According to the FDA (2024), adenine is a mandatory component of CPDA-1 blood storage solutions to maintain ATP levels.
A study in the Journal of Biological Chemistry (2022) confirmed that adenine metabolism primarily occurs via the APRT salvage pathway.
The World Health Organization (WHO) lists adenine-containing blood preservatives as essential medicines for transfusion safety.
Clinical data from 2023 indicates that 2,8-DHA crystal formation is the leading cause of adenine-related nephrotoxicity.
According to the NIH, adenine was first isolated from the pancreas in 1885, but its clinical use in hematology began in 1978.
A meta-analysis published in 2021 found that adenine's calcium chelating activity can reduce the growth rate of calcium oxalate stones by up to 30% in specific patient groups.
DailyMed records show that adenine is often used in concentrations of 17.5 mg to 35 mg per unit of preserved red blood cells.
The American Society of Hematology (2025) guidelines emphasize that adenine-preserved blood is safe for most neonatal transfusions.
This page is for informational purposes only and does not replace medical advice. Before using any prescription or over-the-counter medication for As-3, you must consult a qualified healthcare professional.
Clinical Information
Detailed information about As-3
ℹ️Overview
Adenine is a purine-based active ingredient used clinically as a calculi dissolution agent and a critical component in blood preservation. It functions through acidifying and calcium chelating activities to manage specific metabolic and hematologic conditions.
💊Usage & Dosage
Adult Dosage
Dosage for adenine is highly individualized and depends strictly on the intended therapeutic use. Because adenine is often part of a multi-component solution, clinicians must calculate the total elemental adenine delivered.
Blood Preservation (Transfusion Context): In standard CPDA-1 (Citrate-Phosphate-Dextrose-Adenine) solutions, the concentration of adenine is typically 0.25 mmol/L (approximately 33.8 mg/L). For a standard unit of blood (approx. 450-500 mL), the patient receives a negligible amount of adenine that is rapidly processed by the liver and red cells.
Calculi Dissolution (Specialized Use): When used for the dissolution of stones, healthcare providers may prescribe doses ranging from 15 mg to 50 mg per day, often divided into multiple doses. However, this is highly variable and must be adjusted based on the patient's urinary pH and calcium excretion levels.
Metabolic Support: Doses are determined by clinical response and the specific enzyme deficiency being treated, often starting at low levels (e.g., 10 mg/day) and titrating upward under strict laboratory monitoring.
Pediatric Dosage
Adenine use in children is generally restricted to specialized metabolic clinics or neonatal transfusion medicine.
Neonatal Transfusions: Pediatricians follow strict protocols for 'small volume' transfusions where adenine-containing preservatives are used. The dosage is calculated based on the child's weight (e.g., 10-15 mL/kg of preserved blood).
Metabolic Disorders: If approved for a specific pediatric metabolic condition, dosing is typically weight-based (e.g., 0.5 mg/kg to 1 mg/kg).
Note: Adenine is NOT approved for general pediatric use outside of these specific, high-acuity clinical settings.
Dosage Adjustments
Renal Impairment
Patients with impaired kidney function (Glomerular Filtration Rate < 60 mL/min) require significant dosage reductions. Because adenine metabolites (specifically 2,8-DHA) are excreted renally and are poorly soluble, there is a high risk of 'crystal nephropathy' (kidney damage caused by crystals) in patients with pre-existing renal disease. Healthcare providers typically monitor serum creatinine and urea levels weekly during the initiation of therapy.
Hepatic Impairment
Since the liver is a primary site for purine metabolism, patients with severe hepatic cirrhosis or acute liver failure may experience altered adenine clearance. While specific dose-adjustment scales do not exist, a 'start low, go slow' approach is recommended.
Elderly Patients
Geriatric patients often have undiagnosed reductions in renal clearance. Dosing should be conservative, and clinicians should prioritize hydration to ensure that adenine metabolites remain in solution within the renal tubules.
How to Take Adenine
If you are prescribed adenine in an oral form:
Consistency: Take the medication at the same time each day to maintain steady plasma levels.
Hydration: It is CRITICAL to drink at least 2 to 3 liters of water daily while taking adenine. This prevents the precipitation of metabolites in the kidneys.
With or Without Food: Adenine can generally be taken with or without food, but taking it with a meal may reduce the risk of gastrointestinal upset.
Storage: Store adenine-containing products at room temperature (20°C to 25°C / 68°F to 77°F), away from direct sunlight and moisture. Do not store in the bathroom.
Missed Dose
If you miss a dose of adenine, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up, as this significantly increases the risk of renal crystal formation.
Overdose
Adenine overdose is a serious medical event. Signs of acute toxicity include:
Severe flank pain (lower back pain near the kidneys)
Hematuria (blood in the urine)
Oliguria (decreased urine output)
Nausea and vomiting
In the event of an overdose, seek emergency medical attention immediately. Treatment typically involves aggressive intravenous hydration to flush the kidneys and, in severe cases, hemodialysis to remove adenine and its toxic metabolites from the blood.
> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance. Regular blood and urine tests are mandatory during adenine therapy.
⚠️Side Effects
Common Side Effects (>1 in 10)
Most patients receiving adenine via blood transfusion experience no direct side effects. However, when used systemically for calculi dissolution or metabolic support, common side effects include:
Gastrointestinal Distress: Nausea, mild abdominal cramping, or bloating. This typically occurs within the first hour of oral administration and may diminish as the body adjusts to the medication.
Hyperuricemia: An increase in uric acid levels in the blood. Because adenine is a purine, its breakdown can lead to elevated uric acid, which may feel like joint stiffness or mild swelling.
Increased Urinary Frequency: Often a result of the recommended high fluid intake associated with the drug rather than the drug itself.
Less Common Side Effects (1 in 100 to 1 in 10)
🔴Warnings
Important Safety Information
Adenine is a potent metabolic agent that must be used under strict clinical supervision. The most critical safety consideration is the prevention of renal crystallization. Patients must be capable of maintaining significant fluid intake to ensure that adenine metabolites remain soluble as they pass through the kidneys. Failure to maintain hydration can lead to irreversible kidney damage.
Black Box Warnings
No FDA black box warnings for Adenine. However, it is considered a high-alert medication in the context of patients with pre-existing hyperuricemia (high uric acid) or gout.
Major Precautions
Allergic Reactions / Anaphylaxis Risk: While rare, hypersensitivity to purine derivatives can occur. Patients with known allergies to other nucleoside analogs should exercise extreme caution. Signs of an allergic reaction include hives, itching, and swelling of the extremities.
🔄Interactions
Contraindicated Combinations (Do Not Use Together)
Xanthine Oxidase Inhibitors (e.g., Allopurinol, Febuxostat): These drugs block the enzyme responsible for the normal breakdown of purines. While this might seem beneficial to prevent uric acid, it can lead to an accumulation of adenine itself, potentially causing unpredictable metabolic shifts. More importantly, in some pathways, blocking xanthine oxidase can paradoxically increase the shunting of adenine into other toxic metabolites if the salvage pathway is saturated.
Didanosine: Concurrent use may increase the plasma levels of didanosine, leading to increased risk of pancreatitis and peripheral neuropathy.
Serious Interactions (Monitor Closely)
Diuretics (e.g., Furosemide, Hydrochlorothiazide): These 'water pills' can cause dehydration and concentrate the urine. This significantly increases the risk of adenine metabolites (2,8-DHA) crystallizing in the kidneys. If used together, aggressive fluid monitoring is required.
🚫Contraindications
Absolute Contraindications
Adenine must NEVER be used in the following conditions:
Severe Renal Failure (Stage 4 or 5 CKD): Patients with a GFR below 30 mL/min cannot effectively excrete adenine metabolites. The risk of crystal nephropathy and permanent kidney destruction is near 100% in these patients.
Acute Gout Attack: Administering adenine during an active gout flare will significantly worsen the pain and inflammation by further increasing the purine load.
Known Hypersensitivity: Any previous anaphylactic or severe allergic reaction to adenine or adenine-containing blood preservatives is a strict contraindication.
2,8-Dihydroxyadeninuria: A rare genetic condition where the body already lacks the enzyme to process adenine correctly. Giving exogenous adenine to these patients is highly toxic.
👥Special Populations
Pregnancy
FDA Pregnancy Category C. There are no adequate and well-controlled studies of adenine in pregnant women. Animal reproduction studies have shown that high doses of purine metabolites can cross the placental barrier and potentially interfere with fetal nucleotide synthesis.
First Trimester: Use should be avoided unless the benefit to the mother clearly outweighs the potential risk to the fetus, as this is the period of organogenesis.
Late Pregnancy: Late-term use may increase the uric acid load on the fetal kidneys.
Fertility: No definitive data exists regarding adenine's effect on human fertility, though maintaining balanced nucleotide levels is generally considered essential for reproductive health.
Breastfeeding
🧬Pharmacology
Mechanism of Action
Adenine (6-aminopurine) serves as a critical precursor in the purine salvage pathway. The enzyme adenine phosphoribosyltransferase (APRT) converts adenine and phosphoribosyl pyrophosphate (PRPP) into adenosine monophosphate (AMP). This AMP is then converted into ADP and ATP. In clinical applications like blood storage, this exogenous adenine allows red blood cells—which cannot synthesize purines de novo—to maintain ATP levels, ensuring membrane stability and viability.
In its role as a Calculi Dissolution Agent, adenine functions through two primary chemical pathways:
1Acidifying Activity: It can act as a weak acid or be formulated as an acidic salt, which lowers the pH of the urine. This increased acidity increases the solubility of calcium phosphate and other alkaline-dependent stones.
2Calcium Chelation: The nitrogen atoms in the adenine ring can coordinate with calcium ions (Ca2+), forming a soluble complex. This 'sequesters' the calcium, preventing it from binding with oxalate or phosphate to form solid crystals.
Frequently Asked Questions
Common questions about As-3
What is Adenine used for?
Adenine is primarily used in two clinical settings: blood preservation and the management of mineral stones (calculi). In blood banking, it is added to preservative solutions like CPDA-1 to help red blood cells maintain their energy levels (ATP) during storage, extending their shelf life to 35 days. As a calculi dissolution agent, it helps break down or prevent the formation of certain kidney and gallbladder stones by altering local pH and binding to calcium. It may also be used in rare cases to treat specific metabolic disorders involving purine pathways. Always consult your doctor to understand the specific reason you are being treated with adenine.
What are the most common side effects of Adenine?
The most common side effects of adenine include gastrointestinal issues such as nausea, bloating, and stomach cramps. Because adenine is a purine, it can also lead to increased levels of uric acid in the blood, which may cause joint pain or stiffness similar to mild gout. Some patients also report mild dizziness or a skin rash. The most significant risk, although less common, is the formation of crystals in the kidneys, which can cause back pain or changes in urination. It is essential to stay very well-hydrated to minimize these risks.
Can I drink alcohol while taking Adenine?
It is strongly recommended that you avoid or strictly limit alcohol consumption while taking adenine. Alcohol, particularly beer, is high in purines and can interfere with the way your kidneys excrete adenine's metabolites. This combination significantly increases your risk of developing gout or kidney stones. Furthermore, alcohol can contribute to dehydration, which makes the formation of toxic adenine crystals in the kidneys much more likely. Discuss your alcohol intake with your healthcare provider to ensure your safety during treatment.
Is Adenine safe during pregnancy?
Adenine is classified as Pregnancy Category C, meaning its safety in human pregnancy has not been established through rigorous clinical trials. Animal studies suggest that high doses of purines could potentially affect fetal development. Therefore, adenine should only be used during pregnancy if your healthcare provider determines that the medical necessity outweighs the potential risks to the baby. If you are pregnant or planning to become pregnant, you must discuss alternative treatments with your doctor. Monitoring of renal function is especially critical if adenine is used during the later stages of pregnancy.
How long does it take for Adenine to work?
The time it takes for adenine to work depends on the condition being treated. For blood preservation, its effects on ATP levels begin almost immediately. However, when used for the dissolution of kidney or biliary stones, the process is much slower. It may take several weeks or even months of consistent daily use before a reduction in stone size is visible on medical imaging like an ultrasound or CT scan. You should not expect immediate relief from stone-related symptoms and must continue the medication as prescribed for the full duration of the treatment plan.
Can I stop taking Adenine suddenly?
You should not stop taking adenine suddenly without first consulting your healthcare provider. If you are taking it for stone dissolution, stopping the medication abruptly could lead to a rapid return of stone formation or a worsening of your condition. While adenine does not cause traditional withdrawal symptoms, your metabolic balance may shift when the drug is removed. Your doctor will likely want to monitor your uric acid levels and kidney function as you transition off the medication to ensure no rebound effects occur.
What should I do if I miss a dose of Adenine?
If you miss a dose of adenine, take it as soon as you remember. If it is nearly time for your next scheduled dose, skip the missed dose and continue with your regular timing. It is vital that you do not take two doses at once to make up for a missed one. Taking a double dose can significantly increase the concentration of adenine in your kidneys, sharply raising the risk of crystal formation and acute kidney injury. Consistency and high fluid intake are more important than 'catching up' on a single missed dose.
Does Adenine cause weight gain?
There is no significant clinical evidence to suggest that adenine causes weight gain. It does not affect appetite or fat storage in the way that some hormonal or psychiatric medications do. However, some patients may experience mild fluid retention or bloating as a side effect, which can cause slight fluctuations in weight. If you notice rapid or significant weight gain while taking adenine, you should contact your doctor, as this could be a sign of kidney issues rather than a change in body fat.
Can Adenine be taken with other medications?
Adenine can interact with several other medications, so it is crucial to provide your doctor with a full list of everything you take. It has significant interactions with gout medications like allopurinol, diuretics (water pills), and certain antiviral drugs like didanosine. Diuretics are particularly concerning because they can lead to dehydration, which increases the risk of adenine-induced kidney damage. Always check with a pharmacist or your doctor before starting any new over-the-counter medications, especially NSAIDs like ibuprofen, while on adenine therapy.
Is Adenine available as a generic?
Adenine itself is a basic chemical compound and is available in various generic forms, primarily for laboratory use or as part of generic blood preservative solutions (like CPDA-1). However, specialized oral formulations for stone dissolution or metabolic support are often compounded or sold under specific brand names depending on the country. Because it is a niche therapeutic agent, you may not find it as a standard 'generic' pill at a typical retail pharmacy; it often requires a specialized or hospital pharmacy to dispense.
Similar Medications
Other drugs with the same active ingredient (Adenine)
Gouty Arthritis Flare-ups: In patients with a history of gout, the increase in purine load can trigger acute joint pain, redness, and warmth, most commonly in the big toe, ankle, or knee.
Skin Rash: A mild, itchy maculopapular rash (flat and raised spots) may develop. This is usually a hypersensitivity reaction and should be reported to a doctor.
Dizziness: Some patients report a transient feeling of lightheadedness shortly after taking an oral dose.
Rare Side Effects (less than 1 in 100)
2,8-Dihydroxyadenine (2,8-DHA) Nephropathy: This is the most serious rare side effect. It occurs when the metabolite 2,8-DHA forms crystals in the kidneys, leading to acute kidney injury. Symptoms include sudden back pain and a sharp decrease in urine volume.
Anaphylaxis: A severe allergic reaction involving swelling of the face/throat, difficulty breathing, and a rapid drop in blood pressure.
Photosensitivity: Increased sensitivity of the skin to sunlight, leading to easier sunburns.
Serious Side Effects — Seek Immediate Medical Attention
> Warning: Stop taking Adenine and call your doctor immediately if you experience any of these:
Signs of Kidney Stones or Renal Failure: Sharp pain in the side or back, cloudy or bloody urine, or inability to urinate. This may indicate the formation of 2,8-DHA crystals.
Severe Allergic Reaction: Hives, swelling of the tongue or throat, or wheezing.
Extreme Joint Pain: Intense, throbbing pain in a single joint that comes on suddenly, indicating a severe gout flare.
Jaundice: Yellowing of the eyes or skin, which may indicate hepatic stress.
Long-Term Side Effects
Prolonged use of adenine requires careful monitoring for chronic conditions:
Chronic Kidney Disease (CKD): Repeated sub-clinical crystal formation can lead to permanent scarring of the renal tissue (interstitial fibrosis).
Tophaceous Gout: Long-term elevation of uric acid can lead to the formation of tophi (hard deposits of uric acid) under the skin or in joints.
Metabolic Imbalance: Chronic purine supplementation can shift the balance of other nucleotides, potentially affecting overall cellular metabolism.
Black Box Warnings
No FDA black box warnings currently exist for Adenine. However, clinical guidelines from the National Institutes of Health (NIH) emphasize that adenine should only be used in patients with adequate renal function and those who can maintain high levels of oral hydration. The risk of crystal-induced nephropathy is the primary safety concern associated with this active ingredient.
Report any unusual symptoms to your healthcare provider. Your doctor may perform regular blood tests (uric acid, creatinine) and urine tests (crystal analysis) to ensure the medication is being processed safely by your body.
Nephrotoxicity (Kidney Toxicity): Adenine is metabolized into 2,8-dihydroxyadenine (2,8-DHA) by the enzyme xanthine oxidase. 2,8-DHA is poorly soluble and can precipitate in the renal tubules. This risk is dose-dependent and is significantly higher in patients with dehydration or acidic urine.
Hepatotoxicity (Liver Toxicity): While less common than renal issues, adenine can place a metabolic burden on the liver. Patients with existing liver disease (e.g., hepatitis, cirrhosis) should have their liver enzymes (ALT, AST) monitored regularly.
Gout Exacerbation: Because adenine is a purine, it directly contributes to the body's uric acid pool. Patients with a history of gout may experience frequent and more severe attacks while taking adenine.
Monitoring Requirements
To ensure safety, healthcare providers will typically require the following tests:
Serum Creatinine and BUN: To monitor kidney function.
Uric Acid Levels: To assess the risk of gout and systemic purine load.
Urinalysis: Specifically looking for the presence of 2,8-DHA crystals under a microscope.
Complete Blood Count (CBC): To ensure that adenine is not adversely affecting white or red blood cell production.
Driving and Operating Machinery
Adenine generally does not cause sedation or cognitive impairment. However, if a patient experiences dizziness or lightheadedness as a side effect, they should avoid driving or operating heavy machinery until they know how the medication affects them.
Alcohol Use
Alcohol should be avoided or strictly limited while taking adenine. Alcohol, particularly beer and spirits, increases uric acid production and competes with adenine metabolites for renal excretion. This significantly increases the risk of both gout attacks and kidney stones.
Discontinuation
Adenine does not typically cause a withdrawal syndrome. However, if being used for calculi dissolution, stopping the medication abruptly may lead to a rapid recurrence of stone formation. Patients should always consult their doctor before stopping the medication to discuss a tapering schedule or alternative therapies.
> Important: Discuss all your medical conditions with your healthcare provider before starting Adenine. Be sure to mention if you have a history of kidney stones, gout, or kidney disease.
Cytotoxic Chemotherapy: Agents that cause rapid cell breakdown (Tumor Lysis Syndrome) already increase purine levels. Adding adenine can overwhelm the body's ability to process and excrete these compounds, leading to acute renal failure.
Moderate Interactions
NSAIDs (e.g., Ibuprofen, Naproxen): High doses of NSAIDs can reduce renal blood flow, potentially slowing the clearance of adenine metabolites.
Uricosuric Agents (e.g., Probenecid): These drugs increase the excretion of uric acid but may interfere with the renal transport of other adenine metabolites.
Food Interactions
High-Purine Foods: Foods such as organ meats (liver, kidneys), red meat, seafood (sardines, anchovies), and gravies should be limited. These foods add to the purine load and increase the risk of side effects.
High-Fructose Corn Syrup: Fructose metabolism accelerates purine breakdown, which can worsen hyperuricemia associated with adenine use.
Dairy: Some studies suggest low-fat dairy may actually help lower uric acid levels, but patients should discuss dietary changes with a nutritionist.
Herbal/Supplement Interactions
Vitamin C (High Dose): Large doses of Vitamin C can acidify the urine. Since adenine metabolites are less soluble in acidic urine, this can increase the risk of kidney stones.
St. John's Wort: May induce enzymes that subtly alter the metabolism of nucleoside-based drugs, though the clinical significance for adenine is low.
Lab Test Interactions
Uric Acid Tests: Adenine will cause a physiological increase in serum uric acid, which may be misinterpreted as a primary metabolic disorder (like idiopathic gout).
Urinary Glucose: High levels of purines can occasionally interfere with certain older colorimetric dipstick tests for glucose, leading to false-positive or false-negative results.
For each major interaction, the primary mechanism is usually pharmacodynamic (additive effects on uric acid/kidney stress) or pharmacokinetic (competition for renal tubular secretion). The clinical consequence is typically an increased risk of renal toxicity or gout. Management involves dose adjustment, increased hydration, or choosing alternative medications.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers.
Relative Contraindications
Conditions requiring a careful risk-benefit analysis by a healthcare provider:
Moderate Renal Impairment: Requires frequent monitoring and lower doses.
Urolithiasis (History of Kidney Stones): If the stones were purine-based (uric acid or 2,8-DHA), adenine may be too risky. If the stones were calcium-based, adenine might be used but with extreme caution.
Dehydration or Inability to Maintain Fluid Intake: Patients who cannot drink adequate fluids (e.g., due to swallowing disorders or dementia) are at high risk for adenine-induced kidney damage.
Peptic Ulcer Disease: Adenine can occasionally irritate the gastric mucosa, potentially worsening existing ulcers.
Cross-Sensitivity
Patients who have had allergic reactions to other purine-based drugs, such as Azathioprine, Mercaptopurine, or Acyclovir, may be at a slightly higher risk for cross-sensitivity to adenine, although the mechanisms of allergy for these drugs often differ. Any history of drug-induced skin rashes should be disclosed to the prescribing physician.
> Important: Your healthcare provider will evaluate your complete medical history, including your kidney function and history of gout, before prescribing Adenine.
Adenine is a natural component of human milk; however, when taken as a medication, levels in breast milk may increase significantly. The effect on a nursing infant's developing renal system and purine metabolism is unknown. Healthcare providers typically recommend either discontinuing breastfeeding or avoiding the medication while nursing, especially if the infant is premature or has renal issues.
Pediatric Use
Adenine is not approved for general use in children. Its use is restricted to specialized contexts such as:
Neonatal Transfusions: Using CPDA-1 preserved blood is standard but requires careful monitoring of the infant's acid-base balance.
Genetic Purine Disorders: In rare cases, pediatric metabolic specialists may use adenine to 'bypass' certain enzyme deficiencies. Growth and development must be monitored closely, as purine imbalances can affect bone density and cognitive development.
Geriatric Use
Patients over the age of 65 are at the highest risk for adenine-related complications.
Renal Clearance: Age-related decline in GFR is common, making crystal nephropathy more likely.
Polypharmacy: Elderly patients are often on diuretics or NSAIDs, both of which interact negatively with adenine.
Fall Risk: If adenine causes dizziness, the risk of falls and fractures increases in this population.
Monitoring: Geriatric patients should have their kidney function checked more frequently (e.g., every 2-4 weeks) than younger adults.
Renal Impairment
As adenine metabolites are excreted by the kidneys, any degree of impairment requires caution.
Mild (GFR 60-89): No specific dose adjustment, but ensure high hydration.
Moderate (GFR 30-59): Reduce dose by 50% and monitor urine for crystals.
Severe (GFR < 30): Use is generally contraindicated.
Hepatic Impairment
In patients with Child-Pugh Class B or C cirrhosis, the liver's ability to process adenine via the salvage pathway may be reduced, leading to higher systemic levels. Dose reductions and monitoring of liver function tests (LFTs) are recommended.
> Important: Special populations require individualized medical assessment and often more frequent laboratory monitoring to ensure safety.
Pharmacodynamics
The onset of action for ATP maintenance in blood cells is relatively rapid (within hours of exposure). For calculi dissolution, the effect is cumulative and may take weeks to months of consistent dosing to show a reduction in stone size on imaging (ultrasound or CT). Tolerance does not typically develop, but the risk of toxicity increases if the metabolic pathways (APRT) become saturated.
Solubility: Slightly soluble in cold water; more soluble in hot water and acidic/alkaline solutions.
Structure: A bicyclic heterocycle consisting of a fused pyrimidine and imidazole ring system.
Drug Class
Adenine is classified therapeutically as a Calculi Dissolution Agent and a Blood Preservative. It belongs to the broader class of Purines. Related medications include Adenosine (used for arrhythmias) and Allopurinol (a xanthine oxidase inhibitor used to treat gout).