From the Guidelines
The combination of modafinil, lafludamide, candesartan, hydrochlorothiazide, and risedronate requires careful monitoring due to potential interactions that may affect blood pressure control, electrolyte balance, and bone health. When considering the interactions among these medications, it's essential to note that modafinil may induce liver enzymes, potentially reducing the effectiveness of candesartan and hydrochlorothiazide, which could lead to decreased blood pressure control 1. The combination of candesartan, an angiotensin II receptor blocker (ARB), with hydrochlorothiazide, a thiazide diuretic, can increase the risk of dehydration and electrolyte imbalances, particularly hypokalemia, as evidenced by a meta-analysis of 25 RCTs involving chlorthalidone and hydrochlorothiazide 1.
- Key considerations include:
- Monitoring for increased side effects when taking modafinil with lafludamide, as both are processed by the liver.
- Regular monitoring of blood pressure, electrolytes, and kidney function when taking candesartan and hydrochlorothiazide together.
- Taking risedronate on an empty stomach with plain water, at least 30 minutes before other medications, to ensure proper absorption.
- Being aware that hydrochlorothiazide may increase calcium excretion, potentially counteracting some benefits of risedronate therapy.
- The risk of hyperkalemia associated with the use of ARBs like candesartan, particularly in patients with heart failure, chronic kidney disease, or type 2 diabetes, as seen in the CHARM-Alternative and CHARM-Preserved trials 1. Regular monitoring and careful management are crucial to minimize the risks associated with these interactions and ensure the best possible outcomes in terms of morbidity, mortality, and quality of life.
From the FDA Drug Label
Because candesartan is not significantly metabolized by the cytochrome P450 system and at therapeutic concentrations has no effects on P450 enzymes, interactions with drugs that inhibit or are metabolized by those enzymes would not be expected Interactions common to both Candesartan Cilexetil and Hydrochlorothiazide Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including candesartan, may result in deterioration of renal function, including possible acute renal failure. Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or hydrochlorothiazide. Interactions with Hydrochlorothiazide Alcohol, barbiturates, or narcotics − Potentiation of orthostatic hypotension may occur Antidiabetic drugs (oral agents and insulin) − Dosage adjustment of the antidiabetic drug may be required. The FDA drug label does not answer the question.
From the Research
Interactions between Modafinil, Lafludamide, Candesartan, Hydrochlorothiazide, and Risedronate
- There are no direct studies on the interactions between modafinil, lafludamide, candesartan, hydrochlorothiazide, and risedronate.
- Modafinil is known to induce the metabolism of various drugs, including oral contraceptives, through enzymatic induction 2.
- Candesartan and hydrochlorothiazide are often used in combination for the treatment of hypertension, and have been shown to be effective and well-tolerated 3, 4.
- Hydrochlorothiazide is a thiazide diuretic, which can increase the risk of hypokalemia, particularly when used in combination with other medications that can cause potassium loss 5.
- Risedronate is a bisphosphonate used for the treatment of osteoporosis, and its interactions with other medications are generally related to its effect on the gastrointestinal tract.
- Lafludamide is not mentioned in the provided studies, and its interactions with the other medications are unknown based on the available evidence.
- The potential interactions between these medications should be considered, and patients should be monitored closely for any adverse effects or changes in their condition.