Hydrocodone Bitartrate and Acetaminophen

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Hydrocodone Bitartrate and Acetaminophen Quick Reference
Hydrocodone
Acetaminophen
IUPAC Name
4,5α-epoxy-3-methoxy-

17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5).

Chemical Information
Empirical Formula Hydrocodone: C18H21NO•C4H6O6•2.5H2O

Acetaminophen: C8H9NO2

Molecular Weight Hydrocodone= 494.490

Acetaminophen= 151.16

General Drug Information
Classification Opioid analgesic
Schedule Legend- C-III
How Supplied Insert formulation followed by strength here Ex: Oral Tablets: 5/325, 5/500, 7.5/325, 7.5/500, 7.5/650, 10/325, 10/500, 10/650, 10/660, 10/750 mg
Trade Names Anexsia®, Bancap HC®, Ceta-Plus™, Co-Gesic®, ComfortPak™, Dolagesic™, Dolorex™ Forte, Duocet™, Hy-Phen®, Hycet™, Hydrocet®, Hydrogesic™, Liquicet™, Lorcet®, Lorcet® Plus, Lorcet®-HD, Lortab®, Margesic-H™, Maxidone™, Norco®, Stagesic®, Vanacet™, Vicodin®, Vicodin® ES, Vicodin® HP, Xodol®, Zydone®
Pregnancy Category C
Breast Feeding Hydrocodone/Acetaminophen should generally be avoided in breast feeding mothers to avoid a withdrawal syndrome in infants
Generic Availability Generic Available
Patent Expiration Date Generic Available
Administration Information
Route(s) Oral
Method(s) Take as directed with a drink of water for pain. Do not take more often than directed.
Pharmacokinetic Information
Absorption F = High; the bioavailability of acetaminophen is 80%
Cmax = Hydrocodone:23.6+/-5.2ng/mL
tmax = Hydrocodone: 1.3 hours
Distribution Vd = Volume of distribution for acetaminophen is 1.5-3L/kg
Protein binding = 0.9% (acetaminophen)
Metabolism Acetaminophen: hepatic conjugation with glucuronic acid (60%), sulfuric acid (35%), and cysteine (3%). Some of the drug may be hydroxylated and deacetylated. CYP2A6,CYP2E1. Hydrocodone is metabolized by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone
Excretion T1/2 = Hydrocodone: 3.8 hours Acetaminophen: 1.25 to 3 hours
Acetaminophen: 85% or oral dose appears in the urine most as the glucuronide conjugate. Hydrocodone is excreted in an uncretain manner, one report found 26% of the dose as hydrocodone and O- and N-demethylated metabolites in the urine.


Contents

Brand/Trade Names of Drug

Anexsia®, Bancap HC®, Ceta-Plus™, Co-Gesic®, ComfortPak™, Dolagesic™, Dolorex™ Forte, Duocet™, Hy-Phen®, Hycet™, Hydrocet®, Hydrogesic™, Liquicet™, Lorcet®, Lorcet® Plus, Lorcet®-HD, Lortab®, Margesic-H™, Maxidone™, Norco®, Stagesic®, Vanacet™, Vicodin®, Vicodin® ES, Vicodin® HP, Xodol®, Zydone®

Generic Name of Drug

Ex: Hydrocodone Bitartrate and Acetaminophen

hye droe koe' done & a set a mee' noe fen

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Description

Hydrocodone is an opioid analgesic and antitussive which is structurally related to codeine.[1][2] It was first created in the 1920’s. A combination of hydrocodone and acetaminophen is used, because by utilizing two drugs with different mechanisms of action, more analgesia can be provided with a lower risk of adverse effects. [3] Pain is the most common reason that people seek medical attention.[4] Acetaminophen has very weak anti-inflammatory actions; however it is generally safer than anti-inflammatory agents like aspirin and NSAIDs.[5] Acetaminophen does not affect the bleeding time, cause stomach ulcers, or alter the acid-base status of the body.

There have been several studies comparing the efficacy of hydrocodone/acetaminophen in the treatment of acute pain compared with other analgesics. In a study comparing oxycodone and hydrocodone with acetaminophen for the analgesic properties, there was no difference between the pain relieving properties at 30 and 60 minutes. Hydrocodone was found to have a higher incidence of constipation than did oxycodone, and all other side effects were statistically equivalent. [4] Another study compared oxycodone 5mg with ibuprofen 400mg vs. oxycodone 5mg and acetaminophen 325mg vs. hydrocodone 7.5 and acetaminophen 500mg for postoperative pain. It was found that oxycodone with ibuprofen was the most efficacious for pain relief.[3]


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Mechanism of action

Hydrocodone is a semisynthetic narcotic analgesic and antitussive. The exact mechanism of hydrocodone is unknown; however it seems to target the opioid receptors in the central nervous system. Opioids are known to cause drowsiness and alterations in mood. [2] The drug acts on the µ receptors.[5] Hydrocodone has very weak binding to the µ receptor; though its active metabolite, hydromorphone, formed from the CYP2D6 metabolism of hydrocodone, binds to the µ receptor tightly.[6] Hydromorphone binds to the µ receptors 30 times greater than does hydrocodone. [1] The µ receptors activation is responsible for the effects on mood and analgesic effects of the drug.[5]

When this dug and other morphine like compounds are administered to patients in pain, it produces pain relief, drowsiness and possibility euphoria. When the same drug is administered to patients who are not in pain, nausea and vomiting are often the result. Sedation is also probable.[5]

Opioids have many effects on the body. They tend to impact the hypothalamus causing the body temperature to decrease slightly. Opioids induce neuroendocrine effects by acting on the hypothalamus to decrease the release of gonadotrophin-releasing hormone and corticotropin-releasing hormone. The effect of decreasing these two hormones is to cause a lowered amount of luteinizing hormone, follicle-stimulating hormone, ACTH and beta-endorphin. Miosis is caused from µ agonist, which is especially prominent in overdoses. High doses can produce convulsions.[5]

Respiration is typically depressed in people taking morphine-like compounds. Usually with an overdose of opioid, respiratory depression is the result of death. The antitussive properties stem from this drugs ability to decrease the cough reflex in the medulla. It can cause nausea and vomiting because of its actions on the chemoreceptor trigger zone in the medulla.[5]

Patients with a CYP2D6 deficiency may have altered effects of hydrocodone. Patients who are extensive metabolizes of CYP2D6 convert hydrocodone to hydromorphone faster and report more “good effects” and less “bad opiate effects” compared to those patients who were established poor metabolizes of CYP2D6.[7] Approximately 7% of Caucasians have a defect in CYP2D6. [1]

Acetaminophen is an analgesic whose exact mechanism of action is unknown. It seems to work peripherally. It is an antipyretic via its action on the hypothalamus. Acetaminophen inhibits prostaglandin synthesis. [2] It is the active metabolite of phenacetin. The maximum daily dose of acetaminophen is 4 grams per day. Acetaminophen lacks antiinflammatory properties because it only weakly inhibits cyclooxygenase. It works as an antipyretic via its inhibition of cyclooxygenase in the brain.

The most severe adverse effect occurs when excessive acetaminophen is administered. Overdosage can lead to fatal hepatic necrosis. The mechanism of hepatic injury occurs from metabolism with the cytochrome P450 system leading to the production of the metabolite, N-acetyl-para-benzoquinonimine. N-acetyl-para-benzoquinonimine is conjugated with glutathione and further metabolized to mercapturic acid and excreted in the urine. When too much acetaminophen is consumed, glutathione becomes in short supply. Thus N-acetyl-para-benzoquinonimine, which is very reactive, is free to cause oxidant injury to the liver. [5]

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Time Required for Therapeutic Response

  • Onset= 30 minutes
  • Maximum pain relief= 2.3 hours [3]


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Pharmacokinetics

Absorption

Acetaminophen is almost completely absorbed from the gastrointestinal tract with peak plasma concentrations occurring in 30-60 minutes. [5] The bioavailability is around 80%.[8]

Hydrocodone’s peak concentrations are achieved at 1.3 hours after dosing and the maximum concentrations after a 10mg dose were 23.6n/mL.[2]

Distribution

Acetaminophen is uniformly distributed throughout the body. The binding to plasma proteins is variable, however when over doses have occurred, approximately 20-50% of the drug is bound to plasma proteins. [5] 3% of the dose is oxidized by CYP2A6 and CYP2E1. This forms to metabolites, 3-hydroxy-acetaminophen which is nontoxic and N-acetyl-p-benzoquinone imine (NAPQI) (Also called N-acetyl-benzoquinoneimine ) which is toxic. NAPQI must be conjugated with glutathione to avoid hepatotoxicity. There are no active metabolites produced.[8]

Hydrocodone has a mean peak concentration of 23.6ng/mL and the maximum serum levels occur at 1.3 hours after the dose. The half life is around 3.8 hours.[2]

Metabolism

Acetaminophen undergoes hepatic metabolism. It undergoes hepatic conjugation with glucuronic acid (60%), sulfuric acid (35%), and cysteine (3%). Some of the drug may be hydroxylated and deacetylated. A small amount of acetaminophen undergoes N-hydroxylation to form N-acetyl-benzoquinoneimine which is very reactive.[5]

Hydrocodone is metabolized by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone. It has some other oxidative enzymatic metabolism by UGT. The active metabolite of hydrocodone is hydromorphone.[6] Hydrocodone has very weak binding to the µ receptor; however its active metabolite, hydromorphone, formed from the CYP2D6 metabolism of hydrocodone, binds to the µ receptor tightly.[6]

Excretion

Acetaminophen is excreted in the urine approximately 90-100% after 24 hours, mostly as the metabolites of acetaminophen.[5]The clearance of acetaminophen is 0.144-0.14 L/hr*kg.[8]

Hydrocodone is excreted in an uncertain manner. One report found 26% of the dose as hydrocodone and O- and N-demethylated metabolites in the urine.[9]Another found 16% of the hydrocodone as conjugated and unconjugated hydrocodone and hydromorphone in the urine.


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Special Population Pharmacokinetics

  • Renal insufficiency

Hydrocodone and acetaminophen both have metabolites which are eliminated in the urine and the risk of toxic reactions from the build up of these metabolites is possible.[2]

  • Hepatic insufficiency

Patients with a CYP2D6 deficiency may have altered effects of hydrocodone. Patients who are extensive metabolizes of CYP2D6 convert hydrocodone to hydromorphone faster and report more “good effects” and less “bad opiate effects” compared to those patients who were established poor metabolizes of CYP2D6.[7] Approximately 7% of Caucasians have a defect in CYP2D6. [1]

  • Hemodialysis

No data[10]

  • Geriatric

There are no specific studies in the elderly. The elderly should be started at the low end of the dosing range and titrated to effect. Caution should be exhibited because of the population’s predisposition for hepatic and renal insufficiency. Hydrocodone can cause confusion and increased sedation in the geriatric population. [2] It is unknown how the kinetics will change in the elderly.

  • Pediatric

Safety has not been established. [2]


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Indications

FDA Approved Indications

  • Moderate pain[2]


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Non-FDA Approved Indications



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Dosage

Hydrocodone Bitartrate and Acetaminophen Dosing[2]

Hydrocodone Bitartrate and Acetaminophen Dosing Chart
Drug Strength Typical Dosage for Pain Maximum Daily Dosage
5/325 mg 1-2 tablets every 4-6 hours. 12 tablets.
5/ 500 mg 1-2 tablets every 4-6 hours. 8 tablets.
7.5/325 mg 1 tablet every 4-6 hours. 8 tablets.
7.5/500 mg 1 tablet every 4-6 hours. 6 tablets.
7.5/650 mg 1 tablet every 4-6 hours. 6 tablets.
7.5/750 mg 1 tablet every 4-6 hours. 5 tablets.
10/325 mg 1 tablet every 4-6 hours. 6 tablets.
10/500 mg 1 tablet every 4-6 hours. 6 tablets.
10/650 mg 1 tablet every 4-6 hours. 6 tablets.
10/660 mg 1 tablet every 4-6 hours. 6 tablets.
10/750 mg 1 tablet every 4-6 hours. 5 tablets.


  • Maximum Dosage Limits Note there is no maximum daily dose for hydrocodone
    • Adults: 4 grams/day acetaminophen
    • Elderly: 4 grams/day acetaminophen
    • Adolescents and children : [13]
      • Adolescents >= 46 kg (101 pounds): acetaminophen 3 g/day by mouth;.
      • Adolescents or children >= 2 years and 32—45 kg (70—100 pounds): acetaminophen 2 g/day by mouth
      • Children >= 2 years and 23—31 kg (51—69 pounds): acetaminophen 1.5 g/day by mouth
      • Children >= 2 years and 16—22 kg (35—50 pounds): acetaminophen 1 g/day by mouth
      • Children >= 2 years and 12—15 kg (27—34 pounds): acetaminophen 750 mg/day by mouth
      • Children < 2 years or < 12 kg: No data


  • Dosage Adjustment
    • Renal insufficiency: No specific recommendations are obtainable. Use clinical judgment.
    • Hepatic insufficiency: No specific recommendations are obtainable. Use clinical judgment.
    • Hemodialysis: No specific recommendations are obtainable. Use clinical judgment.
    • Geriatric: No specific recommendations are obtainable. Use clinical judgment.
    • Pediatric: See above
    • Gender: No Data

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Administration

  • Route: Oral
  • Method: Take as directed with a glass of water
  • Special considerations: Take with food or milk to decrease stomach upset.

May be habit-forming


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Monitoring Parameters

  • Serum Creatinine
  • Respiratory rate
  • BUN
  • LFTs


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Contraindications/Precautions

Contraindications

  • Should not be prescribed for a patient who has a history of a hypersensitivity to hydrocodone or to acetaminophen
  • Should not be prescribed for a patient who has a history of a hypersensitivity to another opioid because cross-sensitivity may be an issue.[2]


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Warnings

  • Respiratory depression- at high doses or in patients sensitive to the effects of hydrocodone, this drug may produce respiratory depression or irregular breathing
  • Head injury- patients with a head injury or increased intracranial pressure, may be more subject to this drug's predisposition to increase cerebrospinal fluid pressure. Additionally, this drug tends to produce more severe adverse effects in this population including respiratory depression
  • Acute abdominal conditions- The use of this medication may make the diagnosis of acute abdominal conditions more difficult.[2]


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Precautions

  • Use with caution in the elderly, those with severe renal or hepatic dysfunction, hypothyroidism, Addison’s disease, prostatic hypertrophy, or urethral stricture.
  • Use with caution in patients with pulmonary disease and in patients who are post-op.[2]


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Pregnancy indications

  • Pregnancy category: Category C infants born to mothers who take opioids during pregnancy will be physically dependent when they are born. They will undergo withdrawal including irritability, crying, tremors, elevated respiratory rate, sneezing, yawning, vomiting, diarrhea and fever.[2]
  • Teratogenicity: No well controlled studies.[2]

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Breast-feeding indications

  • Secretion into breast milk: Acetaminophen is excreted in breast milk; however the impact on infants is unknown. It is unknown if hydrocodone is excreted in breast milk.[2]

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Drug-Drug Interactions

Hydrocodone Bitartrate and Acetaminophen Drug/Drug Interaction Chart
Severity Level Click here to see Severity Level Legend Increased Effect/Toxicity Decreased Effect
4 None. naltrexone[14] block action, can lead to withdrawal symptoms. nalmefene[14] block action, can lead to withdrawal symptoms. naloxone[14] block action, can lead to withdrawal symptoms.
3 Analgesics such as buprenorphine, butorphanol, nalbuphine, or pentazocine [15] may cause additive CNS depressive effects, e.g. drowsiness, respiratory depression, hypotension. Propoxyphene [16] Additive CNS effects. Acetaminophen[17][18] can decrease glutathione which may lead to increase production of a hepatotoxic metabolite. Busulfan[15] increases the risk of hepatotoxicity. Tramadol,monoamine oxidase inhibitors or tricyclic antidepressants [19] May cause additive sedation. Imatinib[20][21] increases the risk of hepatotoxicity. Isoniazid[22][7][9] increases the risk of hepatotoxicity. None.
2 Diflunisal[10] increased risk of hepatotoxicity because diflunisal increases the concentrations of acetaminophen. Lamotrigine [23] increase risk of hepatotoxicity. Rifampin and rifabutin [14][24][25] increased liver toxicity and decreased analgesic effects of acetaminophen.Warfarin[26][27] increase risk of bleeding. Salicylates[28][29] Combination increases risk of nephropathy. Narcotic analgesics[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Antipsychotics[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. anti-anxiety agents[15] block action, can lead to withdrawal symptoms. CNS depressants[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Amoxapine[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Clozapine[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Droperidol[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. entacapone[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Maprotiline[15] block action, can lead to withdrawal symptoms. Nefazodone[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Olanzapine[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. phenothiazines[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. pimozide[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Pregabalin[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Quetiapine[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Risperidone[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Skeletal muscle relaxants[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. trazodone[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. amiodarone[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . Fluoxetine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . paroxetine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced Thioridazine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . Quinidine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . bupropion[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . chloroquine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . haloperidol[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . Ritonavir[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . Terbinafine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . Propafenone[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . Quinacrine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . Quinine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . delavirdine[15] This drug inhibits CYP2D6 and can increase the plasma level of hydrocodone acetaminophen leading to toxicity. The dosage of hydocodone acetaminophen may need to be reduced . nabilone[15][30] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. chlorpheniramine[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Diphenhydramine[15] may potentiate additive CNS depression, dose reductions in one or both agents may be indicated. Antidiarrheals[15] constipation, additive depressant effects. antimuscarinics[15] constipation, additive depressant effects. Cholestyramine [31][32] decreases the intestinal adsorption of acetaminophen. Lamotrigine[23] decreases the AUC of lamotrigine by 20% when given with acetaminophen. Rifampin and rifabutin[14][24][25] increased liver toxicity and decreased analgesic effects of acetaminophen. Carbamazepine[15] Induce cytochrome P450 isoenzymes, may lead to altered clinical response with reduction in analgesia and may increase acetaminophen toxicity. Oxcarbazepine[15] Induce cytochrome P450 isoenzymes, may lead to altered clinical response with reduction in analgesia and may increase acetaminophen toxicity. Ethotoin[15] Induce cytochrome P450 isoenzymes, may lead to altered clinical response with reduction in analgesia and may increase acetaminophen toxicity. Phenytoin[33] Induce cytochrome P450 isoenzymes, may lead to altered clinical response with reduction in analgesia and may increase acetaminophen toxicity. Fosphenytoin[33] Induce cytochrome P450 isoenzymes, may lead to altered clinical response with reduction in analgesia and may increase acetaminophen toxicity. rifapentine[15] Induce cytochrome P450 isoenzymes, may lead to altered clinical response with reduction in analgesia and may increase acetaminophen toxicity.
1 Carbamazepine, Oxcarbazepine, barbiturates and phenytoin or Fosphenytoin[33][34] increase the risk of hepatotoxicity because these drugs induce CYP2E1 and CYP1A2. Cimetidine[35] mild-moderate CYP2D6 inhibitor. None.



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Drug-Food-Herb Interactions

Hydrocodone Bitartrate and Acetaminophen Drug/Food/Herb Interaction Chart
Severity Level Click here to see Severity Level Legend Increased Effect/Toxicity Decreased Effect
4 None. None.
3 Ethanol[36][5][6] Can increase CNS depressive effects, e.g. drowsiness, confusion, respiratory depression, hypotension. Increased risk of hepatotoxicity, especially in chronic or heavy users of alcohol. None.
2 Tobacco,[37] [34] smoking induces CYP1A2, thus increasing the possibility of development of hepatotoxicity from acetaminophen. Valerian[38] May increase depressant, sedative effects. None.
1 St John's Wort,[39] [40] increased risk of hepatotoxicity . Echinacea and kava kava[41] increased risk of hepatotoxicity. Ginkgo[41] increased risk of bleeding. None.

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Adverse Reactions/Side Effects

Hydrocodone/Acetaminophen is generally well tolerated with the most common reactions being dizziness, vomiting, sedation, and nausea. Side effects may be more pronounced in patients with a genetic alteration of CYP2D6.[2]


Hydrocodone Bitartrate and Acetaminophen Adverse Reactions Chart
Incidence Body System Adverse Reactions
> 10 % CNS Drowsiness, Mental clouding, Dizziness, Sedation, Nausea
2-10% CNS Lethargy, Impairment of mental and physical performance
CV
Dermatologic Skin rash, Pruritis
GI Constipation, Vomiting
GU Ureteral spasm, Urinary retention
Neuromuscular & skeletal
Respiratory Respiratory depression
Misc List misc AEs
< 2% All Anxiety, Fear, Dependence, Mood alteration, Hearing impairment (with overdose)


Abuse: Psychic dependence is not common when hydrocodone is used as directed for a small length of time.

Physical dependence is defined by the need for continued administration to prevent the physical signs and symptoms of withdrawal. This is typically seen after weeks of chronic use of opioids.

Tolerance is defined by the person's need for increasingly larger doses to obtain the same effects as they did initially, on the smaller daily doses.[2]


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Overdosage Measures

Symptoms and signs of hydrocodone overdose include respiratory depression, cyanosis, somnolence, coma, muscle flaccidity; skin is cool to the touch, slow heart rate, low blood pressure. If the overdosage is very severe, it can result in apnea, cardiac arrest and death.[2]

Symptoms and signs of acetaminophen toxicity: Initially present with nausea, vomiting and sweating and then may cause hepatic necrosis which may be fatal. It may take 2-3 days before the hepatic involvement is realized. Other signs include renal tubular necrosis, and hypoglycemic coma and thrombocytopenia.[2] The typical toxic dose is greater than 10 grams. Hepatic enzymes should be monitored throughout treatment of overdose.[2]

If the drug was recently ingested, vomiting should be induced with syrup of ipecac. The hypotension should be corrected with fluids, though vasopressors may be needed.

If hypoprothrombinemia occurs, vitamin K should be administered.[2]

Naloxone 0.4-2 mg can be given if the patient is suffering from respiratory depression or coma. Caution because naloxone has a shorter half-life than hydrocodone.[2]

If the dose of acetaminophen has exceeded 140mg/kg, then acetylcysteine should be given. [2] Methylene blue should be administered IV (slowly) if methemoglobinemia is greater than 30%.[2]


Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management.


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Product Information and Distribution

Hydrocodone Bitartrate and Acetaminophen Product Availability Information
Name Manufacturer Dosage Form Strength Quantity NDC Storage
Hydrocodone Bitartrate and Acetaminophen[2] Mallinckrodt Inc. Oral Tablets 5/325 mg 100 0406-0365-01 20-25°C (68-77°F)
100 blister Pk 0406-0365-62
5/500 mg 100 0406-0357-01
500 0406-0357-05
100 blister Pk 0406-0357-62
7.5/325 mg 100 0406-0366-01
100 blister Pk 0406-0366-62
7.5/500 mg 100 0406-0358-01
500 0406-0358-05
100 blister Pk 0406-0358-62
7.5/650 mg 100 0406-0359-01
500 0406-0359-05
7.5/750 mg 100 0406-0360-01
500 0406-360-05
10/325 mg 90 0406-0367-01
500 0406-0367-05
100 blister Pk 0406-0367-62
10/500 mg 90 0406-0363-01
500 0406-0363-05
100 blister Pk 0406-0363-62
10/650 mg 100 0406-0361-01
500 0406-0361-05
100 blister Pk 0406-0361-62
10/660 mg 100 0406-0362-01
10/750 mg 90 0406-0364-01
Hydrocodone Bitartrate and Acetaminophen Product Availability Information
Name Manufacturer Dosage Form Strength Quantity NDC Storage
Hydrocodone Bitartrate and Acetaminophen[42] Watson Oral Tablets 7.5/650 mg 100 0591-0502-01 15-30°C (59-86°F)
500 0591-0502-05
10/650 mg 100 0591-0503-01
500 0591-0503-05
10/650 mg 100 0591-0517-01
500 0591-0517-05


  • Manufacturers/Distributors

Abbott Pharmaceutical, Endo Pharmaceuticals Inc, Forest Pharmaceuticals Inc, Magna Pharmaceuticals, Major Pharmaceuticals Inc, Mallinckrodt, Qualitest Pharmaceuticals Inc, Schwarz Pharma Inc, UCB Pharma Inc,Victory Pharma, Inc., Watson Pharmaceuticals Inc, Xanodyne Pharmaceutical, List May not be all inclusive


  • Inactive ingredients

Crospovidone, Magnesium stearate, Microcrystalline cellulose, Providone, Pregelatinized starch, Silicon dioxide, Stearic acid

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Pharmacogenomic information

Hydrocodone/Acetaminophen Pharmacogenomic Information

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Patient Information

  • May be taken with or without food. Food or milk may decrease the chance that this medication will upset your stomach
  • Swallow tablets with a glass of water
  • May cause dizziness. Use caution when driving or operating heavy machinery.
  • Take for the shortest time necessary to alleviate pain or cough to decrease the chance of dependence
  • May cause nausea, vomiting and somnolence
  • Avoid alcohol


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References

  1. ↑ 1.0 1.1 1.2 1.3 Hutchinson MR, Menelaou A, Foster DJ, Coller JK, Somogyi AA, Hutchinson MR, et al. CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. British Journal of Clinical Pharmacology. 2004 Mar;57(3):287-97.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 Mallinckrodt Inc. Hydrocodone Bitartrate and Acetaminophen Tablets USP. St. Louis, Missouri: Mallinckrodt.
  3. ↑ 3.0 3.1 3.2 3.3 Litkowski LJ, Christensen SE, Adamson DN, Van Dyke T, Han SH, Newman KB, et al. Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: a randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model. Clinical Therapeutics. 2005 Apr;27(4):418-29.
  4. ↑ 4.0 4.1 4.2 Marco CA, Plewa MC, Buderer N, Black C, Roberts A. Comparison of oxycodone and hydrocodone for the treatment of acute pain associated with fractures: a double-blind, randomized, controlled trial. Acad Emerg Med. 2005 Apr;12(4):282-8.
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 Hardman JG L, LE, editor. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001.
  6. ↑ 6.0 6.1 6.2 6.3 Armstrong SC, Cozza KL. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II. Psychosomatics. 2003 Nov-Dec;44(6):515-20.
  7. ↑ 7.0 7.1 7.2 Otton SV, Schadel M, Cheung SW, Kaplan HL, Busto UE, Sellers EM. CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clinical pharmacology and therapeutics. 1993 Nov;54(5):463-72.
  8. ↑ 8.0 8.1 8.2 Burton M, Shaw L, Schentag J, Evans W, editors. Applied Pharmacokinetics and Pharmacodynamics: Principles of therapeutic drug monitoring. 4th ed. Baltimore: Lippincott Williams and Wilkins; 2006.
  9. ↑ 9.0 9.1 Cone EJ, Darwin WD, Gorodetzky CW. Comparative metabolism of codeine in man, rat, dog, guinea-pig and rabbit: identification of four new metabolites. The Journal of pharmacy and pharmacology. 1979 May;31(5):314-7.
  10. ↑ 10.0 10.1 Vasist L PP. Codeine. 21 March 2005 [cited 12 March 2007]; Available from: http://hopkins-hivguide.org/drug/analgesics/full_codeine.html?contentInstanceId=29682&siteId=7151.
  11. ↑ 11.0 11.1 11.2 Adams NJ, Plane MB, Fleming MF, Mundt MP, Saunders LA, Stauffacher EA. Opioids and the treatment of chronic pain in a primary care sample. Journal of pain and symptom management. 2001 Sep;22(3):791-6.
  12. ↑ Fricke JR, Jr., Karim R, Jordan D, Rosenthal N. A double-blind, single-dose comparison of the analgesic efficacy of tramadol/acetaminophen combination tablets, hydrocodone/acetaminophen combination tablets, and placebo after oral surgery. Clin Ther. 2002 Jun;24(6):953-68.
  13. ↑ Hydrocodone Bitartrate and Acetaminophen [Lortab] Clinical Pharmacology 2007 [cited 12 March 2007]; Available from: http://www.clinicalpharmacology.com
  14. ↑ 14.0 14.1 14.2 14.3 14.4 Stephenson I, Qualie M, Wiselka MJ. Hepatic failure and encephalopathy attributed to an interaction between acetaminophen and rifampicin. The American journal of gastroenterology. 2001 Apr;96(4):1310-1.
  15. ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 15.13 15.14 15.15 15.16 15.17 15.18 15.19 15.20 15.21 15.22 15.23 15.24 15.25 15.26 15.27 15.28 15.29 15.30 15.31 15.32 15.33 15.34 15.35 15.36 15.37 15.38 15.39 15.40 15.41 15.42 Wishart DS et al., DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006 1;34
  16. ↑ Darvon-N® package insert. Indianapolis, IN: Eli Lilly & Company;2003 Sep.
  17. ↑ Kurtovic J, Riordan SM. Paracetamol-induced hepatotoxicity at recommended dosage. J Intern Med 2003;253:240—3.
  18. ↑ Jones A. Over-the-counter analgesics: a toxicology perspective. American journal of therapeutics. 2002 May-Jun;9(3):245-57.
  19. ↑ Hydrocodone Bitartrate and Acetaminophen. In: Package ins