Hydrocodone and chlorpheniramine - Uses, Dose, MOA, Brands

Hydrocodone and chlorpheniramine are available in combination as tablets (including extended-release tablets) and syrups (suspensions). It is used for the symptomatic treatment of patients with cough and upper respiratory tract symptoms.

Hydrocodone and chlorpheniramine Uses:

  • Cough and upper respiratory tract symptoms:

    • It is indicated for temporary relief of cough and upper respiratory tract symptoms associated with allergy or the common cold
    • Limitations of use: It should be given in patients where the benefits of cough suppression are more than risks, and cause of cough is known and opioid use is indicated

Hydrocodone and chlorpheniramine Dose in Adults

Note: Vituz has been discontinued in the US for more than 1 year.

Hydrocodone and chlorpheniramine Dose in the treatment of cough and upper respiratory tract symptoms: Oral:

Note: Dosage units are different in different product formulations (extended-release vs immediate release); use caution when verifying dose with product formulation.

  • Extended-release:

    • Capsules (hydrocodone 10 mg and chlorpheniramine 8 mg per capsule): 1 capsule twice a day
      • Maximum: 2 capsules (hydrocodone 20 mg/chlorpheniramine 16 mg) twice day
    • Suspension (hydrocodone 10 mg and chlorpheniramine 8 mg per 5 mL): 5 mL twice a day
      • Maximum: 10 mL/day (hydrocodone 20 mg/chlorpheniramine 16 mg)
  • Immediate release:

    • Oral solution (hydrocodone 5 mg and chlorpheniramine 4 mg per 5 mL): 5 mL every 4 - 6 hours as needed
      • Maximum: 20 mL/day (hydrocodone 20 mg/chlorpheniramine 16 mg).
  • Discontinuation of therapy:

    • After prolonged use of opioids, gradually reduce the dose by 25% - 50% every 2 - 4 days; monitor for signs/symptoms of withdrawal.
    • In case of the development of withdrawal symptoms, increase the dose to the prior level and then reduce the dose more slowly at prolonged intervals.

Hydrocodone and chlorpheniramine Dose in Children

Note: In 2018 FDA restricted its use as cough or cold products above 18 years of age because of the risk of serious adverse effects (slowed or difficult breathing, misuse, abuse, addiction, overdose, and death)

Hydrocodone and chlorpheniramine Dose in the treatment of Cough (antitussive/antihistamine):

Note: Oral liquid products (immediate-release solution and extended-release suspension) are NOT indicated for patients <18 years.

  • Extended-release capsules: Oral:

    • Children 6 to <12 years: Half-strength capsule (Hydrocodone 5 mg, chlorpheniramine 4 mg per capsule): twice daily
      • Maximum daily dose: 2 capsules/24 hours
    • Children ≥12 years and Adolescents: Full-strength capsule (Hydrocodone 10 mg and chlorpheniramine 8 mg per capsule): twice daily
      • Maximum daily dose: 2 capsules/24 hours

Pregnancy Risk Factor C

  • [US Boxed Warning] - Pregnancy is not recommended.
  • After prolonged opioid use by the mother during pregnancy, withdrawal syndrome can develop in neonates. 
  • This can be fatal if it is not treated as per the protocols of neonatology specialists.
  • Pregnant women who require prolonged opioid therapy should be notified of the risks to their baby.
  • Talk to individual agents.

Use during breastfeeding:

  • Breast milk contains hydrocodone and chlorpheniramine.
  • Breastfeeding infants can experience serious adverse reactions
  • It is not advised to breastfeed, as there are serious adverse side effects.

Dose in Kidney Disease:

The manufacturer has not provided any dose adjustment in labeling; use cautiously in severe renal impairment.

Dose in Liver disease:

The manufacturer has not provided any dose adjustment in labeling; use cautiously in severe liver impairment.


Also, refer to the Chlorpheniramine monograph.

Side effects of Hydrocodone and chlorpheniramine:

  • 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

Contraindications to Hydrocodone and chlorpheniramine:

  • Hypersensitivity to any ingredient of the formulation
  • Children under 6 years old (ER formulations).

Additional contraindications to oral solution and ER suspension

  • Acute or severe bronchial asthma in an unmonitored setting, or without resuscitative devices
  • Paralytic ileus, GI obstruction (known or suspected).
  • Respiratory depression is a serious problem

There is not much evidence of cross-reactivity between opioids and allergens. Cross-sensitivity cannot be excluded with absolute certainty, however.

Warnings and precautions

  • CNS depression:

    • CNS depression can result from opioid use, which may lead to impairment of mental or physical abilities.
    • Patients should be warned about driving or operating machinery that requires mental alertness.
  • Hypotension

    • Opioid abuse can cause severe hypotension (including orthostatic Hypotension and syncope).
    • Patients with hypovolemia, heart disease (including acute MI) or medications that can exaggerate hypotensive effects (such as phenothiazines and general anesthetics) should be cautious.
    • After dose titration or initiation, monitor for hypotension symptoms.
    • If the patient is experiencing a circulatory crisis, do not use it.
  • Phenanthrene hypersensitivity:

    • Use cautiously if the patient has hypersensitivity reactions to other phenanthrene-derivative opioid agonists like codeine, hydromorphone, levorphanol, morphine, oxycodone, oxymorphone.
  • Respiratory depression [US Boxed Warning]

    • Use of opioids can cause severe, life-threatening or fatal respiratory depression, particularly at the beginning of treatment or when patients are receiving higher doses
    • Pay attention to respiratory depression
    • Due to the carbon dioxide retention and opioid, the patient might experience an additional sedative effect.
  • Conditions abdominales:

    • It can be used to relieve pain and may also mask the clinical course or diagnosis of acute abdominal conditions.
  • Adrenocortical Insufficiency

    • Avoid using this product if you have adrenal insufficiency or Addison disease.
  • Insufficiency of the biliary tract:

    • Avoid using opioids in the presence of biliary dysfunction or acute pancreatitis.
  • CNS depression/coma:

    • If the patient is experiencing impaired consciousness or coma, do not use it. Significant intracranial effects can be caused by CO2 retention.
  • Delirium tremens:

    • Avoid delirium tremens.
  • Head trauma

    • If the patient has suffered a head injury, intracranial lesion, or severe elevation of intracranial Pressure (ICP), do not use.
  • Hepatic impairment

    • In severe hepatic impairment, use caution
  • Glaucoma/increased intraocular pressure

    • Take care when using glaucoma or increased intraocular pressure.
    • Contraindicated for narrow-angle glaucoma
  • Obesity:

    • Be cautious with patients who are morbidly obese.
  • Obstructive bowel Disease:

    • Be careful with obstructive intestinal disease
  • Prostatic hyperplasia/urinary block:

    • Avoid prostatic hyperplasia or urinary stricture.
    • Patients with urinary retention should not use the oral solution.
  • Psychosis:

    • Avoid toxic psychosis.
  • Renal impairment

    • For severe renal impairment, be careful
  • Respiratory disease

    • Monitor closely if you suspect that the patient may have respiratory depression.
      • COPD and cor Pulmonale
      • Patients with significantly reduced respiratory reserve, hypoxia or hypercarbia or pre-existing respiratory depression
    • Even at therapeutic doses, respiratory depression can still occur.
  • Seizures:

    • Be cautious if you have a history of seizure disorder. This could lead to an exacerbation.
  • Thyroid dysfunction:

    • Thyroid dysfunction: Use caution

Hydrocodone and chlorpheniramine: Drug Interaction

Risk Factor C (Monitor therapy)

Acetylcholinesterase Inhibitors

May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.

Ajmaline

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Alizapride

May enhance the CNS depressant effect of CNS Depressants.

Amantadine

May enhance the anticholinergic effect of Anticholinergic Agents.

Amezinium

Antihistamines may enhance the stimulatory effect of Amezinium.

Amphetamines

May enhance the analgesic effect of Opioid Agonists.

Amphetamines

May diminish the sedative effect of Antihistamines.

Anticholinergic Agents

May enhance the adverse/toxic effect of other Anticholinergic Agents.

Anticholinergic Agents

May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination.

Aprepitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Betahistine

Antihistamines may diminish the therapeutic effect of Betahistine.

Bosentan

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Botulinum Toxin-Containing Products

May enhance the anticholinergic effect of Anticholinergic Agents.

Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

Bromopride

May enhance the CNS depressant effect of CNS Depressants.

Cannabidiol

May enhance the CNS depressant effect of CNS Depressants.

Cannabis

May enhance the CNS depressant effect of CNS Depressants.

Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

Clofazimine

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Cobicistat

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

CYP2D6 Inhibitors (Moderate)

May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).

CYP3A4 Inducers (Moderate)

May decrease the serum concentration of HYDROcodone.

CYP3A4 Inducers (Strong)

May decrease the serum concentration of HYDROcodone.

CYP3A4 Inhibitors (Moderate)

May increase the serum concentration of HYDROcodone.

CYP3A4 Inhibitors (Strong)

May increase the serum concentration of HYDROcodone.

Darunavir

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Deferasirox

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Desmopressin

Opioid Agonists may enhance the adverse/toxic effect of Desmopressin.

Dimethindene (Topical)

May enhance the CNS depressant effect of CNS Depressants.

Diuretics

Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.

Dronabinol

May enhance the CNS depressant effect of CNS Depressants.

Duvelisib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Erdafitinib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Erdafitinib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Fosaprepitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Fosnetupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Fosphenytoin-Phenytoin

Chlorpheniramine may increase the serum concentration of Fosphenytoin-Phenytoin.

Gastrointestinal Agents (Prokinetic)

Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

Gastrointestinal Agents (Prokinetic)

Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

Glucagon

Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.

Imatinib

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Itopride

Anticholinergic Agents may diminish the therapeutic effect of Itopride.

Ivosidenib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Kava Kava

May enhance the adverse/toxic effect of CNS Depressants.

Larotrectinib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Lofexidine

May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Lumefantrine

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Magnesium Sulfate

May enhance the CNS depressant effect of CNS Depressants.

MetyroSINE

CNS Depressants may enhance the sedative effect of MetyroSINE.

Minocycline

May enhance the CNS depressant effect of CNS Depressants.

Mirabegron

Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.

Nabilone

May enhance the CNS depressant effect of CNS Depressants.

Netupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Nitroglycerin

Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption.

Palbociclib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Panobinostat

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Peginterferon Alfa-2b

May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Pegvisomant

Opioid Agonists may diminish the therapeutic effect of Pegvisomant.

Perhexiline

CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Piribedil

CNS Depressants may enhance the CNS depressant effect of Piribedil.

Pramipexole

CNS Depressants may enhance the sedative effect of Pramipexole.

QuiNINE

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Ramosetron

Anticholinergic Agents may enhance the constipating effect of Ramosetron.

Ramosetron

Opioid Agonists may enhance the constipating effect of Ramosetron.

ROPINIRole

CNS Depressants may enhance the sedative effect of ROPINIRole.

Rotigotine

CNS Depressants may enhance the sedative effect of Rotigotine.

Rufinamide

May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.

Sarilumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

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.

Serotonin Modulators

Opioid Agonists may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.

Siltuximab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Simeprevir

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Succinylcholine

May enhance the bradycardic effect of Opioid Agonists.

Tetrahydrocannabinol

May enhance the CNS depressant effect of CNS Depressants.

Tetrahydrocannabinol and Cannabidiol

May enhance the CNS depressant effect of CNS Depressants.

Thiazide and Thiazide-Like Diuretics

Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics.

Tocilizumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Risk Factor D (Consider therapy modification)

Abiraterone Acetate

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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.

Alvimopan

Opioid Agonists 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.

Asunaprevir

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

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.

Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin.

Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

CNS Depressants

May enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

CYP2D6 Inhibitors (Strong)

May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).

Dabrafenib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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).

Dacomitinib

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.

Droperidol

May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Enzalutamide

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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.

Flunitrazepam

CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.

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.

HYDROcodone

CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

Lorlatinib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.

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.

MiFEPRIStone

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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.

Mitotane

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.

Monoamine Oxidase Inhibitors

May enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible.

Nalmefene

May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of nalmefene and opioid agonists. Discontinue nalmefene 1 week prior to any anticipated use of opioid agonistss. If combined, larger doses of opioid agonists will likely be required.

Naltrexone

May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations.

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.

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.

OxyCODONE

CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

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.

PHENobarbital

May enhance the CNS depressant effect of HYDROcodone. PHENobarbital may decrease the serum concentration of HYDROcodone. Management: Avoid use of hydrocodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased hydrocodone efficacy and withdrawal if combined.

Pitolisant

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.

Pramlintide

May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.

Primidone

May enhance the CNS depressant effect of HYDROcodone. Primidone may decrease the serum concentration of HYDROcodone. Management: Avoid use of hydrocodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased hydrocodone efficacy and withdrawal if combined.

Secretin

Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin.

Sincalide

Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.

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.

St John's Wort

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.

Stiripentol

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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.

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.

Tapentadol

May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

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.

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.

Risk Factor X (Avoid combination)

Aclidinium

May enhance the anticholinergic effect of Anticholinergic Agents.

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.

Azelastine (Nasal)

CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).

Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

Cimetropium

Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.

Conivaptan

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Eluxadoline

Opioid Agonists may enhance the constipating effect of Eluxadoline.

Eluxadoline

Anticholinergic Agents may enhance the constipating effect of Eluxadoline.

Fusidic Acid (Systemic)

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Glycopyrrolate (Oral Inhalation)

Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).

Glycopyrronium (Topical)

May enhance the anticholinergic effect of Anticholinergic Agents.

Idelalisib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Ipratropium (Oral Inhalation)

May enhance the anticholinergic effect of Anticholinergic Agents.

Levosulpiride

Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.

Opioids (Mixed Agonist / Antagonist)

May diminish the analgesic effect of Opioid Agonists. 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.

Orphenadrine

CNS Depressants may enhance the CNS depressant effect of Orphenadrine.

Oxatomide

May enhance the anticholinergic effect of Anticholinergic Agents.

Oxomemazine

May enhance the CNS depressant effect of CNS Depressants.

Paraldehyde

CNS Depressants may enhance the CNS depressant effect of Paraldehyde.

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.

Potassium Citrate

Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.

Revefenacin

Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.

Thalidomide

CNS Depressants may enhance the CNS depressant effect of Thalidomide.

Tiotropium

Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.

Umeclidinium

May enhance the anticholinergic effect of Anticholinergic Agents.

 

Monitoring parameters:

  • Relief of symptoms
  • Respiratory and mental status
  • Bowel function
  • Signs/symptoms of misuse, abuse, and addiction

How to administer Hydrocodone and chlorpheniramine?

Capsule:

  • Can be given with or without meals. Do not mix with fluids or other medications.

Oral solution, suspension:

  • Should be given with accurate measuring device; a household teaspoon is not accurate.
  • Can be given with or without meals. Shake well before each use; do not mix with fluid or other medications

Mechanism of action of Hydrocodone and chlorpheniramine:

  • Hydrocodone is an opioid receptor agonist that acts in Mu.
  • It binds to it in CNS and alters the perception and response of pain.
  • It suppresses coughing in the medullary centre; causes generalized CNS depression.
  • Chlorpheniramine is a competitor to histamine in H -receptor locations on effector cells of the GI tract and blood vessels.

Chlorpheniramine: See Chlorpheniramine monograph.

Hydrocodone:

Duration:

  • 4 - 8 hours

Metabolism:

  • Hepatic; By the following mechanism
    • CYP2D6: Produces hydromorphone via O-demethylation (major, active metabolite with higher binding affinity for the mu-opioid receptor than hydrocodone)
    • CYP3A4: Produces norhydrocodone by N-demethylation (major metabolite)
    • 40% of the drug is eliminated via non-CYP routes, such as 6-ketosteroid degradation to 6-alpha- and 6-beta-hydrocol and other elimination pathways (eg, fecal, biliary, intestinal, renal).

Half-life elimination:

  • About 4 - 5 hours

Time to peak, plasma:

  • About 1 - 2 hours (solution);
  • About 3 hours (capsules, suspension)

Excretion:

  • Urine contains 26% of a single dose over the course of 72 hours; this includes 12% of the drug as its unmodified form, 5% of nor-hydrocodone, 4% of conjugated hydrocodone, 3% of 6-hydrocodol, and 0.21% of conjugated 6-hydromorphol.

International Brand Names of Hydrocodone and chlorpheniramine:

  • TussiCaps
  • Tussionex Pennkinetic ER
  • Vituz

Hydrocodone and chlorpheniramine Brand Names in Pakistan:

No Brands Available in Pakistan.]