Hydrocodone/ibuprofen

Opioids such as hydrocodone cross the placenta, and can therefore affect the fetus. Studies have shown a possible association between opioids and adverse outcomes such as birth defects, poor fetal growth, stillbirth, and preterm delivery. Prolonged use of opioids by a pregnant mother can also lead to neonatal withdrawal syndrome.[4][5] NSAIDs such as ibuprofen should generally be avoided in pregnancy, as there are conflicting reports of birth defects after in utero exposure. However, it is accepted that NSAIDs prevent closure of the fetal ductus arteriosus, which happens during the later stages of pregnancy. Because of this, ibuprofen should be avoided after 30 weeks gestation.[4][5]

Hydrocodone and ibuprofen are excreted in breast milk, so appropriate caution should be taken when prescribing to breastfeeding mothers.[4][5]

There is no evidence to support altered pharmacokinetic properties due to differences in gender or age. However, this drug combination has not been tested in children.[3]

The two active components of the drug, ibuprofen and hydrocodone, do not affect each other's absorption characteristics or other pharmacokinetic parameters.[3] After an oral dose, the peak level of hydrocodone in the blood is reached 1.7 hours after administration.[3] The blood levels of ibuprofen peak 1.8 hours after oral administration.[3]

The patent for Vicoprofen was filed in December 1984, and U.S. patent number 4,587,252 was granted in May 1986.[6] Although ibuprofen and hydrocodone were already available on the market at this time, the fact that they had never been supplied together in a single formulation required approval from the FDA as if it were a new drug. Knoll filed an investigational new drug application on 30 December 1986. A new drug application was later filed by Knoll on 25 April 1996, and received final approval from the FDA on 23 September 1997.[7] Vicoprofen tablets were initially formulated and packaged by Knoll, with ibuprofen supplied by Albemarle Corporation and hydrocodone supplied by Mallinckrodt Pharmaceuticals.[8]

The validity of Knoll's patent on Vicoprofen has been challenged in federal court. In September 2002, the U.S. District Court for the Norther District of Illinois granted a motion of invalidity filed by Teva Pharmaceuticals against Knoll's patent on Vicoprofen, ruling the patent was invalid as obvious.[9] This ruling paved the way for Teva's abbreviated new drug application to be approved by the FDA which would allow them to manufacture and market their own generic.[10] Knoll appealed the decision. In April 2003, Teva announced that its abbreviated new drug application had been approved by the FDA, and its generic would begin shipping immediately.[10] In May 2004, the United States Court of Appeals for the Federal Circuit vacated the previous judgment by the U.S. District Court for the Northern District of Illinois, and the case was remanded back for further court proceedings. Teva continued to sell its generic during this time.[11] The patent for Vicoprofen expired on 18 December 2004, officially opening the drug to generic manufacture.[6] In July 2016, the FDA approved another generic equivalent, manufactured by Aurobindo Pharma Limited.[12]

Knoll pharmaceuticals, originally founded in Germany in 1886, became a subsidiary of BASF (a German chemical company) in 1975.[13] It was under their control when Vicoprofen was originally developed and approved. In March 2000, Knoll Pharmaceuticals and Abbott Laboratories, an American health care company, announced a co-promotion agreement for Vicoprofen, in which Abbott would promote Vicoprofen to its network of buyers, including physicians, hospitals, and surgical centers.[14] In June 2002, Abbott Laboratories, paid $6.9 billion to acquire the entire Knoll pharmaceutical unit from BASF, including Vicoprofen.[15]

Vicoprofen was originally approved as a schedule III drug, but was later reclassified to a schedule II drug based on the DEA reclassification of hydrocodone containing products effective 6 October 2014.[16]

The average wholesale price (AWP) of generic Vicoprofen varies based on the strength of the preparation. Pricing data gathered from Lexicomp in October 2017 indicates the AWP for a 100 count bottle of 7.5 mg/200 mg strength to be $114.62, a 100 count of 5 mg/200 mg strength to be $356.62 and a 100 count of 10 mg/200 mg strength to be $470.35.[4] These prices are all for generic equivalents of Vicoprofen.

In 2003, at the time of the approval announcement for the first generic equivalent, it was reported that annual sales of brand name Vicoprofen totaled $104 million.[10] According to IMS, the hydrocodone/ibuprofen tablets 7.5 mg/200 mg, had an estimated market size of $15.7 million for the 12 months preceding May 2016.[17]