Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Some topical anesthetics can be systemically absorbed and cause methemoglobinemia, particularly when applied to mucous membranes. Coadministration with other oxidizing agents that can also induce methemoglobinemia such as injectable local anesthetics, antimalarials (e.g., chloroquine, primaquine, quinine, tafenoquine), nitrates and nitrites, sulfonamides, aminosalicylic acid, dapsone, dimethyl sulfoxide, flutamide, metoclopramide, nitrofurantoin, phenazopyridine, phenobarbital, phenytoin, and rasburicase may increase the risk. Additional risk factors include very young age (e.g., infants less than 6 months); application to inflamed/abraded areas or broken skin; anemia; cardiac or pulmonary disease; peripheral vascular disease; liver cirrhosis; shock; sepsis; acidosis; and genetic predisposition (e.g., NADH cytochrome-b5 reductase deficiency; glucose-6-phosphate dehydrogenase (G6PD) deficiency; hemoglobin M). There have been rare reports of significant methemoglobinemia associated with administration of topical anesthetics, primarily following application to mucous membranes prior to dental procedures or via the oropharyngeal route prior to procedures such as intubation, laryngoscopy, bronchoscopy, and endoscopy. Very rarely, methemoglobinemia has also been reported with use of anesthetic throat lozenges.

MANAGEMENT: Caution is advised when topical anesthetics are used concomitantly with other methemoglobin-inducing agents. Clinicians should be aware of the potential for methemoglobinemia, particularly when topical anesthetics are applied to mucous membranes or given via the oropharyngeal route. Signs and symptoms of methemoglobinemia may be delayed some hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia such as slate-grey cyanosis in buccal mucous membranes, lips, and nail beds; nausea; headache; dizziness; lightheadedness; lethargy; fatigue; dyspnea; tachypnea; tachycardia; palpitation; anxiety; and confusion. In severe cases, patients may progress to central nervous system depression, stupor, seizures, acidosis, cardiac arrhythmias, syncope, shock, coma, and death. Methemoglobinemia should be considered if central cyanosis is unresponsive to oxygen. Calculated oxygen saturation and pulse oximetry are generally not accurate in the setting of methemoglobinemia. The diagnosis can be confirmed by an elevated methemoglobin level of at least 10% using co-oximetry. Methemoglobin concentrations greater than 10% of total hemoglobin will typically cause cyanosis, and levels over 70% are frequently fatal. However, symptom severity is not always related to methemoglobin levels. Experts suggest that treatment of methemoglobinemia varies from supplemental oxygen and symptom support to the administration of methylene blue, depending on severity of symptoms and/or the presence of G6PD deficiency. Institutional guidelines and/or individual product labeling should be consulted for further guidance.

Citrate, or citric acid, can increase the absorption of aluminum hydroxide. This may lead to elevated blood levels of aluminum, particularly in individuals with reduced kidney function, since aluminum is primarily eliminated by the kidneys. Excess aluminum may deposit and cause problems in various tissues including bone, brain, heart, liver, muscles, and spleen. Over time, weak bones, bone pain, fractures, skeletal deformity, brain disorders, and anemia may develop. Talk to your doctor before using aluminum hydroxide if you have kidney impairment or are on hemodialysis. You should avoid or limit the consumption of citrate-containing foods and beverages (e.G., soft drinks, citrus fruits, fruit juices) during treatment with aluminum hydroxide. Be aware that some effervescent and dispersible drug formulations may also contain citrate and should be restricted as well. Even if you do not have kidney problems, it may be best to separate the dosing of aluminum hydroxide and citrate-containing products by 2 to 3 hours. Talk to a healthcare professional if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

When aluminum hydroxide is taken during enteral nutrition therapy (tube feeding), the tube may get clogged. Therefore, aluminum hydroxide should not be mixed with or given after high-protein tube feedings. The dose should be separated from the feeding by as much as possible, and the tube should be thoroughly flushed before administration of the dose.

Food significantly enhances the absorption of atovaquone. You should take each dose of atovaquone at the same time each day with a meal or a milky drink. If you receive enteral nutrition (tube feeding), take atovaquone with your feeding. Taking it on an empty stomach may lead to inadequate blood levels and reduced effectiveness of the medication. Talk to your doctor if you have questions or have difficulty taking atovaquone with food.

Ask your doctor before using diphenhydrAMINE together with ethanol (alcohol). Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking diphenhydrAMINE. You should be warned not to exceed recommended dosages and to avoid activities requiring mental alertness. If your doctor prescribes these medications together, you may need a dose adjustment to safely take this combination. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.