WHY WAS DARVOCET TAKEN OFF THE MARKET, AND 
WHAT DRUG SHOULD BE TAKEN INSTEAD?

Propoxyphene, one of the most commonly prescribed medications in America, has been removed from the market. All propoxyphene-containing products (including Darvocet and Darvon) are no longer available. After a thorough review, the FDA concluded that the risks associated with propoxyphene outweigh the benefits. Safer alternatives exist for the treatment of mild to moderate pain.

Although patients may be surprised about the sudden discontinuation, both the safety and efficacy of propoxyphene have been a matter for controversy for years. Many agencies have advocated for market removal of the drug, and it is listed on the Beers Criteria as potentially unsafe in the elderly. In 2009, the FDA modified the labeling of propoxyphene to include a boxed warning of potential risks and required a medication guide to be dispensed to patients with each prescription.


Safety concerns that prompted removal of the drug include new data on adverse cardiovascular effects such as increased PR interval, QRS widening, and QT prolongation. These ECG changes can occur at normal doses but are completely reversible upon drug discontinuation. A further criticism of propoxyphene involves efficacy. A meta-analysis of 26 trials revealed that the combination of propoxyphene and acetaminophen was no more effective than acetaminophen alone for treatment of arthritis, musculoskeletal, and postoperative pain.1 A different trial of patients with moderate to severe postoperative pain showed that propoxyphene combined with acetaminophen was as effective as tramadol and less effective than ibuprofen.2


So what drug should be used instead? Many providers are switching to tramadol; however, this may not be appropriate for everyone. First assess whether your patient truly needs an opiate. Try acetaminophen dosed around the clock, or consider an NSAID if no contraindications exist. If an opiate is required, consider acetaminophen combined with codeine or hydrocodone. Patients who have received adequate pain control with propoxyphene rarely need stronger analgesics (such as oxycodone, hydromorphone, or morphine). Although tramadol is an alternative, it—contrary to popular belief—is an opiate narcotic with the potential for abuse and dependence. It also inhibits the reuptake of serotonin and norepinephrine and has the potential to cause seizures.


Before you tell patients to discard any remaining propoxyphene, consider the risk of withdrawal and recommend a taper if necessary (not required if switching to another opiate analgesic). Advise patients to dispose of the drug by mixing it with coffee grinds, kitty litter, or other undesirable substance prior to throwing it in the trash.


WHAT IS THE DIFFERENCE BETWEEN MACROBID AND MACRODANTIN?


Not all products containing nitrofurantoin are created equal. The primary difference is that for the treatment of urinary tract infections (UTIs), Macrodantin is dosed four times daily and Macrobid is dosed twice daily (think bid for MacroBID). Macrobid is generally preferred for its ease of administration. However, if dosed appropriately, the two drugs are likely to be clinically equivalent. 


Although nitrofurantoin is an excellent drug for UTIs, it should not be used to treat other infections (including pyelonephritis) because tissue penetration is negligible. Nitrofurantoin concentrates in the urine and is effective against the two most common organisms isolated in uncomplicated UTIs (Escherichia coli and Staphylococcus saprophyticus). Nitrofurantoin is also active against Enterococcus, including vancomycin-resistant strains. 


The usual duration of nitrofurantoin therapy is 7 days. However, a recent study in women with uncomplicated cystitis showed that treatment with Macrobid 100 mg twice daily for 5 days is equivalent to a 3-day course of trimethoprim-sulfamethoxazole.3 Therefore, shorter durations of therapy are becoming popular.


Remember to avoid nitrofurantoin in patients with renal dysfunction (creatinine clearance < 60 mL/min). Finally, if nitrofurantoin is used for prophylaxis of recurrent UTIs, the dosing is slightly different. A single dose of Macrodantin 50 to 100 mg at bedtime is sufficient. JAAPA

Larissa DeDea, PharmD, BCPS, PA-C, is a clinical pharmacist with Northern Arizona Healthcare, Flagstaff, Arizona. In addition to being board certified in pharmacotherapy, she is a graduate of the Yale University PA Program.

REFERENCES


1. Li Wan Po A, Zhang WY. Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol. BMJ. 1997;315(7122):1565-1571.


2. Collins SL, Edwards JE, Moore RA, McQuay HJ. Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain. Cochrane Database Syst Rev. 2000;(2):CD001440.


3. Gupta K, Hooton TM, Roberts PL, Stamm WE. Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. Arch Intern Med. 2007;167(20):2207-2212.