Periodic monitoring for adverse effects is essential when prescribing preventative medications in patients with recurrent kidney stones (see Table 7 below for suggested laboratory studies and monitoring frequency). More frequent monitoring may be necessary for some patients, including those with CKD, with some medications. Drug interactions are common and important to check prior to initiating pharmacotherapy. For thiazide use, the most common adverse effects are hypokalemia with concurrent decrease in urinary citrate (leading to low urinary citrate in some patients), high blood sugar/hyperglycemia, hyponatremia, hypercalcemia, hyperlipidemia, hyperuricemia, and hypotension.236 General symptoms can include dizziness, weakness, increased urination, and headaches.236 It is not recommended to start a thiazide in a patient with suspected primary hyperparathyroidism as it may cause a dangerous rise in serum calcium levels (hypercalcemia). The Panel recommends checking a BMP within 4 weeks of initiating thiazide treatment or after any dose adjustment, as well as every 6-12 months thereafter. Hypokalemia commonly occurs with thiazide therapy, and potassium repletion and maintenance can be achieved with co-administration of either potassium chloride or potassium citrate, depending on urinary pH and citrate levels. In patients with a marked hypokalemic response who cannot be sufficiently repleted with potassium, use of a potassium-sparing diuretic in combination with a thiazide (e.g., amiloride/hydrochlorothiazide) or the addition of spironolactone may be preferable. However, it should be noted that hyperkalemia is a risk when using potassium-sparing diuretics. Additionally, serum uric acid and lipid profile should be monitored with thiazide use. Potential side effects of potassium alkali therapy include GI upset (e.g., nausea, vomiting, diarrhea, heartburn, stomach pain), metabolic alkalosis, and side effects from sodium bicarbonate include metabolic alkalosis, GI upset/bloating, headache, and muscle cramps.237, 238 Potassium citrate should not be used in patients with or who are at risk of hyperkalemia, or in patients on potassium-sparing diuretics unless closely monitored. It is of the panel’s expert opinion that patients be periodically monitored with a BMP to assess creatinine and potassium every 6-12 months or at a higher frequency in those at increased risk of hyperkalemia. Allopurinol is generally a well-tolerated medication with relatively few side effects (see Statement 22).55, 66, 239 GI upset and maculopapular pruritic rash are among the more commonly reported effects.239 Other less common adverse effects include hepatotoxicity and transaminitis, and consequently liver enzymes should be periodically monitored in those with suspected liver disease.239 The most feared, albeit rare, side effects of allopurinol are Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), which are life threatening severe cutaneous hypersensitivity reactions.240 Patients should be warned to discontinue the medication immediately if they develop a rash of any kind while on allopurinol. The use of AHA for the prevention of struvite stones requires close monitoring as it is associated with a high side effect profile, which may limit its use (see Statement 34).57, 58 Adverse reactions include hemolytic anemia, headache, and GI symptoms. The Panel recommends periodic monitoring for adverse events including a complete blood count (CBC) to evaluate for anemia (approximately 2 weeks after initiation of therapy and then every 3 months or more thereafter). BMP is recommended prior to and periodically during treatment to facilitate dosage adjustments (creatinine, creatinine clearance; contraindicated in patients with creatinine >2.5 mg/dL).224 As discussed under Statement 34, other side effects may include depression, anxiety, nervousness, and tremulousness. AHA is also contraindicated in pregnancy or in patients with childbearing potential without use of effective contraception.225 Patients should also be monitored for phlebitis and hypercoagulable effects such as blood clots.226 The use of thiol drugs (tiopronin) to prevent cystine stones in patients with cystinuria requires close monitoring because of the relatively high potential for side effects (See Statement 39). The most common side effects include GI upset and dermatologic, hematologic, and hepatic/renal effects. As such, periodic laboratory studies should be performed (see Table 7 below for recommended monitoring). More severe adverse effects include proteinuria and nephrotic syndrome, bone marrow suppression, and hepatotoxicity. Patients should be monitored for proteinuria, and the medication should be discontinued if detected. D-penicillamine is less well-tolerated than tiopronin, with high discontinuation rates due to fever, rash, GI upset, pyridoxine deficiency, proteinuria, neutropenia, and anemia.220, 241