nsaids including butalbital, aspirin, and caffeine capsules, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. oligohydramnios/neonatal renal impairment use of nsaids, including butalbital, aspirin, and caffeine capsules, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. oligohydramnios is often, but not always, reversible with treatment discontinuation. complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. in some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. if nsaid treatment is necessary between about 20 weeks and 30 weeks gestation, limit butalbital, aspirin, and caffeine capsules use to the lowest effective dose and shortest duration possible. consider ultrasound monitoring of amniotic fluid if butalbital, aspirin, and caffeine capsules treatment extends beyond 48 hours. discontinue butalbital, aspirin, and caffeine capsules if oligohydramnios occurs and follow up according to clinical practice [ see precautions ; pregnancy ]. drug reaction with eosinophilia and systemic symptoms (dress) drug reaction with eosinophilia and systemic symptoms (dress) has been reported in patients taking nsaids such as butalbital, aspirin, and caffeine capsules. some of these events have been fatal or life-threatening. dress typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. sometimes symptoms of dress may resemble an acute viral infection. eosinophilia is often present. because this disorder is variable in its presentation, other organ systems not noted here may be involved. it is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. if such signs or symptoms are present, discontinue butalbital, aspirin, and caffeine capsules and evaluate the patient immediately.

cribed below. aspirin the systemic availability of aspirin after an oral dose is highly dependent on the dosage form, the presence of food, the gastric emptying time, gastric ph, antacids, buffering agents, and particle size. these factors affect not necessarily the extent of absorption of total salicylates but more the stability of aspirin prior to absorption. during the absorption process and after absorption, aspirin is mainly hydrolyzed to salicylic acid and distributed to all body tissues and fluids, including fetal tissues, breast milk, and the central nervous system (cns). highest concentrations are found in plasma, liver, renal cortex, heart, and lung. in plasma, about 50% to 80% of the salicylic acid and its metabolites are loosely bound to plasma proteins. the clearance of total salicylates is subject to saturable kinetics; however, first-order elimination kinetics are still a good approximation for doses up to 650 mg. the plasma half-life for aspirin is about 12 minutes and for salicylic acid and/or total salicylates is about 3 hours. the elimination of therapeutic doses is through the kidneys either as salicylic acid or other biotransformation products. the renal clearance is greatly augmented by an alkaline urine as is produced by concurrent administration of sodium bicarbonate or potassium citrate. the biotransformation of aspirin occurs primarily in the hepatocytes. the major metabolites are salicyluric acid (75%), the phenolic and acyl glucuronides of salicylate (15%), and gentisic and gentisuric acid (1%). the bioavailability of the aspirin component of butalbital, aspirin, and caffeine capsules is equivalent to that of a solution except for as lower rate of absorption. a peak concentration of 8.8 mcg/ml was obtained at 40 minutes after a 650 mg dose. see overdosage for toxicity information . butalbital butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most of the tissues in the body. barbiturates, in general, may appear in breast milk and readily cross the placental barrier. they are bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility. elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drug or metabolites. the plasma half-life is about 35 hours. urinary excretion products included parent drug (about 3.6% of the dose), 5-isobutyl-5-(2, 3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. of the material excreted in the urine, 32% was conjugated. the bioavailability of the butalbital component of butalbital, aspirin, and caffeine capsules is equivalent to that of a solution except for a decrease in the rate of absorption. a peak concentration of 2,020 ng/ml is obtained at about 1.5 hours after a 100 mg dose. the in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5 to 20 mcg/ml. this falls within the range of plasma protein binding (20% to 45%) reported with other barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. the plasma-to-blood concentration ratio was almost unity indicating that there is no preferential distribution of butalbital into either plasma or blood cells. see overdosage for toxicity information . caffeine like most xanthines, caffeine is rapidly absorbed and distributed in all body tissues and fluids, including the cns, fetal tissues, and breast milk. caffeine is cleared rapidly through metabolism and excretion in the urine. the plasma half-life is about 3 hours. hepatic biotransformation prior to excretion results in about equal amounts of 1-methylxanthine and 1-methyluric acid. of the 70% of the dose that has been recovered in the urine, only 3% was unchanged drug. the bioavailability of the caffeine component for butalbital, aspirin, and caffeine capsules is equivalent to that of a solution except for a slightly longer time to peak. a peak concentration of 1,660 ng/ml was obtained in less than an hour for an 80 mg dose. see overdosage for toxicity information .