Adenine

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.

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.

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.

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.

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.

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.

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.

• 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.

• 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.

> 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.

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.

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.

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.

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.

• 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.
• 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.

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.

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 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.

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.

• 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.

• 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.
• 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.

• 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.

• 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.

• 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.

• 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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:

1. 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.
2. 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.

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.

| Parameter | Value |

|---|---|

| Bioavailability | 40% - 60% (Oral) |

| Protein Binding | < 5% |

| Half-life | 30 - 60 minutes (Systemic) |

| Tmax | 1 - 2 hours (Oral) |

| Metabolism | Primary: APRT (Salvage); Secondary: Xanthine Oxidase |

| Excretion | Renal (80% - 90% as metabolites) |

• Molecular Formula: C5H5N5
• Molecular Weight: 135.13 g/mol
• 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.

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).