Generic drug: butalbital, aspirin, caffeine, and codeine phosphate
Brand name: Fiorinal with Codeine
What is Fiorinal with Codeine, and how does it work?
Fiorinal with Codeine (butalbital, aspirin, caffeine, and codeine phosphate) is a prescription medicine used to treat the symptoms of Tension Headache. Fiorinal with Codeine may be used alone or with other medications.
Fiorinal with Codeine belongs to a class of drugs called Analgesics, Opioid Combos.
It is not known if Fiorinal with Codeine is safe and effective in children younger than 16 years of age.
What are the side effects of Fiorinal with Codeine?
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 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
- 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:
- difficulty breathing,
- swelling of your face, lips, tongue, or throat,
- slow breathing with long pauses,
- blue colored lips,
- difficulty to wake up,
- noisy breathing,
- shallow breathing,
- breathing that stops during sleep,
- slow heart rate,
- weak pulse,
- unusual thoughts or behavior,
- easy bruising or bleeding,
- bleeding gums,
- severe constipation,
- bloody or tarry stools,
- coughing up blood,
- vomit that looks like coffee grounds,
- loss of appetite,
- worsening tiredness,
- fast heart rate,
- muscle stiffness
- loss of coordination, and
- Get medical help right away, if you have any of the symptoms listed above.
- The most common side effects of Fiorinal with Codeine include:
- 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.
Does Fiorinal with Codeine cause addiction or withdrawal symptoms?
Drug Abuse And Dependence
- Fiorinal with Codeine contains codeine. Codeine in combination with butalbital, aspirin, and caffeine is a Schedule III controlled substance.
- 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.
- 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.
- 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
- Infants born to mothers physically dependent on opioids will also be
physically dependent and may exhibit respiratory difficulties and withdrawal
What is the dosage for Fiorinal with Codeine?
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.
- 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
- Other signs and symptoms also may develop, including
- 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.
Latest Migraine News
- Can You Eat Your Way to Fewer Migraines?
- What Works Best for Migraines?
- Pot May Not Be the Best Rx for a Migraine
- Migraines? Get Moving: Exercise Can Curb Attack
- Can Mindfulness Help Ease Migraine?
- Want More News? Sign Up for MedicineNet Newsletters!
Daily Health News
- H5N6 Bird Flu Infection in China
- COVID Vaccine Misinformation
- Antibiotic-Resistant Pneumonia
- Mask Mandate Returns to L.A.
- Fermented Foods Help Microbiome
- More Health News »
Trending on MedicineNet
- Guillain-Barre Syndrome
- What Triggers Shingles?
- Normal Blood Sugar Levels
- Identify Tick Bites
- Why Is Autism Increasing?
What are your other options?
Learn More on
What drugs interact with Fiorinal with Codeine?
Table 1 includes clinically significant drug interactions with Fiorinal with
Table 1: Clinically Significant Drug Interactions with
Fiorinal with Codeine
Inhibitors of CYP3A4
The concomitant use of Fiorinal with Codeine with CYP3A4 inhibitors may result in an increase in codeine plasma concentrations with subsequently metabolism by cytochrome CYP2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fat depression, particularly when an inhibitor is added after a stable dose of
Fiorinal with Codeine is achieved.
After stopping a CYP3A4 inhibitor, as the effects of the
inhibitor decline, it may result in lower codeine levels, greater
norcodeine levels, and less metaboli with resultant lower morphine
levels, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who developed physical dependence to codeine.
If concomitant use with CYP3A4 inhibitor is necessary, consider dosage reduction of
Fiorinal with Codeine until stable drug effects are achieved. M patients for respiratory depression and sedation at frequent intervals.
If a CYP3A4 inhibitor is discontinued, consider increasing the
Fiorinal with Codeine dosage until stable drug effects are achieved. Monitor for signs withdrawal.
Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir)
The concomitant use of Fiorinal with Codeine and CYP3A4 inducers
can result in lower codeine levels, greater norcodeine levels, and
less metabolis with resultant lower morphine levels, resulting in
decreased efficacy or onset of a withdrawal syndrome in patients who
developed physical dependence.
After stopping a CYP3A4 inducer, as the effects of the inducer
decline, the codeine plasma concentration may increase with
subsequently greater metaboli cytochrome CYP2D6, resulting in
greater morphine levels, which could increase or prolong both the therapeutic effect reactions, and may cause serious respiratory depression.
If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy and signs of opioid withdrawal and consider increasing the FI with CODEINE dosage as needed.
If a CYP3A4 inducer is discontinued, consider Fiorinal with
Codeine dosage reduction, and monitor for signs of respiratory depression and sedation intervals.
Rifampin, carbamazepine, phenytoin
Inhibitors of CYP2D6
Codeine in Fiorinal with Codeine is metabolized by CYP2D6 to form morphine. The concomitant use of
Fiorinal with Codeine and CYP2D6 i increase the plasma concentration of codeine, but can decrease the plasma concentrations of active metabolite morphine which could result in reduced anal
efficacy or symptoms of opioid withdrawal, particularly when an
inhibitor is added after a stable dose of Fiorinal with Codeine is
After stopping a CYP2D6 inhibitor, as the effects of the inhibitor
decline, the codeine plasma concentration will decrease but the
active metabolite morphin concentration will increase, which could
increase or prolong adverse reactions and may cause potentially
fatal respiratory depression.
If concomitant use with a CYP2D6 inhibitor is necessary, or if a CYP2D6 inhibitor is discontinued after concomitant use, consider dosage adjustment of FI with CODEINE 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 the
Fiorinal with Codeine as needed.
After stopping use of a CYP2D6 inhibitor, consider reducing the
Fiorinal with Codeine and monitor the patient for signs and symptoms of respiratory or sedation.
paroxetine, fluoxetine, bupropion, quinidine
Benzodiazepines and other Central Nervous System (CNS) Depressants
Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, increases the risk of respiratory profound sedation, coma, and death.
Reserve concomitant prescribing of these drugs for use in
patients for whom alternative treatment options are inadequate.
Limit dosages and durations to th required. Follow patients closely
for signs of respiratory depression and sedation.
Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.
The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue FIORINAL with C serotonin syndrome is suspected.
Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methyle
Monoamine Oxidase Inhibitors (MAOIs)
MAOI interactions with opioids may manifest as serotonin
syndrome or opioid toxicity (e.g., respiratory depression, coma)
Do not use Fiorinal with Codeine 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.
phenelzine, tranylcypromine, linezolid
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
May reduce the analgesic effect of Fiorinal with Codeine and/or precipitate withdrawal symptoms.
Avoid concomitant use.
butorphanol, nalbuphine, pentazocine, buprenorphine
Codeine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of
Fiorinal with Codeine an muscle relaxant as necessary.
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
The effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin du inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Monitor patients for signs of urinary retention or reduced gastric motility when
Fiorinal with Codeine is used concomitantly with anticholinergic dru
Aspirin may enhance the effects of anticoagulants. Concurrent use may increase the risk of bleeding. Aspirin can also displace warfarin from protein bindin leading to prolongation of both the prothrombin time and the bleeding time.
Monitor patients for signs of bleeding.
Warfarin, heparin, enoxaparin, clopidogrel, prasugrel, rivaroxaban, apixaban
Aspirin inhibits the uricosuric effects of uricosuric agents.
Avoid concomitant use.
Carbonic Anhydrase Inhibitors
Concurrent use with aspirin can lead to high serum concentrations of the carbonic anhydrase inhibitor and cause toxicity due to competition at the renal tub secretion.
Consider reducing the dose of the carbonic anhydrase inhibitor and monitor patient for any adverse effects from the carbonic anhydrase inhibitor.
Aspirin may enhance the toxicity of methotrexate by displacing it from its plasma protein binding sites and/or reducing its renal clearance.
Use caution if using concomitantly, especially in elderly patients or patients with renal impairment. Monitor patients for methotrexate toxicity.
Concomitant use with aspirin may lead to additive nephrotoxicity due to the inhibition of renal prostaglandins by aspirin. Also, the plasma concentration of increased by conditions that reduce the glomerular filtration rate or tubular secretion.
Use Fiorinal with Codeine with caution if used concomitantly with nephrotoxic agents. Closely monitor the renal function of patients
Aminoglycosides, amphotericin B, systemic bacitracin, cisplatin, cyclosporine, foscarnet, or parenteral vancomycin
Angiotensin Converting Enzyme (ACE) Inhibitors
The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to its indirect effect on th angiotensin conversion pathway.
Use caution if using concomitantly. Monitor the blood pressure and renal function of patients.
The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading renal blood flow, and salt and fluid retention.
Use caution if using concomitantly. Monitor the blood pressure and renal function of patients
Aspirin may increase the serum glucose-lowering action of insulin and sulfonylureas leading to hypoglycemia.
Patients should be advised to consult a physician if any signs or symptoms of hypoglycemia occur.
Insulin, glimepiride, glipizide
Aspirin can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic levels.
Use caution if using concomitantly.
Phenytoin, valproic acid
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Concurrent use with aspirin may increase the risk of bleeding or lead to decreased renal function. Aspirin may enhance serious side effects and toxicity of k displacing it from its plasma protein binding sites and/or reducing its renal clearance.
Avoid concomitant use.
Ketorolac, ibuprofen, naproxen, diclofenac
In patients receiving concomitant corticosteroids and chronic use of aspirin, withdrawal of corticosteroids may result in salicylism because corticosteroids e clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Avoid concomitant use
Who suffers more frequently from migraine headaches?
Is Fiorinal with Codeine safe to use while pregnant or breastfeeding?
- 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