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DRUGS & SUPPLEMENTS
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Flucol
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Flucol uses
Flucol consists of Acetaminophen, Caffeine, Codeine Phosphate, Phenylephrine Hydrochloride, Pyrilamine Maleate.Acetaminophen:
Pharmacological action
Flucol is an analgesic-antipyretic. It has analgesic, antipyretic and weak anti-inflammatory action. The mechanism of action is associated with inhibition of prostaglandin synthesis, the predominant influence on the thermoregulation center in the hypothalamus, enhances heat transfer.
Why is Flucol (Acetaminophen) prescribed?
Pain weak and moderate intensity of different genesis (including headache, migraine, toothache, neuralgia, myalgia, algomenorrhea; pain in trauma, burns). Fever in infectious and inflammatory diseases.
Flucol dosage and administration
Oral or rectally adults and adolescents with a body weight over 60 kg is used in a single dose of 500 mg, the multiplicity of admission - up to 4 times / Maximum duration of treatment - 5-7 days.
Maximum dose: single - 1 g, daily - 4 g.
Single dose for oral administration for children aged 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg / kg. Single dose rectal in children aged 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.
Multiplicity - 4 at intervals of not less than 4 h. The maximum duration of treatment - 3 days.
Maximum dose: 4 single dose per day.
Flucol side effects, adverse reactions
Digestive system: rarely - dyspepsia; long-term use at high doses - hepatotoxic effects, methemoglobinemia, renal dysfunction and liver, hypochromic anemia. Hemopoietic system: rarely - thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis. Allergic reactions: rarely - skin rash, itching, hives.
Contraindications
Chronic active alcoholism, increased sensitivity to Flucol, marked disturbances of liver function and / or kidney disease, anemia, pregnancy (I term).
Using during pregnancy and breastfeeding
Flucol (Acetaminophen) crosses the placental barrier. So far, no observed adverse effects of Flucol (Acetaminophen) on the fetus in humans.
Flucol (Acetaminophen) is excreted in breast milk: the content in milk was 0.04-0.23% of the dose adopted mother.
If necessary, use of Flucol (Acetaminophen) during pregnancy and lactation (breastfeeding) should carefully weigh the potential benefits of therapy for the mother and the potential risk to the fetus or child.
In experimental studies found no embryotoxic, teratogenic and mutagenic action of Flucol (Acetaminophen).
Special Instructions
Flucol is used with caution in patients with disorders of the liver and kidneys, with benign hyperbilirubinemia, as well as in elderly patients.
With prolonged use of Flucol (Acetaminophen) is necessary to monitor patterns of peripheral blood and functional state of the liver.
Used for treatment of premenstrual tension syndrome in combination with pamabrom (diuretic, a derivative of xanthine) and mepyramine (Histamine H1-receptors blocker).
Flucol (Acetaminophen) Drug Interactions
With the simultaneous use with inducers of microsomal liver enzymes, means having hepatotoxic effect, increasing the risk of hepatotoxic action of Flucol (Acetaminophen).
With the simultaneous use of anticoagulants may be slight to moderate increase in prothrombin time.
With the simultaneous use of anticholinergics may decrease absorption of Flucol (Acetaminophen).
With the simultaneous use of oral contraceptives accelerated excretion of Flucol (Acetaminophen) from the body and may reduce its analgesic action.
With the simultaneous use with urological means reduced their effectiveness.
With the simultaneous use of activated charcoal reduced bioavailability of Flucol (Acetaminophen).
When Flucol (Acetaminophen) applied simultaneously with diazepam may decrease excretion of diazepam.
There have been reports about the possibility of enhancing mielodepression effect of zidovudine while applying with Flucol (Acetaminophen). A case of severe toxic liver injury.
Described cases of toxic effects of Flucol (Acetaminophen), while the use of isoniazid.
When applied simultaneously with carbamazepine, phenytoin, phenobarbital, primidonom decreases the effectiveness of Flucol (Acetaminophen), which is caused by an increase in its metabolism and excretion from the body. Cases of hepatotoxicity, while the use of Flucol (Acetaminophen) and phenobarbital.
In applying cholestyramine a period of less than 1 h after administration of Flucol (Acetaminophen) may decrease of its absorption.
At simultaneous application with lamotrigine moderately increased excretion of lamotrigine from the body.
With the simultaneous use of metoclopramide may increase absorption of Flucol (Acetaminophen) and its increased concentration in blood plasma.
When applied simultaneously with probenecid may decrease clearance of Flucol (Acetaminophen), with rifampicin, sulfinpyrazone - may increase clearance of Flucol (Acetaminophen) due to increasing its metabolism in the liver.
At simultaneous application of Flucol (Acetaminophen) with ethinylestradiol increases absorption of Flucol (Acetaminophen) from the gut.
Enhances the effect of indirect anticoagulants (coumarin derivatives and indandione). Antipyretic and analgesic activity of caffeine increases, reduce - rifampicin, phenobarbital and alcohol (accelerated biotransformation, inducing microsomal liver enzymes).
Flucol in case of emergency / overdose
At a reception in toxic doses (10-15 g in adults) may develop liver necrosis.
Symptoms of overdose may include: nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in the upper right part of the stomach, yellowing of the skin or eyes, flu-like symptoms
Caffeine:
Active ingredient (in each tablet)
Flucol (Caffeine) 200mg
Purpose
Alertness aid
Use
- helps restore mental alertness or wakefulness when experiencing fatigue or drowsiness
Warnings
For occasional use only
Do not use
- in children under 12 years of age
- as a substitute for sleep
When using this product limit the use of Flucol (Caffeine) containing medications, foods, or beverages because too much Flucol (Caffeine) may cause nervousness, irritability, sleeplessness, and occasionally, rapid heartbeat. The recommended dose of this product contains about as much Flucol (Caffeine) as a cup of coffee.
Stop use and ask a doctor if fatigue or drowsiness persists or continues to recur
If pregnant or breast-feeding, ask a health professional before use.
Keep out of reach of children.
In case of overdose, get medical help or contact a Poison Control Center right away.
Directions
- adults and children 12 years of age and over: take 1 tablet not more often than every 3 to 4 hours.
Other information
- store at room temperature
- avoid excessive heat (greater than 100°F) or humidity
Inactive ingredients
carnauba wax, colloidal silicon dioxide, D&C yellow #10 aluminum lake, dextrose, FD&C yellow #6 aluminum lake, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, starch, titanium dioxide
Questions or comments?
Call toll-free 1-855-874-0970 weekdays
Display Panel Flucol (Caffeine): 16 ct. Package
Flucol (Caffeine)®
CAFFEINE ALERTNESS AID
16 TABLETS
200mg each
FUNCTIONAL Flucol (Caffeine)® for Mental Alertness
SAFE & EFFECTIVE
One tablet is equal to about a cup of coffee
Flucol (Caffeine)®
Making the Most of Every Day.®
Tamper Evident Feature: individually sealed in foil for your protection. Do not
use if foil or plastic bubble is torn or punctured.
Vivarin®, Vivarin® and design, stylization and trade dress, and FUNCTIONAL
CAFFEINE® are registered trademarks of Meda AB.
Distributed by:
Meda Consumer Healthcare Inc.
Marietta, GA 30062 ©2011 Meda AB
www.vivarin.com
16 ct. Package
Display Panel Flucol (Caffeine): 40 ct. Package
SAFE & EFFECTIVE
FUNCTIONAL Flucol (Caffeine)® for Mental Alertness
Flucol (Caffeine)®
Flucol (Caffeine) ALERTNESS AID
40 Tablets
200mg each
FUNCTIONAL Flucol (Caffeine)® for Mental Alertness
Tamper Evident Feature: Individually sealed in foil for your protection. Do not use if foil or plastic bubble is torn or punctured.
VIVARIN® helps restore mental alertness or wakefulness when experiencing fatigue or drowsiness (FDA approved uses), so you can accomplish all the things you want to do and all the things you need to do.
Vivarin®, Vivarin® and design, stylization and trade dress, and FUNCTIONAL
CAFFEINE® are registered trademarks of Meda AB.
Made in the U.S.A.
Flucol (Caffeine)®
Making the Most of Every Day.®
Distributed by:
Meda Consumer Healthcare Inc.
Marietta, GA 30062 ©2013 Meda AB
www.vivarin.com
40 ct. Package
Codeine Phosphate:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Drug abuse and dependence
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- How supplied/storage and handling
- Patient counseling information
- Medication guide
1 INDICATIONS AND USAGE
Flucol (Codeine Phosphate) Sulfate Tablets are indicated for the management of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate.
Limitations of Use
Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses , reserve Flucol (Codeine Phosphate) Sulfate Tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:
- Have not been tolerated, or are not expected to be tolerated,
- Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
Flucol (Codeine Phosphate) Sulfate Tablets are an opioid agonist, indicated for the management of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate. (1)
Limitations of Use (1)
Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Flucol (Codeine Phosphate) Sulfate Tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:
- Have not been tolerated, or are not expected to be tolerated,
- Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
2 DOSAGE AND ADMINISTRATION
- Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
- Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. (2.1)
- Initiate treatment with 15 to 60 mg every 4 hours as needed. (2.2)
- Do not stop Flucol (Codeine Phosphate) Sulfate Tablets abruptly in a physically dependent patient. (2.4)
2.1 Important Dosage and Administration Instructions
Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals .
Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse .
Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with Flucol (Codeine Phosphate) Sulfate Tablets and adjust the dosage accordingly .
2.2 Initial Dosage
Initiating Treatment with Flucol Sulfate Tablets
Initiate treatment with Flucol (Codeine Phosphate) Sulfate Tablets in a dosing range of 15 to 60 mg every 4 hours as needed for pain.
Adult doses of Flucol (Codeine Phosphate) Sulfate Tablets higher than 60 mg provide no further efficacy but are associated with greater adverse reactions. The maximum 24 hour dose is 360 mg.
Conversion from Other Opioids to Flucol (Codeine Phosphate) Sulfate Tablets
There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of Flucol (Codeine Phosphate) Sulfate Tablets. It is safer to underestimate a patient’s 24-hour Flucol (Codeine Phosphate) Sulfate Tablets dosage than to overestimate the 24-hour Flucol (Codeine Phosphate) Sulfate Tablets dosage and manage an adverse reaction due to overdose.
2.3 Titration and Maintenance of Therapy
Individually titrate Flucol (Codeine Phosphate) Sulfate Tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Flucol (Codeine Phosphate) sulfate to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse . Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.
If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the Flucol (Codeine Phosphate) Sulfate Tablets dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
2.4 Discontinuation of Flucol Sulfate Tablets
When a patient who has been taking Flucol (Codeine Phosphate) Sulfate Tablets regularly and may be physically dependent no longer requires therapy with Flucol (Codeine Phosphate) Sulfate Tablets, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue Flucol (Codeine Phosphate) Sulfate Tablets in a physically-dependent patient .
3 DOSAGE FORMS AND STRENGTHS
Each 15 mg tablet for oral administration contains 15 mg of Flucol (Codeine Phosphate) sulfate USP. It is a white to off-white biconvex tablet with “15” debossed on the scored side and “54 613” debossed on the other side.
Each 30 mg tablet for oral administration contains 30 mg of Flucol (Codeine Phosphate) sulfate USP. It is a white to off-white biconvex tablet with “30” debossed on the scored side and “54 783” debossed on the other side.
Each 60 mg tablet for oral administration contains 60 mg of Flucol (Codeine Phosphate) sulfate USP. It is a white to off-white biconvex tablet with “60” debossed on the scored side and “54 412” debossed on the other side.
Tablets: 15 mg, 30 mg, and 60 mg (3)
4 CONTRAINDICATIONS
Flucol (Codeine Phosphate) Sulfate Tablets are contraindicated for:
- All children younger than 12 years of age .
- Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy .
Flucol (Codeine Phosphate) Sulfate Tablets are also contraindicated in patients with:
- Significant respiratory depression .
- Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment .
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days .
- Known or suspected gastrointestinal obstruction, including paralytic ileus .
- Hypersensitivity to Flucol (Codeine Phosphate) (e.g., anaphylaxis) .
- Children younger than 12 years of age.
- Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. (4)
- Significant respiratory depression. (4)
- Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. (4)
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days. (4)
- Known or suspected gastrointestinal obstruction, including paralytic ileus. (4)
- Hypersensitivity to Flucol (Codeine Phosphate). (4)
5 WARNINGS AND PRECAUTIONS
- Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration.
- Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. (5.9)
- Severe Hypotension: Monitor during dosage initiation and titration. Avoid use of Flucol (Codeine Phosphate) Sulfate Tablets in patients with circulatory shock. (5.10)
- Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression. Avoid use of Flucol (Codeine Phosphate) Sulfate Tablets in patients with impaired consciousness or coma. (5.11)
5.1 Addiction, Abuse, and Misuse
Flucol (Codeine Phosphate) Sulfate Tablets contain Flucol (Codeine Phosphate), a Schedule II controlled substance. As an opioid, Flucol (Codeine Phosphate) Sulfate Tablets exposes users to the risks of addiction, abuse, and misuse .
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Flucol (Codeine Phosphate) Sulfate Tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Flucol (Codeine Phosphate) Sulfate Tablets, and monitor all patients receiving Flucol (Codeine Phosphate) Sulfate Tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as Flucol (Codeine Phosphate) Sulfate Tablets, but use in such patients necessitates intensive counseling about the risks and proper use of Flucol (Codeine Phosphate) Sulfate Tablets along with intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Flucol (Codeine Phosphate) Sulfate Tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug . Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
5.2 Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status . Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Flucol (Codeine Phosphate) Sulfate Tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of Flucol (Codeine Phosphate) Sulfate Tablets.
To reduce the risk of respiratory depression, proper dosing and titration of Flucol (Codeine Phosphate) Sulfate Tablets are essential . Overestimating the Flucol (Codeine Phosphate) Sulfate Tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of Flucol (Codeine Phosphate) Sulfate Tablets, especially by children, can result in respiratory depression and death due to an overdose of Flucol (Codeine Phosphate).
5.3 Ultra-Rapid Metabolism of Flucol (Codeine Phosphate) and Other Risk Factors for Life-Threatening Respiratory Depression in Children
Life-threatening respiratory depression and death have occurred in children who received Flucol (Codeine Phosphate). Flucol (Codeine Phosphate) is subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to an increased exposure to the active metabolite morphine. Based upon post-marketing reports, children younger than 12 years old appear to be more susceptible to the respiratory depressant effects of Flucol (Codeine Phosphate), particularly if there are risk factors for respiratory depression. For example, many reported cases of death occurred in the post-operative period following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of Flucol (Codeine Phosphate). Furthermore, children with obstructive sleep apnea who are treated with Flucol (Codeine Phosphate) for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to its respiratory depressant effect. Because of the risk of life-threatening respiratory depression and death:
- Flucol (Codeine Phosphate) Sulfate Tablets are contraindicated for all children younger than 12 years of age .
- Flucol (Codeine Phosphate) Sulfate Tablets are contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy .
- Avoid the use of Flucol (Codeine Phosphate) Sulfate Tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of Flucol (Codeine Phosphate) unless the benefits outweigh the risks. Risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.
- As with adults, when prescribing Flucol (Codeine Phosphate) for adolescents, healthcare providers should choose the lowest effective dose for the shortest period of time and inform patients and caregivers about these risks and the signs of morphine overdose .
Nursing Mothers
At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of Flucol (Codeine Phosphate). Breastfeeding is not recommended during treatment with Flucol (Codeine Phosphate) Sulfate Tablets .
CYP2D6 Genetic Variability: Ultra-Rapid Metabolizers
Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (e.g., gene duplications denoted as *1/*1xN or *1/*2xN). The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 1 to 10% for Whites (European, North American), 3 to 4% for Blacks (African Americans), 1 to 2% for East Asians (Chinese, Japanese, Korean), and may be greater than 10% in certain racial/ethnic groups (i.e., Oceanian, Northern African, Middle Eastern, Ashkenazi Jews, Puerto Rican).
These individuals convert Flucol (Codeine Phosphate) into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing) . Therefore, individuals who are ultra-rapid metabolizers should not use Flucol (Codeine Phosphate) Sulfate Tablets.
5.4 Neonatal Opioid Withdrawal Syndrome
Prolonged use of Flucol Sulfate Tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
5.5 Risks of Interactions with Drugs Affecting Cytochrome P450 Isoenzymes
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Flucol (Codeine Phosphate) are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Flucol (Codeine Phosphate) Sulfate Tablets requires careful consideration of the effects on the parent drug, Flucol (Codeine Phosphate), and the active metabolite, morphine.
Cytochrome P450 3A4 Interaction
The concomitant use of Flucol (Codeine Phosphate) Sulfate Tablets with all cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in Flucol (Codeine Phosphate) plasma concentrations with subsequently greater metabolism by cytochrome P450 2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.
The concomitant use of Flucol (Codeine Phosphate) Sulfate Tablets with all cytochrome P450 3A4 inducers or discontinuation of a cytochrome P450 3A4 inhibitor may result in lower Flucol (Codeine Phosphate) levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels. This may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal. Follow patients receiving Flucol (Codeine Phosphate) Sulfate Tablets and any CYP3A4 inhibitor or inducer for signs and symptoms that may reflect opioid toxicity and opioid withdrawal when Flucol (Codeine Phosphate) Sulfate Tablets are used in conjunction with inhibitors and inducers of CYP3A4.
If concomitant use of a CYP3A4 inhibitor is necessary or if a CYP3A4 inducer is discontinued, consider dosage reduction of Flucol (Codeine Phosphate) Sulfate Tablets until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals.
If concomitant use of a CYP3A4 inducer is necessary or if a CYP3A4 inhibitor is discontinued, consider increasing the Flucol (Codeine Phosphate) Sulfate Tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal [Drug Interactions (7)].
Risks of Concomitant Use or Discontinuation of Cytochrome P450 2D6 Inhibitors
The concomitant use of Flucol (Codeine Phosphate) Sulfate Tablets with all cytochrome P450 2D6 inhibitors (e.g., amiodarone, quinidine) may result in an increase in Flucol (Codeine Phosphate) plasma concentrations and a decrease in active metabolite morphine plasma concentration which could result in an analgesic efficacy reduction or symptoms of opioid withdrawal.
Discontinuation of a concomitantly used cytochrome P450 2D6 inhibitor may result in a decrease in Flucol (Codeine Phosphate) plasma concentration and an increase in active metabolite morphine plasma concentration which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.
Follow patients receiving Flucol (Codeine Phosphate) Sulfate Tablets and any CYP2D6 inhibitor for signs and symptoms that may reflect opioid toxicity and opioid withdrawal when Flucol (Codeine Phosphate) Sulfate Tablets are used in conjunction with inhibitors of CYP2D6.
If concomitant use with a CYP2D6 inhibitor is necessary, follow the patient for signs of reduced efficacy or opioid withdrawal and consider increasing the Flucol (Codeine Phosphate) Sulfate Tablets dosage. After stopping use of a CYP2D6 inhibitor, consider reducing the Flucol (Codeine Phosphate) Sulfate Tablets dosage and follow the patient for signs and symptoms of respiratory depression or sedation .
5.6 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Flucol Sulfate Tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics .
If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.
Advise both patients and caregivers about the risks of respiratory depression and sedation when Flucol (Codeine Phosphate) Sulfate Tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs .
5.7 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients
The use of Flucol (Codeine Phosphate) Sulfate Tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease
Flucol (Codeine Phosphate) Sulfate Tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Flucol (Codeine Phosphate) Sulfate Tablets .
Elderly, Cachectic, or Debilitated Patients
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients .
Monitor such patients closely, particularly when initiating and titrating Flucol (Codeine Phosphate) Sulfate Tablets and when Flucol (Codeine Phosphate) Sulfate Tablets are given concomitantly with other drugs that depress respiration . Alternatively, consider the use of non-opioid analgesics in these patients.
5.8 Interaction with Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors may potentiate the effects of morphine, codeine’s active metabolite, including respiratory depression, coma, and confusion. Flucol (Codeine Phosphate) Sulfate Tablets should not be used in patients taking MAOIs or within 14 days of stopping such treatment .
5.9 Adrenal Insufficiency
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
5.10 Severe Hypotension
Flucol Sulfate Tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) . Monitor these patients for signs of hypotension after initiating or titrating the dosage of Flucol (Codeine Phosphate) Sulfate Tablets. In patients with circulatory shock, Flucol (Codeine Phosphate) Sulfate Tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Flucol (Codeine Phosphate) Sulfate Tablets in patients with circulatory shock.
5.11 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness
In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), Flucol (Codeine Phosphate) Sulfate Tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Flucol (Codeine Phosphate) Sulfate Tablets.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Flucol (Codeine Phosphate) Sulfate Tablets in patients with impaired consciousness or coma.
5.12 Risks of Use in Patients with Gastrointestinal Conditions
Flucol Sulfate Tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The Flucol (Codeine Phosphate) in Flucol (Codeine Phosphate) Sulfate Tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
5.13 Increased Risk of Seizures in Patients with Seizure Disorders
The Flucol (Codeine Phosphate) in Flucol (Codeine Phosphate) Sulfate Tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Flucol (Codeine Phosphate) Sulfate Tablets therapy.
5.14 Withdrawal
Avoid the use of mixed agonist/antagonist or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including Flucol (Codeine Phosphate) Sulfate Tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms .
When discontinuing Flucol (Codeine Phosphate) Sulfate Tablets in a physically-dependent patient, gradually taper the dosage . Do not abruptly discontinue Flucol (Codeine Phosphate) Sulfate Tablets in these patients .
5.15 Risks of Driving and Operating Machinery
Flucol (Codeine Phosphate) Sulfate Tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Flucol (Codeine Phosphate) Sulfate Tablets and know how they will react to the medication .
6 ADVERSE REACTIONS
The following serious adverse reactions are described, or described in greater detail, in other sections:
- Addiction, Abuse, and Misuse
- Life-Threatening Respiratory Depression
- Ultra-Rapid Metabolism of Flucol (Codeine Phosphate) and Other Risk Factors for Life-Threatening Respiratory Depression in Children
- Neonatal Opioid Withdrawal Syndrome
- Interactions with Benzodiazepines and Other CNS Depressants
- Adrenal Insufficiency
- Severe Hypotension
- Gastrointestinal Adverse Reactions
- Seizures
- Withdrawal
The following adverse reactions associated with the use of Flucol (Codeine Phosphate) were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Serious adverse reactions associated with Flucol (Codeine Phosphate) were respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest.
The most frequently observed adverse reactions with Flucol (Codeine Phosphate) administration included drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating, and constipation.
Other adverse reactions included allergic reactions, euphoria, dysphoria, abdominal pain, and pruritis.
Other less frequently observed adverse reactions expected from opioid analgesics, including Flucol (Codeine Phosphate) Sulfate Tablets, include:
Cardiovascular System: faintness, flushing, hypotension, palpitations, syncope
Digestive System: abdominal cramps, anorexia, diarrhea, dry mouth, gastrointestinal distress, pancreatitis
Nervous System: anxiety, drowsiness, fatigue, headache, insomnia, nervousness, shakiness, somnolence, vertigo, visual disturbances, weakness
Skin and Appendages: rash, sweating, urticaria
Serotonin Syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Anaphylaxis:Anaphylaxis has been reported with ingredients contained in Flucol (Codeine Phosphate) Sulfate Tablets.
Androgen Deficiency: Cases of androgen deficiency have occurred with chronic use of opioids .
The most common adverse reactions include: drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, and sweating. (6)
To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
7 DRUG INTERACTIONS
Table 1 includes clinically significant drug interactions with Flucol (Codeine Phosphate) Sulfate Tablets.
| Inhibitors of CYP3A4 | |
| Clinical Impact: | The concomitant use of Flucol (Codeine Phosphate) Sulfate Tablets with CYP3A4 inhibitors, may result in an increase in Flucol (Codeine Phosphate) plasma concentrations with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of Flucol (Codeine Phosphate) Sulfate Tablets is achieved . After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, it may result in lower Flucol (Codeine Phosphate) levels, greater norcodeine levels, and less metabolism via CYP2D6 with resultant lower morphine levels , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to Flucol (Codeine Phosphate). |
| Intervention: | If concomitant use of CYP3A4 inhibitor is necessary, consider dosage reduction of Flucol (Codeine Phosphate) Sulfate Tablets until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the Flucol (Codeine Phosphate) Sulfate Tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. |
| Examples: | Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) |
| CYP3A4 Inducers | |
| Clinical Impact: | The concomitant use of Flucol (Codeine Phosphate) Sulfate Tablets and CYP3A4 inducers can result in lower Flucol (Codeine Phosphate) levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence [see Warnings and Precautions (5.5)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, Flucol (Codeine Phosphate) plasma concentrations may increase with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels [see Clinical Pharmacology (12.3)], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. |
| Intervention: | If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy and signs of opioid withdrawal and consider increasing the Flucol (Codeine Phosphate) Sulfate Tablets dosage as needed. If a CYP3A4 inducer is discontinued, consider Flucol (Codeine Phosphate) Sulfate Tablets dosage reduction and monitor for signs of respiratory depression and sedation at frequent intervals. |
| Examples: | Rifampin, carbamazepine, phenytoin |
| Inhibitors of CYP2D6 | |
| Clinical Impact: | Flucol (Codeine Phosphate) is metabolized by CYP2D6 to form morphine. The concomitant use of Flucol (Codeine Phosphate) Sulfate Tablets and CYP2D6 inhibitors can increase the plasma concentration of Flucol (Codeine Phosphate), but can decrease the plasma concentration of active metabolite morphine, which could result in reduced analgesic efficacy or symptoms of opioid withdrawal, particularly when an inhibitor is added after a stable dose of Flucol (Codeine Phosphate) Sulfate Tablets is achieved . After stopping a CYP2D6 inhibitor, as the effects of the inhibitor decline, the Flucol (Codeine Phosphate) plasma concentration will decrease but the active metabolite morphine plasma concentration will increase, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression . |
| Intervention: | If concomitant use with a CYP2D6 inhibitor is necessary, or if a CYP2D6 inhibitor is discontinued after concomitant use, consider dosage adjustment of Flucol (Codeine Phosphate) Sulfate Tablets and monitor patients closely at frequent intervals. If concomitant use with CYP2D6 inhibitors is necessary, follow the patient for reduced efficacy or signs and symptoms of opioid withdrawal and consider increasing the Flucol (Codeine Phosphate) Sulfate Tablets as needed. After stopping use of a CYP2D6 inhibitor, consider reducing the Flucol (Codeine Phosphate) Sulfate Tablets and monitor the patient for signs and symptoms of respiratory depression or sedation. |
| Examples | Paroxetine, fluoxetine, bupropion, quinidine. |
| Benzodiazepines and Other Central Nervous System (CNS) Depressants | |
| Clinical Impact: | Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. |
| Intervention: | Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation . |
| Examples: | Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. |
| Serotonergic Drugs | |
| Clinical Impact: | The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. |
| Intervention: | If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Flucol (Codeine Phosphate) Sulfate Tablets if serotonin syndrome is suspected. |
| Examples: | Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). |
| Monoamine Oxidase Inhibitors (MAOIs) | |
| Clinical Impact: | MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) . |
| Intervention: | Do not use Flucol (Codeine Phosphate) Sulfate Tablets in patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. |
| Examples: | Phenelzine, tranylcypromine, linezolid. |
| Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics | |
| Clinical Impact: | May reduce the analgesic effect of Flucol (Codeine Phosphate) Sulfate Tablets and/or precipitate withdrawal symptoms. |
| Intervention: | Avoid concomitant use. |
| Examples: | Butorphanol, nalbuphine, pentazocine, buprenorphine. |
| Muscle Relaxants | |
| Clinical Impact: | Flucol (Codeine Phosphate) may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. |
| Intervention: | Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Flucol (Codeine Phosphate) Sulfate Tablets and/or the muscle relaxant as necessary. |
| Diuretics | |
| Clinical Impact: | Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. |
| Intervention: | Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. |
| Anticholinergic Drugs | |
| Clinical Impact: | The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. |
| Intervention: | Monitor patients for signs of urinary retention or reduced gastric motility when Flucol (Codeine Phosphate) Sulfate Tablets are used concomitantly with anticholinergic drugs. |
- Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue Flucol (Codeine Phosphate) sulfate if serotonin syndrome is suspected. (7)
- Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with Flucol (Codeine Phosphate) Sulfate Tablets because they may reduce analgesic effect of Flucol (Codeine Phosphate) Sulfate Tablets or precipitate withdrawal symptoms. (7)
8 USE IN SPECIFIC POPULATIONS
- Pregnancy: May cause fetal harm.
- Lactation: Breastfeeding not recommended. (8.2)
8.1 Pregnancy
Pregnancy Category C
Risk Summary
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome . Available data with Flucol (Codeine Phosphate) Sulfate Tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, Flucol (Codeine Phosphate) administration during organogenesis has been shown to produce delayed ossification in the offspring of mice at 1.4 times maximum recommended human dose (MRHD) of 360 mg/day, embryolethal and fetotoxic effects in the offspring of rats and hamsters at approximately 2 to 3 times the MRHD, and cranial malformations/cranioschisis in the offspring of hamsters between 2 and 8 times the MRHD [see Data ].
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions: Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly .
Labor or Delivery: Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Flucol (Codeine Phosphate) Sulfate Tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Flucol (Codeine Phosphate) Sulfate Tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.
Data
Animal Data: Studies on the reproductive and developmental effects of Flucol (Codeine Phosphate) have been reported in the published literature in hamsters, rats, mice and rabbits.
In a study in which pregnant hamsters were administered 150 mg/kg twice daily of Flucol (Codeine Phosphate) (oral; approximately 7 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) during organogenesis cranial malformations (i.e., meningoencephalocele) in several fetuses were reported; as well as the observation of increases in the percentage of resorptions per litter. Doses of 50 and 150 mg/kg, bid resulted in fetotoxicity as demonstrated by decreased fetal body weight. In an earlier study in hamsters, single oral doses of 73 to 360 mg/kg level on Gestation Day 8 (oral; approximately 2 to 8 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis), reportedly produced cranioschisis in all of the fetuses examined.
In studies in rats, doses at the 120 mg/kg level (oral; approximately 3 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) during organogenesis, in the toxic range for the adult animal, were associated with an increase in embryo resorption at the time of implantation.
In pregnant mice, a single 100 mg/kg dose (subcutaneous; approximately 1.4 times the recommended daily dose of 360 mg/day for adults on a mg/mg2 basis) administered between Gestation Day 7 and 12 reportedly resulted in delayed ossification in the offspring.
No teratogenic effects were observed in rabbits administered up to 30 mg/kg (approximately 2 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) of Flucol (Codeine Phosphate) during organogenesis.
Flucol (Codeine Phosphate) (30 mg/kg) administered subcutaneously to pregnant rats during pregnancy and for 25 days after delivery increased neonatal mortality at birth. This dose is 0.8 times the maximum recommended human dose of 360 mg/day on a body surface area comparison.
8.2 Lactation
Risk Summary
Flucol and its active metabolite, morphine, are present in human milk. There are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to Flucol (Codeine Phosphate) via breast milk. Women who are ultra-rapid metabolizers of Flucol (Codeine Phosphate) achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants. In women with normal Flucol (Codeine Phosphate) metabolism (normal CYP2D6 activity), the amount of Flucol (Codeine Phosphate) secreted into human milk is low and dose-dependent.
There is no information on the effects of Flucol (Codeine Phosphate) on milk production. Because of the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Flucol (Codeine Phosphate) Sulfate Tablets [see Warnings and Precautions (5.3)].
Clinical Considerations
If infants are exposed to Flucol (Codeine Phosphate) Sulfate Tablets through breast milk, they should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped.
8.3 Females and Males of Reproductive Potential
Infertility
Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible .
8.4 Pediatric Use
The safety and effectiveness of Flucol Sulfate Tablets in pediatric patients have not been established.
Life-threatening respiratory depression and death have occurred in children who received Flucol (Codeine Phosphate) . In most of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of Flucol (Codeine Phosphate) (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of Flucol (Codeine Phosphate). Because of the risk of life-threatening respiratory depression and death:
- Flucol (Codeine Phosphate) Sulfate Tablets are contraindicated for all children younger than 12 years of age .
- Flucol (Codeine Phosphate) Sulfate Tablets are contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy .
- Avoid the use of Flucol (Codeine Phosphate) Sulfate Tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of Flucol (Codeine Phosphate) unless the benefits outweigh the risks. Risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression .
8.5 Geriatric Use
Elderly patients (aged 65 years or older) may have increased sensitivity to Flucol (Codeine Phosphate). In general, use caution when selecting a dosage for an elderly patient, 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.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Flucol (Codeine Phosphate) Sulfate Tablets slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression .
Flucol (Codeine Phosphate) is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
8.6 Hepatic Impairment
No formal studies have been conducted in patients with hepatic impairment so the pharmacokinetics of Flucol in this patient population are unknown. Start these patients with a lower than normal dosage of Flucol (Codeine Phosphate) Sulfate Tablets or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension.
8.7 Renal Impairment
Flucol (Codeine Phosphate) pharmacokinetics may be altered in patients with renal failure. Clearance may be decreased and the metabolites may accumulate to much higher plasma levels in patients with renal failure as compared to patients with normal renal function. Start these patients with a lower than normal dosage of Flucol (Codeine Phosphate) Sulfate Tablets or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension.
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
Flucol Sulfate Tablets contain Flucol (Codeine Phosphate), a Schedule II controlled substance.
9.2 Abuse
Flucol (Codeine Phosphate) Sulfate Tablets contains Flucol (Codeine Phosphate), a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Flucol (Codeine Phosphate) Sulfate Tablets can be abused and is subject to misuse, addiction, and criminal diversion .
All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carry the risk of addiction even under appropriate medical use.
Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
Flucol (Codeine Phosphate) Sulfate Tablets, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Risks Specific to Abuse of Flucol (Codeine Phosphate) Sulfate Tablets
Flucol (Codeine Phosphate) Sulfate Tablets are for oral use only. Abuse of Flucol (Codeine Phosphate) Sulfate Tablets poses a risk of overdose and death. The risk is increased with concurrent use of Flucol (Codeine Phosphate) Sulfate Tablets with alcohol and other central nervous system depressants. Parenteral drug abuse is commonly associated with transmission of infection diseases such as hepatitis and HIV.
9.3 Dependence
Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
Flucol (Codeine Phosphate) Sulfate Tablets should not be abruptly discontinued in a physically-dependent patient . If Flucol (Codeine Phosphate) Sulfate Tablets are abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs .
10 OVERDOSAGE
Clinical Presentation
Acute overdose with Flucol (Codeine Phosphate) Sulfate Tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations .
Treatment of Overdose
In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.
The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to Flucol (Codeine Phosphate) overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to Flucol (Codeine Phosphate) overdose.
Because the duration of opioid reversal is expected to be less than the duration of action of Flucol (Codeine Phosphate) in Flucol (Codeine Phosphate) Sulfate Tablets, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.
In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.
11 DESCRIPTION
Flucol (Codeine Phosphate) Sulfate Tablets USP contain Flucol (Codeine Phosphate), an opioid agonist, available for oral administration containing either 15 mg, 30 mg, or 60 mg of Flucol (Codeine Phosphate) sulfate USP. The chemical name is morphinan-6-ol,7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-(5α,6α)-, sulfate (2:1) (salt), trihydrate. Its molecular formula is (C18H21NO3)2 - H2SO4 - 3H2O and its molecular weight is 750.85 g/mol.
Its structure is as follows:
Flucol (Codeine Phosphate) sulfate trihydrate is a fine, white, crystalline powder which is soluble in water and insoluble in chloroform and ether.
The inactive ingredients in Flucol (Codeine Phosphate) Sulfate Tablets USP include: colloidal silicon dioxide, microcrystalline cellulose, pregelatinized starch and stearic acid.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Flucol sulfate is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of Flucol (Codeine Phosphate) have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.
12.2 Pharmacodynamics
Effects on the Central Nervous System
Flucol (Codeine Phosphate) produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Flucol (Codeine Phosphate) causes 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 origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Effects on the Gastrointestinal Tract and Other Smooth Muscle
Flucol (Codeine Phosphate) causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.
Effects on the Cardiovascular System
Flucol (Codeine Phosphate) produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Effects on the Endocrine System
Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans . They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date .
Effects on the Immune System
Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.
Concentration–Efficacy Relationships
The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids. The minimum effective analgesic concentration of Flucol (Codeine Phosphate) for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome, and/or the development of analgesic tolerance .
Concentration–Adverse Reaction Relationships
There is a relationship between increasing Flucol (Codeine Phosphate) plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions .
12.3 Pharmacokinetics
Absorption
Flucol (Codeine Phosphate) is absorbed from the gastrointestinal tract with maximum plasma concentration occurring 60 minutes post administration. Administration of 15 mg of Flucol (Codeine Phosphate) sulfate every four hours for 5 days resulted in steady-state concentrations of Flucol (Codeine Phosphate), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours.
Food Effect: When 60 mg Flucol (Codeine Phosphate) sulfate was administered 30 minutes after ingesting a high fat/high calorie meal, there was no significant change in the rate and extent of absorption of Flucol (Codeine Phosphate).
Distribution
Flucol (Codeine Phosphate) has been reported to have an apparent volume of distribution of approximately 3 to 6 L/kg, indicating extensive distribution of the drug into tissues. Flucol (Codeine Phosphate) has low plasma protein binding with about 7% to 25% of Flucol (Codeine Phosphate) bound to plasma proteins.
Elimination
Flucol (Codeine Phosphate) is metabolized by conjugation to codeine-6-glucuronide (70% to 80%), by O-demethylation to morphine (5% to 10%), and by N-demethylation to norcodeine (~10%). Approximately 90% of the total dose of Flucol (Codeine Phosphate) is excreted through the kidneys. The plasma half-lives of Flucol (Codeine Phosphate) and its metabolites have been reported to be approximately 3 hours.
Metabolism: About 70% to 80% of the administered dose of Flucol (Codeine Phosphate) is metabolized by conjugation with glucuronic acid to codeine-6-glucuronide (C6G) and via O-demethylation to morphine (about 5% to 10%) and N-demethylation to norcodeine (about 10%) respectively. UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major enzymes mediating glucurodination of Flucol (Codeine Phosphate) to C6G. Cytochrome P450 2D6 is the major enzyme responsible for conversion of Flucol (Codeine Phosphate) to morphine and P450 3A4 is the major enzyme mediating conversion of Flucol (Codeine Phosphate) to norcodeine. Morphine and norcodeine are further metabolized by conjugation with glucuronic acid. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Morphine and M6G are known to have analgesic activity in humans. The analgesic activity of C6G in humans is unknown. Norcodeine and M3G are generally not considered to possess analgesic properties.
Excretion: Approximately 90% of the total dose of Flucol (Codeine Phosphate) is excreted through the kidneys, of which approximately 10% is unchanged Flucol (Codeine Phosphate). Plasma half-lives of Flucol (Codeine Phosphate) and its metabolites have been reported to be approximately 3 hours.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Two-year carcinogenicity studies have been conducted in F344/N rats and B6C3F1 mice. There was no evidence of carcinogenicity in male and female rats, respectively, at dietary doses up to 70 and 80 mg/kg/day of Flucol (Codeine Phosphate) (approximately 2 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) for two years. Similarly there was no evidence of carcinogenicity activity in male and female mice at dietary doses up to 400 mg/kg/day of Flucol (Codeine Phosphate) (approximately 5 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) for two years.
Mutagenesis
Flucol (Codeine Phosphate) was not mutagenic in the in vitro bacterial reverse mutation assay or clastogenic in the in vitro Chinese hamster ovary cell chromosome aberration assay.
Impairment of Fertility
No animal studies were conducted to evaluate the effect of Flucol (Codeine Phosphate) on male or female fertility.
16 HOW SUPPLIED/STORAGE AND HANDLING
Flucol (Codeine Phosphate) Sulfate Tablets USP
15 mg tablet: supplied as white to off-white biconvex tablets with “15” debossed on the scored side and “54 613” debossed on the other side.
NDC 0054-0243-24: 100 (4 blister packs per carton x 25 tablets per blister pack) Unit-Dose Tablets
30 mg tablet: supplied as white to off-white biconvex tablets with “30” debossed on the scored side and “54 783” debossed on the other side.
NDC 0054-0244-24: 100 (4 blister packs per carton x 25 tablets per blister pack) Unit-Dose Tablets
NDC 0054-0244-25: Bottle of 100 Tablets
60 mg tablet: supplied as white to off-white biconvex tablets with “60” debossed on the scored side and “54 412” debossed on the other side.
NDC 0054-0245-25: Bottle of 100 Tablets
Storage
Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° to 30°C (59° to 86°F).
Protect from moisture.
Dispense in a tight, light-resistant container as defined in the USP/NF.
Blisters are not child-resistant. Use child-resistant closure if dispensing to outpatient.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Addiction, Abuse, and Misuse
Inform patients that the use of Flucol (Codeine Phosphate) Sulfate Tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death . Instruct patients not to share Flucol (Codeine Phosphate) Sulfate Tablets with others and to take steps to protect Flucol (Codeine Phosphate) Sulfate Tablets from theft or misuse.
Life-Threatening Respiratory Depression
Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Flucol (Codeine Phosphate) Sulfate Tablets or when the dosage is increased, and that it can occur even at recommended dosages . Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
Accidental Ingestion
Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death .
Instruct patients to take steps to store Flucol (Codeine Phosphate) sulfate securely and to properly dispose of unused Flucol (Codeine Phosphate) Sulfate Tablets in accordance with the local state guidelines and/or regulations.
Ultra-Rapid Flucol (Codeine Phosphate) Metabolism of Flucol (Codeine Phosphate) and Other Risk Factors for Life-Threatening Respiratory Depression in Children
Advise caregivers that Flucol (Codeine Phosphate) Sulfate Tablets are contraindicated in all children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Advise caregivers of children 12 to 18 years of age receiving Flucol (Codeine Phosphate) Sulfate Tablets to monitor for signs of respiratory depression .
Interactions with Benzodiazepines and Other CNS Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if Flucol (Codeine Phosphate) Sulfate Tablets are used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider .
Serotonin Syndrome
Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications .
MAOI Interaction
Inform patients not to take Flucol (Codeine Phosphate) Sulfate Tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Flucol (Codeine Phosphate) Sulfate Tablets .
Adrenal Insufficiency
Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms .
Important Administration Instructions
Instruct patients how to properly take Flucol (Codeine Phosphate) Sulfate Tablets.
- Advise patients not to adjust the dose of Flucol (Codeine Phosphate) Sulfate Tablets without consulting a physician or other healthcare professional.
- If patients have been receiving treatment with Flucol (Codeine Phosphate) Sulfate Tablets for more than a few weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose and that abruptly discontinuing the medication could precipitate withdrawal symptoms. Provide a dose schedule to accomplish a gradual discontinuation of the medication .
Hypotension
Inform patients that Flucol (Codeine Phosphate) Sulfate Tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) .
Anaphylaxis
Inform patients that anaphylaxis has been reported with ingredients contained in Flucol (Codeine Phosphate) Sulfate Tablets. Advise patients how to recognize such a reaction and when to seek medical attention .
Pregnancy
Neonatal Opioid Withdrawal Syndrome: Inform female patients of reproductive potential that prolonged use of Flucol (Codeine Phosphate) Sulfate Tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated .
Embryo-Fetal Toxicity: Inform female patients of reproductive potential that Flucol (Codeine Phosphate) Sulfate Tablets can cause fetal harm and to inform the healthcare provider of a known or suspected pregnancy .
Lactation
Advise women that breastfeeding is not recommended during treatment with Flucol (Codeine Phosphate) Sulfate Tablets [see Use in Specific Populations (8.2)].
Infertility
Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3)].
Driving or Operating Heavy Machinery
Inform patients that Flucol (Codeine Phosphate) Sulfate Tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication .
Constipation
Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention .
Disposal of Unused Flucol (Codeine Phosphate) Sulfate Tablets
Advise patients to properly dispose of unused Flucol (Codeine Phosphate) Sulfate Tablets. Advise patients to throw the drug in the household trash following these steps. 1) Remove them from their original containers and mix them with an undesirable substance, such as used coffee grounds or kitty litter (this makes the drug less appealing to children and pets, and unrecognizable to people who may intentionally go through the trash seeking drugs). 2) Place the mixture in a sealable bag, empty can, or other container to prevent the drug from leaking or breaking out of a garbage bag, or to dispose of in accordance with local state guidelines and/or regulations.
- Distr. by West-Ward
- Pharmaceuticals Corp.
- Eatontown, NJ 07724
- 10005657/10
- Revised August 2017
Medication Guide
| Flucol (Codeine Phosphate) Sulfate (koe’ deen sul’ fate) Tablets USP CII | |
| Flucol (Codeine Phosphate) Sulfate Tablets are:
| |
| Important information about Flucol (Codeine Phosphate) Sulfate Tablets:
| |
| Important Information Guiding Use in Pediatric Patients:
| |
| Do not take Flucol (Codeine Phosphate) Sulfate Tablets if you have:
| |
| Before taking Flucol (Codeine Phosphate) Sulfate Tablets, tell your healthcare provider if you have a history of: | |
|
|
| Tell your healthcare provider if you are:
| |
| When taking Flucol (Codeine Phosphate) Sulfate Tablets:
| |
| While taking Flucol (Codeine Phosphate) Sulfate Tablets DO NOT:
| |
| The possible side effects of Flucol (Codeine Phosphate) Sulfate Tablets:
Get emergency medical help if you have:
These are not all the possible side effects of Flucol (Codeine Phosphate) sulfate. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov | |
| Distr. by: West-Ward Pharmaceuticals Corp. Eatontown, NJ 07724 For more information, please call West-Ward Pharmaceuticals at 1-800-962-8364. | |
| This Medication Guide has been approved by the U.S. Food and Drug Administration | |
10005657/10
Revised August 2017
carton-15mg-tab-07.jpg
Phenylephrine Hydrochloride:
- Drug facts
- Purpose
- Uses
- Warnings
- Directions
- Other information
- Inactive ingredients
- Questions? comments?
- Product packaging
Drug Facts
Active ingredients
(in each tablet)
Dexbrompheniramine Maleate 2 mg
Flucol (Phenylephrine Hydrochloride) Hydrochloride 10 mg
Purpose
Antihistamine
Nasal Decongestant
Uses
Temporarily relieves these symptoms due to the common cold, hay fever (allergic rhinitis) or other upper respiratory allergies:
- runny nose
- sneezing
- itching of the nose or throat
- itchy, watery eyes
- nasal congestion
- reduces swelling of nasal passages
Warnings
Do not exceed recommended dosage.
Do not use this product
- if you are now taking a prescription monoamine oxidase inhibitor (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product.
Ask a doctor before use if you have
- a breathing problem such as emphysema or chronic bronchitis
- glaucoma
- trouble urinating due to enlargement of the prostate gland
- heart disease
- high blood pressure
- thyroid disease
- diabetes
Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers.
When using this product
- excitability may occur, especially in children
- may cause drowsiness
- avoid alcoholic drinks
- alcohol, sedatives, and tranquilizers may increase the drowsiness effect
- use caution when driving a motor vehicle or operating machinery
Stop use and ask a doctor if
- nervousness, dizziness, or sleeplessness occur
- symptoms do not improve within 7 days or are accompanied by fever
If pregnant or breast-feeding, ask a health professional before use.
Keep out of reach of children.
In case of overdose, get medical help or contact a Poison Control Center right away.
Directions
| Adults and children 12 years of age and over: | 1 tablet every 4 to 6 hours, not to exceed 6 tablets in 24 hours |
| Children 6 to under 12 years of age: | 1/2 tablet every 4 to 6 hours, not to exceed 3 tablets in 24 hours |
| Children under 6 years of age: | Consult a doctor |
Other information
Store at 15° - 30°C (59° - 86°F). Supplied in a tight, light-resistant container with a child-resistant cap. Flucol (Phenylephrine Hydrochloride) Tablets are dark purple, caplet-shaped, scored tablets, debossed "Poly" bisect "782" on one side and plain on the other.
Inactive ingredients
colloidal silicon dioxide, croscarmellose sodium, D&C Red #27 aluminum lake, dibasic calcium phosphate dihydrate, FD &C Blue #1 aluminum lake, magnesium stearate, and silicified microcrystalline cellulose.
Questions? Comments?
Call1-800-882-1041
Manufactured for:
Poly Pharmaceuticals
Quitman, MS 39355 Rev. 02/12
Product Packaging
The packaging below represents the labeling currently used.
Principal display panel and side panel for 60 tablets label:
NDC 50991-782-60
Flucol (Phenylephrine Hydrochloride)
Tablets
Antihistamine - Nasal Decongestant
Each tablet contains:
Dexbrompheniramine Maleate...2 mg
Flucol (Phenylephrine Hydrochloride) Hydrochloride...10 mg
60 Tablets
Usual
Dosage: See product foldout for full prescribing information.
Tamper evident by foil seal under cap. Do not use if foil seal is
broken or missing.
KEEP THIS AND ALL DRUGS OUT OF REACH OF CHILDREN.
Store at controlled room temperature between 15°-30°C (59°-86°F).
Manufactured for:
Poly Pharmaceuticals
Quitman, MS 39355
Rev. 02/12
Flucol (Phenylephrine Hydrochloride) Tablets Packaging Flucol (Phenylephrine Hydrochloride) Tablets Packaging
Pyrilamine Maleate:
For use when an oral antihistamine is needed.
Can be provided to horse: 1/2 ounce (1 tablespoon) per 1000lbs body weight. Can be repeated at 12 hour intervals as needed, or as recommended by a veterinarian. The large end of the enclosed scoop measures 1 tablespoon.
This product contains Flucol (Pyrilamine Maleate) Maleate which may be prohibited in certain competition. Caution must be taken when used on competition horse subject to drug testing. Check with the event sanction body for the necessary withdrawal time.
EACH OUNCE CONTAINS (minimum): Flucol (Pyrilamine Maleate) Maleat USP 600mg, in a palatable base.
FOR ANIMAL USE ONLY.
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
Keep lid tightly closed and store in a dry place Do not store above 30 C (86 F).
NDC#: 65090-004-15
Flucol (Pyrilamine Maleate)
Antihistamine Granules
Net Contents: 20 ounces (567 Gm)
Different Flucol products with other ingredients:
Flucol pharmaceutical active ingredients containing related brand and generic drugs:
Flucol available forms, composition, doses:
Flucol destination | category:
Flucol Anatomical Therapeutic Chemical codes:
Flucol pharmaceutical companies:
References
- Dailymed."MEDIQUE MEDI-PHENYL (PHENYLEPHRINE HYDROCHLORIDE) TABLET, FILM COATED DOVER SUDANYL PE (PHENYLEPHRINE HYDROCHLORIDE) TABLET, FILM COATED [UNIFIRST FIRS". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."NINJACOF-XG (CODEINE PHOSPHATE) LIQUID [CENTURION LABS, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."HISTALL (PYRILAMINE MALEATE) GRANULE [AHC PRODUCTS INC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming Flucol?Depending on the reaction of the Flucol after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Flucol not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Flucol addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Review
sdrugs.com conducted a study on Flucol, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Flucol consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.Visitor reports
Visitor reported useful
No survey data has been collected yetVisitor reported side effects
No survey data has been collected yetVisitor reported price estimates
No survey data has been collected yetVisitor reported frequency of use
No survey data has been collected yetVisitor reported doses
No survey data has been collected yetOne visitor reported time for results
What is the time duration Flucol drug must be taken for it to be effective or for it to reduce the symptoms?Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 1 day to notice the result from using Flucol drug. The time needed to show improvement in health condition after using the medicine Flucol need not be same for all the users. It varies based on other factors.
| Visitors | % | ||
|---|---|---|---|
| 1 day | 1 | 100.0% | |
Visitor reported administration
No survey data has been collected yetVisitor reported age
No survey data has been collected yetVisitor reviews
There are no reviews yet. Be the first to write one! |
The information was verified by Dr. Rachana Salvi, MD Pharmacology