.....Mg (1/2 gr) butalbital, USP .............50 mg caffeine, USP ..............Mg aspirin, USP .............325 mg Codeine phosphate occurs as fine, white, needle-shaped crystals, or white, crystalline powder.Is affected by light.Chemical name is 7,8-didehydro-4,5О±-epoxy-3-methoxy-17-methylmorphinan-6О±-ol phosphate (1:1) (salt) hemihydrate.Molecular weight is 406.Its molecular formula is C18H21NO3H3PO4H2O.Butalbital, 5-allyl-5-isobutyl-barbituric acid, a white odorless crystalline powder, is a short- to intermediate-acting barbiturate.Is 224.Its molecular formula is C11H16N2O3.Caffeine, 1,3,7-trimethylxanthine, is a central nervous stimulant which occurs as a white powder or white glistening needles.Molecular weight is (anhydrous) 194.Its molecular formula is C8H10N4O2.Aspirin is benzoic acid, 2-(acetyloxy)-, with a molecular formula of C9H8O4 and its molecular weight is 180.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, FD&C Blue #2 Aluminum Lake, FD 2) codeine; 3) butalbital, aspirin and caffeine; 4) placebo.Was assessed over the course of the first 4 hours of each of 2 distinct headaches, separated by at least 24 hours.Product of butalbital, aspirin, caffeine and codeine proved statistically significantly superior to each of itsponents and to placebo on measures of pain relief.Evidence supporting the efficacy and safety of butalbital, aspirin, caffeine and codeine in the treatment of multiple recurrent headaches is unavailable.In this regard is required because codeine and butalbital are habit-forming and potentially abusable.Thisbination product is contraindicated under the following conditions: Hypersensitivity or intolerance to aspirin, caffeine, butalbital or codeine. Patients with hemorrhagic diathesis (e.Hemophilia, hypoprothrombinemia, von Willebrand's disease, the thrombocytopenias, thrombasthenia and other ill-defined hereditary platelet dysfunctions, severe vitamin K deficiency and severe liver damage. Patients with the syndrome of nasal polyps, angioedema and bronchospastic reactivity to aspirin or other nonsteroidal anti-inflammatory drugs.Reactions have occurred in such patients. Peptic ulcer or other serious gastrointestinal lesions. Patients with porphyria.Therapeutic doses of aspirin can cause anaphylactic shock and other severe allergic reactions.Should be ascertained if the patient is allergic to aspirin, although a specific history of allergy may be lacking.Significant bleeding can result from aspirin therapy in patients with peptic ulcer or other gastrointestinal lesions, and in patients with bleeding disorders.Administered pre-operatively may prolong the bleeding time.In the presence of head injury or other intracranial lesions, the respiratory depressant effects of codeine and other narcotics may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure.Also produce other CNS depressant effects, such as drowsiness, that may further obscure the clinical course of patients with head injuries.Codeine or other narcotics may obscure the signs on which to judge the diagnosis or clinical course of patients with acute abdominal conditions.And codeine are both habit-forming and potentially abusable.The extended use of this product is not rmended.Results from epidemiologic studies indicate an association between aspirin and Reye Syndrome.Should be used in administering this product to children, including teenagers, with chicken pox or flu.PRECAUTIONS GENERAL Butalbital, aspirin, caffeine and 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.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.To aspirin is particularly likely in patients with nasal polyps, and relativelymon in those with asthma.ULTRA-RAPID METABOLIZERS OF CODEINE Some individuals may be ultra-rapid metabolizers due to a specific CYP2D62x2 genotype.Individuals convert codeine into its active metabolite, morphine, more rapidly andpletely than other people.Conversion results in higher than expected serum morphine levels.At labeled dosage regiments, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing.The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.1% in Chinese and Japanese, 0.1% in Hispanics, 1-10% in Caucasians, 3% in African Americans, and 16-28% in North Africans, Ethiopians and Arabs.In not available for other ethnic groups.When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and should inform their patients about these risks and the signs of morphine overdose.) INFORMATION FOR PATIENTS Patients should be informed that thisbination product contains aspirin and should not be taken by patients with an aspirin allergy.Butalbital, aspirin, caffeine and codeine may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery.Tasks should be avoided while taking this product.And other CNS depressants may produce an additive CNS depression when taken with this product, and should be avoided.And butalbital may be habit-forming.Should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.Caution patients that some people have a variation in a liver enzyme and change codeine into morphine more rapidly andpletely than other people.People are ultra-rapid metabolizers and are more likely to have higher-than-normal levels of morphine in their blood after taking codeine which can result in overdose symptoms such as extreme sleepiness, confusion, or shallow breathing.Most cases, it is unknown if someone is an ultra-rapid codeine metabolizer.Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers.Higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies.Nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness.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 coitant 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.Butalbital, aspirin, caffeine and codeine may enhance the effects of: Oral anticoagulants, causing bleeding by inhibiting prothrombin formation in the liver and displacing anticoagulants from plasma protein binding sites. Oral antidiabetic agents and insulin, causing hypoglycemia by contributing to an additive effect, if dosage of this product exceeds maximum rmended daily dosage. 6-mercaptopurine and methotrexate, causing bone marrow toxicity and blood dyscrasias by displacing these drugs from secondary binding sites, and, in the case of methotrexate, also reducing its excretion. Non-steroidal anti-inflammatory agents, increasing the risk of peptic ulceration and bleeding by contributing additive effects. Other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.Caffeine and codeine may diminish the effects of: Uricosuric agents such as probenecid and sulfinpyrazone, reducing their effectiveness in the treatment of gout.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.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.MUTAGENESIS, IMPAIRMENT OF FERTILITY Adequate long-term studies have been conducted in mice and rats with aspirin, alone or inbination with other drugs, in which no evidence of carcinogenesis was seen.Adequate studies have been conducted in animals to determine whether aspirin has a potential for mutagenesis or impairment of fertility.Adequate studies have been conducted in animals to determine whether butalbital has a potential for carcinogenesis, mutagenesis, or impairment of fertility.PREGNANCY TERATOGENIC EFFECTS: Pregnancy Category C.Reproduction studies have not been conducted with butalbital, aspirin, caffeine and codeine.Is also not known whether thisbination product can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity and should be given to a pregnant woman only when clearly needed.NONTERATOGENIC EFFECTS: Although Butalbital, Aspirin, Caffeine with Codeine was not implicated in the birth defect, a female infant was born with lissencephaly, pachygyria and heterotopic gray matter.Infant was born 8 weeks prematurely to a woman who had taken an average of 90 Butalbital, Aspirin, Caffeine with Codeine capsules each month from the first few days of pregnancy.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 butalbital-containing drug during the last 2 months of pregnancy.Was found in the infant's serum.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.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.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.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.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.Of codeine during labor may lead to respiratory depression in the neonate.NURSING MOTHERS Aspirin, caffeine, barbiturates and codeine are excreted in breast milk in small amounts, but the significance of their effects on nursing infants is not known.Potential for serious adverse reactions in nursing infants from this product, 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.Codeine is secreted into human milk.Women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent.Use of codeine products to manage postpartum pain, reports of adverse events in infants are rare.Some women are ultra-rapid metabolizers of codeine.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.Maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.1% in Chinese and Japanese, 0.1% in Hispanics, 1-10% in Caucasians, 3% in African Americans, and 16-28% in North Africans, Ethiopians and Arabs.Is not available for other ethnic groups.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.Should be exercised when codeine is administered to a nursing woman.A codeine containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect.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.Mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing.Read more How do paracetamol, co-codamol 8/500, co-codamol 30/500 and tramadol compare in terms of efficacy and rate of side effects?
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