Hydrocodone dosing

Fig. 3. Modeled hydromorphone accumulation following repeated hydrocodone dosing as a function of CYP2D6 metabolizer status. Hydromorphone concentrations calculated are approximately five times higher in EMs compared with PMs following 10-mg hydrocodone dosing every 6 hours, based on genotype-specific peak hydromorphone serum concentrations [39]. EM, extensive metabolizer PM, poor metabolizer.

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

Dose based on codeine—children 1 mg/kg per dose every 6 hours adult 30-60 mg/dose Hydrocodone + acetaminophen... 

Dose based on hydrocodone—children 0.2 mg/kg per dose every 6 hours adults 5-10 mg/dose Anti-inflammatory agents... 

HydroNarcotic Analgesic/NSAID] Uses Mod-severe pain (<10 d) Action Narcotic w/ NSAID Dose 1—2 tabs q4-6h PRN Caution [C, M] Renal insuff -1- effect w/ ACE inhibitors diuretics t effect w/ CNS d ressants, EtOH, MAOI, ASA, TCA, anticoagulants Contra Component sensitivity Disp Tabs SE Sedation, fatigue, GI upset see Hydrocodone Acetaminophen Interactions -1- Effects OF ACEIs, diuretics EMS See Hydrocodone Acetaminophen T risk of bleeding w/ heparin use OD See individual agents... 

Codeine,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. 

Each teaspoonful (5 mL) of TUSSIONEX Pennkinetic extended-release suspension contains hydrocodone polistirex equivalent to 10 mg of hydrocodone bitartrate and chlorpheniramine polistirex equivalent to 8 mg of chlorpheniramine maleate. TUSSIONEX Pennkinetic extended-release suspension provides up to 12-hour relief per dose. Hydrocodone is a centrally acting narcotic antitussive. Chlorpheniramine is an antihistamine. TUSSIONEX Pennkinetic extended-release suspension is for oral use only. Hydrocodone polistirex sulfonated styrene-divinylbenzene copolymer complex with... 

Dosages and routes of administration Hydrocodone is used orally in doses of 5-10 mg. 

Hydrocodone has multiple actions, mainly involving the CNS and smooth muscle. Peak serum concentrations after single therapeutic doses are typically less than 30 ng/ml and occur within 1.5 h after drug administration.25 The plasma half-life has been reported to range from 3.4 to 8.8 h with a volume of distribution of 3.3 to 4.7 L/kg.25 In humans, hydrocodone is metabolized by O-demethylation (by the action of CYP2D6) and N-demethy 1 ation (by the action of CYP3A4) and... 

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... 

Codeine, hydrocodone, and hydromorphone decrease the sensitivity of CNS cough centers to peripheral stimuli, and decrease mucosal secretion. These actions occur at doses lower than required for analgesia (see p. 135 for a more complete discussion of the opiates). Dextromethorphan [dex troe meth OR fan], a synthetic derivative of morphine, suppresses the response of the cough center. It has no analgesic or addictive potential, and is less constipating than codeine. 

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)... 

If additional analgesia is required beyond that afforded by the nonnarcotic analgesics, an opioid such as oxycodone, hydrocodone, or codeine should be used. If opioid side effects are unacceptable or become problematic, the narcotic dose is reduced or an alternative opioid is selected. 

Hydrocodone has the potential for abuse. Chronic users may develop tolerance, thus necessitating larger doses for the desired effect. Abrupt cessation can cause withdrawal, yielding restlessness, insomnia,... 

Naloxone may be of benefit in reversing the neurological and respiratory depressant effects of hydrocodone. A dose of 0.4-2.0 mg is given intravenously slowly, titrated to resumption of adequate respirations, and can be repeated as needed. The therapeutic effect of naloxone may be of shorter duration than that of hydrocodone activity therefore, it is imperative that hydrocodone intoxicated patients who demonstrated improvement after naloxone be closely monitored for resedation. Vital sign measurements and neurological checks should be monitored frequently. 

Figure 34-37 Hydrocodone and hydromorphone metabolic transformations.The figures in parenthesis are percent of a dose of hydrocodone excreted in urine. Rapid metabolizers excrete more hydromorphone conjugates (5.9%) compared with slow metabolizers (1.0%). Hydrocodo and hydromorphoi exist as 6-a and jl-stereiosomers. 6-a-hydrocodol is dihydrocodeine 6-a-hydromorphoi is dihydromorphine. For hydromorphone administration, 6% of the dose is excreted as the free parent drug and 30% as conjugates. Only trace amounts of hydromorphoi conjugates are formed.

In a study examining the potential activity of Celebrex in orthopedic surgery it was found that, after a single dose, Celebrex was equal to hydrocodone/paracetamolj but with multiple doses, Celebrex was superior (409). 

Canada has the dubious distinction of having the world s largest per capita consumption of precursor opiate-containing compounds (e g., codeine, oxycodone, and hydrocodone) (Korcok 1979). A drug utilization review of opiate use in Canada from 1978 to 1989 shows continued increase in the use of prescribed codeine combination products. The defined daily dose (DDD)/1000 inhabitants/day for prescribed codeine-acetaminophen products has increased from 3.3 DDD/1000 inhabitants/day in 1982 to 8.1 DDD/1000 inhabitants/day in 1989. Oxycodone-acetaminophen containing products have also been increasing from 0.04 DDD/1000 inhabitants/day in 1978 to 0.21... 

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]. 

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