Codeine Polistirex, Chlorpheniramine Polistirex Extended-release Oral Suspension

TUZISTRA® XR (codeine polistirex and chlorpheniramine polistirex) extended-release oral suspension is a pink to reddish pink, cherry-flavored liquid suspension that contains an opiate agonist antitussive codeine and a histamine-1 (H1) receptor antagonist (antihistamine) chlorpheniramine. Each 5 mL of TUZISTRA XR contains 14.7 mg of codeine (equivalent to 20 mg of codeine phosphate) and 2.8 mg of chlorpheniramine (equivalent to 4 mg of chlorpheniramine maleate) bound to sulfonated styrenedivinylbenzene copolymer (polistirex).

TUZISTRA XR contains the following inactive ingredients: cherry flavor, citric acid, D&C Red No. 30, ethyl maltol, glycerin, methylparaben, polysorbate 80, polyvinyl acetate, povidone, propyl gallate, propylparaben, purified water, sodium citrate, sodium polystyrene sulfonate, starch, sucrose, triacetin, xanthan gum.

Codeine is (5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol, has the following molecular formula, C18H21NO3, and a molecular weight of 299.36. Codeine polistirex is a complex of codeine with sulfonated styrene-divinylbenzene copolymer, having the following structural formula:

Chlorpheniramine is γ-(4-chlorophenyl)-N, N-dimethyl-2-pyridinepropanamine, has the following molecular formula, C16H19ClN2, and a molecular weight of 274.80. Chlorpheniramine polistirex is a complex of chlorpheniramine with sulfonated styrene-divinylbenzene copolymer, having the following structural formula:

No human overdosage data are available for TUZISTRA XR.

Codeine

Overdosage with codeine is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.

Codeine may cause miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Chlorpheniramine

Manifestations of chlorpheniramine overdosage may vary from central nervous system depression to stimulation. Central toxic effects are characterized by agitation, anxiety, delirium, disorientation, hallucinations, hyperactivity, sedation, and seizures. Severe overdosage may produce coma, medullary paralysis, and death. Peripheral toxicity includes hypertension, tachycardia, dysrhythmias, vasodilation, hyperpyrexia, mydriasis, urinary retention, and diminished gastrointestinal motility. Dry mouth, pharynx, bronchi, and nasal passages may be observed. Impaired secretion from sweat glands following toxic doses of drugs with anticholinergic side effects may predispose to hyperthermia.

An adult ingested 400 mg chlorpheniramine with no reported serious adverse effects. Toxic psychosis, a possible class effect from overdose of sedating antihistamines, has been reported with accidental overdose of chlorpheniramine.

Treatment of overdosage consists of discontinuation of TUZISTRA XR together with institution of appropriate therapy.

Give primary attention to re-establishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride is a specific antidote for respiratory depression that may result from overdosage or unusual sensitivity to opioids including codeine. Therefore, an appropriate dose of naloxone hydrochloride should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. For further information, see full prescribing information for naloxone hydrochloride. An antagonist should not be administered in the absence of clinically significant respiratory or circulatory depression. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Gastric emptying may be useful in removing unabsorbed drug.

Hemodialysis is not routinely used to enhance the elimination of codeine or chlorpheniramine from the body. Urinary excretion of chlorpheniramine is increased when the pH of the urine is acidic; however, acid diuresis is NOT recommended to enhance elimination in overdose, as the risks of acidemia and acute tubular necrosis in patients with rhabdomyolysis far outweigh any potential benefits.

TUZISTRA® XR
(two-zis-tra)
(codeine polistirex and chlorpheniramine polistirex) Extended-Release Oral Suspension

What is the most important information I should know about TUZISTRA XR?

• TUZISTRA XR can cause children to stop breathing (respiratory depression) and cause death.
  • Do not give TUZISTRA XR to children younger than 12 years of age, or to children younger than 18 years of age after tonsillectomy or adenoidectomy surgery.
  • You should not give TUZISTRA XR to children between 12 to 18 years of age who have certain risk factors for breathing problems, including:
    • recent surgery
    • obstructive sleep apnea
    • are obese
    • severe lung problems
    • other medical conditions that can cause difficulty breathing, such as neuromuscular problems
    • taking other medicines that cause breathing problems
• You should not breastfeed during treatment with TUZISTRA XR because it may cause your child to stop breathing and cause death.
• Severe drowsiness, breathing problems (respiratory depression), coma, and death can happen in adults and children who take TUZISTRA XR with benzodiazepines, or other central nervous system depressants, including alcohol.
  • Avoid taking other medicines that can cause drowsiness or sleepiness, or drinking alcohol during treatment with TUZISTRA XR. Ask your healthcare provider for a list of these medicines if you are not sure.
• TUZISTRA XR can cause breathing problems (respiratory depression) and drowsiness
  • Take TUZISTRA XR exactly as prescribed by your healthcare provider. If you take the wrong dose of TUZISTRA XR, you could overdose and die. See the Medication Guide section called “How should I take TUZISTRA XR?” for important information about how to take TUZISTRA XR correctly.
  • Avoid driving a car or operating machinery during treatment with TUZISTRA XR.
• Call your healthcare provider or get emergency medical help right away if anyone taking TUZISTRA XR, or your breastfeeding baby has any of the symptoms listed below:
  • increased sleepiness
  • shallow breathing
  • confusion
  • limpness
  • difficulty breathing

your baby has difficulty breastfeeding Keep TUZISTRA XR in a safe place away from children. Accidental use by a child is a medical emergency and can cause death. If a child accidentally takes TUZISTRA XR, get emergency help right away.

What is TUZISTRA XR?

• TUZISTRA XR is a prescription medicine used to treat cough and upper respiratory symptoms that you can have with allergies or a common cold. TUZISTRA XR is for adults 18 years and older only. TUZISTRA XR contains 2 medicines, codeine and chlorpheniramine. Codeine is a narcotic cough suppressant. Chlorpheniramine is an antihistamine.
• TUZISTRA XR is a federal controlled substance (C-III) because it contains codeine that can be abused or lead to dependence. Keep TUZISTRA XR in a safe place to prevent misuse and abuse. Selling or giving away TUZISTRA XR may harm others, and is against the law. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription medicines or street drugs.
• TUZISTRA XR is not for children under 18 years of age. It is not known if TUZISTRA XR is safe and effective in children under 18 years of age.

Who should not take TUZISTRA XR?

• Do not give TUZISTRA XR to any children younger than 12 years of age.
• Do not give TUZISTRA XR to children younger than 18 years of age after tonsillectomy or adenoidectomy surgery.
• Do not take TUZISTRA XR if you are allergic to any of the ingredients in TUZISTRA XR. See the end of this Medication Guide for a complete list of ingredients in TUZISTRA XR. You may have an increased risk of having an allergic reaction to TUZISTRA XR if you are allergic to certain other opioid medicines.

Before you take TUZISTRA XR, tell your healthcare provider about all your medical conditions, including if you:

• have a drug dependence
• have problems with your urinary tract (urethral stricture)
• have lung or breathing problems
• plan to have surgery
• have had a head injury
• drink alcohol
• have pain in your stomach-area (abdomen)
• have kidney or liver problems
• have a history of severe or persistent cough
• have diabetes
• have prostate problems
• have thyroid problems, such as hypothyroidism
• are pregnant or plan to become pregnant. It is not known if TUZISTRA XR will harm your unborn baby. You and your healthcare provider should decide if you should take TUZISTRA XR while you are pregnant.
• are breastfeeding or plan to breastfeed. Codeine and chlorpheniramine pass into your breast milk and may harm your baby. You should not breastfeed during treatment with TUZISTRA XR.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking TUZISTRA XR with certain other medicines can cause side effects or affect how well TUZISTRA XR or the other medicines work. Do not start or stop other medicines without talking to your healthcare provider.

Especially tell your healthcare provider if you:

• take pain medicines such as narcotics
• take cold or allergy medicines that contain antihistamines or cough suppressants
• take medicines for mental illness (anti-psychotics, anti-anxiety)
• drink alcohol
• take medicines for depression including monoamine oxidase inhibitors (MAOIs)
• take medicines for stomach or intestine problems
  Ask your healthcare provider if you are not sure if you take one of these medicines.

How should I take TUZISTRA XR?

• Take TUZISTRA XR exactly as your healthcare provider tells you.
• Your healthcare provider will tell you how much TUZISTRA XR to take and when to take it. Do not change your dose without talking to your healthcare provider.
• TUZISTRA XR is usually taken every 12 hours.
• Do not take more than 20 mL of TUZISTRA XR in 24 hours.
• Take TUZISTRA XR by mouth only.
• Shake the TUZISTRA XR bottle well before you use it.
• TUZISTRA XR can be taken with or without food.
• Do not mix TUZISTRA XR with other fluids or medicines.
• TUZISTRA XR should be taken using an accurate milliliter measuring device.
• Ask your pharmacist to give you a measuring device to help you measure the correct amount of TUZISTRA XR. Do not use a household teaspoon to measure your medicine. You may accidently take too much.
• If you take too much TUZISTRA XR, call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid doing while taking TUZISTRA XR?

• TUZISTRA XR can cause you to be drowsy. Avoid driving a car or using machinery during treatment with TUZISTRA XR.
• Avoid drinking alcohol during treatment with TUZISTRA XR. Drinking alcohol can increase your chances of having serious side effects.

What are the possible side effects of TUZISTRA XR?

TUZISTRA XR may cause serious side effects, including:

• See “What is the most important information I should know about TUZISTRA XR?”
• Breathing problems (respiratory depression) which can lead to death. Call your healthcare provider or get emergency treatment right away if you have excessive sleepiness, shallow or slow breathing, or confusion.
• Physical dependence or abuse. Take TUZISTRA XR exactly as your healthcare provider tells you to take it. Stopping TUZISTRA XR suddenly could cause withdrawal symptoms.
• Increased intracranial pressure.
• Bowel problems including constipation or stomach pain.

The most common side effects of TUZISTRA XR include:

• nausea and vomiting
• dizziness
• general feeling of discomfort or illness
• constipation swelling or bloating of your stomach-area
• depression
• drowsiness
• unable to control muscle movements
• excitability, nervousness
• stomach-area pain
• headache
• agitation, restlessness, irritability
• vision problems, including blurred vision and double-vision
• feel high (euphoria)
• feeling faint
• sleepiness
• difficulty sleeping (insomnia)
• confusion
• lightheadedness
• tremor

These are not all the possible side effects of TUZISTRA XR.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store TUZISTRA XR?

• Store TUZISTRA XR in a safe place at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep TUZISTRA XR in a tightly closed, child-resistant container and out of the light.
• Safely throw away medicine that is out of date or no longer needed.
• Keep TUZISTRA XR and all medicines out of the reach of children.

General information about the safe and effective use of TUZISTRA XR:

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TUZISTRA XR for a condition for which it was not prescribed. Do not give TUZISTRA XR to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about TUZISTRA XR that is written for health professionals.

What are the ingredients in TUZISTRA XR?

Active ingredients: codeine and chlorpheniramine.

Inactive ingredients: cherry flavor, citric acid, D&C Red No. 30, ethyl maltol, glycerin, methylparaben, polysorbate 80, polyvinyl acetate, povidone, propyl gallate, propylparaben, purified water, sodium citrate, sodium polystyrene sulfonate, starch, sucrose, triacetin, xanthan gum

This Medication Guide has been approved by the U.S. Food and Drug Administration.