Ascomp with Codeine

• Breckenridge Pharmaceutical, Inc.

• Genetco, Inc.

• Nexgen Pharma, Inc.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Like other narcotic medicines, codeine can slow your breathing. Death may occur if breathing becomes too weak.

A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.

Call your doctor at once if you have:

• noisy breathing, sighing, shallow breathing;

• a slow heart rate or weak pulse;

• a light-headed feeling, like you might pass out;

• confusion, unusual thoughts or behavior;

• severe constipation;

• symptoms of stomach bleeding--bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or

• symptoms of low adrenal gland hormones--worsening tiredness or muscle weakness, feeling light-headed, nausea, vomiting, and loss of appetite.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

Serious side effects may be more likely in older adults and those who are overweight, malnourished, or debilitated.

Long-term use of opioid medication may affect fertility (ability to have children) in men or women. It is not known whether opioid effects on fertility are permanent.

Common side effects include:

• nausea, vomiting, stomach pain, constipation;

• headache, dizziness, drowsiness; or

• feeling tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Trouble breathing, slow breathing, or shallow breathing.
• Noisy breathing.
• Feeling very sleepy.
• Very bad dizziness or passing out.
• Feeling confused.
• Chest pain or pressure or a fast heartbeat.
• Any unexplained bruising or bleeding.
• Ringing in ears.
• Seizures.
• Very bad belly pain.
• Very hard stools (constipation).
• Feeling very tired or weak.
• Mood changes.
• A very bad and sometimes deadly health problem called serotonin syndrome may happen if you take Ascomp with Codeine with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
• Very bad stomach ulcers or bleeding can happen with this medicine. Taking it in high doses or for a long time, smoking, or drinking alcohol raises the chance of these side effects. Taking Ascomp with Codeine with food will not lower the chance of these effects. Call your doctor or get medical help right away if you get very bad stomach or back pain; black, tarry, or bloody stools; throwing up blood or throw up that looks like coffee grounds; or weight gain or swelling that is not normal.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Ascomp with Codeine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Ascomp with Codeine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Ascomp with Codeine (butalbital, aspirin, caffeine, and codeine).

Review Date: October 4, 2017

General

Ascomp with Codeine should be prescribed with caution for certain special-risk patients such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, coagulation disorders, or head injuries, elevated intracranial pressure, acute abdominal conditions, hypothyroidism, urethral stricture, Addison’s disease, prostatic hypertrophy, and peptic ulcer.

Aspirin should be used with caution in patients on anticoagulant therapy and in patients with underlying hemostatic defects.

Precautions should be taken when administering salicylates to persons with known allergies. Hypersensitivity to aspirin is particularly likely in patients with nasal polyps, and relatively common in those with asthma.

Information for patients

Patients should be informed that Ascomp with Codeine contains aspirin and should not be taken by patients with an aspirin allergy.

Ascomp with Codeine may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking Ascomp with Codeine .

Alcohol and other CNS depressants may produce an additive CNS depression when taken with Ascomp with Codeine , and should be avoided.

Codeine and butalbital may be habit-forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.

For information on use in geriatric patients, refer to PRECAUTIONS, Geriatric use.

Advise patients that some people have a genetic variation that results in codeine changing into morphine more rapidly and completely than other people. Most people are unaware of whether they are an ultra-rapid codeine metabolizer or not. These higher-than-normal levels of morphine in the blood may lead to life-threatening or fatal respiratory depression or signs of overdose such as extreme sleepiness, confusion, or shallow breathing. Children with this genetic variation who were prescribed codeine after tonsillectomy and/or adenoidectomy for obstructive sleep apnea may be at greatest risk based on reports of several deaths in this population due to respiratory depression. Ascomp with Codeine is contraindicated in children who undergo tonsillectomy and/or adenoidectomy. Advise caregivers of children receiving Ascomp with Codeine for other reasons to monitor for signs of respiratory depression.

Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. Instruct nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Instruct nursing mothers to talk to the baby's doctor immediately if they notice these signs and, if they cannot reach the doctor right away, to take the baby to an emergency room or call 911 (or local emergency services).

Laboratory tests

In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

Drug interactions

The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors.

In patients receiving concomitant corticosteroids and chronic use of aspirin, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Ascomp with Codeine may enhance the effects of:

Ascomp with Codeine may diminish the effects of:

Uricosuric agents such as probenecid and sulfinpyrazone, reducing their effectiveness in the treatment of gout. Aspirin competes with these agents for protein binding sites.

Drug/laboratory test interactions

Aspirin: Aspirin may interfere with the following laboratory determinations in blood: serum amylase, fasting blood glucose, cholesterol, protein, serum glutamic-oxalacetic transaminase (SGOT), uric acid, prothrombin time and bleeding time. Aspirin may interfere with the following laboratory determinations in urine: glucose, 5-hydroxy-indoleacetic acid, Gerhardt ketone, vanillylmandelic acid (VMA), uric acid, diacetic acid, and spectrophotometric detection of barbiturates.

Codeine: Codeine may increase serum amylase levels.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Adequate long-term studies have been conducted in mice and rats with aspirin, alone or in combination with other drugs, in which no evidence of carcinogenesis was seen. No adequate studies have been conducted in animals to determine whether aspirin has a potential for mutagenesis or impairment of fertility. No adequate studies have been conducted in animals to determine whether butalbital has a potential for carcinogenesis, mutagenesis, or impairment of fertility.

Usage in Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Ascomp with Codeine. It is also not known whether Ascomp with Codeine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Ascomp with Codeine should be given to a pregnant woman only when clearly needed.

Although Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP was not implicated in the birth defect, a female infant was born with lissencephaly, pachygyria and heterotopic gray matter. The infant was born 8 weeks prematurely to a woman who had taken an average of 90 Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP each month from the first few days of pregnancy. The child’s development was mildly delayed and from one year of age she had partial simple motor seizures.

Withdrawal seizures were reported in a two-day-old male infant whose mother had taken a butalbitalcontaining drug during the last 2 months of pregnancy. Butalbital was found in the infant’s serum. The infant was given phenobarbital 5 mg/kg, which was tapered without further seizure or other withdrawal symptoms.

Studies of aspirin use in pregnant women have not shown that aspirin increases the risk of abnormalities when administered during the first trimester of pregnancy. In controlled studies involving 41,337 pregnant women and their offspring, there was no evidence that aspirin taken during pregnancy caused stillbirth, neonatal death or reduced birth weight. In controlled studies of 50,282 pregnant women and their offspring, aspirin administration in moderate and heavy doses during the first four lunar months of pregnancy showed no teratogenic effect.

Reproduction studies have been performed in rabbits and rats at doses up to 150 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to codeine.

Therapeutic doses of aspirin in pregnant women close to term may cause bleeding in mother, fetus, or neonate. During the last 6 months of pregnancy, regular use of aspirin in high doses may prolong pregnancy and delivery.

Labor and delivery

Ingestion of aspirin prior to delivery may prolong delivery or lead to bleeding in the mother or neonate. Use of codeine during labor may lead to respiratory depression in the neonate.

Nursing mothers

Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.

The risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when codeine is administered to a nursing woman. If a codeine containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of codeine during breastfeeding. (See WARNINGS - Death Related to Ultra-Rapid Metabolism of Codeine to Morphine )

Aspirin, caffeine, and barbiturates are also excreted in breast milk in small amounts. Because of potential for serious adverse reactions in nursing infants from Ascomp with Codeine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use

Safety and effectiveness in pediatric patients have not been established.

Respiratory depression and death have occurred in children with obstructive sleep apnea who received codeine in the post-operative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). These children may be particularly sensitive to the respiratory depressant effects of codeine that has been rapidly metabolized to morphine. Ascomp with Codeine is contraindicated for post-operative pain management in all pediatric patients undergoing tonsillectomy and/or adenoidectomy [seeContraindications].

Geriatric use

Clinical studies of Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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.

Butalbital is known to be substantially excreted by the kidney, and the risk of toxic 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.

Controlled Substance

Ascomp with Codeine is controlled by the Drug Enforcement Administration and is classified under Schedule III.

Abuse and Dependence

Codeine

Codeine can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic medications.

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.

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

Extended and repeated use of this product is not recommended because of the potential for physical dependence.

Applies to aspirin / butalbital / caffeine / codeine: oral capsule

Along with its needed effects, aspirin / butalbital / caffeine / codeine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking aspirin / butalbital / caffeine / codeine:

• Back, leg, or stomach pains
• black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of the skin
• blood in the vomit
• bloody urine
• blurred vision
• chills, fever
• confusion
• cough
• dark urine
• decreased frequency or amount of urine
• diarrhea
• difficulty breathing
• difficulty swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast, irregular, pounding, or racing heartbeat or pulse
• general tiredness and weakness
• headache
• hives, itching, or skin rash
• increased thirst
• joint or muscle pain
• light-colored stools
• lower back or side pain
• nausea or vomiting
• nosebleeds
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• shakiness in the legs, arms, hands, or feet skin
• sores, ulcers, or white spots in the mouth or on the lips
• sweating
• swelling of the face, fingers, or lower legs
• tightness or pain in the chest
• trembling or shaking of the hands or feet
• upper right abdominal or stomach pain
• weight gain
• yellow eyes and skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking aspirin / butalbital / caffeine / codeine:

• Confusion as to time, place, or person
• continuing ringing or buzzing or other unexplained noise in the ears
• convulsions
• difficult or troubled breathing
• drowsiness
• extremely high fever or body temperature
• hallucinations
• headache
• hearing loss
• holding false beliefs that cannot be changed by fact
• irregular, fast or slow, or shallow breathing
• loss of consciousness
• muscle cramps
• pale or blue lips, fingernails, or skin
• pale, clammy skin
• pinpoint pupils (black part of the eyes)
• restlessness
• trouble sleeping
• unusual bleeding or bruising

Some side effects of aspirin / butalbital / caffeine / codeine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Anxiety
• blurred vision
• burning, tingling, numbness, or pain in the hands, arms, feet, or legs
• confusion about identity, place, and time
• constricted, pinpoint, or small pupils (black part of the eye)
• depression
• difficulty having a bowel movement (stool)
• dry mouth
• feeling of constant movement of self or surroundings
• feeling of warmth
• feeling that others are watching you or controlling your behavior
• feeling that others can hear your thoughts
• heartburn
• high energy
• hyperventilation
• irregular heartbeats
• irritability
• loss in sexual ability, desire, drive, or performance
• pain in the legs
• redness of the face, neck, arms, and occasionally, upper chest
• sensation of spinning
• severe mood or mental changes
• shaking
• sleepiness
• sluggishness
• slurred speech
• trouble sitting still
• unexplained weight loss
• unusual behavior
• weakness

Ascomp® with Codeine capsules have a plain blue opaque cap with a yellow opaque body imprinted with "B 074" in black ink. They are available in bottles of 100's and 500’s.

Store And Dispense

Below 25°C (77°F); tight, light resistant container. Protect from moisture.

Manufactured By: Nexgen Pharma, Inc. Irvine, CA 92614. Revised: Dec 2015.

Patients should be informed that Ascomp with Codeine contains aspirin and should not be taken by patients with an aspirin allergy.

Ascomp with Codeine may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking Ascomp with Codeine .

Alcohol and other CNS depressants may produce an additive CNS depression when taken with Ascomp with Codeine , and should be avoided.

Codeine and butalbital may be habit-forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.

For information on use in geriatric patients, refer to PRECAUTIONS, Geriatric Use.

Advise patients that some people have a genetic variation that results in codeine changing into morphine more rapidly and completely than other people. Most people are unaware of whether they are an ultrarapid codeine metabolizer or not. These higher-than-normal levels of morphine in the blood may lead to life-threatening or fatal respiratory depression or signs of overdose such as extreme sleepiness, confusion, or shallow breathing. Children with this genetic variation who were prescribed codeine after tonsillectomy and/or adenoidectomy for obstructive sleep apnea may be at greatest risk based on reports of several deaths in this population due to respiratory depression. Ascomp with Codeine is contraindicated in children who undergo tonsillectomy and/or adenoidectomy. Advise caregivers of children receiving Ascomp with Codeine for other reasons to monitor for signs of respiratory depression.

Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. Instruct nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Instruct nursing mothers to talk to the baby's doctor immediately if they notice these signs and, if they cannot reach the doctor right away, to take the baby to an emergency room or call 911 (or local emergency services).