Adenosine by Orthoplex Green

EFFECTIVE

• Cardiovascular disease diagnosis. Adenosine intravenous infusion is FDA-approved for use in cardiac stress testing to diagnose coronary artery disease (CAD). Details: Adenosine is infused at a dose of 0.14 mg/kg/minute for 6 minutes as an adjunct to thallium stress testing in patients who are unable to exercise adequately (15). Caffeine is a competitive antagonist at adenosine receptors and should be avoided for 24 hours prior to the test (9157,11770).
• Paroxysmal supraventricular tachycardia. Adenosine intravenous injection is FDA-approved for acute management of paroxysmal supraventricular tachycardia (PSVT). Details: Adenosine is indicated for termination of PSVT. It is given intravenously as a bolus of 6 mg over 1-2 seconds, followed by 1 or 2 further boluses of 12 mg at 1-2 minute intervals if necessary (15).

POSSIBLY EFFECTIVE

• Cachexia. Intravenous adenosine triphosphate may be beneficial in cachexic patients with various cancers. Oral adenosine has not been evaluated for this purpose. Details: Administering adenosine triphosphate (ATP) intravenously, up to 75 mcg/kg/minute for 30 hours every 2-4 weeks for up to 28 weeks, seems to stabilize body composition, appetite, and dietary intake, and to improve quality of life in people with advanced non-small-cell lung cancer and other tumors (9149,9151,9152).

POSSIBLY INEFFECTIVE

• Myocardial Infarction (MI). Intravenous or intracoronary adenosine does not seem to be beneficial for acute coronary syndrome. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 17 clinical studies in patients with acute coronary syndrome undergoing revascularization shows that administration of intracoronary or intravenous adenosine does not reduce major adverse cardiac events when compared with placebo. Adenosine also does not reduce all-cause death, non-fatal MI, or heart failure when compared with placebo. However, adenosine is associated with an increased risk of atrioventricular block (111744). The interpretation of these findings is limited by the heterogeneity of the included studies. In addition, most studies were in patients treated with percutaneous coronary intervention; the generalizability of these results to patients treated with thrombolysis is unclear.
• Postoperative nausea and vomiting (PONV). Parenteral adenosine does not seem to be beneficial for PONV. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 4 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce PONV when compared with placebo (97981).
• Postoperative pain. Parenteral adenosine does not seem to be helpful for postoperative pain. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 9 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce postoperative pain scores when compared with placebo (97981).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. It is unclear if topical adenosine is beneficial in patients with androgenic alopecia. Details: Preliminary clinical research shows that topical application of adenosine 0.75% solution to the scalp twice daily for 6 months does not improve hair growth in males with androgenic alopecia. However, patients applying topical minoxidil 5% (Rogaine) also experienced no improvement at 6 months, with over 97% of patients in each group reporting less than 30% hair growth in the affected area (93689).
• Athletic performance. It is unclear if oral adenosine triphosphate is beneficial for improving athletic performance. Details: Preliminary clinical research in healthy males performing 10 repeated sprinting bouts shows that taking adenosine triphosphate (PEAK ATP, TSI USA, Inc) 400 mg orally daily for 2 weeks prior to the exercise increases muscle excitability during the first two bouts and attenuates reductions in power output and muscle excitability during the final three bouts when compared with placebo (97982).
• Erectile dysfunction (ED). Oral adenosine monophosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking adenosine monophosphate 200 mg plus arginine aspartate 8 grams orally 1-2 hours prior to sexual intercourse improves erectile function and sexual satisfaction scores when compared with placebo in patients with erectile dysfunction (93690). It is not clear if this effect is due to adenosine, arginine, or the combination.
• Hearing loss. Oral adenosine triphosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with idiopathic sudden sensorineural hearing loss shows that taking adenosine triphosphate 300 mg orally daily with vitamin B12 1.5 mg orally daily for 8-16 weeks is associated with modestly reduced hearing loss after 4-6 months when compared with taking this combination for less than 8 weeks (104924). The validity of this finding is limited by the observational nature of the study and the lack of a control group.
• Herpes labialis (cold sores). It is unclear if intramuscular adenosine monophosphate is beneficial in patients with herpes labialis. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research shows that a gel formulation of adenosine monophosphate 1.5-2 mg/kg IM every other day for a total of 9-12 injections might accelerate the healing of cold sores and reduce the risk of recurrence (9590). The validity of these findings is limited by the lack of a control group.
• Herpes zoster (shingles). It is unclear if intramuscular adenosine monophosphate is beneficial in adults with herpes zoster. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in adults with shingles shows that giving adenosine monophosphate in a gel formulation, 100 mg IM three times weekly for 4 weeks, increases the number of patients classified as pain-free at 4 weeks by 45% and might also accelerate viral clearance when compared with placebo (9155,10067).
• Lung cancer. Intravenous adenosine triphosphate does not seem to be beneficial in patients with advanced non-small-cell lung cancer (NSCLC). Oral adenosine has not been evaluated for this purpose. Details: One very small clinical study in adults with advanced NSCLC shows that giving adenosine triphosphate in at least 3, 96-hour infusions at a dose of 50 mcg/kg/min or more does not induce complete or partial responses when compared to baseline (9154).
• Neuropathic pain. It is unclear if intrathecal adenosine is beneficial for experimentally-induced neuropathic pain. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in healthy volunteers with areas of allodynia and hyperalgesia induced by topical capsaicin shows that giving single doses of intrathecal adenosine 0.5-2 mg modestly reduces these areas (9157). The clinical significance of this finding is unclear.
• Porphyria cutanea tarda. It is unclear if oral adenosine monophosphate is beneficial in patients with porphyria cutanea tarda. Details: A case series of 21 patients with porphyria cutanea tarda shows that taking adenosine monophosphate 160-200 mg orally daily for at least 4 weeks resolves or reduces symptoms, including photosensitivity, hyperpigmentation, and hypertrichosis, and decreases urinary and fecal excretion of porphyrins, when compared to baseline (106423). The validity of these findings is limited by the lack of a control group.
• Pulmonary hypertension. Adenosine given by central venous infusion might be beneficial in patients who develop pulmonary hypertension during cardiac surgery. Details: Preliminary clinical research in patients who develop pulmonary hypertension during cardiac surgery shows that giving a central venous infusion of adenosine, 50 mcg/kg/minute for 15 minutes after weaning from cardiopulmonary bypass, produces pulmonary vasodilation and reduces mean pulmonary arterial pressure (106424). The validity of these findings is limited by the lack of a control group. More evidence is needed to rate adenosine for these uses.

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LIKELY SAFE ...when adenosine is used intravenously and appropriately. Adenosine injection (Adenocard, Adenoscan) is an FDA-approved prescription drug (15).

POSSIBLY SAFE ...when adenosine triphosphate (ATP) is used intravenously and appropriately. ATP appears to be safe in intravenous doses of 75 mcg/kg per minute for 30 hours given every 2 weeks for 28 weeks (9149,9154). There is insufficient reliable information available about the safety of adenosine when used orally or intramuscularly.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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CARBAMAZEPINE (Tegretol) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Carbamazepine might increase the risk of heart block when used concomitantly with adenosine.  Details Carbamazepine and adenosine can both cause heart block. Giving them concurrently might produce an additive effect (15).

DIPYRIDAMOLE (Persantine) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = D Dipyridamole can increase the therapeutic and toxic effects of adenosine.  Details Dipyridamole decreases the metabolism of adenosine. Intravenous infusion of adenosine in patients who are taking dipyridamole can cause dizziness, bradycardia, and syncope. Dipyridamole should be discontinued for several days prior to a cardiac stress test using adenosine (12209).

METHYLXANTHINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Methylxanthines are competitive antagonists of adenosine and can block its pharmacologic effects.  Details The methylxanthines, aminophylline, caffeine, and theophylline, can block the effects of adenosine by acting as competitive antagonists at adenosine cell surface receptors (9157). It is recommended that methylxanthines be avoided for 24 hours prior to cardiac stress tests (11770).

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General ...Intravenously, the prescription form of adenosine can cause cardiovascular and respiratory adverse effects. When used orally or intramuscularly, no adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Intravenously: Chest pain, dizziness, dyspnea, facial flushing, headache, hypotension, nausea, nervousness, numbness, paresthesias, and tingling.
Serious Adverse Effects (Rare):
Intravenously: Arrhythmias, first- and second-degree heart block, hypersensitivity reactions, myocardial infarction, ST segment depression, and ventricular tachycardia.

Cardiovascular ...Intravenously, adenosine causes chest pain, palpitations, hypotension, and supraventricular tachycardia (15,9148). Intravenous adenosine has also been associated with arrhythmias, fatal or nonfatal cardiac arrest, ventricular tachycardia, and myocardial infarction (15). Intravenously, adenosine triphosphate (ATP) causes chest pain, particularly at doses greater than 50 mcg/kg per minute (9154).

Dermatologic ...Intravenously, adenosine causes flushing in up to 44% of patients in clinical research (15). Topically, folliculitis and pruritus can occur after application of adenosine to the scalp (93689).

Gastrointestinal ...Intravenously, adenosine can cause abdominal discomfort (15).

Neurologic/CNS ...Rapid intravenous injection of adenosine can cause headache, lightheadedness, insomnia, and anxiety (9148,9151,9152,9154,9158). New onset seizures, including tonic-clonic seizures, have also occurred (15). Intrathecally, adenosine has been reported to cause headache (9157).

Pulmonary/Respiratory ...Intravenously, adenosine can cause dyspnea, bronchospasm, bronchoconstriction, and respiratory arrest (15). Intravenously, adenosine triphosphate (ATP) causes dyspnea, which can be severe, particularly at doses greater than 50 mcg/kg/minute (9154).

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