Fiorinal with Codeine (butalbital, aspirin, caffeine, and codeine phosphate)

WARNING

ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFETHREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWL SYNDROME; and INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES

Addiction, Abuse, and Misuse

• Fiorinal with Codeine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Fiorinal with Codeine, and monitor all patients regularly for the development of these behaviors and conditions.

Life-Threatening Respiratory Depression

• Serious, life-threatening, or fatal respiratory depression may occur with use of Fiorinal with Codeine. Monitor for respiratory depression, especially during initiation of Fiorinal with Codeine or following a dose increase.

Accidental Ingestion

• Accidental ingestion of even one dose of Fiorinal with Codeine, especially by children, can result in a fatal overdose of Fiorinal with Codeine.

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

• Reserve concomitant prescribing of Fiorinal with Codeine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.

Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children

• Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism.
• Fiorinal with Codeine is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy.
• Avoid the use of Fiorinal with Codeine in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.

Neonatal Opioid Withdrawal Syndrome

• Prolonged use of Fiorinal with Codeine during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
• If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

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 codeine are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Fiorinal with Codeine requires careful consideration of the effects on codeine, and the active metabolite, morphine.
• Fiorinal with Codeine may cause serious side effects including:
  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • slow breathing with long pauses,
  • blue colored lips,
  • difficulty to wake up,
  • noisy breathing,
  • sighing,
  • shallow breathing,
  • breathing that stops during sleep,
  • slow heart rate,
  • weak pulse,
  • lightheadedness,
  • confusion,
  • unusual thoughts or behavior,
  • easy bruising or bleeding,
  • nosebleeds,
  • bleeding gums,
  • severe constipation,
  • bloody or tarry stools,
  • coughing up blood,
  • vomit that looks like coffee grounds,
  • nausea,
  • vomiting,
  • loss of appetite,
  • dizziness,
  • worsening tiredness,
  • weakness,
  • agitation,
  • hallucinations,
  • fever,
  • sweating,
  • shivering,
  • fast heart rate,
  • muscle stiffness
  • twitching,
  • loss of coordination, and
  • diarrhea
• Get medical help right away, if you have any of the symptoms listed above.
• The most common side effects of Fiorinal with Codeine include:
  • nausea,
  • vomiting,
  • stomach pain,
  • constipation,
  • headache,
  • dizziness,
  • drowsiness, and
  • tiredness
• Tell the doctor if you have any side effect that bothers you or that does not go away.
• These are not all the possible side effects of Fiorinal with Codeine. For more information, ask your doctor or pharmacist.
• Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Drug Abuse And Dependence

Controlled Substance

• Fiorinal with Codeine contains codeine. Codeine in combination with butalbital, aspirin, and caffeine is a Schedule III controlled substance.

Abuse

• Fiorinal with Codeine contains codeine, a substance with a high potential for abuse similar to other opioids, including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Fiorinal with Codeine 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 carries 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.
• Fiorinal with Codeine, 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 Fiorinal with Codeine

• Fiorinal with Codeine is for oral use only. Abuse of Fiorinal with Codeine poses a risk of overdose and death. The risk is increased with concurrent abuse of Fiorinal with Codeine with alcohol and other central nervous system depressants.
• Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Butalbital

• Barbiturates may be habit-forming. Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates.
• The average daily dose for the barbiturate addict is usually about 1,500 mg. As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than twofold. As this occurs, the margin between an intoxication dosage and fatal dosage becomes smaller.
• The lethal dose of a barbiturate is far less if alcohol is also ingested.
• Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs.
• Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days.
• Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug.
• Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens.
• One method involves initiating treatment at the patient’s regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

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 is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting 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.
• Do not abruptly discontinue Fiorinal with Codeine in a patient physically dependent on opioids. Rapid tapering of Fiorinal with Codeine in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.
• When discontinuing Fiorinal with Codeine, gradually taper the dosage using a patient-specific plan that considers the following: the dose of Fiorinal with Codeine the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper.
• Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs.

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.

Dosing Information

• One or two capsules every 4 hours. Total daily dosage should not exceed 6 capsules.

Safe Reduction Or Discontinuation Of FIORINAL With CODEINE

• Do not abruptly discontinue Fiorinal with Codeine in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.
• Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.
• When a decision has been made to decrease the dose or discontinue therapy in an opioid dependent patient taking Fiorinal with Codeine, there are a variety of factors that should be considered, including the dose of Fiorinal with Codeine the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.
• It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.
• There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on Fiorinal with Codeine who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
• It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge.
• Common withdrawal symptoms include
  • 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.
• If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.
• When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic.

Table 1 includes clinically significant drug interactions with Fiorinal with Codeine.

Table 1: Clinically Significant Drug Interactions with Fiorinal with Codeine

• Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome.
• Use of aspirin, including Fiorinal with Codeine, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus.
• Avoid use of NSAIDs, including Fiorinal with Codeine, in pregnant women starting at 30 weeks of gestation (third trimester).
• Available data with Fiorinal with Codeine in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.
• Breastfeeding is not recommended during treatment with Fiorinal with Codeine.