Flowtuss

Use of hydrocodone bitartrate is associated with the following:

• Respiratory depression [see WARNINGS AND PRECAUTIONS and OVERDOSAGE]
• Drug dependence [see WARNINGS AND PRECAUTIONS and Drug Abuse and Dependence]
• Increased intracranial pressure [see WARNINGS AND PRECAUTIONS]
• Decreased mental alertness with impaired mental and/or physical abilities [see WARNINGS AND PRECAUTIONS]
• Paralytic ileus [see WARNINGS AND PRECAUTIONS]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The most common adverse reactions experienced by subjects taking a single dose of FLOWTUSS in the clinical setting include the following: Central Nervous System: headache, dizziness, sedation (somnolence); Gastrointestinal System: nausea, diarrhea; Cardiovascular System: decreased blood pressure; Vascular System: hot flush.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
• Do not take this medicine (Flowtuss) for longer than you were told by your doctor.
• Avoid driving and doing other tasks or actions that call for alertness while you take this medicine. Talk with your doctor.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• This medicine may be habit-forming with long-term use.
• If you have been taking this medicine (Flowtuss) on a regular basis and you stop it all of a sudden, you may have signs of withdrawal. Do not stop taking this medicine all of a sudden without calling your doctor. Tell your doctor if you have any bad effects.
• Do not take this medicine (Flowtuss) with other strong pain drugs or if you are using a pain patch without talking to your doctor first.
• Keep away from children. Accidental exposure may cause death. If a child takes this medicine by accident, get medical help right away.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine (Flowtuss).
• If you are 65 or older, use this medicine with care. You could have more side effects.
• The use of hydrocodone in children younger than 6 years has led to deadly breathing problems. Talk with the doctor.
• This medicine is not approved for use in children younger than 18 years of age. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine (Flowtuss) while you are pregnant.
• Using this medicine for a long time during pregnancy may lead to withdrawal in the newborn baby. This can be life-threatening. Talk with the doctor.
• Tell your doctor if you are breast-feeding or plan to breast-feed. This medicine passes into breast milk and may harm your baby.

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 child's doctor or get medical help right away if your child has 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.
• Very bad dizziness or passing out.
• Chest pain or pressure or a fast heartbeat.
• Feeling confused.
• A heartbeat that does not feel normal.
• Hallucinations (seeing or hearing things that are not there).
• Mood changes.
• Seizures.
• Very bad belly pain.
• Very bad headache.
• Trouble passing urine.
• Shakiness.
• Change in eyesight.
• Very upset stomach or throwing up.
• Very hard stools (constipation).
• Feeling very tired or weak.
• Feeling very sleepy.
• 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.

Oral solution: Each 5 mL contains hydrocodone bitartrate, USP, 2.5 mg; and guaifenesin, USP, 200 mg [ see Description (11)].

5.1 Respiratory Depression

Hydrocodone bitartrate, one of the active ingredients in Flowtuss, produces dose-related respiratory depression by directly acting on brain stem respiratory centers. Overdose of hydrocodone bitartrate in adults has been associated with fatal respiratory depression, and the use of hydrocodone bitartrate in children less than 6 years of age has been associated with fatal respiratory depression. Exercise caution when administering Flowtuss because of the potential for respiratory depression. If respiratory depression occurs, it may be antagonized by the use of naloxone hydrochloride and other supportive measures when indicated [ see Overdosage (10)].

5.2 Drug Dependence

Hydrocodone can produce drug dependence of the morphine type and therefore, has the potential for being abused. Psychic dependence, physical dependence, and tolerance may develop upon repeated administration of Flowtuss. Prescribe and administer Flowtuss with the same degree of caution appropriate to the use of other opioid drugs [ see Drug Abuse and Dependence (9.2), (9.3)].

5.3 Head Injury and Increased Intracranial Pressure

The respiratory depression effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a pre-existing increase in intracranial pressure. Furthermore, opioids produce adverse reactions which may obscure the clinical course of patients with head injuries. The use of Flowtuss should be avoided in these patients.

5.4 Activities Requiring Mental Alertness

Hydrocodone bitartrate, one of the active ingredients in Flowtuss, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of Flowtuss. Concurrent use of Flowtuss with alcohol or other central nervous system depressants should be avoided because additional impairment of central nervous system performance may occur.

5.5 Acute Abdominal Conditions

Flowtuss should be used with caution in patients with acute abdominal conditions since the administration of hydrocodone may obscure the diagnosis or clinical course of patients with acute abdominal conditions. The concurrent use of other anticholinergics with hydrocodone may produce paralytic ileus [ see Drug Interactions (7.3)].

5.6 Co-administration with Anticholinergics

The concurrent use of anticholinergics with hydrocodone may produce paralytic ileus. Exercise caution when using Flowtuss in patients taking anticholinergic medications [ see Drug Interactions (7.3)].

5.7 Co-administration with Monoamine Oxidase Inhibitors (MAOIs) or Tricyclic Antidepressants

Flowtuss should not be used in patients receiving monoamine oxidase inhibitors (MAOI) therapy or within 14 days of stopping such therapy. The use of MAOIs or tricyclic antidepressants with hydrocodone bitartrate may increase the effect of either the antidepressant or hydrocodone [ see Contraindications (4) and Drug Interactions (7.2)].

5.8 Persistent Cough

Flowtuss should not be used in patients with a persistent or chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema, or where cough is accompanied by excessive phlegm (mucus).

5.9 Dosing

Patients should be advised to measure Flowtuss 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, which can result in serious adverse reactions [ see Overdosage (10)]. Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.

5.10 Coexisting Conditions

Flowtuss should be used with caution in patients with diabetes, thyroid disease, Addison’s disease, prostatic hypertrophy or urethral stricture, and asthma.

5.11 Renal Impairment

Flowtuss should be used with caution in patients with severe renal impairment [ see Use in Specific Populations (8.6)].

5.12 Hepatic Impairment

Flowtuss should be used with caution in patients with severe hepatic impairment [ see Use in Specific Populations (8.7)].

8.1 Pregnancy

Teratogenic Effects
Pregnancy Category C
There are no adequate and well controlled studies of Flowtuss in pregnant women. Reproductive toxicity studies have not been conducted with Flowtuss; however, studies are available with an individual active ingredient or related active ingredient. Hydrocodone was teratogenic in hamsters. Codeine, an opiate related to hydrocodone, increased resorptions and decreased fetal weight in rats. Because animal reproduction studies are not always predictive of human response, Flowtuss should be used during pregnancy only if the benefit justifies the potential risk to the fetus.

Hydrocodone
Hydrocodone has been shown to be teratogenic in hamsters when given in a dose approximately 27 times the maximum recommended human daily dose (MRHDD) (on a mg/m 2 basis at a single subcutaneous dose of 102 mg/kg on gestation day 8). Reproductive toxicology studies were also conducted with codeine, an opiate related to hydrocodone. In a study in which pregnant rats were dosed throughout organogenesis, a dose of codeine approximately 40 times the MRHDD of hydrocodone (on a mg/m 2 basis at an oral dose of 120 mg/kg/day of codeine) increased resorptions and decreased fetal weight; however, these effects occurred in the presence of maternal toxicity. In studies in which rabbits and mice were dosed throughout organogenesis, doses of codeine up to approximately 20 and 100 times, respectively, the MRHDD of hydrocodone (on a mg/m 2 basis at oral doses of 30 and 600 mg/kg/day, respectively), produced no adverse developmental effects.

Non-teratogenic Effects
Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose.

8.2 Labor and Delivery

As with all opioids, administration of Flowtuss to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.

8.3 Nursing Mothers

Caution should be exercised when Flowtuss is administered to nursing mothers. Hydrocodone is known to be excreted in human milk. No studies have been performed to determine if guaifenesin is excreted into breastmilk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Flowtuss, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness of Flowtuss in pediatric patients under 18 years of age has not been established. The use of hydrocodone in children less than 6 years of age is associated with fatal respiratory depression [ see Warnings and Precautions (5.1)].

8.5 Geriatric Use

Clinical studies have not been conducted with Flowtuss in geriatric populations. Other reported clinical experience with the individual active ingredients of Flowtuss has not identified differences in responses between the elderly and patients younger than 65 years of age. In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Renal Impairment

Flowtuss should be given with caution in patients with severe impairment of renal function.

8.7 Hepatic Impairment

Flowtuss should be given with caution in patients with severe impairment of hepatic function.

Flowtuss (hydrocodone bitartrate and guaifenesin) oral solution contains hydrocodone bitartrate (a centrally-acting opioid antitussive) and guaifenesin (an expectorant).

Each 5 mL dose of Flowtuss contains: hydrocodone bitartrate, USP, 2.5 mg; and guaifenesin, USP, 200 mg.

Flowtuss also contains: black raspberry flavor, citric acid, D&C Red #33, FD&C Blue #1, glycerin, methylparaben, polyethylene glycol, propylparaben, purified water, saccharin sodium, sodium citrate, and sorbitol.

Hydrocodone Bitartrate
Hydrocodone bitartrate is a centrally-acting opioid antitussive and analgesic. It is affected by light and occurs as fine white crystals or crystalline powder which is derived from the opium alkaloid, thebaine. Its chemical name is morphinan-6-one, 4,5-epoxy-3-methoxy- 17-methyl-, (5α)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1), hydrate (2:5). It is also known as 4,5α-Epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5); and may be represented by the following structural formula:

Guaifenesin
Guaifenesin is an expectorant and occurs as a white powder. Its chemical name is 3-(2-methoxyphenoxy)-1,2-propanediol, and may be represented by the following structural formula:

Efficacy studies were not conducted with Flowtuss. Efficacy of Flowtuss is based on demonstration of bioequivalence to the individual comparator products [ see Clinical Pharmacology (12.3)].

Applies to guaifenesin / hydrocodone: oral capsule, oral liquid, oral solution, oral syrup, oral tablet, oral tablet extended release

Along with its needed effects, guaifenesin / hydrocodone 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 while taking guaifenesin / hydrocodone:

• Difficult or troubled breathing
• irregular, fast or slow, or shallow breathing
• pale or blue lips, fingernails, or skin

Some side effects of guaifenesin / hydrocodone 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:

• Diarrhea
• dizziness
• feeling of warmth
• headache
• nausea
• redness of the face, neck, arms, and occasionally, upper chest
• sleepiness or unusual drowsiness
• sudden sweating