(hye droe KOE done & klor fen IR a meen)
Symptomatic relief of cough and upper respiratory symptoms associated with cold and allergy
Hypersensitivity to hydrocodone, chlorpheniramine, or any component of the formulation
ER capsule and ER suspension: Additional contraindications: Use in children <6 years of age due to the risk of fatal respiratory depression
Solution: Additional contraindications: Concurrent use during or within 14 days of MAO inhibitor therapy, narrow angle glaucoma, urinary retention, severe hypertension, severe coronary artery disease
Antitussive/antihistamine: Oral:
Capsules: Extended release: Hydrocodone 10 mg and chlorpheniramine 8 mg: One capsule every 12 hours (maximum: 2 capsules daily)
Solution: Immediate release: 5 mL every 4-6 hours as needed; do not exceed 20 mL daily
Suspension: Extended release: 5 mL every 12 hours; do not exceed 10 mL daily
Refer to adult dosing.
Antitussive/antihistamine: Oral: Note: Solution is not indicated for patients <18 years.
Children 6 to <12 years:
Capsules: Extended release: Hydrocodone 5 mg and chlorpheniramine 4 mg: One capsule every 12 hours (maximum: 2 capsules daily)
Suspension: Extended release: 2.5 mL every 12 hours; do not exceed 5 mL daily
Children ≥12 years and Adolescents: Refer to adult dosing.
Capsule: Administer without regard to meals. Do not dilute with fluid or mix with other medications. Do not give more frequently than every 12 hours.
Solution: To prevent overdose, use calibrated oral syringe to measure doses.
Suspension: Shake well before using. Use calibrated oral syringe to measure doses. Do not give more frequently than every 12 hours.
May be taken without regard to meals.
Store at 20 � �C to 25 � �C (68 � �F to 77 � �F); protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Extended Release 12 Hour, Oral:
TussiCaps: Hydrocodone polistirex [equivalent to hydrocodone bitartrate 5 mg] and chlorpheniramine polistirex [equivalent to chlorpheniramine maleate 4 mg], Hydrocodone polistirex [equivalent to hydrocodone bitartrate 10 mg] and chlorpheniramine polistirex [equivalent to chlorpheniramine maleate 8 mg] [contains fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #10 (quinoline yellow), fd&c yellow #10 aluminum lake]
Liquid Extended Release, Oral:
Tussionex Pennkinetic ER: Hydrocodone polistirex [equivalent to hydrocodone bitartrate 10 mg] and chlorpheniramine polistirex [equivalent to chlorpheniramine maleate 8 mg] per 5 mL (115 mL) [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow), methylparaben, polyethylene glycol, polysorbate 80, propylene glycol, propylparaben]
Generic: Hydrocodone polistirex [equivalent to hydrocodone bitartrate 10 mg] and chlorpheniramine polistirex [equivalent to chlorpheniramine maleate 8 mg] per 5 mL (115 mL, 473 mL)
Solution, Oral:
Vituz: Hydrocodone bitartrate 5 mg and chlorpheniramine maleate 4 mg per 5 mL (480 mL) [contains methylparaben, propylene glycol, propylparaben, saccharin sodium; grape flavor]
Suspension Extended Release, Oral:
Generic: Hydrocodone polistirex [equivalent to hydrocodone bitartrate 10 mg] and chlorpheniramine polistirex [equivalent to chlorpheniramine maleate 8 mg] per 5 mL (115 mL, 473 mL)
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Ajmaline: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Alcohol (Ethyl): May enhance the CNS depressant effect of HYDROcodone. Alcohol (Ethyl) may increase the serum concentration of HYDROcodone. Management: Patients using the Zohydro ER brand of extended-release hydrocodone must not consume alcohol or alcohol-containing products due to possibly fatal outcomes. Other hydrocodone products are also expected to interact, but to a less significant degree. Avoid combination
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Consider therapy modification
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ceritinib: May increase the serum concentration of CYP3A4 Substrates. Management: Use of ceritinib with a narrow therapeutic index CYP3A substrate (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) should be avoided when possible. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
CNS Depressants: May enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of HYDROcodone. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of HYDROcodone. Monitor therapy
CYP3A4 Inducers (Weak): May decrease the serum concentration of HYDROcodone. Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of HYDROcodone. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of HYDROcodone. Monitor therapy
CYP3A4 Inhibitors (Weak): May increase the serum concentration of HYDROcodone. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Avoid combination
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MAO Inhibitors: May enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Consider therapy modification
Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Ombitasvir, Paritaprevir, and Ritonavir: May increase the serum concentration of HYDROcodone. Management: Reduce the hydrocodone dose by 50% during concurrent use of ombitasvir, paritaprevir, and ritonavir; monitor closely for both analgesic effectiveness and for signs of toxicity or withdrawal. Consider therapy modification
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of HYDROcodone. Management: Reduce the hydrocodone dose by 50% during concurrent use of ombitasvir, paritaprevir, ritonavir, and dasabuvir; monitor closely for both analgesic effectiveness and for signs of toxicity or withdrawal. Consider therapy modification
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Thioridazine: Chlorpheniramine may enhance the arrhythmogenic effect of Thioridazine. Thioridazine may increase the serum concentration of Chlorpheniramine. Management: Avoid this combination when possible. If used, monitor closely for arrhythmia as well as general toxicity of chlorpheniramine. Consider therapy modification
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Signs or symptoms of hypogonadism or hypoadrenalism (Brennan, 2013)
Chlorpheniramine: May suppress the wheal and flare reactions to skin test antigens.
Also refer to Chlorpheniramine monograph. Frequency not defined.
Cardiovascular: Chest tightness
Central nervous system: Agitation, anxiety, confusion, decreased mental acuity, dizziness, drowsiness, drug dependence, dysphoria, euphoria, fear, headache, irritability, lethargy, mood changes, sedation
Dermatologic: Diaphoresis, erythema, pruritus, skin rash, urticaria
Gastrointestinal: Abdominal distention, abdominal pain, acute pancreatitis, constipation, decreased appetite, dyspepsia, epigastric distress, nausea, vomiting, xerostomia
Genitourinary: Dysuria, ureteral spasm, urinary frequency, urinary hesitancy, urinary retention
Neuromuscular & skeletal: Facial dyskinesia, tremor, vesicle sphincter spasm
Ophthalmic: Blurred vision, diplopia, visual disturbance
Respiratory: Dry throat, dyspnea, laryngismus, respiratory depression, wheezing
<1% (Limited to important or life-threatening): Hypogonadism (Brennan 2013; Debono 2011)
Concerns related to adverse effects:
- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
- Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydromorphone, levorphanol, morphine, oxycodone, oxymorphone).
- Respiratory depression: May cause dose-related respiratory depression, risk increased in children, elderly, patients with pulmonary disease, and when used postoperatively.
Disease-related concerns:
- Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
- Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addisons disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan, 2013).
- Biliary tract impairment: Use hydrocodone with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.
- Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
- Head trauma: Avoid use in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
- Hepatic impairment: Use with caution in patients with severe hepatic impairment.
- Increased intraocular pressure/glaucoma: Use with caution in patients with increased intraocular pressure or glaucoma. Use contraindicated in narrow angle glaucoma (Vituz manufacturer 's labeling).
- Obstructive bowel disease: Use with caution in patients with obstructive bowel disease.
- Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction. Use contraindicated in patients with urinary retention (Vituz manufacturer 's labeling).
- Renal impairment: Use with caution in patients with severe renal impairment.
- Respiratory disease: Use with caution in patients with pulmonary disease (including asthma) or decreased ventilatory function; dose-related respiratory depression occurs.
- Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
- Anticholinergics: Concurrent use may result in paralytic ileus; use caution.
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
- CYP2D6 "poor metabolizers " �: Due to the role of CYP2D6 in the metabolism of hydrocodone to hydromorphone (an active metabolite with higher binding affinity to mu-opioid receptors compared to hydrocodone), patients with genetic variations of CYP2D6, including "poor metabolizers " � or "extensive metabolizers, " � may have decreased or increased hydromorphone formation, respectively. Variable effects in positive and negative opioid effects have been reported in these patients; however, limited data exists to determine if clinically significant differences of analgesia and toxicity can be predicted based on CYP2D6 phenotype (Hutchinson, 2004; Otton, 1993; Zhou, 2009).
- Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
- Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.
- Neonates: Neonatal withdrawal syndrome: After chronic maternal exposure to opioids, neonatal withdrawal syndrome may occur in the newborn; monitor neonate closely. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn. Opioid withdrawal syndrome in the neonate, unlike in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts.
- Pediatric: Use with caution in children ≥6 years of age; may be more sensitive to adverse effects. Contraindicated in children <6 years of age.
Dosage form specific issues:
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer 's labeling.
- Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP, 1997; Zar, 2007).
Other warnings/precautions:
- Cough: Appropriate use: Underlying cause of cough should be determined prior to prescribing.
- Frequency of dosing: Appropriate use: Extended release capsules and suspension should not be given any more frequently than every 12 hours.
- Measuring device: Appropriate use: Accurate measuring devices should be used to measure solution and suspension doses. Calibrated oral syringes are most accurate. Household teaspoons and tablespoons are not recommended for measurement.
C
Animal reproduction studies have not been conducted with this combination product. See individual agents.
Hydrocodone binds to opiate receptors in the CNS, altering the perception of and response to pain; suppresses cough in medullary center; produces generalized CNS depression
Chlorpheniramine competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract
Hydrocodone: Hepatic; O-demethylation via primarily CYP2D6 to hydromorphone (major, active metabolite with ~10- to 33-fold higher or as much as a >100-fold higher binding affinity for the mu-opioid receptor than hydrocodone); N-demethylation via CYP3A4 to norhydrocodone (major metabolite); and ~40% of metabolism/clearance occurs via other non-CYP pathways, including 6-ketosteroid reduction to 6-alpha-hydrocol and 6-beta-hydrocol, and other elimination pathways (eg, fecal, biliary, intestinal, renal) (Hutchinson, 2004; Volpe, 2011; Zhou, 2009)
Hydrocodone: Urine (26% of single dose in 72 hours, with ~12% as unchanged drug, 5% as norhydrocodone, 4% as conjugated hydrocodone, 3% as 6-hydrocodol, and 0.21% as conjugated 6-hydromorphol (Zhou, 2009)
Hydrocodone: Plasma: ~1-2 hours (solution); ~3 hours (capsules, suspension)
Hydrocodone: 4-8 hours
Hydrocodone: ~4-5 hours
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, anxiety, or sweating a lot. Have patient report immediately to prescriber severe dizziness, passing out, angina, tachycardia, difficulty breathing, slow breathing, shallow breathing, confusion, arrhythmia, hallucinations, mood changes, seizures, severe abdominal pain, severe headache, severe loss of strength and energy, severe constipation, difficult urination, tremors, vision changes, severe vomiting, or severe nausea (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.