Caffeine is used orally as a mild CNS stimulant to aid in staying awake and to restore mental alertness in fatigued patients.
Caffeine also is used orally in combination with antihistamines to overcome the sedative properties of the latter drugs, but the efficacy of caffeine and the dosage required have not been adequately established.
Caffeine and sodium benzoate injection has been used in conjunction with supportive measures to treat respiratory depression associated with overdosage of CNS depressant drugs (e.g., opiate analgesics, alcohol) and with electric shock. However, because of the questionable benefit and transient action, most authorities believe caffeine and other analeptics should not be used in these conditions and recommend other supportive therapy.
Apnea of Prematurity
Caffeine citrate is used IV or orally in the short-term (10-12 days) treatment of apnea of prematurity in neonates who are between 28 and less than 33 weeks of gestational age. Caffeine is designated an orphan drug by the US Food and Drug Administration (FDA) for use in apnea in premature neonates.
The use of caffeine citrate in apnea of prematurity was established in a randomized, placebo-controlled clinical trial of the drug in premature neonates (gestational age 28 to less than 33 weeks) with apnea of prematurity (defined as having at least 6 episodes of apnea of greater than 20 seconds' duration in a 24-hour period with no other identifiable causes of apnea). A 20-mg/kg loading dose of caffeine citrate (10 mg/kg of caffeine) was administered IV, followed by a daily maintenance dose of 5 mg/kg of caffeine citrate (2.5 mg/kg of caffeine) IV or orally (generally via a feeding tube). Patients randomized to placebo were allowed to cross over to caffeine treatment if their apnea became uncontrolled during the double-blind phase of the trial; the study period lasted 10-12 days. The percentage of patients without apnea on the second day of treatment (i.e., 24-48 hours after the loading dose) was greater in the caffeine-treated patients compared with placebo-treated patients (26.7 versus 8.1%, respectively). The mean number of days with zero apnea events was 3 in the caffeine-treated group and 1.2 in the placebo group, while the mean number of days with a 50% reduction from baseline in apnea events was 6.8 in the caffeine-treated group and 4.6 in the placebo group. Serum caffeine concentrations ranged from 8-40 mcg/mL in treated patients; however, a therapeutic plasma concentration could not be determined from this clinical trial. In low-birthweight neonates, the drug has decreased the frequency of apneic episodes without any substantial effect on heart rate. Some clinicians recommend that when conservative measures (e.g., tactile stimulation, flotation on a waterbed) are ineffective in preventing severe, recurrent apnea in neonates, caffeine may be used as an alternative to mechanical ventilation. The manufacturer states that the safety and efficacy of treatment with caffeine citrate in neonates with apnea of prematurity for longer than 10-12 days have not been established. The manufacturer also states that use of caffeine citrate in the prevention of sudden infant death syndrome (SIDS) or prior to extubation in mechanically ventilated neonates also has not been established. Use of the combination preparation containing caffeine and sodium benzoate in neonates is generally avoided because of the potential for sodium benzoate to produce kernicterus.
(See Cautions: Pediatric Precautions.)
Caffeine is used orally or rectally in combination with ergotamine tartrate to abort vascular headaches such as migraine and cluster headaches (histamine cephalalgia). There is conflicting evidence regarding the efficacy of this combination in the treatment of acute migraine attacks. Caffeine's cerebral vasoconstrictor effect is reportedly additive with that of ergotamine, but the results of one study suggest that the principal value of caffeine in this combination is related to its ability to increase GI absorption of ergotamine tartrate. Some clinicians question the value of the combination because caffeine may keep patients awake and sleep can contribute to the relief of migraine.
Caffeine is used orally alone and in combination with analgesics (e.g., acetaminophen, aspirin) for the treatment of headache. Some experts state that the combination of acetaminophen, aspirin, and caffeine is a reasonable first-line therapy for mild to moderate migraine attacks or for severe migraine attacks that have responded in the past to similar nonsteroidal anti-inflammatory agents (NSAIAs) or non-opiate analgesics. Caffeine exerts no intrinsic analgesic activity. Although analgesic-caffeine combinations have been reported to produce slightly more analgesia than analgesic agents alone and to have a beneficial effect on mood, which may be clinically important in some patients with headache, these results have not always been reproducible in well-controlled studies and additional studies are needed to determine the role, if any, of caffeine as an analgesic adjuvant.
Caffeine and sodium benzoate injection has been used for the symptomatic relief of headache following spinal puncture.
Caffeine is used orally alone and in combination with other drugs (e.g., analgesics, diuretics) to relieve tension, fatigue, and fluid retention associated with menstruation. However, because caffeine's diuretic activity in patients with fluid retention is minimal, its usefulness in this condition is questionable.
Caffeine (30% in a topical hydrophilic base) has been used effectively alone or in combination with topical hydrocortisone in the topical treatment of atopic dermatitis.
Caffeine also has been used in combination with ephedrine to promote weight loss in patients with exogenous obesity. It has been suggested that weight loss may be associated with increased energy expenditure (thermogenesis) and appetite suppression. However, the US Food and Drug Administration (FDA), which did not evaluate the efficacy of ephedrine dietary supplements in obesity therapy, has stated that such use of ephedrine may be associated with an unacceptable incidence of adverse effects.