Hydrocodone, Chlorpheniramine and Pseudoephedrine

Common Cold

Hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine hydrochloride oral solution is indicated for relief of cough and nasal congestion associated with the common cold in adults 18 years of age and older.

Upper Respiratory Allergies

Hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine hydrochloride oral solution is indicated for relief of symptoms including nasal congestion associated with upper respiratory allergies in adults 18 years of age and older.

Important Limitations of Use
Not indicated for pediatric patients under 18 years of age [see Pediatric Use (8.4)].

No specific interaction studies have been conducted with hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine hydrochloride oral solution.

Opioids, Antihistamines, Antipsychotics, Anti-anxiety Agents, or Other CNS Depressants (Including Alcohol)

The use of benzodiazepines, opioids, antihistamines, antipsychotics, anti-anxiety agents, or other CNS depressants concomitantly with hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution may cause an additive CNS depressant effect, profound sedation, respiratory depression, coma, and death and should be avoided [see Warnings and Precautions (5.1)].

MAOIs and Tricyclic Antidepressants

Do not prescribe hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution if the patient is taking a prescription MAOI (i.e., certain drugs used for depression, psychiatric or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping a MAOI drug. The use of MAOIs or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone. An increase in blood pressure or hypertensive crisis may also occur when pseudoephedrine containing preparations are used with MAOIs [see Warnings and Precautions (5.8)].

Hydrocodone and chlorpheniramine should be administered cautiously to persons receiving other  anticholinergic drugs in order to avoid paralytic ileus and excessive anticholinergic effects.

Additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, or constipation) may occur when anticholinergic drugs are administered with chlorpheniramine [see Warnings and Precautions (5.7)].

Mechanism of Action

Hydrocodone is a semisynthetic narcotic antitussive and analgesic with multiple actions qualitatively similar to those of codeine. The precise mechanism of action of hydrocodone and other opiates is not known; however, hydrocodone is believed to act directly on the cough center. In excessive doses, hydrocodone will depress respiration. Hydrocodone can produce miosis, euphoria, and physical and physiological dependence.

Chlorpheniramine is an antihistamine drug (H1 receptor antagonist) that also possesses anticholinergic and sedative activity. It prevents released histamine from dilating capillaries and causing edema of the respiratory mucosa.

Pseudoephedrine hydrochloride is an orally active sympathomimetic amine and exerts a decongestant action on the nasal mucosa. Pseudoephedrine hydrochloride is recognized as an effective agent for the relief of nasal congestion due to upper respiratory allergies or common cold. Pseudoephedrine produces peripheral effects similar to those of ephedrine and central effects similar to, but less intense than, amphetamines. It has the potential for excitatory side effects.

Pharmacokinetics

Systemic exposure (in terms of peak plasma concentrations and area under plasma concentration versus time curve) of hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine hydrochloride after single dose administration of 5 mL hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine hydrochloride oral solution are equivalent to respective reference solutions of 5 mL hydrocodone bitartrate (5 mg/5 mL), 5 mL chlorpheniramine maleate (4 mg/5 mL), and 5 mL pseudoephedrine hydrochloride (60 mg/5 mL).

Hydrocodone had a mean (SD) peak plasma concentration of 10.6 (2.63) ng/mL at 1.4 (0.55) hours. The mean plasma half-life of hydrocodone is approximately 4.9 hours. Pseudoephedrine had a mean (SD) peak plasma concentration of 212 (46.2) ng/mL at 1.8 (0.56) hours. The mean plasma half-life of pseudoephedrine is approximately 5.6 hours. Chlorpheniramine had a mean (SD) plasma peak concentration of 7.20 (1.98) ng/mL at 3.5 (1.6) hours. The mean plasma half-life of chlorpheniramine is approximately 24 hours.

Specific Populations

Renal Impairment

Pseudoephedrine is primarily excreted unchanged in the urine as unchanged drug with the remainder apparently being metabolized in the liver. Therefore, pseudoephedrine may accumulate in patients with renal impairment.

hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine hydrochloride oral solution is supplied as a clear, colorless to light yellow, grape-flavored solution containing 5 mg hydrocodone bitartrate, 4 mg chlorpheniramine maleate, and 60 mg pseudoephedrine hydrochloride in each 5 mL. It is available in:

Amber HDPE bottles of one pint (480 mL): NDC 59741-267-16

Amber PET bottles of one pint (480 mL): NDC 59741-267-17

Store solution at 20° to 25°C (68° to 77°F). [USP Controlled Room Temperature.]

Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure.

[See FDA-Approved Patient Labeling]

Overdosage

Patients should be advised not to increase the dose or dosing frequency of hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution because serious adverse events such as respiratory depression may occur with overdosage [see Warnings and Precautions (5.2); Overdosage (10)].

Dosing

Patients should be advised to measure hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution with an accurate milliliter measuring device. Patients should be informed that a household teaspoon is not an accurate measuring device and could lead to overdosage, especially when half a teaspoon is measured.  Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose [see Warnings and Precautions (5.10)].

Concomitant Use of Alcohol and Other Central Nervous System Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution is used with benzodiazepines or other CNS depressants, including alcohol. Because of this risk, patients should avoid concomitant use of hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution with benzodiazepines or other CNS depressants, including alcohol [see Warnings and Precautions (5.1), Drug Interactions (7.1)].

Activities Requiring Mental Alertness

Patients should be advised to avoid engaging in hazardous tasks that require mental alertness and motor coordination such as operating machinery or driving a motor vehicle as hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution may produce marked drowsiness [see Warnings and Precautions (5.5)].

Drug Dependence

Patients should be cautioned that hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution contains hydrocodone bitartrate and can produce drug dependence [see Warnings and Precautions (5.3)].

MAOIs

Patients should be informed that due to its pseudoephedrine component, they should not use hydrocodone bitartrate, pseudoephedrine hydrochloride, and chlorpheniramine maleate oral solution with a MAOI or within 14 days of stopping use of an MAOI [see Warnings and Precautions (5.8)].

Manufactured by:
Bio-Pharm, Inc., Levittown, PA 19057

Rev. Mar 03/2017

• If you have an allergy to hydrocodone, chlorpheniramine, pseudoephedrine, or any other part of hydrocodone, chlorpheniramine, and pseudoephedrine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Glaucoma, heart disease, high blood pressure, or trouble passing urine.
• If you have had a recent head injury, brain injury or tumor, or raised pressure in the brain.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
• If you are taking any of these drugs: Linezolid or methylene blue.

This is not a list of all drugs or health problems that interact with hydrocodone, chlorpheniramine, and pseudoephedrine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food. Take with food if it causes an upset stomach.
• Measure liquid doses carefully. Use the measuring device that comes with hydrocodone, chlorpheniramine, and pseudoephedrine. If there is none, ask the pharmacist for a device to measure this medicine.

What do I do if I miss a dose?

• If you take hydrocodone, chlorpheniramine, and pseudoephedrine on a regular basis, take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• Many times this medicine is taken on an as needed basis. Do not take more often than told by the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Feeling nervous and excitable.
• Not able to sleep.
• Feeling sleepy.
• Hard stools (constipation).
• Upset stomach or throwing up.
• Sweating a lot.
• Feeling tired or weak.
• Headache.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.