artotec) and Diclofenac (Artotec).

See also:
What is the most important information I need to know about Artotek?

Patients with known hypersensitivity to Diclofenac (Artotec), aspirin, other NSAIDs, Misoprostol (Artotec), other prostaglandins, or any other Artotec ingredient.

Patients with active peptic ulcer disease/bleeding or perforation, as well as with active gastrointestinal bleeding or other active bleeding, such as cerebrovascular bleeding.

Patients with a history of gastrointestinal bleeding or perforation associated with prior NSAID therapy, active or recurrent peptic ulcer disease, or a history of bleeding.

Patients who have asthma attacks, urticaria, or acute rhinitis are provoked by aspirin or other non-steroidal anti-inflammatory drugs.

Treatment of perioperative pain in conditions of coronary artery bypass grafting (CABG).

Patients with severe cardiac, renal, and hepatic insufficiency.

Use during pregnancy: Artotec is contraindicated in pregnant women and women planning pregnancy, since Misoprostol (Artotec) causes uterine contractions and is associated with abortion, premature birth and fetal death. The use of Misoprostol (Artotec) has been associated with birth defects. In addition, Diclofenac (Artotec) can cause premature closure of the ductus arteriosus.

Women with childbearing potential should not start taking Artotec until pregnancy is ruled out, and should be fully informed of the importance of adequate contraception during treatment. If pregnancy is suspected, the use of Artotek should be discontinued.

Use Artotec as directed by your doctor. Check the label on the medicine for accurate dosage instructions.

• Artotek comes with an additional patient information sheet called Medication guide. Read it carefully. Read it again every time you fill up the Art Library again.
• Take Artotec orally with or without food. If an upset stomach occurs, take with food to reduce stomach irritation.
• Swallow the Artotek whole. Do not disturb, suppress, or chew until swallowed.
• Do not take broken pills.
• Do not take magnesium-containing antacids while taking Artotek. If an antacid is required, use it with calcium or aluminum.
• If you missed a dose of Artotek, take it as soon as possible. If it's almost time for the next dose, skip the missed dose and return to your normal dosing schedule. Do not take 2 doses at the same time.

Ask your doctor any questions about how to use Artotek.

There are specific as well as general uses of a drug or medicine. A medicine can be used to prevent a disease, treat a disease over a period or cure a disease. It can also be used to treat the particular symptom of the disease. The drug use depends on the form the patient takes it. It may be more useful in injection form or sometimes in tablet form. The drug can be used for a single troubling symptom or a life-threatening condition. While some medications can be stopped after few days, some drugs need to be continued for prolonged period to get the benefit from it.

Usage: Marked indications

Osteoarthritis/rheumatoid arthritis: Treatment of signs and symptoms of osteoarthritis or rheumatoid arthritis in patients at high risk of NSAID-induced gastric and duodenal ulcers and their complications.

See also:
What other drugs will affect Artotek?

Table 1: Clinically significant drug interactions with Artotec

Drugs that violate hemostasis
Clinical impact:	Diclofenac (Artotec) and anticoagulants such as warfarin have a synergistic effect on bleeding. Concomitant use of Diclofenac (Artotec) and anticoagulants has an increased risk of serious bleeding compared to the use of either of these drugs alone. The release of serotonin by platelets plays an important role in hemostasis. Epidemiological studies in follow-up and cohort control groups have shown that the simultaneous use of drugs that prevent serotonin reuptake and NSAIDs can potentiate the risk of bleeding more than NSAIDs alone.
Intervention:	Monitor patients with concomitant use of Artotec with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding.
Aspirin
Clinical impact:	Controlled clinical studies have shown that concomitant use of NSAIDs and pain-relieving doses of aspirin does not have a greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of NSAIDs and aspirin was associated with a significantly higher incidence of gastrointestinal adverse reactions compared to the use of NSAIDs alone.
Intervention:	Concomitant use of Artotec and pain-relieving doses of aspirin is usually not recommended due to the increased risk of bleeding.
	Artotec is not a substitute for low-dose asprin to protect the cardiovascular system.
ACE inhibitors, angiotensin receptor blockers, and beta blockers
Clinical impact	NSAIDs may reduce the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta blockers (including propranolol). In elderly, volume-depleted patients (including those on diuretic therapy), or those with renal insufficiency, concomitant use of NSAIDs with ACE inhibitors or ARBs may lead to deterioration of renal function, including possible acute renal failure. These effects are usually reversible.
Intervention:	The simultaneous use of these drugs should be carried out with caution. Patients should be adequately hydrated, and the clinical need for kidney function monitoring should be evaluated at the beginning of concomitant treatment and periodically thereafter.. During the simultaneous use of Artotec and ACE inhibitors, ARBs or beta-blockers, monitor your blood pressure to make sure that the desired blood pressure is reached. During the simultaneous use of Artotec and ACE inhibitors or ARBs in elderly patients who are exhausted by volume or have impaired renal function, monitor for signs of deterioration of renal function.
Diuretics
Clinical impact:	Clinical studies, as well as post-marketing observations, have shown that NSAIDs reduce the natriuretic effect of loop diuretics (for example, furosemide) and thiazide diuretics in some patients. This effect has been attributed to the inhibition of NSAID synthesis of renal prostaglandins.
Intervention:	During concomitant use of Artotec with diuretics, monitor patients for signs of impaired renal function, in addition to ensuring the effectiveness of diuretics, including antihypertensive effects.
Digoxin
Clinical impact:	It has been reported that the simultaneous use of diclofenac (Artotec) with digoxin increases the concentration of digoxin in the blood serum and prolongs the half-life of digoxin.
Intervention:	During the simultaneous use of Artotek and digoxin, monitor the level of digoxin in the blood serum.
Lithium
Clinical impact:	NSAIDs cause an increase in the level of lithium in the blood plasma and a decrease in the renal clearance of lithium. The average minimum lithium concentration increased by 15%, and the renal clearance decreased by about 20%. This effect has been attributed to the inhibition of NSAID synthesis of renal prostaglandins.
Intervention:	During simultaneous use of Artotec and lithium, monitor patients for signs of lithium toxicity.
Methotrexate
Clinical impact:	Concomitant use of NSAIDs and methotrexate may increase the risk of methotrexate toxicity (e.g., neutropenia, thrombocytopenia, impaired renal function).
Intervention:	During the simultaneous use of Artotec and methotrexate, monitor patients for the toxicity of methotrexate.
Cyclosporine
Clinical impact:	Concomitant use of diclofenac (Artotec) and cyclosporine may increase the nephrotoxicity of cyclosporine.
Intervention:	During the simultaneous use of Artotek and cyclosporine, monitor patients for signs of deterioration of renal function.
NSAIDs and salicylates
Clinical impact:	Concomitant use of Diclofenac (Artotec) with other NSAIDs or salicylates (for example, diflunisal, salsalate) increases the risk of gastrointestinal toxicity with little or no increase in efficacy.
Intervention:	Concomitant use of Artotec with other NSAIDs or salicylates is not recommended.
Pemetrexed
Clinical impact:	Concomitant use of Diclofenac (Artotec) and pemetrexed may increase the risk of pemetrexed-related myelosuppression, renal and gastrointestinal toxicity.
Intervention:	With the simultaneous use of Artotek and pemetrexed in patients with impaired renal function, whose creatinine clearance ranges from 45 to 79 mL/min, myelosuppression, renal and gastrointestinal toxicity are controlled. NSAIDs with a short half-life (for example, Diclofenac (Artotec), indomethacin) should be avoided for two days before, on the day and two days after administration of pemetrexed. In the absence of data on the potential interaction between pemetrexed and NSAIDs with a longer half-life (for example, meloxicam, nabumetone), patients taking these NSAIDs should discontinue the drug for at least five days before, on the day and two days after administration of pemetrexed.
Antacids
Clinical impact:	Antacids reduce the bioavailability of Misoprostolic (Artotecic) acid. Antacids can also delay the absorption of Diclofenac (Artoteca). Magnesium-containing antacids increase the diarrhea associated with Misoprostol (Artotec).
Intervention:	Simultaneous use of Artotek and magnesium-containing antacids is not recommended.
Corticosteroids
Clinical impact:	Concomitant use of corticosteroids with Diclofenac (Artotec) may increase the risk of gastrointestinal ulceration or bleeding.
Intervention	Monitor patients with concomitant use of Artotec with corticosteroids for signs of bleeding.
Inhibitors or inducers of SUR2C9
Clinical impact:	Diclofenac (Artotec) is metabolized by cytochrome P450 enzymes, mainly CYP2C9. Concomitant use of Diclofenac (Artotec) with CYP2C9 inhibitors (e.g., voriconzaol) may increase the effects and toxicity of Diclofenac (Artotec), while concomitant use with CYP2C9 inducers (e.g., rifampicin) may reduce the effectiveness of Diclofenac (Artotec).
Intervention:	2C9 ZPG inhibitors: If simultaneous use of 2C9 inhibitors is necessary, the total daily dose of Diclofenac (Artotec) should not exceed the lowest recommended dose of Artotec 50 twice a day. CYP2C9 inducers: When Artotec is administered with CYP2C9 inducers, a dose adjustment may be required. Prescribe separate preparations of Misoprostol (Artotec) and Diclofenac (Artotec), if a higher dose of Diclofenac (Artotec) is considered necessary.

See also:
What are the possible side effects of Artotek?

The following adverse reactions are discussed in more detail in other sections of the label:

• Cardiovascular thrombotic events
• Bleeding, Ulceration and perforation of the gastrointestinal tract
• Hepatotoxicity
• Hypertension
• Heart failure and edema
• Kidney intoxication and hyperkalemia
• Anaphylactic Reactions
• Serious Skin Reactions
• Hematological toxicity

Clinical Trial Experience

Since clinical trials are conducted under a wide variety of conditions, the frequency of adverse reactions observed in clinical trials of one drug cannot be directly compared with the frequency of clinical trials of another drug and may not reflect the frequency observed in practice.

Information on adverse reactions to Artotec was obtained from multinational controlled phase III clinical trials in more than 2,000 patients treated with Artotec 50 or Artotec, as well as from blind controlled trials of Diclofenac tablets (Artotec) of delayed release and Misoprostol tablets (Artotec).

Gastrointestinal

Gastrointestinal disorders had the highest incidence of adverse events in patients treated with Artotec. These events were generally minor, but led to discontinuation of therapy in 9% of patients treated with Artotec and in 5% of patients treated with Diclofenac (Artotec). For cases of gastrointestinal ulcers,.

Gastrointestinal disorder	Artotek	Diclofenac (Artotec)
Abdominal pain	21%	15%
Diarrhea	19%	11%
Dyspepsia	14%	11%
Nausea	11%	6%
Flatulence	9%	4%

Artotec may cause more abdominal pain, diarrhea, and other gastrointestinal symptoms than Diclofenac (Artotec) alone.

Diarrhea and abdominal pain developed at the beginning of the course of therapy and were usually self-limiting (resolved after 2-7 days). Rare cases of deep diarrhea leading to severe dehydration have been reported in patients treated with Misoprostol (Artotec). Patients with an underlying condition, such as inflammatory bowel disease, or those with dehydration, if it occurred, would be dangerous, should be carefully monitored when prescribing Artotek. The frequency of diarrhea can be minimized by prescribing Artotec with food and avoiding concomitant administration with magnesium-containing antacids.

Gynecological

Gynecological disorders previously reported with Misoprostol (Artotec) have also been reported in women treated with Artotec. Postmenopausal vaginal bleeding may be associated with taking Artotec. If this happens, a diagnostic examination should be performed to exclude gynecological pathology.

Elderly

Overall, there were no significant differences in the safety profile of Artotec in more than 500 patients aged 65 years and older compared to younger patients.

Other side effects that have sometimes been reported with Artotec, Diclofenac (Artotec), or other NSAIDs, as well as Misoprostol (Artotec), include:

The body as a whole: asthenia, fatigue, malaise.

Central and peripheral nervous system: dizziness, drowsiness, headache, insomnia, paresthesia, dizziness.

Digestive: anorexia, changes in appetite, constipation, dry mouth, dysphagia, ulceration of the esophagus, esophagitis, belching, gastritis, gastroesophageal reflux, benign neoplasm of the gastrointestinal tract, peptic ulcer, tenesmus, vomiting.

Female reproductive disorders: chest pain, dysmenorrhea, menstrual disorders, menorrhagia, vaginal bleeding.

Blood and lymphatic system: epistaxis, leukopenia, melena, purpura, decreased hematocrit.

Metabolism and nutrition: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, dehydration, hyponatremia.

Musculoskeletal system: arthralgia, myalgia.

Psychiatric hospital: anxiety, impaired concentration, depression, irritability.

Respiratory system: asthma, cough, hyperventilation.

Skin and appendages: alopecia,eczema, pemphigoid reaction, photosensitivity, increased sweating, itching.

Special feelings: perversion of taste, tinnitus.

Disorders of the kidneys and urinary tract: dysuria, nocturia, polyuria, proteinuria, urinary tract infection.

Vision: diplopia.

Post-Marketing Experience

The following adverse reactions were identified after the approval of Artotec, Diclofenac (Artotec) or Misoprostol (Artotec). Since these reactions are reported voluntarily from a large apopulation, it is not always possible to reliably estimate their frequency or establish a causal relationship with drug exposure.

The body as a whole: death, fever, infection, sepsis, chills, edema.

Cardiovascular system: arrhythmia, atrial fibrillation, congestive heart failure, hypertension, hypotension, increased CPK, increased LDH, myocardial infarction, palpitations, phlebitis, premature ventricular contractions, fainting, tachycardia, vasculitis.

Central and peripheral nervous system: coma, convulsions, hyperesthesia, hypertension, hypoesthesia, meningitis, migraine, neuralgia, drowsiness, stroke, tremor.

Congenital, familial, and genetic disorders: birth defects.

Digestive: enteritis, gastrointestinal bleeding, glossitis, heartburn, hematemesis, hemorrhoids, intestinal perforation, stomatitis and ulcerative stomatitis.

Female reproductive disorders: intermenstrual bleeding, leukorrhea, vaginitis, uterine spasms, uterine bleeding.

Blood and lymphatic system: agranulocytosis, anemia, aplastic anemia, increased blood clotting time, ecchymosis, eosinophilia, hemolytic anemia, leukocytosis, lymphadenopathy, pancytopenia, pulmonary embolism, rectal bleeding, thrombocytemia, thrombocytopenia.

Hypersensitivity: Angioedema, laryngeal/pharyngeal edema, urticaria.

Liver and biliary system: liver dysfunction, bilirubinemia, liver failure, pancreatitis, hepatitis, jaundice.

Male reproductive disorders: impotence, pain in the perineum.

Metabolism and nutrition: BUN elevated, glucosuria, gout, hypercholesterolemia, hyperglycemia, hyperuricemia, hypoglycemia, periorbital edema, porphyria, body weight change, fluid retention.

Pregnancy, postpartum period and perinatal conditions: abnormal uterine contractions, uterine rupture / perforation, placental retention, amniotic fluid embolism, incomplete abortion, premature birth, fetal death.

Psychiatric hospital: confusion, disorientation, sleep disturbances, hallucinations, nervousness, paranoia, psychotic reactions.

Disorders of the reproductive system and breast: female fertility has declined.

Respiratory system: shortness of breath, pneumonia, respiratory depression.

Skin and appendages: acne, bruising, erythema multiforme, exfoliative dermatitis, pruritus ani, rash, skin ulceration, Stevens-Johnson syndrome, toxic epidermal necrolysis, skin reactions (bullous rash).

Special feelings: hearing loss, loss of taste.

Disorders of the kidneys and urinary tract: cystitis, hematuria, interstitial nephritis, frequency of urination, nephrotic syndrome, oliguria, papillary necrosis, renal failure, membranous glomerulonephritis, minimal glomerulonephritis, glomerulogephritis.

Vision: amblyopia, blurred vision, conjunctivitis, glaucoma, iritis, lacrimation disorder, night blindness, visual impairment.