Tuzistra XR

Included as part of the PRECAUTIONS section.

Tuzistra XR is a prescription medication used to relieve cough and symptoms associated with upper respiratory allergies or the common cold. It is a single product containing 2 medications: codeine and chlorpheniramine.

Codeine belongs to a group of drugs called opiate (narcotic) analgesics and to a class of medications called antitussives. It works by decreasing the activity in the part of the brain that causes coughing. Chlorpheniramine belongs to a group of drugs called antihistamines. It works by blocking the action of histamine, a substance in the body that causes allergic symptoms.

This medication comes in an extended release oral suspenison and is taken typically every 12 hours (twice a day), with or without food.

Common side effects of Tuzistra XR include nausea, vomiting, and constipation. 

Tuzistra XR can also cause blurred vision, drowsiness, and dizziness. Do not drive or operate heavy machinery until you know how Tuzistra XR affects you.

Serious side effects have been reported with Tuzistra XR . See the “Drug Precautions” section.

Common side effects of Tuzistra XR include the following:

• nausea
• vomiting
• constipation
• stomach distension
• stomach pain
• blurred vision
• diplopia
• visual disturbances
• confusion
• dizziness
• depression
• drowsiness
• sedation
• headache
• euphoria
• facial dyskinesia
• feeling faint
• light-headedness
• general feeling of discomfort or illness
• excitability
• nervousness
• agitation
• restlessness
• somnolence
• insomnia
• dyskinesia
• irritability
• tremor

This is not a complete list of Tuzistra XR side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

WARNING: Death Related to Ultra-Rapid Metabolism of Codeine to Morphine
Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism

This medicine may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Do not drink alcohol while you are taking medicine that contains codeine. Dangerous side effects or death can occur when alcohol is combined with a narcotic medicine.

Ask a doctor or pharmacist before using any other cold, allergy, cough, or sleep medicine. Many combination medicines contain antihistamines or cough suppressants. Taking certain products together can cause you to get too much of a certain drug.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Acid or sour stomach
• anxiety
• belching
• bloating
• blurred or loss of vision
• chills
• cold clammy skin
• cold sweats
• confusion
• dark colored urine
• depression
• diarrhea
• difficult or painful urination
• disturbed color perception
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• double vision
• dryness or spasm of the throat
• feeling of constant movement of self or surroundings
• fever
• halos around lights
• headache
• heartburn
• increased hunger
• indigestion
• irregular, fast or slow, or shallow breathing
• loss of appetite
• nausea
• nervousness
• night blindness
• nightmares
• overbright appearance of lights
• pain in the stomach, side, or abdomen, possibly radiating to the back
• pain or discomfort in the chest, upper stomach, or throat
• pale or blue lips, fingernails, or skin
• pressure in the stomach
• pounding in the ears
• seizures
• sensation of spinning
• shakiness
• sleepiness or unusual drowsiness
• slow, fast, or irregular heartbeat
• slurred speech
• stomach discomfort, upset, or pain
• sweating
• tunnel vision
• unusual tiredness or weakness
• vomiting
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Anxiety
• blistering, crusting, or irritation of the skin
• continuing ringing or buzzing or other unexplained noise in the ears
• cracked, dry, scaly skin
• dry mouth
• early menstrual periods
• face is warm or hot to touch
• false or unusual sense of well-being
• general feeling of discomfort or illness
• hearing loss
• hiccups
• increased appetite
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse
• irritability
• lack or loss of strength
• redness of the face
• restlessness
• skin rash, itching, redness, hives, swelling
• swelling of the breasts or breast soreness in both females and males
• trouble sleeping
• twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• watering of eyes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
• Chest pain or pressure or a fast heartbeat.
• Noisy breathing.
• Feeling very sleepy.
• Feeling very tired or weak.
• Feeling confused.
• Slow heartbeat.
• A heartbeat that does not feel normal.
• Hallucinations (seeing or hearing things that are not there).
• Low mood (depression).
• Mood changes.
• Seizures.
• Trouble passing urine.
• Shakiness.
• Change in eyesight.
• Very upset stomach or throwing up.
• Very hard stools (constipation).
• Very bad belly pain.
• Trouble controlling body movements.
• Feeling agitated.
• Restlessness.
• This medicine may cause very bad and sometimes deadly breathing problems. Call your doctor right away if you have slow, shallow, or trouble breathing.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Tuzistra XR is a pink to reddish pink, cherry-flavored liquid oral suspension.

Extended-release oral suspension contains: codeine polistirex, which contains 14.7 mg of codeine (equivalent to 20 mg codeine phosphate), and chlorpheniramine polistirex, which contains 2.8 mg of chlorpheniramine (equivalent to 4 mg chlorpheniramine maleate) per 5 mL [see Description (11) and How Supplied/Storage and Handling (16)].

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.

Applies to chlorpheniramine / codeine: oral liquid, oral suspension, oral suspension extended release, oral tablet

Cardiovascular

Codeine or Chlorpheniramine:
Frequency not reported: Fast, or slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitations, shock-like state, syncope[Ref]

Nervous system

Codeine or Chlorpheniramine:
Frequency not reported: Weakness, dizziness, drowsiness, sedation, headache, facial dyskinesia, lightheadedness, somnolence, dyskinesia, tremor[Ref]

Gastrointestinal

Codeine or Chlorpheniramine:
Frequency not reported: Nausea, vomiting, constipation, abdominal distension, abdominal pain, acute pancreatitis, dry mouth, dyspepsia, epigastric distress, diarrhea, gastro-esophageal reflux, gastrointestinal hypomotility[Ref]

Respiratory

Codeine:
Frequency not reported: Respiratory depression, dryness of the pharynx and respiratory passages, laryngismus, atelectasis, wheezing, troubled breathing, hiccups[Ref]

Endocrine

Codeine or Chlorpheniramine:
Frequency not reported: Decreased lactation, early menses, gynecomastia, increased libido, pheochromocytoma stimulation[Ref]

Dermatologic

Codeine or Chlorpheniramine:
Frequency not reported: Redness or flushing of face, skin rash, pruritus, erythema, urticaria, excessive perspiration, dermatitis[Ref]

Hypersensitivity

Codeine or Chlorpheniramine:
Frequency not reported: Allergic laryngospasm, nasal stuffiness, bronchospastic allergic reaction, hives, itching, swelling of face[Ref]

Ocular

Codeine or Chlorpheniramine:
Frequency not reported: Blurred vision, diplopia, visual disturbances, hypermetropia, lacrimation increased, mydriasis, photophobia[Ref]

General

The more commonly reported adverse effects have included nausea, vomiting, constipation, blurred vision, confusion, dizziness, depression, drowsiness, headache, lightheadedness, insomnia, irritability, and tremor.[Ref]

Other

Codeine or Chlorpheniramine:
Frequency not reported: Asthenia, feeling of relaxation, unusual tiredness, labyrinthitis, tinnitus, vertigo[Ref]

Metabolic

Codeine or Chlorpheniramine:
Frequency not reported: Changes in glucose utilization, glycosuria, hypoglycemia, increased appetite, loss of appetite[Ref]

Psychiatric

Codeine:
Frequency not reported: Drug dependence, confusion, depression, euphoria, false sense of well-being, excitability, nervousness, agitation, restlessness, insomnia, irritability[Ref]

Some side effects of Tuzistra XR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.