Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local, or emergency room immediately. Instanac-TPM may be harmful if swallowed.
Proper storage of Instanac-TPM:
Store Instanac-TPM at 77 degrees F (25 degrees C) in the sealed pouch. Brief storage between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Throw away any unused patches 3 months after opening the pouch. The pouch is not child-resistant. Keep Instanac-TPM out of the reach of children and away from pets.
Overdose of Instanac-TPM in details
When a dose is taken in higher dose than the recommended doses, it is called Overdose. Overdose always needs a clinical supervision. Any medicine or drug when consumed in Overdose produces untoward side effects on one or various organs in the body. A medicine is excreted in the kidney or metabolized in the liver most of the times. This process goes without any hurdles when taken in normal dose, but when taken in an overdose, the body is not able to metabolize it or send it out properly which causes the effects of anoverdose.
Overdosage will not ordinarily cause acute problems. If Instanac-TPM ophthalmic solution, 0.1% is accidentally ingested, fluids should be taken to dilute the medication.
What should I avoid while taking Instanac-TPM?
Avoid drinking alcohol. It may increase your risk of stomach bleeding.
Avoid taking aspirin or other NSAIDs while you are taking this medicine.
Ask a doctor or pharmacist before using any cold, allergy, or pain medication. Many medicines available over the counter contain aspirin or other medicines similar to Instanac-TPM. Taking certain products together can cause you to get too much of this type of medication. Check the label to see if a medicine contains aspirin, ibuprofen, ketoprofen, or naproxen.
Warnings are a mix of Precautions. Contraindications and interactions and serious harmful effects associated with the medicine intake. A diabetic or Hypertensive patient need to be warned about few drug interactions. A known hypersensitivity patient needs to be careful about the reactions or anaphylactic shock. A pregnant woman or a breastfeeding woman should be warned of certain medications. A Hepatitis [liver disease] patient or a cardiac patient should avoid few drugs.
Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as Instanac-TPM, increases the risk of serious gastrointestinal (GI) events.
Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG.
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.
Avoid the use of Instanac-TPM delayed-release tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Instanac-TPM delayed-release tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
Gastrointestinal Bleeding, Ulceration, and Perforation
NSAIDs, including Instanac-TPM, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. However, even short-term therapy is not without risk.
Risk Factors for GI Bleeding, Ulceration, and Perforation
Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy, concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs);, smoking, use of alcohol, older age, and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.
Strategies to Minimize the GI Risks in NSAID-Treated Patients
Use the lowest effective dosage for the shortest possible duration.
Avoid administration of more than one NSAID at a time.
Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs.
Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Instanac-TPM delayed-release tablets until a serious GI adverse event is ruled out.
In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding.
In clinical trials of Instanac-TPM-containing products, meaningful elevations (i.e., more than 3 times the ULN) of AST (SGOT) were observed in about 2% of approximately 5,700 patients at some time during Instanac-TPM treatment (ALT was not measured in all studies).
In a large, open-label, controlled trial of 3,700 patients treated with oral Instanac-TPM for 2 to 6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of patients and included marked elevations (greater than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3 to 8 times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in patients receiving Instanac-TPM when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.
Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with Instanac-TPM in 42 of the 51 patients in all trials who developed marked transaminase elevations.
In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with Instanac-TPM. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.
In a European retrospective population-based, case-controlled study, 10 cases of Instanac-TPM associated drug-induced liver injury with current use compared with non-use of Instanac-TPM were associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this particular study, based on an overall number of 10 cases of liver injury associated with Instanac-TPM, the adjusted odds ratio increased further with female gender, doses of 150 mg or more, and duration of use for more than 90 days.
Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with Instanac-TPM, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with Instanac-TPM. However, severe hepatic reactions can occur at any time during treatment with Instanac-TPM.
If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), Instanac-TPM delayed-release tablets should be discontinued immediately.
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Instanac-TPM delayed-release tablets immediately, and perform a clinical evaluation of the patient.
To minimize the potential risk for an adverse liver related event in patients treated with Instanac-TPM delayed-release tablets, use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing Instanac-TPM delayed-release tablets with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, anti-epileptics).
NSAIDs, including Instanac-TPM delayed-release tablets, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazides diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs.
Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.
Heart Failure and Edema
The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately 2-fold increase in hospitalization for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of Instanac-TPM may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).
Avoid the use of Instanac-TPM delayed-release tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Instanac-TPM delayed-release tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Renal Toxicity and Hyperkalemia
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of Instanac-TPM delayed-release tablets in patients with advanced renal disease. The renal effects of Instanac-TPM delayed-release tablets may hasten the progression of renal dysfunction in patients with pre-existing renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating Instanac-TPM delayed-release tablets. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of Instanac-TPM delayed-release tablets. Avoid the use of Instanac-TPM delayed-release tablets in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If Instanac-TPM delayed-release tablets are used in patients with advanced renal disease, monitor patients for signs of worsening renal function.
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
Instanac-TPM has been associated with anaphylactic reactions in patients with and without known hypersensitivity to Instanac-TPM and in patients with aspirin-sensitive asthma.
Exacerbation of Asthma Related to Aspirin Sensitivity
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Instanac-TPM delayed-release tablets are contraindicated in patients with this form of aspirin sensitivity. When Instanac-TPM delayed-release tablets are used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
Serious Skin Reactions
NSAIDs, including Instanac-TPM, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions and to discontinue the use of Instanac-TPM delayed-release tablets at the first appearance of skin rash or any other sign of hypersensitivity. Instanac-TPM delayed-release tablets are contraindicated in patients with previous serious skin reactions to NSAIDs.
Premature Closure of Fetal Ductus Arteriosus
Instanac-TPM may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Instanac-TPM delayed-release tablets, in pregnant women starting at 30 weeks of gestation (third trimester).
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with Instanac-TPM delayed-release tablets, has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including Instanac-TPM delayed-release tablets, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding.
What should I discuss with my healthcare provider before taking Instanac-TPM?
Some medical conditions may interact with Instanac-TPM. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding
if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
if you have allergies to medicines, foods, or other substances
if you have a history of kidney or liver problems, diabetes, or stomach or bowel problems (eg, bleeding, perforation, ulcers)
if you have a history of swelling or fluid buildup, asthma, growths in the nose (nasal polyps), or mouth inflammation
if you have high blood pressure, blood disorders (eg, porphyria), bleeding or clotting problems, heart problems (eg, heart failure), or blood vessel disease (eg, in the brain or heart), or if you are at risk of any of these diseases
if you have poor health, dehydration or low fluid volume, or low blood sodium levels, or if you smoke, drink alcohol, or have a history of alcohol abuse
Some MEDICINES MAY INTERACT with Instanac-TPM. Tell your health care provider if you are taking any other medicines, especially any of the following:
Anticoagulants (eg, warfarin), aspirin, clopidogrel, corticosteroids (eg, prednisone), direct factor Xa inhibitors (eg, rivaroxaban), heparin, prasugrel, or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the risk of bleeding, including stomach bleeding, may be increased
Azole antifungals (eg, itraconazole, voriconazole), bisphosphonates (eg, risedronate), or probenecid because they may increase the risk of Instanac-TPM's side effects
Rifamycins (eg, rifampin) because they may decrease Instanac-TPM's effectiveness
Cyclosporine, lithium, methotrexate, other NSAIDs (eg, ibuprofen), quinolones (eg, ciprofloxacin), or tenofovir because the risk of their side effects may be increased by Instanac-TPM
Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril) or diuretics (eg, furosemide, hydrochlorothiazide) because their effectiveness may be decreased by Instanac-TPM
Medicines that may harm the liver (eg, acetaminophen, ketoconazole, isoniazid, certain medicines for HIV infection, certain antibiotics or seizure medicines) because the risk of liver side effects may be increased. Ask your doctor if you are unsure if any of your medicines might harm the liver.
This may not be a complete list of all interactions that may occur. Ask your health care provider if Instanac-TPM may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Certain people who are very sick or very old or who are sensitive show an exacerbation of side effect of the drug which can turn dangerous at times. So, it is very important to remember the precautions while taking the medicine. Pregnancy and Breastfeeding are also special categories wherein extra care or precaution is needed when taking a drug. Few patients may have a hypersensitivity reaction to few medications, and that can be life-threatening rarely. Penicillin hypersensitivity is one example. Diarrhea, rashes are few other symptoms which need a watch. A patient with other co-existing diseases like liver disease, heart disease, kidney disease should take special precautions.
All topical nonsteroidal anti-inflammatory drugs (NSAIDs) may slow or delay healing.
Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.
Use of topical NSAIDs may result in keratitis. In some susceptible patients continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal infiltrates, corneal erosion, corneal ulceration, and corneal perforation. These events may be sight-threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.
Postmarketing experience with topical NSAIDs suggests that patients experiencing complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface disease (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events, which may become sight-threatening.
Topical NSAIDs should be used with caution in these patients.
Postmarketing experience with topical NSAIDs also suggests that use more than 24 hours prior to surgery or use beyond 14 days postsurgery may increase patient risk for occurrence and severity of corneal adverse events.
It is recommended that Instanac-TPM ophthalmic solution, 0.1%, like other NSAIDs, be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time. Use of the same bottle for both eyes is not recommended with topical eye drops that are used in association with surgery.
Results from clinical studies indicate that Instanac-TPM ophthalmic solution, 0.1% has no significant effect upon ocular pressure. However, elevations in intraocular pressure may occur following cataract surgery.
Information for Patients
Except for the use of a bandage hydrogel soft contact lens during the first 3 days following refractive surgery, Instanac-TPM ophthalmic solution, 0.1% should not be used by patients currently wearing soft contact lenses due to adverse events that have occurred in other circumstances.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term carcinogenicity studies in rats given Instanac-TPM ophthalmic solution, 0.1% in oral doses up to 2mg/kg/day (approximately 500 times the human topical ophthalmic dose) revealed no significant increases in tumor incidence. A 2-year carcinogenicity study conducted in mice employing oral Instanac-TPM ophthalmic solution, 0.1% up to 2 mg/kg/day did not reveal any oncogenic potential. Instanac-TPM ophthalmic solution, 0.1% did not show mutagenic potential in various mutagenicity studies including the Ames test. Instanac-TPM ophthalmic solution, 0.1% administered to male and female rats at 4 mg/kg/day (approximately 1000 times the human topical ophthalmic dose) did not affect fertility.
No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.
Pregnancy Category C. Reproduction studies performed in mice at oral doses up to 5,000 times (20 mg/kg/day) and in rats and rabbits at oral doses up to 2,500 times (10 mg/kg/day) the human topical dose have revealed no evidence of teratogenicity due to Instanac-TPM ophthalmic solution, 0.1% despite the induction of maternal toxicity and fetal toxicity. In rats, maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. Instanac-TPM ophthalmic solution, 0.1% has been shown to cross the placental barrier in mice and rats. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Because of the known effects of prostaglandin biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of ductus arteriosus), the use of Instanac-TPM ophthalmic solution, 0.1% during late pregnancy should be avoided.
It is not known whether topical ophthalmic administration of Instanac-TPM ophthalmic solution, 0.1% could result in sufficient systemic absorption to produce detectable quantities in breast milk. Because many drugs are excreted in human milk, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
What happens if I miss a dose of Instanac-TPM?
When you miss a dose, you should take it as soon as you remember, but you should take care that it should be well spaced from the next dose. You should not take an extra dose at the time of the second dose as it will become a double dose. The double dose can give unwanted side effects, so be careful. In chronic conditions or when you have a serious health issue, if you miss a dose, you should inform your health care provider and ask his suggestion.
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
DailyMed. "DICLOFENAC EPOLAMINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).