Colchicine is the most widely used of the colchicum alkaloids. It comes in both brand and generic forms. Some Medicare and insurance programs cover generic colchicine.
Why colchicine is so expensive?
Hello, Dr. Jonathan Kay is a professor of medicine at the University of Massachusetts Medical School in Worcester, where he directs the Division of Rheumatology. The usage of colchicine in the treatment of gout is the topic of today’s discussion. When a 92-year-old man came to visit me last week with a right elbow effusion that had been aspirated in an emergency room, I was reminded of this. Despite the lack of crystals, he was prescribed colchicine 0.6 mg twice daily by oral. His right elbow effusion improved, but he had to discontinue taking colchicine due to severe diarrhea. When he stopped taking colchicine, his diarrhea stopped. His daughter, on the other hand, told me that they paid $105 for a month’s supply of Colcrys (URL Pharma, Inc.)
What is the reason behind the high cost of colchicine? Colchicine, it turns out, was never examined for safety by the US Food and Drug Administration (FDA) prior to its commercialization because it was accessible before the 1938 Food, Drug, and Cosmetic Act. This statute requires the FDA to evaluate newly introduced medications but not previously available drugs. The FDA launched the Unapproved Treatments Initiative in 2006, encouraging companies to look into unapproved drugs and collect the requisite safety data for FDA clearance. The Hatch-Waxman Act of 1984, which sets the road for generic medication approval, provided an incentive for firms to do so: three years of market exclusivity. InURL Pharma, Inc., a Philadelphia, Pennsylvania-based business, has started 17 pharmacokinetic and pharmacodynamic investigations, as well as drug-drug interaction studies and a randomized, placebo-controlled trial using colchicine in the treatment of acute gout. They compared a shorter course of colchicine (1.2 mg followed by a single dosage of 0.6 mg an hour later) to a standard regimen of 1.2 mg followed by 0.6 mg hourly for six hours. Both of these regimens were tested against a placebo and found to be superior. Furthermore, compared to the standard 6-hour regimen for the treatment of acute gout, the shorter regimen showed a much decreased incidence of nausea and diarrhea.
Thus, in July 2009, authorisation was obtained for the marketing of Colcrys for the treatment of acute gout and for the treatment of familial Mediterranean fever under the Orphan Drug Act. As a result, URL Pharma received three years of market exclusivity for the use of colchicine in acute gout and seven years for the use of colchicine in familial Mediterranean fever. In October 2009, they were also given three-year market exclusivity for gouty arthritis prevention.
This is a fair compensation for a corporation that devotes significant resources to researching a drug, even if the drug had previously been offered in an unapproved version. However, as a rheumatologist, I am concerned about my patients’ capacity to obtain drugs. It has been established that when starting treatment with a xanthine oxidase inhibitor to lower serum uric acid levels chronically and avoid gouty arthritis, colchicine prophylaxis should be used for the first 6 months of treatment to prevent acute gout flares. To prevent acute gout flares, patients should take colchicine for 6 months after starting allopurinol or febuxostat. Unapproved colchicine was sold for around ten cents a pill prior to the approval of Colcrys.
Why is my medication not covered by insurance?
It’s possible that your insurance company won’t cover a medicine because it’s not in the plan’s “formulary,” or list of medicines covered by the plan. The following are some suggestions to assist you in obtaining the drug that is most suited to your health needs.
Is there a generic for colchicine?
Colchicine is a generic drug, which implies it’s a knockoff of the active ingredient in a brand-name drug. A generic medicament is thought to be just as safe and effective as a brand-name medication. Generics are also less expensive than brand-name medications.
Colchicine comes in the form of the brand names Colcrys, Gloperba, and Mitigare. If your doctor has prescribed colchicine and you’d like to switch to a brand-name version, let them know. They might have a preference for one of the two options. You should also verify with your insurance provider because some policies only cover one or the other.
Consult your doctor, pharmacy, or insurance provider to see how the price of these brand-name versions compares to the price of generic colchicine.
Why was colchicine taken off the market?
According to data published in JAMA Internal Medicine, despite the FDA-mandated exclusivity of colchicine ending and generics being released to the market, prices have remained high.
According to experts, a recent clinical experiment revealed that colchicine could be repurposed for secondary prevention after a myocardial infarction. The medicine, which predates the FDA’s inception, was previously available in unapproved forms for less than 50 cents per pill, and generic variants are currently available for around 30 cents per pill outside the United States.
Colcrys (colchicine, Takeda Pharmaceuticals) the first FDA-regulated pharmaceutical was launched in 2009 at a cost of $5 per pill and was granted 3-year exclusivity to treat gout. As a result, the other unapproved colchicine formulation was taken off the market.
“Moreover, Colcrys was granted patents for this centuries-old medication until 2029,” Natalie McCormick, PhD, post-Doctoral research fellow at Massachusetts General Hospital and Harvard Medical School, said. “As a result, despite the FDA’s approval of more than six independent generics to date, only authorized generics with price points determined by brand-name businesses are currently available to treat acute gout, pericarditis, and now possibly millions of people with myocardial infarction.”
From 2008 through 2017, McCormick and colleagues gathered Medicaid and Medicare data on all available forms of colchicine, including unregulated/unapproved colchicine, generic probenecid-colchicine combinations, and authorized generics.
They discovered that Medicare and Medicaid claims for colchicine totaled more than $340 million in 2017.
After accounting for inflation and rebates, McCormick and colleagues discovered that Medicaid prices increased from 24 cents per pill in 2008 for unapproved formulations to $4.20 per pill in 2011 for Colcrys alone. The highest price was $4.66 a pill in 2015, which included both Colcrys and authorized generics that were released that year.
From 2012 to 2017, the researchers noticed similar increases in Medicare prices, according to the study.
When authorized generics hit the market, McCormick and colleagues found that they were only somewhat cheaper than Colcrys, which was still a lot more expensive than the previously utilized unapproved colchicine formulations.
They discovered that Medicaid spending on colchicine has climbed by 2,833 percent since 2008, with price hikes accounting for 58 percent of the increase.
According to the researchers, Medicaid spent $32.2 million on colchicine in 2017. They calculated that Medicaid spending on colchicine would have been $2.1 million in the same year if the medicine had maintained at its pre-Colcrys pricing levels.
When the researchers factored in inflation rebates, the results were nearly identical.
“Public spending on colchicine has grown exponentially, primarily as a result of ongoing price increases following Colcrys’ approval and market exclusivity, potentially preventing millions of Americans from benefiting from its benefits as a long-term therapy for gout or after a heart attack,” McCormick and colleagues wrote.
Is it OK to take colchicine every day?
Adults should take 0.6 milligrams (mg) once or twice a day. As needed and tolerable, your doctor may increase your dose. However, the daily intake is normally limited to 1.2 mg. Your doctor will determine the appropriate use and dosage for your child.
Is there an alternative to colchicine?
ColciGel, a novel therapy for acute gout flares, has recently become available. ColciGel is a topically administered transdermal gel formulation of Colchicinum (colchicine in its homeopathic state). ColciGel is a patented Organogel that includes Colchicinum 4X and is applied directly to the site of acute flares. It comes in an airless 15ml jar with 0.25 ml of ColciGel delivered per pump. When ColciGel is administered to the region of an acute gout flare, it penetrates the dermal layer and relieves the flare’s inflammation and pain. Only trace amounts of colchicine enter the systemic circulation when ColciGel is applied topically, reaching subclinical levels of colchicine.
The reduction of pain and inflammation is the major goal of acute gout flare treatment. The current American College of Rheumatology (ACR) treatment guidelines for acute gout flares state unequivocally that the sooner pain and inflammation are treated (within 24 hours of start), the better the outcome. In contrast, the longer a patient waits for a medical appointment or attempts treatment with an ineffective agent (NSAIDs or oral colchicine), the less likely he or she will have a positive outcome and, as a result, the higher their healthcare costs will be.
The American College of Rheumatology (ACR) recommends using nonsteroidal anti-inflammatory medications (NSAIDs), oral colchicine, and corticosteroids to treat acute gout flares. Each of these therapeutic alternatives, however, has major drawbacks.
Most people who have an acute gout flare will try to self-medicate with an OTC NSAID, either alone or in conjunction with another medicine (for example, oral colchicine), but they may not get much relief. Many of these patients, the majority of whom are over 60, will have co-morbidities such as cardiovascular disease, which may limit long-term use of high-dose NSAIDs due to an elevated risk of heart attacks and strokes, as noted in the Black Box warning for this medicine class.
Although oral colchicine has been used to treat gout flares for millennia, it is only moderately effective and is associated with a high level of toxicity and adverse medication events. In 2009, a clinical trial comparing high- versus low-dose oral colchicine in the treatment of gout flares found that the low-dose treatment was more effective and patient-friendly. Colycrs was authorized by the FDA in 2012, making it the only approved and suggested dose for treating acute gout flares.
“Based on only two published trials, there is low-quality evidence that low-dose (oral) colchicine is likely to be an effective treatment for acute gout,” wrote van Echteld of the clinical data supporting low-dose oral colchicine. A total of 184 individuals were treated for one day in a clinical trial comparing low-dose oral colchicine to high-dose oral colchicine. Only 38% of patients in the low-dose group had pain reduction, which was better than the 33% in the high-dose group and placebo (15 percent ). In the majority of cases, oral colchicine therapy was ineffective, with 62 percent of low-dose patients and 67 percent of high-dose patients not experiencing meaningful pain reduction.
Oral colchicine medication has a high risk of Drug-Drug Interactions (DDIs), which is one of the reasons it can have major side effects. P-glycoprotein transports colchicine after it is processed by the cytochrome P450-3A4 (CYP3A4) enzyme (Pgp). Colchicine concentrations in the blood can be increased if you take it with CYP3A4 or Pgp inhibitors. Colchicine circulation concentrations can be elevated to dangerous levels by DDIs since the effective concentrations are just slightly below those that induce toxicity. There are 26 medicines on the Colcrys PI list of drugs that can cause DDIs, plus grapefruit juice. Oral colchicine can also cause rhabdomyolysis (myopathy), which can be exacerbated by taking cholesterol-lowering medications that are linked to myopathy (statins and fibrates). This new issue adds eight more medicines to the list of pharmaceuticals that could cause severe DDIs when taken with oral colchicine (several of which are widely used). Colchicine poisoning is extremely dangerous and can be lethal. 2 Colchicine has been linked to 117 deaths when administered orally, intravenously, or intramuscularly. DDIs have been blamed for more than half of these deaths.
Due to the high oral doses required and the risk of rebound episodes when the steroid is swiftly weaned down, corticosteroids are considered the last of the first-line therapeutic medicines. These medications are most effective when given as an intra-articular injection in a doctor’s office or an emergency room, which reduces inflammation while increasing treatment costs.
ColciGel is a first-line treatment for acute gout flares and an alternative to oral colchicine in individuals who experience adverse drug reactions (ADRs) or do not receive enough symptom relief with oral colchicine. Patients and physicians require a better option because up to 80% of patients using oral colchicine experience some level of related ADRs, such as nausea, vomiting, diarrhea, and abdominal cramping, and only 38% of these patients receive a 50% or more pain relief.a href=”# edn4> ColciGel is a superior alternative because it is applied topically to the site of inflammation, bypassing the gastrointestinal tract (and its associated ADRs).
ColciGel is a 4X attenuation of Colchicinium, the homeopathic name for colchicine, mixed with a unique improved transdermal base produced by Gensco Pharma. A low concentration of Colchicinium could be applied to the location of a gout flare, halting the inflammatory cascade and eliciting a favourable clinical outcome without the side effects associated with oral colchicine formulations, according to the idea. This idea was confirmed by previous studies that demonstrated colchicine’s favorable transdermal characteristics and its ability to effectively mitigate inflammation caused by monosodium urate (MSU) crystals in animal models when administered via a transdermal route. Following tests and clinical trials have confirmed the hypothesis.
In-vitro testing of samples of the transdermal Colchicinium gel formulation for drug release and diffusion through a synthetic skin model was performed (Franz cell diffusion). The findings revealed a high rate of drug release and considerable transmembrane diffusion (flux).
Animal trials to replicate the pharmacokinetic and safety profile of ColciGel began once the drug’s positive in vitro features were established. In rabbits, single and multiple high dose treatments resulted in negligible serum presence, no symptoms of toxicity, and no cutaneous discomfort. When this data was extrapolated to a human model, the expected serum level was found to be below clinical relevance.
Single dose and repeated dosage (dose stacking) applications of ColciGel were used in human PK testing in healthy subjects. There was no measurable presence of colchicine in any of the individuals after serial serum samples. There were no symptoms of toxicity or adverse drug reactions (ADRs), such as skin irritation, this time. These findings back up the theory that ColciGel won’t have the same level of drug-drug interactions (through the P450 3A4 hepatic enzyme pathway) and side effects as oral colchicine. Furthermore, these findings, combined with the unique mode of administration, support the claim of low gastrointestinal (GI) side effects, which are typical in oral formulations. Physicians with experience in gout treatment performed a proof of concept test on a small group of patients13 with acute GF. The results were remarkable, with all patients reporting a 50% or more reduction in pain after 48 hours of the first application, and even better pain relief with subsequent administrations. Within a few hours of first administration, several of these patients reported a considerable reduction in pain and inflammation. ADRs such as cutaneous irritation and GI distress were not reported by any of the participants. This preliminary evidence substantially supports ColciGel’s efficacy in treating acute gout flares.
Gensco’s next step is a post-marketing monitoring study that will examine efficacy changes and the occurrence of reported ADRs in a larger number of patients and subgroups. This open label post-marketing study is currently in the final stages of development.
Colchicine in Gout, by I. Morris, G. Varughese, and P. Mattingly. 327: 1275-1276, British Medical Journal, 2003.
Systemic steroid therapy for acute gout: a clinical trial and review of the literature, Groff GD, Franck WA, Raddatz DA. Semin Arthritis Rheum, 1990, vol. 19, no. 3, pp. 329-336.
Maduri S, Atla VR: Colchicine ointment formulation for the treatment of acute gout. Singapore Medical Journal, November 2012, 53(11), 750-4.
Elastic liposomal formulation for sustained administration of colchicine: In Vitro characterisation and In Vivo evaluation of anti-gout action, Hardevinder Pal Singh and Puneet Utreja. Vol. 11, No. 1 (March 2009) of the AAPS Journal
Can a pharmacist red flag you?
Pharmacies have the authority to refuse transactions if they believe the person is purchasing excessive amounts of the same prescribed drug. If the pharmacist refuses to give you the medication, you’ll be Red Flagged since they’ll have to visit an online system to figure out when your next dose should be administered.
Why did my insurance deny my prescription?
Prior permission is frequently required by a health plan, both to guarantee that specific prescriptions are prescribed for the proper purpose and to save money. Some health plans require your doctor to submit a prior authorization paperwork, even if your doctor may just call in the prior authorization over the phone. For typical requests, this process can take up to 72 hours. Ask your doctor if he or she can file an urgent request to the health plan, which will be assessed within 24 hours. Keep in mind that even if the prescription is granted, the approval may only be valid for a short period of time, so plan your refills appropriately, allowing enough time to secure a prior permission. While you wait for your medicine to be authorized, you may be able to ask your pharmacist if your health plan will allow for an emergency fill, which normally lasts 10-15 days.
Also, your plan may have quantity restrictions, which means it may only cover certain amounts of a prescription. The prescription may be refused if your doctor is prescribing at higher-than-normal doses. Because persons with CF are often prescribed greater dosages to maintain proper weight and growth, quantity limits are common with pancreatic enzymes. Finally, your strategy may necessitate step therapy. This implies that before your plan would pay the prescription drug, your doctor must show that you have tried and failed to take a less priced or preferred medication on the formulary.
Whether your insurance company refuses to cover your medicine due to coverage restrictions, consult your doctor to determine if an unrestricted covered medication may suffice. If taking the prescribed medication is medically necessary, your doctor must submit a formal request to your insurance provider to override the coverage restriction by submitting a supporting statement to your insurance provider stating that the standard dosage or medication has been or is likely to be less effective than the one being prescribed.
Are antibiotics covered by insurance?
Most Medicare and insurance plans cover generic amoxicillin, although certain drugstore coupons or cash pricing may be lower. Antibiotics that contain penicillin are compared.