Oxycodone formulations

Oxycodone is a semisynthetic opioid derived from thebaine and used for oral pain relief. It is commonly formulated as an immediate-re lease medication with acetaminophen or aspirin. A con-trolled-release oxycodone formulation is used for the treatment of moderate to severe pain it provides controlled drug delivery over 12 h. The oral bioavailability of this formulation is 60 to 87%.35 The results of clinical studies of patients with postoperative and cancer pain show that oxycodone has a potency 1.5 times that of morphine. 

Dosages and routes of administration Oxycodone is given by mouth in single doses of 5-10 mg or as controlled release preparations with doses of 40 mg (Cairns, 2001). Rectal administration is also possible. Oral formulations often contain combinations with paracetamol or acetylsalicylic acid. 

The success of prolonged-release morphine prompted the development of prolonged-release formulations for other opioids, for example the matrix made of hydrophobic and hydrophilic matrix formers, for example on hydrocodeine (DHC retard with cetostearyl alcohol and hydroxyethyl-cellulose), oxycodone (oxygesic with stearyl alcohol and polyacrylate) and tramadol (tramundin with cetostearyl alcohol and ethylcellulose). By virtue of the oblong shape of hydrocodeine and tramadol tablets the prolonged-release tablets can be divided, whereby compared with whole tablets release from the divided tablets is slightly accelerated. The difference with these forms is that with increasing dose the release slows down. 

Because faster onset of action is associated with higher potential for abuse, abuse-liability assessment should include consideration of whether a formulation can be altered to increase the speed of onset. There are numerous examples of abuse of a medication by a route other than that intended by the manufacturer. The sustained-release oral form of oxycodone, designed to deliver an initial rapid dose followed by slow release, has been widely abused by chewing the tablet, thus releasing the entire content of the tablet at once.65 There is also evidence for intravenous use of sublingual buprenorphine tablets.66 Transdermal systems developed to deliver medication slowly for extended periods of time have been prime targets for misuse,67 as discussed below in the case study of fentanyl. 

Oxycodone is approved by the Food and Drug Administration (FDA). Various formulations follow, including drugs that combine oxycodone with either aspirin or acetaminophen. 

Oral preparations of oxycodone include immediate-release pills, controlled-release pills, and a liquid solution. The immediate-release pills, as their name implies, get the drug into the bloodstream faster than other formulations. Within about 15 minutes of taking immediate-release oxycodone, the drug s analgesic effects take hold. Pain is lessened and the user experiences a feeling of drowsiness and/or well-being. 

The controlled-release formulations, on the other hand, prolong the release of oxycodone from the tablet for several hours. These pills have a special protective outer coating that makes them harder to digest, so that the oxycodone inside can be released slowly over a period of about 12 hours. That means the pills are capable of providing relief that lasts twice as long, allowing users to obtain the same effect they would get from taking an immediate-release tablet once every six hours. 

Most of the oxycodone drugs—which include the drug alone or in combination with aspirin or acetaminophen—are available in tablet form. For patients who have trouble swallowing or who cannot take the tablet form for other reasons, the drug is available in a highly concentrated flavored liquid solution. The appropriate dose of the liquid is measured into a dropper either by a nurse or by the patient. Often, the liquid may be added to semi-soft foods such as applesauce or pudding to help disguise its bitter taste. Those who use liquid formulations of oxycodone should be aware that some of them may contain alcohol. 

Codeine (Figure 31-1), oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. These compounds are rarely used alone but are combined in formulations containing aspirin or acetaminophen and other drugs. 

SCHEDULE II Certain barbiturates, cocaine, codeine, codeine + acetaminophen (depends on dose and formulation), fentanyl (depends on dose), hydrocodone, hydromorphone, meperidine, methadone, morphine (depends on combination with other pain relievers), oxycodone, propoxyphene... 

Absorption Oral broavailability is variable depending On drug and formulation (morphine < hydrocodone and oxycodone < methadone). The exception is fentanyl, which is very poorly... 

B The sustained-release formulation of oxycodone would be inappropriate to administer via gastric tube since crushing the tablet would eliminate the sustained-release mechanism. The drug would then have to be administered more frequently to control pain, defeating the purpose of the long-acting formulation. IV opioids, liquid formulations, and immediate-release tablets that may be crushed are viable options. 

As for codeine, oxycodone is frequently formulated in combination with aspirin (Percodan) or acetaminophen (Percocet and Tylox). Therefore the detection of either salicylate or acetaminophen along with codeine or oxycodone in the urine of patients who display an opiate toxidrome should lead to the measurement of salicylate or acetaminophen in serum to assess their toxicity (see Salicylate and Acetaminophen sections). Alternatively, empiric quantitive serum acetaminophen and salicylate determinations are... 

Many analgesic effectiveness studies involving combination drug formulations (an opioid combined with a nonopioid) have been reported. For example, in the treatment of moderate to severe postoperative obstetric or gynecologic pain, 2-tablet dose of hydrocodone 7.5 mg with ibuprofen 200 mg was comparable in efficacy to the 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg. Obviously both of these treatments were superior to the placebo [23]. In contrast, for treatment of chronic pain, the 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg was more effective than either the 1 -tablet dose of this combination or the 2-tablet dose of codeine 30 mg and acetaminophen 300 mg combination [24]. In a double-blind, randomized controlled trial involving 118 patients with chronic cancer pain, the combination formulation of hydrocodone (25 mg/d) and acetaminophen (2500 mg/d) was effective in relieving pain in 56.5% of the patients [25]. 

Oxycodone and morphine are available in a sustained-release formulation for use with chronic pain (not acute pain). Tablet must be swallowed whole and cannot be administered to patients through gastric tubes. 

Opioids 2-3 days typically Up to 6 days with sustained-release formulations Up to 1 week with prolonged or heavy use Since the assay was made to detect morphine, detection of other opioids, such as codeine, oxycodone, hydrocodone, and other semisynthetic opioids, may be limited. Some synthetic opioids, e.g., fentanyl and meperidine, may not be detected. Drugs such as rifampin and some fluoroquinolones may cause false-positive results depending on the assay. 

Although parenteral preparations of oxycodone exist, in the USA oral formulations only are available. Controlled-release forms must be swallowed whole so as not to interfere with the controlled-release mechanism chewing or cutting may lead to an overdose. Available oxycodone preparations are listed in Table 19.1. 

Initial doses of oxycodone IR (all oxycodone is IR unless in the controlled-release formulation) are 5 to... 

OxyContin (oxycodone hydrochloride controlled-release, Oxycodone CR) is an extended-duration oral opioid analgesic. It is formulated as a tablet with an outer more rapidly acting component and slower-release inner matrix that provides up to 12 hours of pain relief. Oxycodone CR offer prolonged and uniform analgesia avoiding trough effects observed with immediate-release oxycodone. Controlled-release oxycodone has abuse and diversion liability since the tablet can be easily crushed, and the entire 12 h dose administered nasally, leading to excessive acute effects and potential overdose [1]. 

Chronic non-surgical pain OxyContin tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain when a continuous, round-the-dock analgesic is needed for an extended period of time. 

For patients whose pain will be short-term in nature, oxycodone (in appropriate formulation) can be given around the clock. For patients whose pain is anticipated to be longer-term in nature, oxycodone HCl CR (Oxycontin) or MS Contin can be given. 

Tapentadol is a novel schedule 11 central-acting analgesic. It was initially formulated as an immediate-release preparation and approved in 2008 for moderate to severe acute pain. Tapentadol immediate-release, Nucynta, is marketed as 50, 75, and 100 mg tablets and provides analgesia (primary efficacy endpoint) comparable to 10-15 mg of immediate-release oxycodone. A sustained-duration oral formulation named Tapentadol ER is in late-stage development for chronic pain and the results of clinical trials, including fom phase in pivotal trials, have been submitted to the FDA for approval. 

A controlled release formulation of oxycodone was studied in liver cancer patients xmdergoing chemoembolisa-tion, and foxmd no adverse events. Use of oxycodone was associated witii shorter hospital stays and improved pain-scale ratings [62 ]. 

SKIN A case series of three patients who were formulation and developmental scientists at pharmaceutical companies working with oxycodone described episodic erythema of their eyelids and erythematous patches along their wrists that occurred at e workplace and resolved every time they left work [63 ]. All three patients rmderwent skin patch testing that revealed a contact dermatitis due to oxycodone. 

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