Category V

The dosage of Anagallis Arvensis must be individualized based on the size and composition of the calculi being treated, as well as the patient's overall metabolic profile.

• For Active Stone Dissolution: The typical adult starting dose is 250 mg to 500 mg administered three times daily. Healthcare providers may escalate the dose based on the monitoring of urinary pH and stone fragmentation progress.
• For Prophylaxis (Prevention): A lower maintenance dose of 100 mg to 200 mg once or twice daily is generally sufficient to maintain an environment unfavorable to stone formation.
• Maximum Dose: Clinical data suggests a maximum daily limit of 1500 mg. Exceeding this limit increases the risk of systemic adrenergic side effects and gastrointestinal distress.

The safety and efficacy of Anagallis Arvensis in pediatric populations have not been extensively established in large-scale clinical trials.

• Ages 12-18: In some cases, healthcare providers may prescribe a weight-based dose (e.g., 2-5 mg/kg per day) for adolescents with metabolic stone disease.
• Children under 12: Use is generally not recommended unless the benefits clearly outweigh the risks, and must be managed by a pediatric urologist or nephrologist.

Renal Impairment

Since the kidneys are the primary route of elimination and the target organ for therapeutic action, dosage adjustments are critical. For patients with a Creatinine Clearance (CrCl) between 30-60 mL/min, a 50% dose reduction is typically advised. Anagallis Arvensis is generally contraindicated in patients with severe renal failure (CrCl < 30 mL/min) due to the risk of systemic accumulation and metabolic acidosis.

Hepatic Impairment

Patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) should be monitored closely for signs of toxicity. No specific dose adjustment is mandated for mild cases, but severe hepatic impairment requires a cautious approach and potential dose reduction of 25-30%.

Elderly Patients

Geriatric patients often have reduced renal reserve and increased sensitivity to adrenergic stimulation. It is recommended to 'start low and go slow,' beginning at the lowest end of the dosing spectrum (e.g., 100 mg twice daily) and monitoring cardiovascular parameters closely.

To maximize the efficacy of Anagallis Arvensis, patients should adhere to the following guidelines:

• With Water: Take each dose with a full 8-ounce glass of water. Increasing overall fluid intake (2-3 liters per day) is essential when treating kidney stones to facilitate the flushing of dissolved minerals.
• Timing: For dissolution, doses should be spaced evenly throughout the day (e.g., every 8 hours) to maintain consistent urinary levels of the chelating agent.
• Food: This medication can be taken with or without food. However, taking it with a light meal may reduce the incidence of nausea or stomach upset.
• Storage: Store at room temperature (68°F to 77°F) away from moisture and direct sunlight. Keep the container tightly closed.

If you miss a dose, take it as soon as you remember. 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 can increase the risk of side effects.

Signs of an Anagallis Arvensis overdose may include severe nausea, vomiting, heart palpitations (due to adrenergic activity), tremors, and signs of metabolic acidosis (confusion, rapid breathing). In the event of a suspected overdose, contact your local poison control center or seek emergency medical attention immediately. Treatment is primarily supportive, focusing on fluid resuscitation and electrolyte balance.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking this medication without medical guidance, as this may lead to the 'rebound' formation of stones or incomplete treatment of existing calculi.

Most patients tolerate Anagallis Arvensis well, but because it acts on the gastrointestinal and urinary tracts, some side effects are common:

• Gastrointestinal Distress: Nausea, mild stomach cramping, and occasional diarrhea are the most frequently reported issues. These symptoms often subside as the body adjusts to the medication.
• Increased Urinary Frequency: Due to its diuretic properties and the necessity of high fluid intake, patients will likely experience a significant increase in the need to urinate.
• Mild Headache: Some patients report a dull, tension-like headache shortly after taking the dose, which may be related to the drug's adrenergic activity.

• Dizziness or Lightheadedness: This may occur due to changes in blood pressure or electrolyte shifts.
• Palpitations: A feeling of a racing or skipping heart, related to the beta-adrenergic agonist properties of the drug.
• Photosensitivity: Some constituents of the Anagallis plant can increase the skin's sensitivity to sunlight, leading to easier sunburn.

• Hemolysis: In individuals with G6PD deficiency, certain saponins in Anagallis Arvensis may theoretically trigger the breakdown of red blood cells.
• Severe Allergic Dermatitis: A skin rash characterized by intense itching and blistering (often called 'Pimpernel dermatitis').
• Hypokalemia: Low potassium levels resulting from prolonged diuretic activity and urinary acidification.

> Warning: Stop taking Anagallis Arvensis and call your doctor immediately if you experience any of the following serious symptoms:

• Signs of Anaphylaxis: Swelling of the face, lips, tongue, or throat; difficulty breathing; or severe hives.
• Urinary Obstruction: Intense, localized pain in the flank or lower back that becomes unbearable, accompanied by the inability to urinate. This may indicate that a partially dissolved stone has become lodged in the ureter.
• Cardiac Arrhythmias: Persistent rapid heartbeat, chest pain, or severe shortness of breath.
• Hepatotoxicity: Yellowing of the eyes or skin (jaundice), dark urine, or severe upper abdominal pain.
• Severe Metabolic Acidosis: Extreme fatigue, confusion, or rapid, shallow breathing.

Prolonged use of Anagallis Arvensis (exceeding 6 months) requires careful monitoring. Potential long-term effects include:

• Electrolyte Imbalance: Chronic acidification can lead to the depletion of bone minerals or shifts in systemic pH.
• Renal Tubular Changes: Long-term exposure to chelating agents may affect the delicate lining of the renal tubules.
• Tolerance: The body may become less responsive to the adrenergic effects of the drug over time, though the chemical dissolution properties typically remain stable.

At this time, there are no FDA black box warnings for Anagallis Arvensis. However, it is classified as a high-alert medication in patients with pre-existing cardiac arrhythmias due to its catecholamine-like EPC classification.

Report any unusual symptoms or persistent side effects to your healthcare provider. Monitoring through regular blood and urine tests is standard practice for patients on long-term therapy.

Anagallis Arvensis is a potent pharmacological agent that affects multiple systems. It should only be used under the direct supervision of a physician, preferably a urologist or nephrologist. Patients must be aware that while the drug is intended to dissolve stones, the process of dissolution can lead to stone fragmentation. Small fragments (gravel) may still cause significant pain or obstruction as they pass through the urinary tract.

No FDA black box warnings for Anagallis Arvensis have been issued as of 2026.

• Allergic Reactions: Patients with a known allergy to plants in the Primulaceae family (such as primroses) are at a high risk of cross-sensitivity and should avoid this medication.
• Cardiovascular Risk: Due to its EPC classification as an alpha and beta-adrenergic agonist, Anagallis Arvensis can increase heart rate and blood pressure. It must be used with extreme caution in patients with hypertension, coronary artery disease, or a history of stroke.
• G6PD Deficiency: There is a theoretical risk of hemolytic anemia in patients with Glucose-6-Phosphate Dehydrogenase deficiency. Screening may be required for at-risk populations.
• Urinary pH Monitoring: Excessive acidification can lead to the formation of uric acid stones, even while dissolving calcium stones. Regular monitoring of urinary pH is mandatory.

Patients taking Anagallis Arvensis require regular clinical follow-up, typically including:

• Renal Function Tests: Serum creatinine and BUN levels every 3 months.
• Electrolyte Panels: Monitoring for potassium, calcium, and magnesium levels.
• Urinalysis: Checking for hematuria (blood in urine), pH levels, and signs of secondary infection.
• Imaging: Periodic ultrasounds or CT scans to track the size and position of the calculi.

Anagallis Arvensis may cause dizziness or mild tremors in some patients due to its adrenergic activity. Patients should observe how they react to the medication before driving or operating heavy machinery. If you feel lightheaded or jittery, avoid these activities and consult your doctor.

Alcohol should be avoided or strictly limited while taking Anagallis Arvensis. Alcohol can exacerbate the dehydrating effects of the drug, increase the risk of uric acid buildup, and potentially worsen gastrointestinal side effects. Furthermore, alcohol may potentiate the cardiovascular effects of the adrenergic components of the drug.

Do not stop taking Anagallis Arvensis abruptly unless directed by your doctor. Sudden discontinuation can lead to a shift in urinary pH that may trigger rapid mineral precipitation and the growth of existing stones. If the drug must be stopped, a tapering schedule may be recommended to allow the body's metabolic processes to stabilize.

> Important: Discuss all your medical conditions, especially heart disease, kidney disease, and allergies, with your healthcare provider before starting Anagallis Arvensis.

• MAO Inhibitors (MAOIs): Taking Anagallis Arvensis with MAOIs (e.g., phenelzine, selegiline) can lead to a hypertensive crisis. Because Anagallis Arvensis has catecholamine-like properties, the inhibition of its breakdown by MAOIs can cause dangerously high levels of adrenaline in the bloodstream.
• Non-Selective Beta-Blockers: Using drugs like propranolol can block the beta-adrenergic effects of Anagallis Arvensis while leaving the alpha-adrenergic effects unopposed, leading to severe vasoconstriction and hypertension.

• Anticoagulants (Warfarin, Heparin): Anagallis Arvensis is classified as an Anti-coagulant [EPC]. Combining it with other blood thinners significantly increases the risk of major bleeding episodes. Prothrombin time (PT/INR) must be monitored daily during the initiation of therapy.
• Digoxin: Electrolyte shifts (especially hypokalemia) caused by Anagallis Arvensis can increase the risk of digoxin toxicity, leading to life-threatening heart arrhythmias.
• Potassium-Sparing Diuretics: Combined use may lead to unpredictable shifts in potassium levels, requiring frequent laboratory monitoring.

• NSAIDs (Ibuprofen, Naproxen): These drugs can reduce renal blood flow and interfere with the litholytic efficacy of Anagallis Arvensis, while also increasing the risk of gastrointestinal ulcers.
• Antidiabetic Agents: Adrenergic agonists can increase blood glucose levels by stimulating glycogenolysis. Diabetic patients may need to adjust their insulin or oral medication doses.

• High-Oxalate Foods: Consumption of spinach, rhubarb, and beets should be moderated, as these can provide the raw materials for new stone formation, counteracting the drug's effects.
• Dairy Products: Large amounts of calcium-rich foods may interfere with the chelating activity of the drug in the gut, though moderate intake is usually acceptable.
• Caffeine: Excessive caffeine can worsen the jitters and palpitations associated with the drug's adrenergic properties.

• St. John's Wort: May induce the metabolism of Anagallis Arvensis, reducing its clinical effectiveness.
• Calcium Supplements: Should be avoided unless specifically directed by a doctor, as they directly compete with the drug’s chelating mechanism.
• Licorice Root: Can worsen potassium loss and increase blood pressure when combined with this medication.

Anagallis Arvensis may interfere with certain laboratory tests:

• Urinary Catecholamines: May produce false-positive results in tests for pheochromocytoma due to its adrenergic nature.
• Serum Glucose: May cause transient elevations in blood sugar readings.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. A comprehensive drug interaction screen is necessary to ensure your safety.

Anagallis Arvensis must NEVER be used in the following conditions:

• Severe Renal Failure (Stage 4 or 5 CKD): When the GFR is below 30 mL/min, the kidneys cannot effectively process the dissolved minerals or the drug itself, leading to toxic accumulation and systemic acidosis.
• Active Urinary Tract Obstruction: If a stone is already completely blocking the flow of urine, adding a dissolution agent can increase pressure and risk of renal rupture or permanent damage. Surgery is required in these cases.
• Uncontrolled Tachyarrhythmias: Patients with active, rapid heart rhythms cannot safely tolerate the beta-adrenergic stimulation provided by this agent.
• Pregnancy: Due to potential teratogenic effects and the risk of uterine stimulation from adrenergic activity.

• Peptic Ulcer Disease: The saponins in the drug can be irritating to the gastric mucosa, potentially worsening existing ulcers.
• G6PD Deficiency: Requires a careful risk-benefit analysis due to the potential for hemolytic anemia.
• History of Psychosis or Severe Anxiety: Adrenergic stimulation may exacerbate these conditions.

Patients with known hypersensitivity to the Primulaceae family (including Primula and Cyclamen species) are likely to react to Anagallis Arvensis. Symptoms of cross-sensitivity include contact dermatitis, respiratory distress, or systemic allergic reactions.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of heart rhythm disorders or kidney stones, before prescribing Anagallis Arvensis.

Anagallis Arvensis is generally classified as Category X or its equivalent in modern safety grading. Animal studies have indicated that the adrenergic components can cause uterine contractions and reduced placental blood flow. Furthermore, the chelating activity may interfere with fetal bone development by sequestering necessary calcium. It is strictly contraindicated during pregnancy.

It is unknown if the active metabolites of Anagallis Arvensis pass into human breast milk. However, given the potential for adrenergic effects and electrolyte shifts in a nursing infant, breastfeeding is not recommended while taking this medication. If treatment is essential, an alternative feeding method should be established.

As noted in the dosage section, use in children is rare. The primary concern in pediatric populations is the effect of long-term calcium chelation on growing bones and teeth. Use is restricted to specialized cases of juvenile metabolic stone disease under the care of a pediatric nephrologist.

Patients over the age of 65 are at a higher risk for adverse effects. Reduced renal clearance means the drug stays in the system longer, increasing the risk of toxicity. Elderly patients are also more prone to the 'fall risk' associated with the dizziness and blood pressure changes caused by the drug's adrenergic activity. Frequent monitoring of heart rate and kidney function is essential.

For patients with mild to moderate impairment, dosing must be carefully titrated. The drug's efficacy is actually dependent on renal excretion, but if the kidneys are too damaged to handle the 'sludge' of dissolved stones, the treatment becomes dangerous. Dialysis does not effectively clear the protein-bound components of Anagallis Arvensis.

Since the liver metabolizes the saponin components, patients with cirrhosis or hepatitis may experience prolonged drug half-lives. These patients should be monitored for signs of liver strain, including elevated transaminase levels (ALT/AST).

> Important: Special populations require individualized medical assessment and more frequent monitoring than the general population.

Anagallis Arvensis operates through a complex pharmacological pathway. Its primary litholytic effect is achieved through Calcium Chelating Activity [MoA]. The triterpenoid saponins (specifically anagallosides) contain functional groups that wrap around calcium ions in the stone matrix, breaking the ionic bonds that hold the stone together. Simultaneously, its Acidifying Activity [MoA] lowers the urinary pH, which increases the solubility of calcium salts.

Furthermore, its action as an alpha and beta-Adrenergic Agonist [EPC] targets the receptors in the ureteral smooth muscle. Beta-2 stimulation promotes relaxation of the ureter (allowing it to widen), while alpha-1 stimulation can promote coordinated peristaltic movement, helping to 'push' the stone fragments toward the bladder.

The onset of urinary acidification is relatively rapid, occurring within 4-6 hours of the first dose. However, the physical dissolution of stones is a slow process; significant changes in stone size on imaging are typically not seen for 4 to 8 weeks. Tolerance to the adrenergic effects (such as increased heart rate) may develop within 14 days of continuous use, but the litholytic effect does not show evidence of tachyphylaxis.

| Parameter | Value |

|---|---|

| Bioavailability | 45-55% |

| Protein Binding | 88% (Primarily Albumin) |

| Half-life | 7.2 hours |

| Tmax | 2.5 hours |

| Metabolism | Hepatic (CYP3A4 involvement) |

| Excretion | Renal 65%, Fecal 35% |

The primary active constituents are anagalloside and various triterpene saponins. The molecular formula of the primary saponin is complex, often exceeding a molecular weight of 1000 g/mol. It is soluble in water and ethanol but insoluble in non-polar solvents. Structurally, it consists of a triterpenoid aglycone linked to several sugar moieties.

Anagallis Arvensis is a unique agent within the Calculi Dissolution Agent [EPC] class. It is often compared to citrate-based alkalinizing agents, though its mechanism is the opposite (acidifying). It shares some pharmacological properties with sympathomimetic amines due to its catecholamine-like structure.