DUOLIN respules are used to help treat airways narrowing (bronchospasm) that happens with COPD (chronic obstructive pulmonary disease) in adult patients who need to use more than one bronchodilator medicine. This Generic COMBIVENT (ipratropium bromide and levosalbutamol tartarate) is indicated for use in patients with chronic obstructive pulmonary disease (COPD) on a regular aerosol bronchodilator who continue to have evidence of bronchospasm (airway narrowing) and who require a second bronchodilator. Duolin Repsules do not contain steroids. It contains Ipratropium and Levosalbutamol which relaxes the muscles of the airways in the lungs.
Ipratropium bromide is an anticholinergic (parasympatholytic) agent, which inhibits vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve.
Levosalbutamol tartarate is a relatively selective beta2-adrenergic agonist, whose activation leads to an increase in intracellular adenyl cyclase, the enzyme which catalyses the conversion of adenosine triphosphate (ATP) to cyclic-3′, 5′- adenosine monophosphate (cAMP).
The dosage of DUOLIN Inhaler is 2 inhalations, four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours. It is recommended to “test-spray” three times before using for the first time and in cases where the aerosol has not been used for more than 24 hours. Avoid spraying into eyes.
DUOLIN Inhaler may be used with a Zerostat VT Spacer device in patients who find it difficult to synchronize aerosol actuation with inspiration of breath.
Cephalexin (Keflex) is an inexpensive drug used to treat certain kinds of bacterial infections. If your doctor has diagnosed you with a throat, ear, bladder, sinus, or skin infection that is strongly suspected to be caused by bacteria, you may be started on Keflex while waiting for test result to show if your infection is bacterial or viral. This antibiotic treats many bacterial infections caused by Streptococcus, Hemophilus Influenza, Proteus Bacteria, and Escherichia coli (E. coli).
We sell Generic Keflex is in a group of drugs called cephalosporin antibiotics. Keflex fights bacteria in the body. You can Order Cephalexin Online via request page, we have cheap prices, prescription is not needed.
Dissolve the Keflex dispersible tablet in a small amount of water, about 2 teaspoonfuls. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.
Do not swallow or chew a dispersible tablet.
Shake the oral suspension (liquid) well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. Take Keflex for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Keflex will not treat a viral infection such as the common cold or flu.
In first our shipping company works from India, we have generic rifaximin 200mg / 400mg / 550mg, we guarantee delivery to the United States, United Kingdom, Australia. We have the best shipping ways to each country. Rifaximin is an antibiotic medication used to treat travelers’ diarrhea, irritable bowel syndrome, and hepatic encephalopathy. Generic Rifaximin is an antibiotic that works by killing the bacteria and preventing its growth. However, this medicine will not work for colds, flu, or other virus infections.
Rifaximin comes as a tablet to take by mouth with or without food. When rifaximin is used to treat traveler’s diarrhea, it is usually taken three times a day for 3 days. When rifaximin is used to prevent episodes of hepatic encephalopathy, it is usually taken twice a day. When rifaximin is used to treat irritable bowel syndrome, it is usually taken three times a day for 14 days. To help you remember to take rifaximin, take it around the same times every day.
Andriol / Restandol (Testosterone Undecanoate) released in capsules. We offer generic Andriol by brand name Cernos in same capsules, manucatured by Sun Pharma.
Andriol is used by men to make up for testosterone deficiency. Testosterone Undecanoate regulates protein and phosphorus metabolism in the body. Each Testosterone capsule contains 40 mg of testosterone dissolved in olinic acid.
After eating, the capsules are swallowed whole, without chewing, with a small amount of liquid. The initial dose is 120-160 mg per day (half the dose in the morning and the second half in the evening, when taking an odd number of capsules, take a higher dose in the morning) for 2-3 weeks, then 40-120 mg per day.
Storage conditions of the drug Andriol
At a temperature of 2–8 ° C.
DescriptionDosages / How to take?CommonSide EffectsLatest New'sPhoto's
Generic Imatinib under brand name Imatib sold in India company Cipla, many years and shows very good results to treat a cancer.
For best prices you need to order more than 300 pills, we offer better best prices if you will order via Bitcoin, we offer additional 20% discount. Shipping can be via EMS or RMS, also we can ship Imatinib from SIngapore to Europe or Canada. Sometimes we can ask a prescription.
It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells. Imatinib is an antineoplastic agent that inhibits the Bcr-Abl fusion protein tyrosine kinase, an abnormal enzyme produced by chronic myeloid leukemia cells that contain the Philadelphia chromosome.
The Global Imatinib Mesylate Market is a valuable source of insightful data for business strategists. It provides the industry overview with growth analysis and historical & futuristic cost, revenue, demand and supply data (as applicable). The researchers offer a thorough description of the value chain and its distributor analysis. This Market analysis gives in-depth data which enhances the understanding, scope, and application of this report.
Imatinib mesylate (IM) is a first-line treatment option for patients with chronic myeloid leukemia (CML). Patients who fail or are intolerant to IM therapy are treated with more expensive second and third-generation tyrosine kinase inhibitors. Patients show wide variation in trough concentrations in response to standard dosing. Thus, many patients receive subtherapeutic or supratherapeutic doses. Therapeutic drug monitoring (TDM) may improve dose management that, in turn, may reduce costs and improve outcomes. However, TDM also adds to the cost of patient care. The objective of this study was to determine the cost-effectiveness of TDM for generic IM therapy.
Growth Forecast Report on “Imatinib Drugs Market size | Industry Segment by Applications (Hospitals, Drug Stores and Other), by Type (Capsules and Tablets), Regional Outlook, Market Demand, Latest Trends, Imatinib Drugs Industry Share & Revenue by Manufacturers, Company Profiles, Growth Forecasts – 2025.” Analyzes current market size and upcoming 5 years growth of this industry.
An up- to -date information inclusive with this Imatinib Drugs Market report is an exclusive information generated by industry experts for evaluating the Market and supporting deliberate decision making. The report identifies the rapidly growing and competitive environment, Imatinib Drugs Market report provides information on latest trends and expansions, and focuses on market growth in terms of revenue, sales, production and technological advancements etc.
Manufacturer / Potential Investors, Traders, Distributors, Wholesalers, Retailers, Importers and Exporters, Association and government bodies are the main audience for Imatinib Drugs market involved in this report.
DescriptionHow to take?CommonSide EffectsLatest New'sPhoto's
Naltrexone is used to prevent relapse in people who became dependent on opioid medicine and then stopped using it. Naltrexone can help keep you from feeling a “need” to use the opioid.
Generic Revia can be ordering online via contact form of website: wemailmd.com, shipping availalbe from India via two differents way, for future details about how to order Naltexone, please, contact our support team using request page.
Naltrexone in India, made by manufacturer Intas (est: 1993), available in dosages 50mg each tablet.
Naltrexone should not be used to treat people who are still using street drugs or drinking large amounts of alcohol. Naltrexone is in a class of medications called opiate antagonists. It works by decreasing the craving for alcohol and blocking the effects of opiate medications and opioid street drugs.
If naltrexone is taken at home, it is usually taken once a day with or without food. it may be taken once a day, once every other day, once every third day, or once every day except Sunday. Please folow the instruction on your prescription label carefully, and speak with your doctor to explain any part you do not understand. Do not take more or less of it or take it more often than prescribed by your doctor.
Naltrexone is only helpful when it is used as part of an addiction treatment program.
Upset stomach or vomiting
Joint or muscle pain
Analysis and Forecast To 2025
In order to identify growth opportunities in the market, the report has been segmented into regions that are growing faster than the overall market. These regions have been potholed against the areas that have been showing a slower growth rate than the market over the global. Each geographic segment of the Naltrexone HCL market has been independently surveyed along with pricing, distribution and demand data for geographic market notably: North America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), Asia-Pacific (China, Japan, Korea, India and Southeast Asia), South America (Brazil, Argentina, Colombia etc.), Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa).
FDA urged to probe naltrexone implant tests on prison inmates
The FDA is being urged to investigate California biotech BioCorRx amid claims that it tested an unapproved drug implant for dependency on prison inmates without institutional oversight or thoroughly gathered legal consent.
The advocacy group Public Citizen said a pilot project at the company—originally planned for 10 inmates housed within the Louisiana prison system—involved a long-lasting formulation of the anti-addiction therapy naltrexone as a biodegradable implant that slowly releases the drug over 90 days. Naltrexone has previously received U.S. approvals for treating opioid and alcohol dependence as a tablet and injection.
The project was ended soon after it was announced in May following criticism, according to Public Citizen—but the group says BioCorRx may still be conducting trials elsewhere in the U.S. that may be in violation of regulations governing testing in human subjects.
“Naltrexone implants have been utilized by countless medical doctors under their discretion with their patients for over 20 years in the U.S. under the constantly changing pharmacy compounding guidance and from several licensed compounding pharmacies; long before the existence of some researching group” the company added.
Is naltrexone safe for pregnant patients?
Published in the American Journal and Obstetrics & Gynecology, the data are from a cohort of 230 patients taking MAT, 121 of whom were given naltrexone and 109 of whom were given methadone or buprenorphine. The authors looked at the rate of newborns treated for symptoms of neonatal abstinence syndrome (NAS). In a subset of 20 random patients on naltrexone, they also assessed maternal and newborn blood levels of naltrexone and 6-beta-naltrexol at delivery.
In the study, the daily dosage range was 8 to 16 mg for buprenorphine and 50 to 120 mg for methadone. Patients on naltrexone must have been opioid-free for at least 7 days and have had two negative drug screens before taking the drug. The daily oral dosage was 50 mg.
At ≥ 24 weeks’ gestation, fetal heart rate (FHR) monitoring was done for ≥ 60 minutes while the initial naltrexone dose was administered. At < 24 weeks, the FHR was evaluated with Doppler or ultrasound imaging before the first dose, 30 minutes after dosing, and again at 60 minutes. Biophysical profiles were done on all the patients every other week from 28 to 32 weeks’ gestation and weekly thereafter until delivery.
DescriptionHow to take?CommonSide EffectsLatest New'sPhoto's
Acamprosate 333 mg Gastro-resistant Tablets, manufactured by SunPharma, sold under brand name Acamprol, each gastro-resistant tablet contains acamprosate calcium 333.0 mg as the active ingredient. Acamprosate is indicated as therapy to maintain abstinence in alcohol-dependent patients. It should be combined with counselling.
Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcoholism, possibly by blocking glutaminergic N-methyl-D-aspartate receptors, while gamma-aminobutyric acid type A receptors are activated. Reports indicate that acamprosate only works with a combination of attending support groups and abstinence from alcohol.
Acamprosate calcium is a synthetic compound with a chemical structure similar to that of the endogenous amino acid homotaurine, which is a structural analogue of the amino acid neurotransmitter γ-aminobutyric acid and the amino acid neuromodulator taurine. Its chemical name is calcium acetylaminopropane sulfonate. Its chemical formula is C H N O S Ca and molecular weight is 400.48. Its structural formula is:
Adults within the age range 18-65 years
– 2 tablets three times daily with meals (2 tablets in the morning, noon and night) in subjects weighing 60kg or more.
– In subjects weighing less than 60kg, 4 tablets divided into three daily doses with meals (2 tablets in the morning, 1 at noon and 1 at night).
The recommended treatment period is one year. Treatment with acamprosate should be initiated as soon as possible after the withdrawal period and should be maintained if the patient relapses.
Acamprosate does not prevent the harmful effects of continuous alcohol abuse. Continued alcohol abuse negates the therapeutic benefit; therefore acamprosate treatment should only be initiated after weaning therapy, once the patient is abstinent from alcohol.
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
Certain serious side effects include allergic reactions, irregular heartbeats, and low or high blood pressure, while less serious side effects include headaches, insomnia, and impotence. Acamprosate should not be taken by people with kidney problems or allergies to the drug.
Global Acamprosate Calcium Market 2019 – Merck Group, Zydus Pharmaceuticals, Mylan, TevaMerck Group
BY KYONGPITZER ON JUNE 17, 2019
The Global Acamprosate Calcium Market provides a comprehensive outlook of the Global Acamprosate Calcium Market globally. This report gives a thorough examination of the market and, provides the market size and CAGR value for the forecast period 2019-2023, taking into account the past year as the base year. The report provide a meticulous evaluation of all of the segments(type of product, application, and region) included in the report. The segments are studied keeping in view their market share, revenue, market growth rate, and other vital factors.
The global Acamprosate Calcium market research report involves all the substantial evidence related to this market which every viewer would like to know about the Acamprosate Calcium market. The report occupies the mixture of primary and secondary research of Acamprosate Calcium, which includes company financial year report, product knowledge, Acamprosate Calcium press release, interviews as well few other relevant sources that contribute towards assemble of information. It involves analytical data, statistical data, etc. The major part of the report involves various research methodology, Acamprosate Calcium research finding, conclusion and Appendix and data sources. Also includes distributor channels, sales, demand and supply category, import/export, dealers, and traders.
Acamprosate Calcium Market Development:
The worldwide market for Acamprosate Calcium accounted a relatively optimistic growth, the past four years, market size is estimated from XXX million $ in 2015 to XXX million $ in 2018. The Acamprosate Calcium Market is expected to exceed more than US$ XXX million by 2023 at a CAGR of 15 in the given forecast period. Acamprosate Calcium Market research report also provides an overall analysis of the market share, size, segmentation, revenue forecasts and geographic regions of the Acamprosate Calcium Market along with industry leading players are studied with respect to their company profile, product portfolio, capacity, price, cost and revenue. The Acamprosate Calcium market report presents the competitive scenario of the major market players based on the sales revenue, customer demands, company profile, the business tactics used in Acamprosate Calcium market which will help the emerging market segments in making vital business decisions.
Many drugs on the market work in mysterious ways. Scientists still don’t know how aspirin works. They still don’t know how Prozac works, or any of the antipsychotics. But how a drug works is not necessarily important. When you need to prevent suffering and death, what is important is that the drug works, and works safely. How it works can wait.
But sometimes when a drug mechanism reveals itself, it’s a surprise. That was the case in a recent study of acamprosate, one of four drugs approved in the United States as a pharmacological treatment for alcoholism. It turns out that acamprosate itself might not be the active ingredient. Instead, the calcium ions attached to the drug could be driving its anti-relapse effects.
Rainer Spanagel and his colleagues at the Central Institute of Mental Health and the University of Heidelberg in Mannheim, Germany, were one of the first groups to study acamprosate. Their previous studies showed that long-term abstinence from alcohol could produce increases in glutamate levels in the brain. Glutamate is an amino acid and one of the chemical messengers in the brain. The increase in glutamate creates an excited brain state, and could make alcoholics more likely to relapse and drink again.
Studies with acamprosate, or specifically with the calcium salt of acamprosate, a form of the drug that’s coupled with calcium ions, show that it can reduce relapse after withdrawal in mouse models of alcoholism. It also helps calm down the increases in glutamate in human alcoholics.
Spanagel and his group wanted to understand why acamprosate was able to reduce relapse, and if possible, how they could make the drug more effective. Calcium acamprosate is the approved treatment, but relatively little of it gets into the brain. Spanagel commissioned another form of the drug, sodium acamprosate. In this form, more of the drug reached the brain. But, strangely, it didn’t work. It didn’t reduce alcohol consumption in rats after withdrawal.
Mystified, the scientists dug deeper. They showed that calcium acamprosate doesn’t act on receptors for glutamate, called NMDA receptors, which suggests that acamprosate doesn’t affect the glutamate system. Spanagel and his colleagues began to question whether acamprosate was biologically active at all.
So they went back to the original patent for acamprosate, where they found a clue. The patent states that “the calcium salt may be used as neurotropic agent; the magnesium salt as vasculotropic agent; the potassium salt as antiasthenic agent; the lithium salt may be used in for bipolar patients and the sodium salt in local treatments; the zinc salt may be used in dermatology.” Different salts of the same molecule, with very different functions. Right there in the wording of the patent was the suggestion that the ions — calium, lithium, potassium — could be the active agents.
In further tests, Spanagel and his group showed that calcium acamprosate, and not sodium acamprosate, reduced alcohol intake in booze-deprived rats. Even basic calcium chloride was able to reduce alcohol intake. In addition, the researchers found an association between levels of blood calcium and abstinence in people on acamprosate.
“It’s not every day you find an FDA approved medication where the salt is driving the effect,” says Jeff Weiner, an alcohol addiction researcher at Wake Forest School of Medicine. He notes that there needs to be confirmation of the results before acamprosate is declared inactive. There could be functions of acamprosate, or of calcium acamprosate specifically, that are currently undiscovered. “We’re going to need more data,” he says, “before we throw the drug out with the bathwater.”
Spanagel agrees that the results need to be replicated. “We are not claiming that any of the published results are wrong, the interpretation is wrong,” he says. And there are still many unanswered questions. Calcium levels in blood may not correspond to calcium levels in brain. High levels of calcium dosing can have adverse cardiac side effects. The blood levels of calcium in people being treated with calcium acamprosate normalized after the first month, even though abstinence continued. And the rats in the study showed reduced movement in response to calcium treatment. They might be reducing their alcohol intake because they are simply moving less.
And if calcium is the active agent, there’s still an important unanswered question: Scientists still don’t know how that calcium might be working stop alcoholics from going back to the bottle.
Markus Heilig, a psychiatrist with the National Institute of Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse, wrote a commentary on the paper calling for a randomized clinical trial to look at acamprosate, its calcium salt, and calcium alone. “If we could figure out the actual mechanism and find something more specific and more potent, there’s probably something there,” he says. “Whether it’s the calcium or the acamprosate, it’s doing something for some people.”
But Heilig also emphasizes that the paper, while it raises more questions than it answers, “represents some of the best science.” Whether acamprosate will turn out to have effects on its own or whether it all turns out to be calcium, the study helps to further our understanding of how we might prevent relapse. “This is ultimately a story of how science is all about questioning everything,” Helig says, “including the things we think we know.”
Multi-drug approach could be way to treat Alzheimer’s, study suggests
A French pharmaceutical company on Jan. 8 said promising results in preliminary research using a combination of existing medications to treat Alzheimer’s could point the way toward someday combating the dementia-causing disease with a drug cocktail.
Pharnext, in interviews with company officials and a study that appears in Nature’s peer-reviewed online journal Scientific Reports, said preclinical studies suggest that combining two approved drugs can have a synergistic impact in alleviating cognitive impairment and protecting the brain’s neurons and blood vessels from Alzheimer’s-related damage.
The drugs, which are not now used to treat Alzheimer’s, include acamprosate calcium, which has been prescribed since 1989 to reduce cravings and alleviate withdrawal symptoms in alcoholics. It was combined with baclofen, a medication that has been used for decades to treat the spastic movements in people suffering from multiple sclerosis.
The findings, which were obtained in laboratory cultures and animal testing, suggest the way forward to treating Alzheimer’s disease could be the same method discovered years ago to treat HIV, a senior company official said.
“Maybe the illusion we had was that we could treat a disease such as Alzheimer’s with a single silver bullet,” Daniel Cohen, an author of the study and a founder of Pharnext, said Wednesday in a telephone interview. “When you fight a complex disease, you have to use a complex treatment.”
Using already known drugs and at lower doses than usual means the cocktail should be safe and could perhaps lead to an approved therapy in a shorter time than it takes to develop new drugs, Cohen said.
Richard Lipton, who heads the Einstein Aging Study at the Albert Einstein College of Medicine and the division of cognitive aging and dementia at Montefiore Medical Center, said after reviewing the company’s study that its data and therapeutic approach sounded promising.
DescriptionHow to take?CommonSide EffectsLatest New'sPhoto's
Pregabalin, marketed under the brand name Lyrica among others, is a medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, and generalized anxiety disorder. Its use in epilepsy is as an add-on therapy for partial seizures.
Pregabalin capsules, oral solution (liquid), and extended-release (long-acting) tablets are used to relieve neuropathic pain (pain from damaged nerves) that can occur in your arms, hands, fingers, legs, feet, or toes if you have diabetes and postherpetic neuralgia (PHN; the burning, stabbing pain or aches that may last for months or years after an attack of shingles). Pregabalin capsules and oral solution are also used to relieve neuropathic pain that can occur after a spinal cord injury and to treat fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep). Pregabalin capsules and oral solution are used along with other medications to treat certain types of seizures in adults and children 4 years of age and older. Pregabalin is in a class of medications called anticonvulsants. It works by decreasing the number of pain signals that are sent out by damaged nerves in the body.
Pregabalin comes as a capsule, an oral solution, and as an extended-release tablet to take by mouth. Pregabalin capsules and oral solution are usually taken with or without food two or three times a day. Pregabalin extended-release tablets are usually taken once daily after an evening meal. Take pregabalin at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.
”high” or elevated mood
difficulty concentrating or paying attention
difficulty remembering or forgetfulness
lack of coordination
loss of balance or unsteadiness
uncontrollable shaking or jerking of a part of the body
Phase 3 Study Results Announced for Pregabalin in Primary Generalized Tonic-Clonic Seizures
A phase 3 study assessing the use pregabalin as adjunctive therapy for epilepsy patients 5 to 65 years of age with primary generalized tonic-clonic (PGTC) seizures did not meet its primary endpoint to reduce seizure frequency compared with placebo, according to Pfizer.
The 12-week randomized, double-blind, placebo-controlled, multicenter study was conducted at 70 sites in 21 countries and included 219 patients. Patients were randomized in a 1:1:1 ratio to receive placebo, or 1 of 2 fixed doses of pregabalin twice daily. The primary endpoint was the percent reduction of 28 day seizure rate for all PGTC seizures relative to placebo.
Findings from the phase 3 study showed that treatment with pregabalin for PGTC seizures did not result in a statistically significant reduction in seizure frequency versus placebo.
Pregabalin/Lyrica reclassified to a class C drug
A prescription drug linked to 33 deaths in 2017 in Northern Ireland will now be treated as a class C drug.
Pregabalin – also known by the brand name Lyrica, or the street name bud – is an anti-epileptic drug also used to relieve chronic pain.
Northern Ireland has the highest prescription rate for pregabalin in the UK.
It is illegal to have class C drugs without a prescription and illegal to supply or sell them to others.
Meanwhile the mother of a man who took his own life, speaks about her son’s struggle with addiction to prescription drugs.
Prescription drug abuse ‘wrecking lives’
Life on Lyrica: A user’s perspective
There will also be stronger controls in place to ensure accountability and minimise the chances of pregabalin falling into the wrong hands or being stockpiled by patients.
Deaths relating to the prescription drug are on the rise.
In 2016 eight drug deaths were linked to Lyrica misuse – one year later that figure rose to 33.
The Advisory Council for the Misuse of Drugs made the recommendation to reclassify the drug in a letter to ministers, including the then home secretary Theresa May, in January 2016.
The letter cited warnings from the Health and Social Care Board (HSCB), which highlighted “significant misuse and abuse” of the drug.
Where are the drugs coming from?
There is a growing illicit market for the drug in Northern Ireland, with many people purchasing it online from unregulated websites.
It is understood that Lyrica has been coming into Northern Ireland in fairly constant levels for a number of years, along with other prescription drugs including diazepam and temazepam.
Packages of the drug ordered by customers in Northern Ireland are intercepted by the National Crime Agency (NCA) and the UK Border Agency at airports in England every week, according to the Police Service of Northern Ireland (PSNI).
Class C call over abuse of ‘bud’ drug
Grieving mother’s prescription drug warning
While the drugs are referred to as prescription drugs, they are largely not being prescribed through community pharmacies.
They are illicitly bought or sold and supplied through the internet and largely the individuals are appearing to be using a mixture of drugs.
Joe Brogan, the HSCB’s head of pharmacy and medicines management, described the growing numbers of deaths associated with pregabalin and other prescription drugs as a “scourge”.
He added: “In many cases of pregabalin misuse, it has not been prescribed – it has been sourced through family or friends or bought on the street or via the internet.
“Many such drugs that are bought from illicit sources do not actually contain medicines that they purport to be.
“Any medicine or any drug can be a poison – it all depends on three things: Where you get it from – was it prescribed and supplied from a regulated source?; how much you take – was it taken within accepted dosages?; what you take it with – mixing drugs together and with alcohol can create a toxic mix that is lethal.”
Misuse of pregabalin painkiller has risen 900 per cent in Australia
By Alice Klein
Australia is the latest country to report an alarming rise in the misuse of the nerve pain drug pregabalin.
Pregabalin is a non-opioid drug that reduces pain through its actions on calcium channels in the brain. It was originally developed as an epilepsy drug but is now approved for treating nerve pain – the prickling, tingling sensation that can accompany conditions like diabetes and multiple sclerosis. In some countries, it is also approved for treating anxiety and fibromyalgia.
Anecdotal evidence suggests that doctors are also increasingly prescribing …
DescriptionHow to take?CommonSide EffectsLatest New'sPhoto's
Travoprost, is medications used to treat high pressure inside the eye including glaucoma and ocular hypertension (a condition which causes increased pressure in the eye). Travoprost is in a class of medications called prostaglandin analogs. It lowers pressure in the eye by increasing the flow of natural eye fluids out of the eye.
Specifically it is used for open angle glaucoma when other agents are not sufficient. It is used as an eye drop. Effects generally occur within 2 hours. This medication works by regulating the flow of fluid within the eye to maintain a normal pressure.
To instill the eye drops, follow these steps:
Wash your hands thoroughly with soap and water.
Check the dropper tip to make sure that it is not chipped or cracked.
Avoid touching the dropper tip against your eye or anything else; eye drops and droppers must be kept clean.
While tilting your head back, pull down the lower lid of your eye with your index finger to form a pocket.
Hold the dropper (tip down) with the other hand, as close to the eye as possible without touching it.
Brace the remaining fingers of that hand against your face.
While looking up, gently squeeze the dropper so that a single drop falls into the pocket made by the lower eyelid. Remove your index finger from the lower eyelid.
Close your eye for 2 to 3 minutes and tip your head down as though looking at the floor. Try not to blink or squeeze your eyelids.
Place a finger on the tear duct and apply gentle pressure.
Wipe any excess liquid from your face with a tissue.
If you are to use more than one drop in the same eye, wait at least 5 minutes before instilling the next drop.
Replace and tighten the cap on the dropper bottle. Do not wipe or rinse the dropper tip.
Wash your hands to remove any medication.
eye pain or irritation
Travoprost eye drops may change the color of your eye (to brown) and darken the skin around the eye. It may also cause your eyelashes to grow longer and thicker and darken in color. These changes usually occur slowly, but they may be permanent. If you use travoprost eye drops in only one eye, you should know that there may be a difference between your eyes after using travoprost eye drops. Call your doctor if you notice these changes.
Ocular Therapeutix still has an eye on approval despite trial failure
Ocular Therapeutix gave itself a low bar to clear in the latest phase III study of OTX-TP, pitting the glaucoma project against placebo rather than an active comparator – but even that was not low enough. The trial failed to show a decrease in intraocular pressure with OTX-TP, an eye insert that delivers travoprost, versus placebo, across the 12-week study. Despite the failure, Ocular still hopes the project has a future, highlighting an analysis of intraocular pressure at individual timepoints that it said showed a significant benefit with OTX-TP on eight of nine occasions. Still, as the primary endpoint was not hit, these findings can only be considered exploratory. And OTX-TP’s effect appeared to wane over time, raising questions about the company’s sustained delivery approach. Ocular will take the latest data to the FDA but even if the agency decides to be lenient, OTX-TP will struggle to find a place in the market – the project previously failed to beat an active comparator, generic timolol. Investors, who had hoped OTX-TP would fare better against placebo, sent Ocular’s stock down 17% in premarket trading today. Today’s failure might also bode ill for Ocular’s next project, OTX-TIC, a bioresorbable travoprost implant that is in phase I.
JK is a male, age 62 years, in good health. He recently started to take travoprost (Travatan Z, Alcon) 0.004% ophthalmic solution for glaucoma, 1 drop in each eye every evening. JK takes a store brand multivitamin daily, and no other maintenance prescription medications.
While picking up his supply of OTC vitamins, JK asks you if the multivitamins can cause stomach issues. Upon further discussion with the patient, he tells you that he has been experiencing heartburn, nausea, and constipation. There have been no other changes in his diet or routine, and he has been taking this particular vitamin for at least 10 years. Mystery: What is causing JK to have gastrointestinal issues, despite no other change in medications, diet, or routine?
Solution: Travoprost has been reported to cause dyspepsia or gastrointestinal disorder in 1% to 5% of patients in clinical studies. Other uncommon nonocular side effects of travoprost include allergy, angina, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu syndrome, depression, headache, increased cholesterol, hypertension or hypotension, infection, pain, prostate disorder, sinusitis, and urinary incontinence/urinary tract infections.1
A JAMA Ophthalmology article mentions that prostaglandin analogues, such as travoprost, are the first choice in glaucoma treatment.2They work by increasing the outflow of intraocular fluid from the eye and lowering the intraocular pressure. One reason for the popularity of prostaglandin analogues is because of the limited systemic adverse effects.
Although the Travatan package insert lists the GI side effects mentioned above,1 latanoprost (Xalatan, Pfizer), bimatoprost (Lumigan, Allergan), and tafluprost (Zioptan, Akorn), also in the prostaglandin analogue class, do not list GI side effects. However, a few reported case studies showed that patients who had used latanoprost experienced GI effects,2 therefore, any patient who mentions GI upset and is taking a prostaglandin analogue should be evaluated for a correlation between the 2.
JK should speak to his ophthalmologist immediately about changing his glaucoma medication, if possible.
Karen Berger, PharmD, graduated from the University of Pittsburgh School of Pharmacy in 2001. She has worked in community pharmacies for over 17 years as a Pharmacist in Charge, staff, and floater pharmacist for a large chain. Currently, she is a pharmacist at an independent pharmacy in Northern NJ. She can be reached at email@example.com
PhIII setback mars Ocular's glaucoma drug/device, though company remains 'encouraged' by data breakdown
Ocular Therapeutix’s latest drug/device — for glaucoma — has flopped in its Phase III study, failing the primary endpoint to significantly reduce intraocular pressure versus placebo.
The treatment, OTX-TP, is an intracanalicular insert designed to deliver a formulation of the drug travoprost with an effect up to 90 days, which Ocular says can solve the adherence issues seen with daily eye drop regimens that patients are typically prescribed.
Investigators tracked the change in IOP from baseline in 554 patients in the study over several months, taking measurements at nine time points: 8 am, 10 am and 4 pm on one day at 2, 6 and 12 weeks following insertion. The first six sessions, the company says, were just fine — recording statistically significant reductions of IOP with p-values as low as 0.001 — but the seventh threw them off.
In fact, as they lay out in a table, that’s the only time point where OTX-TP did not achieve a statistically significant reduction of IOP compared to placebo.
“We are encouraged by the results of this trial which shows OTX-TP’s ability to lower IOP out to 12 weeks with a single insert using this novel dosage form,” said chief medical officer Michael Goldstein, adding that his team will now take the data to the FDA to determine next steps.
Ocular’s relationship with the FDA, though, has not always been smooth. Its first drug/device eye treatment, Dextenza, was rejected twice before nabbing an approval, forcing a restructuring that claimed a fifth of its staff. The company finally managed to sort out the manufacturing issue and began marketing the therapy for post-surgical pain late last year.
Some investors aren’t sticking around. Shares $OCUL are still down 12% (to $3.37) in pre-market trading, following the announcement at Monday close.
DescriptionHow to take?CommonSide EffectsLatest New'sPhoto's
Bimatoprost in combination with Timolol is used for treating ocular hypertension (by draining fluid from the eye) or increased pressure in the eye and open-angle glaucoma. It comes in the form of eye drops. Bimatoprost & Timolol released under US brand name: Ganfort, we sell 100% analog/generic brand CAREPROST PLUS is included in a class of medications called prostaglandin analogs, Generic Ganfrort – Careprost Plus made by trusted indian company Sun Pharma.
The drug should be used in the morning. If you miss one dose, continue with the next one.. The eye solution may vary from clear, colorless to slightly yellow in color. The medicine is available in 5 ml white opaque polyethylene bottle. Each bottle contains 3 ml of solution. The bottle should be kept tightly closed. It should be used within 30 days of opening the bottle.
Combination Bimatoprost & Timolol, It is generally advised to be used in the affected eye once daily. Both these drugs work differently to control the increased pressure level in the eye. While using these eye drops, be careful not to touch the tip of the dropper, as it may contaminate the tip as well as the solution. Sometimes, brand or generic Ganfort eye drops may temporarily blur your vision, therefore you are advised not to drive a vehicle or operate machinery for some time after using this drug.
Bimatoprost and timilol maleate may cause your eye color to change, which is completely normal. While you are taking this medication, you should go for regular checkup. This drug may also increase your sensitivity. You should consult your doctor if you have a history of allergies. It is also advised that brand or generic Ganfort eye drops be used cautiously if you have decreased liver or kidney function. You should talk with your doctor if you suffer from closed eye glaucoma.
Bimatoprost sustained-release implant shows positive phase 3 data
A bimatoprost sustained-release implant reduced IOP by approximately 30% over 12 weeks in a phase 3 clinical study, according to an Allergan press release.
The multicenter, randomized, masked, parallel-group study, which included 594 subjects with open-angle glaucoma or ocular hypertension, compared the efficacy and safety of two dose strengths of Bimatoprost SR and timolol eye drops used twice daily for up to 20 months. The study showed the majority of patients treated with Bimatoprost SR were potentially able to be treatment-free for 1 year after the last implant was inserted, the release said.
“Considering that as many as 80% of glaucoma patients fail to administer their drops on a regular basis, Bimatoprost SR has the potential to transform the management of glaucoma in millions of patients,” Bill Meury, chief commercial officer at Allergan, said in the release.
The implant was well tolerated in the majority of patients. Additional safety data from this study, as well as results from a second phase 3 study, are expected to be reported in the first half of 2019, and the company expects to file a new drug application with the FDA in the second half of 2019, according to the release.
Efficacy and safety of fixed-combination bimatoprost/timolol ophthalmic solution
Background: Poor adherence to treatment is a problem in glaucoma, and patient dissatisfaction with topical glaucoma medication is a barrier to adherence. The objective of this study was to evaluate glaucoma patients’ satisfaction with fixed-combination bimatoprost/timolol ophthalmic solution (BTFC). Methods: This observational, multicenter study was conducted in China in adults with glaucoma treated with BTFC for 1–3 months. Five hundred patients answered a questionnaire concerning their demographic characteristics, history of glaucoma and topical glaucoma treatment, and use of BTFC. The primary endpoint was patient satisfaction with BTFC assessed on a 10-point scale (1= very dissatisfied, 10= very satisfied). Results: Patients received BTFC alone (65%) or with other treatments (35%), most commonly a carbonic anhydrase inhibitor. Most patients (87%) used BTFC as a replacement for other medication, usually a β-blocker or prostaglandin analog; 13% received BTFC as add-on treatment. Key reasons for initiating BTFC therapy were poor efficacy of previous treatment (72% of patients) and side effects of previous treatment (32% of patients). Most patients agreed or very much agreed that BTFC provided better control of intraocular pressure (85% of patients), had a simpler administration (87% of patients), and was associated with better tolerance and comfort (82% of patients) compared with their previous treatment. Mean satisfaction scores were significantly higher for BTFC than for previous treatments among all patients (7.8 versus 6.0; P<0.0001) and within patient subgroups based on demographic characteristics, pattern of BTFC use, and previous treatment. Conclusion: Patients were highly satisfied with BTFC used alone or concomitantly with another topical medication. Patients previously treated with a β-blocker, prostaglandin analog, carbonic anhydrase inhibitor, α-adrenergic agonist, or combination of two medications were more satisfied with BTFC than with their previous treatment. Most reported that intraocular pressure control, tolerability, and ease of administration improved with BTFC.
Old and New Drug Classes Expanding To Include Glaucoma Treatments
Glaucoma is a heterogeneous disease characterized by the development of increased intraocular pressure (IOP) that leads to structural changes and nerve damage within the eye. Manifestations of this disease include chronic progressive open-angle glaucoma (OAG) and acute angle-closure glaucoma (ACG), both of which may be categorized as either primary or secondary, depending on the underlying cause.Glaucoma ranks among the top five causes of moderate to severe visual impairment and is the third leading cause of blindness worldwide.
Global estimates from 2013 suggest that more than 64 million people aged 40 to 80 years have either primary OAG or primary ACG, and with an increasing elderly population, that number is anticipated to reach 76 million by 2020 and 111.8 million by 2040. As ACG is mainly treated through surgery, this review will focus on chronic therapies used to manage OAG.
Patients with OAG often present with an elevated IOP (normal range: 10–21 mmHg), however, a small subset of patients may develop ocular changes with an IOP < 21 mmHg and are referred to as having normal tension glaucoma. Conversely, some patients with an IOP > 21 mmHg do not go on to develop visual impairment and are referred to as having ocular hypertension (OHT). Control of glaucoma focuses on managing the outflow of the eye’s aqueous humor. The primary exit route is via the trabecular meshwork and through the Schlemm’s canal, also known as conventional outflow, while outflow through the ciliary body and suprachoroidal space, known as unconventional or uveoscleral outflow, accounts for a minor amount of outflow. Topical medications represent the first line of treatment, but if IOP control is inadequate, patients may require escalation to laser-based therapies or surgical procedures.
Several classes of medications are available to treat OAG, but the recommended initial therapy is with a medication from either the beta blocker or prostaglandin analog classes.Prostaglandin analogs work by increasing aqueous humor outflow through the uveoscleral pathway. Beta blockers are believed to act by reducing the production of aqueous humor. A brief overview of the various classes of medications and products available in the United States is provided in Table 1. The usual treatment goal is to achieve a 25%–30% reduction from the patient’s baseline IOP, but other factors such as baseline IOP, pre-existing nerve damage, risk for disease progression, or development of adverse effects may prompt providers to pursue more aggressive or lenient therapeutic goals. Patients may require multiple eye drops from different classes in order to achieve the IOP goal.
Despite the number of effective medications and readily available generic and combination products, there remains a need for new and innovative therapies. One key area for improvement is patient adherence. A survey of patients with glaucoma revealed a number of barriers that prevent effective disease management, including difficulty with effective administration of eye drops, poor medication and disease education, and nonadherence with complex dosing regimens.Some treatments discussed below seek to address adherence through the use of innovative delivery methods that prolong medication activity. Physicians also desire therapies with novel mechanisms that are able to lower IOP more effectively and medications that could provide protection against ocular nerve degeneration.Below (and summarized in Table 2) is a brief overview of several new agents, in no particular order, that have recently been approved or are poised to enter the market in the coming years.
Rhopressa (netarsudil ophthalmic solution)
In December of 2017, the Food and Drug Administration (FDA) approved netarsudil, the first of a new class of medications known as Rho kinase (ROCK) inhibitors. In addition to inhibiting ROCK, this medication also possesses other IOP-lowering mechanisms, such as the inhibition of norepinephrine transport and an ability to reduce episcleral venous pressure. The double-blind, randomized, multicenter trial ROCKET-1 (N=411) compared the efficacy of netarsudil 0.02% dosed once daily at nighttime with timolol maleate 0.5% dosed twice daily. The ROCKET-2 trial (N=756) had a similar design, with an additional netarsudil 0.02% twice-daily dosing arm. Both trials followed patients with OHT or OAG who had an IOP of > 20 mmHg and < 27 mmHg for three months. The primary endpoint in both trials was a reduction in IOP. In ROCKET-1, patients with a baseline IOP < 27 mmHg who received netarsudil demonstrated a 15%–22% reduction in IOP as compared with a 17%–22% reduction in patients who received timolol, but this was not sufficient to demonstrate noninferiority based on prespecified criteria. A post-hoc analysis that focused on patients whose baseline IOP was < 25 mmHg was able to demonstrate noninferiority.
ROCKET-2’s primary efficacy population focused on patients with an IOP < 25 mmHg and was able to demonstrate mean reductions of 3.3–4.6 mmHg and 4.1–5.4 mmHg in patients receiving daily and twice-daily netarsudil, respectively. These reductions were similar to those seen with twice-daily timolol, which produced a 3.7–5.1 mmHg reduction from baseline and demonstrated the noninferiority of netarsudil. In terms of percent reduction in IOP, daily netarsudil was able to achieve a 16%–21% reduction, while twice-daily dosing showed a 22%–24% reduction; twice-daily timolol demonstrated an 18%–23% reduction.
The use of netarsudil appears to be generally well tolerated, with the most common observed adverse effect being conjunctival hyperemia (50%–53%), followed by conjunctival hemorrhage (13%–15%), and cornea verticillata (5%–9%). Other adverse effects including blurred vision, eye pain or erythema, and erythema of the eyelid, were also noted in > 5% of patients.Aerie Pharmaceuticals also conducted the ROCKET-4 trial to demonstrate the six-month safety of netarsudil. Results from this trial, released in April 2017, showed daily netarsudil to be non-inferior to twice-daily timolol. The frequency and severity of effects were seen at similar rates to those in the ROCKET-1 and ROCKET-2 trials.
The entry of netarsudil into the market is exciting as it is a novel, well tolerated, once-daily agent. One limiting factor to this medication is its reduced efficacy in patients with a baseline IOP of 26 mmHg or higher. As Aerie Pharmaceuticals has already obtained approval in the United States, it is anticipated to launch in 2019 in the European Union and in 2021 in Japan.
Roclatan, a combination product containing netarsudil and the prostaglandin analog latanoprost, is also being developed by Aerie Pharmaceuticals. This fixed-dose combination would be administered as a once-daily eye drop in the evening and is formulated as a netarsudil/latanoprost 0.02%/0.005% solution. The IOP-lowering effects of netarsudil are expected to be complemented by increased outflow by way of the uveoscleral pathway, facilitated by latanoprost.
The Mercury 1 trial randomized 718 subjects into three treatment arms: netarsudil monotherapy, latanoprost monotherapy, or netarsudil/latanoprost combination therapy, each dosed once daily. The primary efficacy outcome was mean IOP at three months; patients were observed for 12 months for ocular and systemic safety outcomes. At 90 days, patients who received the combination therapy achieved 1.3–2.5 mmHg lower mean IOP than patients who received latanoprost monotherapy, and 1.8–3.0 mmHg lower mean IOP than patients who received netarsudil monotherapy. Significantly more subjects receiving combination therapy demonstrated a 20% or greater IOP reduction and achieved an IOP of < 18 mmHg. While no serious adverse events were reported, a higher percentage of patients discontinued therapy at three months in the combination (15.5%) and netarsudil monotherapy (17.6%) arms versus latanoprost monotherapy (5.5%), with adverse effects being cited as the most common reason for discontinuation. Conjunctival hyperemia was reported in approximately 50% of patients, with most cases being described as mild. Approximately 5% to 11% of patients reported experiencing conjunctival hemorrhage, pruritus, increased lacrimation, and cornea verticillata.
The Mercury 2 trial evaluated changes in IOP at 90 days in 750 participants receiving netarsudil/latanoprost, netarsudil monotherapy, or latanoprost monotherapy. Similar to the Mercury 1 findings, the combination agent was able to lower IOP an additional 1.5–2.4 mmHg compared with latanoprost monotherapy and an additional 2.2–3.3 mmHg when compared with netarsudil monotherapy. Fifty-six percent of patients receiving netarsudil/latanoprost were able to achieve a diurnal IOP of < 16 mmHg.
An additional clinical trial (Mercury 3) is underway to compare the safety and efficacy of netarsudil/latanoprost with that of the combination bimatoprost/timolol 0.03%/0.5%. This trial, which is still recruiting patients, will aim to enroll 472 participants and evaluate changes in IOP at six months in addition to clinical safety endpoints. Currently, no additional information is available regarding this study, but the anticipated completion date is April 2019. Aerie Pharmaceuticals filed a New Drug Application on May 15, 2018 and expects a decision from the FDA within 10 months.
Ocular Therapeutix is developing a bio-resorbable canalicular implant that will continuously deliver the prostaglandin analog travoprost for up to 90 days. The active medication is encapsulated in a biodegradable polyethylene-glycol hydrogel that will swell upon implantation to retain its position in the eye. This plug is inserted through noninvasive methods by a specialist and does not require removal as it exits through the nasolacrimal system.This novel delivery system addresses the major issue of poor patient adherence and is poised to be the first of several implantable therapies to enter the major markets.
A phase 2b study evaluated efficacy and safety of a punctum plug of travoprost against timolol maleate 0.5% drops twice daily in 79 patients. Participants were enrolled if they had a diagnosis of OHT or OAG with a mean baseline IOP of ≥ 24 mmHg at Hour 0 and an IOP of ≥ 22 mmHg when checked 4 and 8 hours later. Mean reductions in IOP were evaluated at 30, 60, and 90 days at multiple times each day (8 a.m., 12 p.m., and 4 p.m.). Patients in both groups demonstrated a reduction in IOP from baseline, although those receiving OTX–TP showed a 3.27–3.54 mmHg reduction while those receiving timolol experienced a 5.84–6.29 mmHg reduction. These reductions in IOP were observed at all time points throughout the day. The reported rates of ocular (39.4% vs. 37.5%) and non-ocular (9.1% vs. 7.5%) adverse effects were similar in the OTX–TP and timolol arms, respectively. The most common adverse effects were dacryocanaliculitis (12.1% vs. 10%), acquired dacryostenosis (6.1% vs. 5%), eyelid edema (6.1% vs. 0%) and scar (6.1% vs. 0%) in the OTX–TP and timolol groups, respectively.
Ocular Therapeutix is now enrolling patients for a phase 3, placebo-controlled trial evaluating the efficacy and safety of OTX–TP in the treatment of OAG or OHT. This trial will aim to enroll 550 patients with a primary endpoint of changes in IOP at Weeks 2, 6, and 12, at 8 a.m., 10 a.m., and 4 p.m. Ocular Therapeutix expects to complete this trial in December 2018.While OTX–TP has the advantage of a noninvasive route of administration and is likely to be the first long-acting implant to enter the market, the lower impact on IOP as compared with timolol drops observed in the phase 2b trial and lack of active control in the upcoming phase 3 trial may make some providers unsure of its place in therapy.
Bimatoprost Sustained-Release Ocular Implant
Allergan is reformulating its prostaglandin analog, bimatoprost, into a sustained-release ocular implant as a way to enhance patient adherence. Bimatoprost SR would continuously deliver medication over six months after being inserted via injection into the anterior chamber of the eye through a noninvasive procedure.
A phase 1/2 prospective, dose-ranging trial that examined 75 patients with OAG demonstrated a rapid and sustained lowering of IOP with bimatoprost SR. Following a washout period, enrollees intracamerally received various doses in the study eye while the other eye was treated with topical bimatoprost 0.03%. Overall mean IOP reductions of 7.2, 7.4, 8.1, and 9.5 mmHg were seen in patients receiving 6, 10, 15, and 20 mcg of bimatoprost SR, respectively, as compared with an 8.4 mmHg reduction with topical bimatoprost. Patients initially reported higher rates of adverse effects such as eye pain, foreign body sensation in the eye, and conjunctival hemorrhage with bimatoprost SR but these symptoms subsided within two days of onset. Following Day 2, the eye receiving bimatoprost SR had less reported conjunctival hyperemia (6.7% vs. 17.3%) than the eye receiving topical bimatoprost, while reports of other adverse effects remained similar between the eyes. When questioned at Day 8, 79.7% of patients reported the procedure to be less burdensome than anticipated and, at Week 12, 77% of patients were very or extremely likely to have another implant procedure.
An ongoing phase 3 trial enrolling 594 patients with OAG or OHT is comparing twice-daily timolol drops to two undisclosed doses of bimatoprost SR administered on Day 1, at Week 16, and at Week 32. The primary outcome will be changes in IOP from baseline to Week 12; however, patients will continue to be followed for a 12-month treatment duration plus an additional eight-month extended follow-up.A second trial, similarly designed, is aiming to enroll 600 patients and has an estimated primary completion date of March 2019. Two additional trials are comparing bimatoprost SR with selective laser trabeculoplasty in patients with OAG or OHT who are unable to be controlled with topical IOP-lowering therapies. In these trials, an undisclosed dose of bimatoprost SR will be administered on Day 1, at Week 16, and at Week 32. The primary outcome will be changes in IOP at Week 24. Investigators seek to enroll 160 patients for each study and have estimated primary completion dates of November 2019 and May 2020.
Santen Pharmaceutical is developing a novel agent that acts on a new target in the prostaglandin pathway, the prostaglandin EP2 receptor. While other prostaglandin analogs bind to the F2-alpha receptor, DE-117 activates the EP2 receptor and is thought to lower IOP by regulating outflow through the conventional pathways. This novel mechanism may position DE-117 to be a viable option in patients for whom other prostaglandin analogs have not adequately lowered IOP. In November 2017, Santen filed for approval of DE-117 in Japan while continuing to conduct trials in other markets. There are several clinical trials involving DE-117 for which enrollment is complete but results have not yet been posted.
Among these trials: The phase 2 SEE-1 trial, evaluating five doses of DE-117 against latanoprost among 184 participants in several centers across the United States, was listed as having completed enrollment as of April 2018; a long-term, open-label trial known as RENGE, involving 125 patients and that compared two groups of DE-117 monotherapy with patients receiving the combination DE-117 and timolol ophthalmic solution, was listed as having been completed in November 2017, and the AYAME study, which also evaluated two doses of DE-117 against a placebo arm as well as a latanoprost arm in 253 patients with OAG and OHT.
One trial for which results are available evaluated four varying concentrations of DE-117 against placebo and latanoprost in 91 patients. At the end of 4 weeks, investigators found that a concentration of 0.002% of DE-117 performed the best and matched the IOP-lowering effect of latanoprost. The most commonly observed adverse effects in the 0.002% dosing arm, all seen in approximately 14% of patients, included conjunctival and ocular hyperemia, photophobia, and eye pain.28 The only trial listed as recruiting patients is a phase 3 trial comparing DE-117 directly to latanoprost in patients with OAG or OHT in an anticipated 360 patients. The primary outcome is mean diurnal IOP at three months, and the expected completion date is November 2018.
Several other long-acting formulations of established medications are in the early stages of development, which suggests that addressing the issue of poor patient adherence is an area of keen interest. In addition, new medications belonging to established classes, such as prostaglandin analogs, are in early development, as are new therapeutic classes such as guanylate cyclase activators. With these novel treatment options on the horizon, better management of glaucoma looks promising for the near future.
Dr. Kish is an Associate Professor of Pharmacy Practice at Long Island University, LIU Pharmacy (Arnold and Marie Schwartz College of Pharmacy and Health Sciences), in Brooklyn, New York.