Butalbital, Aspirin, Caffeine And Codeine Phosphate

FDA Drug Information • Also known as: Ascomp With Codeine, Butalbital, Aspirin, Caffeine And Codeine Phosphate

Brand Names: Ascomp With Codeine, Butalbital, Aspirin, Caffeine And Codeine Phosphate
Drug Class: Nonsteroidal Anti-inflammatory Drug [EPC], Platelet Aggregation Inhibitor [EPC], Barbiturate [EPC], Central Nervous System Stimulant [EPC], Methylxanthine [EPC]
Route: ORAL
Dosage Form: CAPSULE
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE. WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE See full prescribing information for complete boxed warning. BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE exposes users to the risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing and monitor regularly for these behaviors and conditions. ( 5.1 ) Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. ( 5.2 ) Accidental ingestion of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE, especially by children, can result in fatal overdose. ( 5.2 ) Concomitant use of opioids or a barbiturate with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. ( 5.3 , 5.9 , 7 ) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. ( 5.4 ) To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products ( 5.5 ) Life-threatening respiratory depression and death have occurred in children who received codeine; most cases followed tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. ( 5.6 ) BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy ( 4 ). Avoid the use of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE 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. 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 BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE requires careful consideration of the effects on codeine, and the active metabolite, morphine. ( 5.7 , 5.9 , 7 ) Addiction, Abuse, and Misuse Because the use of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE 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 and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.1 ) ]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE are essential [see Warnings and Precautions ( 5.2 )] Accidental Ingestion Accidental ingestion of even one dose of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE, especially by children, can result in a fatal overdose of aspirin, butalbital, caffeine and codeine phosphate [see Warnings and Precautions ( 5.2 )]. 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 BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. [see Warnings and Precautions ( 5.3 , 5.9 ), Drug Interactions ( 7 )]. Neonatal Opioid Withdrawal Syndrome (NOWS) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions ( 5.4 )]. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMScompliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings and Precautions ( 5.5 )]. 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. [see Warnings and Precautions ( 5.6 )]. BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications ( 4 )]. Avoid the use of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE 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. 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 BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE requires careful consideration of the effects on codeine, and the active metabolite, morphine [see Warnings and Precautions ( 5.7 , 5.9 ), Drug Interactions ( 7 )].

Description

11 DESCRIPTION BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE USP is supplied in capsule form for oral administration. Each capsule contains the following active ingredients: Butalbital, USP……………..50 mg Aspirin, USP………………..325 mg Caffeine, USP………………40 mg Codeine phosphate, USP…...30 mg Butalbital (5-allyl-5-isobutyl-barbituric acid) is a short- to intermediate-acting barbiturate. It has the following structural formula: Its molecular weight is 224.26 and its molecular formula is C 11 H 16 N 2 O 3 . Aspirin (benzoic acid, 2-(acetyloxy)-) is a nonsteroidal anti-inflammatory drug. It has the following structural formula: Its molecular weight is 180.16 and its molecular formula is C 9 H 8 O 4 . Caffeine (1,3,7-trimethylxanthine), a methylxanthine, is a central nervous system stimulant. It has the following structural formula: Its molecular weight is 194.19 and its molecular formula is C 8 H 10 N 4 O 2 . Codeine phosphate (7,8-Didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate) is an opioid agonist. It has the following structural formula: Its molecular weight is 397.37 and its molecular formula is C 18 H 24 NO 7 P. Inactive Ingredients : D&C Yellow #10, D&C Yellow #10 Aluminum Lake, D&C Red #33, D&C Red #28, FD&C Blue #1, FD&C Blue #1 Aluminum Lake, gelatin, microcrystalline cellulose, pregelatinized starch, talc, titanium dioxide, stearic acid, colloidal silicon dioxide. Butalbital Structural Formula Aspirin Structural Formula Caffeine Structural Formula Codeine Phosphate Structural Formula

What Is Butalbital, Aspirin, Caffeine And Codeine Phosphate Used For?

1 INDICATIONS AND USAGE BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE is indicated for the management of the symptom complex of tension (or muscle contraction) headache, when non-opioid analgesic and alternative treatments are inadequate. BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE is a combination of butalbital, a barbiturate, aspirin, a nonsteroidal anti-inflammatory drug, caffeine, a methylxanthine, and codeine phosphate, an opioid agonist, and is indicated for the management of the symptom complex of tension (or muscle contraction) headache, when other non-opioid analgesics and alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain ( 1 , 5.1 ). BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions ( 5.1 ) ] , reserve opioid analgesics, including BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Periodically reassess patients receiving BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse ( 2.1 , 5.1 ) Discuss availability of naloxone with the patient and caregiver and assess each patient's need for access to naloxone, both when initiating and renewing treatment with BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE. Consider prescribing naloxone based on the patient's risk factors for overdose. ( 2.2 , 5.1 , 5.2 , 5.3 ) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ( 2.2 , 5.1 , 5.2 , 5.3 ) BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. ( 2.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Initiate treatment with one or two capsules every 4 hours as needed for pain and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE. Total daily dosage should not exceed 6 capsules. ( 2 , 5 ) Do not rapidly reduce or abruptly discontinue BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.4 ,...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 ) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (( 5.2 ) Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions ( 5.3 ) Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children [see Warnings and Precautions ( 5.6 ) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 ) ] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.8 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.11 ) ] Severe Hypotension [see Warnings and Precautions ( 5.12 ) ] Risks of Use in Patients with Gastrointestinal Conditions Including Peptic Ulcer Disease [see Warnings and Precautions ( 5.14 ) ] Increased Risk of Seizures in Patients with Seizure Disorders [see Warnings and Precautions ( 5.15 ) ] Withdrawal [see Warnings and Precautions ( 5.16 ) ] Coagulation Abnormalities and Bleeding Risks [see Warnings and Precautions ( 5.19 ) ] Reye's Syndrome [see Warnings and Precautions ( 5.20 ) ] Serious Skin Reactions [see Warnings and Precautions ( 5.21 ) ] Allergy [see Warnings and Precautio n s ( 5.23 ) ] Most common adverse reactions (incidence > 1%) are nausea and/or abdominal pain, drowsiness, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Incidence in Controlled Clinical Trials The following table summarizes the incidence rates of the adverse events reported by at least 1% of the BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE treated patients in controlled clinical trials comparing BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE to placebo, and provides a comparison to the incidence rates reported by the placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. Table 1:Adverse Events Reported by at least 1% of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE Treated Patients During Placebo Controlled Clinical Trials Incidence Rate of Adverse Events Body System/Adverse Event BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE (N=382) Placebo (N =377) Central Nervous Drowsiness 2.4% 0.5% Dizziness/Lightheadedness 2.6% 0.5% Intoxicated Feeling 1.0% 0% Gastrointestinal Nausea/Abdominal Pain 3.7% 0.8% Other Adverse Events Reported During Controlled Clinical Trials The listing that follows represents the proportion of the 382 patients exposed to BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE while participating in the controlled clinical trials who reported, on at least one occasion, an adverse event of the type cited. All reported adverse events, except those already presented in the previous table, are included. It is important to emphasize that, although the adverse events reported did occur while the patient was receiving BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE, the adverse events were not necessarily caused by BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE. Adverse events are classified by body system and frequency. “Frequent” is defined as an adverse event which occurred in at...

Drug Interactions

7 DRUG INTERACTIONS Table 2 includes clinically significant drug interactions with BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE. Table 2: Clinically Significant Drug Interactions With BUTALBITAL, ASPIRIN, CAFFEINE And CODEINE PHOSPHATE Inhibitors of CYP3A4 Clinical Impact: The concomitant use of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE with CYP3A4 inhibitors may result in an increase in codeine 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 BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE 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 metabolism via 2D6 with resultant lower morphine levels [see Clinical Pharmacology ( 12.3 )] , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to codeine. Intervention: If concomitant use with a CYP3A4 inhibitor is necessary, consider dosage reduction of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 inhibitor is discontinued, consider increasing the BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE dosage until stable drug effects are achieved. Evaluate 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 BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE and CYP3A4 inducers can result in lower codeine levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels [see Clinical Pharmacology ( 12.3 ) ] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence [see Warnings and Precautions ( 5.16 )]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the codeine plasma concentration 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, evaluate patients at frequent intervals for reduced efficacy and signs of opioid withdrawal and consider increasing the BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE dosage as needed. If a CYP3A4 inducer is discontinued, consider BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE dosage reduction, and evaluate patients at frequent...

Contraindications

4 CONTRAINDICATIONS BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE is contraindicated for: All children younger than 12 years of age [see Warnings and Precautions ( 5.6 ) ] Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy[see Warnings and Precautions ( 5.6 ) ]. BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE is also contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.9 ) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment[see Warnings and Precautions ( 5.9 ) ] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Warnings and Precautions ( 5.10 ) / Drug Interactions ( 7 ) ]. Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.14 ) ] Hypersensitivity or intolerance to aspirin, caffeine, butalbital, or codeine. Hemophilia [see Warnings and Precautions ( 5.19 ) ] Reye's Syndrome [ see Warnings and Precautions ( 5.20 ) ] Known allergy to nonsteroidal anti-inflammatory drugs (NSAIDs) [see Warnings and Precautions ( 5.23 ) ] Syndrome of asthma, rhinitis, and nasal polyps [see Warnings and Precautions ( 5.23 ) ] Children younger than 12 years of age ( 4 ) Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy ( 4 ) Significant respiratory depression ( 4 ) Acute or severe bronchial asthma ( 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 aspirin, caffeine, butalbital, or codeine ( 4 ) Hemophilia ( 4 ) Reye's Syndrome ( 4 ) Known allergy to NSAIDs ( 4 ) Syndrome of asthma, rhinitis, and nasal polyps ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome. [see Warnings and Precautions ( 5.4 ) ]. Use of NSAIDS, including aspirincan cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE use between about 20 and 30 weeks of gestation, and avoid BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE use at about 30 weeks of gestation and later in pregnancy [ see Clinical Considerations , Data ] . Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including aspirin, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Animal reproduction studies have not been conducted with the combination of butalbital, aspirin, caffeine, and codeine phosphate capsules or with butalbital alone. In animal reproduction studies, codeine administration during organogenesis has been shown to produce delayed ossification in the offspring of mice at 2.8 times maximum recommended human dose (MRHD) of 180 mg/day, embryolethal and fetotoxic effects in the offspring of rats and hamsters at approximately 4 to 6 times the MRHD, and cranial malformations/ cranioschisis in the offspring of hamsters between 2 and 8 times the MRHD [ see Data ]. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as aspirin, resulted...

Overdosage

10 OVERDOSAGE Clinical Presentation Acute overdose with BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE 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, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 ) ]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Signs and Symptoms Acute Barbiturate Poisoning: Symptoms include drowsiness, confusion, and coma; respiratory depression; hypotension; hypovolemic shock. Acute Aspirin Poisoning: Symptoms include hyperpnea; acid-base disturbances with development of metabolic acidosis; vomiting and abdominal pain; tinnitus, hyperthermia; hypoprothrombinemia; restlessness; delirium; convulsions. Acute Caffeine Poisoning: Symptoms include insomnia, restlessness, tremor, and delirium; tachycardia and extrasystoles. Codeine: Acute overdose with codeine 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 [see Clinical Pharmacology ( 12.2 ) ]. 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...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Each yellow and blue BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE Capsule USP 50 mg/325 mg/ 40 mg/30 mg is imprinted JSP 507 Bottles of 100 NDC 69238-1993-1 Store and Dispense Below 25°C (77°F); in a tight, light resistant container. Keep out of reach of children

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.