Deuxis® was brought to market by Horizon Pharma as yet one more combination drug offering. The argument for taking a second drug to reduce the incidence of the most common serious ibuprofen side effects, namely dyspepsia, symptomatic and asymptomatic gastric ulcers, and gastrointestinal bleeding is fairly convincing. It is especially a valid approach in moderate to high risk patients like the elderly, those with a history of ulcers or gastritis, and anyone else at a high risk of gastrointestinal bleeding. The argument that it is important to make this a single pill in order to improve compliance and reduce the number of pills ingested is considerably less convincing.
Duexis is being marketed by Pharma reps as “the new ibuprofen.” They show pictures of patients taking 18 pills a day, twelve 200 mg OTC ibuprofen, and four 20 mg OTC famotidine. As a prescription alternative it is more fair to compare it to three 800 mg prescription ibuprofen and two 40 mg prescription famotidine. It is certainly the more expensive way to take ibuprofen. Generic ibuprofen 800 mg costs about $8/ month at a three times daily dosage from Costco. (Costco is an easily available place too check drug prices because they publish their prices online). Generic prescription famotidine 40 mg twice daily costs about $9./ month. Duexis (800 mg ibuprofen + 26.6 mg famotidine) three times daily costs about $150./ month. Horizon provides coupons to reduce maximum copay to $25./ month or less for insured patients, but there is still a huge gap in real cost to pay for the convenience of 3 vs. 5 pills daily.
To my way of thinking there needs to be solid evidence that combination pills truly lead to improved patient compliance and improved outcomes vs. prescribing the separate ingredients. I have yet to see much evidence to support this argument. The reps will tell you that the incidence of non-compliance with taking more pills is much lower, but no controlled studies that I have seen compare the real options of simply writing two separate prescriptions.
Some combination drugs make a great deal of sense. These are usually in situations where the two drugs can naturally be used in combination, the cost of the combination does not greatly exceed the cost of prescribing the two ingredients separately, and when using the fixed-dose combination does not induce us to use suboptimal doses of one or the other of the drugs. Here are some examples of what I consider very good use of drug combinations, followed by some that I consider sketchy:
Good Combo Drugs:
ACE or ARB + Thiazide diuretics. There is good evidence that many hypertension patients need more than one drug to gain optimal BP control. Drugs combinations like lisinopril 20 mg – Hctz 12.5 mg for $4. / month vs. lisinopril 20 mg at $4./ month + HCTZ 12.5 mg for another $4./ month or more makes great sense, especially given the many dosing options for the inexpensive generic ACE-HCTZ and generic ARB combinations. Cost savings, increased convenience, and possibly improved compliance are a great argument.
Acetaminophen + opioid pain medication combos: The most commonly prescribed drug in the U.S. is Vicodin. It’s no coincidence that physicians prefer combination acetaminophen-opioid combinations to opioids alone for treatment of short term pain. Lower doses of opioid are effective reducing opioid side effects and abuse by non-oral use is reduced. These benefits are felt by most physicians to outweigh the risk of acetaminophen toxicity from overdose.
Combinmation Inhaled Corticosteroid and Long-acting Beta Agonists for Refractory Bronchospasm: Drugs like Advair, Symbicort and others are very popular and effective for treatment of difficult asthma and COPD patients because of their symbiotic effects and simplicity. Cost is high, but in the right patients they are great. Most experts recommend against the use of a long-acting beta agonist (LABA) without using a corticosteroid also in asthma patients, so the combination helps prevent patients from using the LABA alone.
MMR and other combination vaccines: Giving one shot instead of three to a baby has to my mind more advantages than swallowing one pill not two at the same time in an adult. Same holds for Td and Tdap for adults, and the various other childhood combination vaccines.
Combination Estrogen-Progestin Products: Combination birth control pills and estrogen-progestin combination drugs for symptom relief in menopausal women provide higher efficacy in the case of BCPs and lower risk of uterine cancer in menopause therapy than single ingredient products.
There are lots of other great combinations like Levodopa-carbidopa, antihistamine-decongestants, and others.
Sketchy or Simply Overpriced Combination Drugs:
Vimovo: Vimovo is the first drug similar to Duexis to market, a combination of Nexium and Naproxen. A high priced combo alternative to omeprazole and naproxen generics.
Caduet: This may have played a valid role prior to Lipitor going generic, but was more likely a preemptive attempt by Merck to retain brand name market share after Lipitor went generic. It is atorvastatin + amlodipine, both now generic.
Axor: An example of a brand name ARB combined with generic amlodipine. It seems that many branded anti-hypertensive drug manufacturers suddenly discovered that their drug works well in combination just after amlodipine became generic and as alternative ARBs became available. The “only take one pill” argument pushed big time here.
There are lots of other examples of where drug combinations benefit of convenience is in my opinion outweighed by their much higher costs. This seems to be a growing pattern, inventing combinations of inexpensive drugs that used in combination becomes an expensive new option. Consumers beware products like Duexis.