Skip to main content

Drug Interactions between oxytetracycline / phenazopyridine / sulfamethizole and sodium nitrite

This report displays the potential drug interactions for the following 2 drugs:

Edit list (add/remove drugs)

Interactions between your drugs

Major

phenazopyridine sodium nitrite

Applies to: oxytetracycline / phenazopyridine / sulfamethizole and sodium nitrite

MONITOR CLOSELY: Sodium nitrite can cause methemoglobin formation, which diminishes oxygen-carrying capacity of the blood. Coadministration with other agents that are also associated with methemoglobinemia including local anesthetics (e.g., benzocaine, lidocaine, prilocaine), antimalarials (e.g., chloroquine, primaquine, quinine, tafenoquine), nitrates and nitrites, sulfonamides, aminosalicylic acid, dapsone, dimethyl sulfoxide, flutamide, metoclopramide (primarily in infants), nitrofurantoin (primarily in infants), phenazopyridine, phenobarbital, phenytoin, and rasburicase may increase the risk. Additional risk factors include very young age, anemia, cardiac/pulmonary disease, peripheral vascular disease, shock, sepsis, acidosis, and genetic predisposition (e.g., NADH cytochrome-b5 reductase deficiency; glucose-6-phosphate dehydrogenase deficiency; hemoglobin M). When sodium nitrite is administered to humans, a wide range of methemoglobin concentrations may occur. Methemoglobin concentrations as high as 58% have been reported after administration of two 300 mg doses to an adult. There have been reports of methemoglobinemia, coma, and death in patients without life-threatening cyanide poisoning but who were treated with injection of sodium nitrite at dosages less than twice those recommended for the treatment of cyanide poisoning.

MANAGEMENT: Sodium nitrite should be used with caution in the presence of other methemoglobin-inducing drugs. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with sodium nitrite. Methemoglobin levels should be monitored and oxygen administered whenever possible. 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; anxiety; and confusion. In severe cases, patients may progress to central nervous system depression, stupor, seizures, acidosis, cardiac arrhythmias, syncope, and shock. 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%. If patient does not respond to administration of oxygen, clinically significant methemoglobinemia should be treated with methylene blue 1 to 2 mg/kg by slow intravenous injection over 5 minutes.

References (3)
  1. Coleman MD, Coleman NA (1996) "Drug-induced methaemoglobinaemia: treatment issues." Drug Saf, 14, p. 394-405
  2. (2012) "Product Information. Sodium Nitrite (sodium nitrite)." Hope Pharmaceuticals
  3. Rehman HU (2001) "Methemoglobinemia." West J Med, 175, p. 193-6
Major

sulfamethizole sodium nitrite

Applies to: oxytetracycline / phenazopyridine / sulfamethizole and sodium nitrite

MONITOR CLOSELY: Sodium nitrite can cause methemoglobin formation, which diminishes oxygen-carrying capacity of the blood. Coadministration with other agents that are also associated with methemoglobinemia including local anesthetics (e.g., benzocaine, lidocaine, prilocaine), antimalarials (e.g., chloroquine, primaquine, quinine, tafenoquine), nitrates and nitrites, sulfonamides, aminosalicylic acid, dapsone, dimethyl sulfoxide, flutamide, metoclopramide (primarily in infants), nitrofurantoin (primarily in infants), phenazopyridine, phenobarbital, phenytoin, and rasburicase may increase the risk. Additional risk factors include very young age, anemia, cardiac/pulmonary disease, peripheral vascular disease, shock, sepsis, acidosis, and genetic predisposition (e.g., NADH cytochrome-b5 reductase deficiency; glucose-6-phosphate dehydrogenase deficiency; hemoglobin M). When sodium nitrite is administered to humans, a wide range of methemoglobin concentrations may occur. Methemoglobin concentrations as high as 58% have been reported after administration of two 300 mg doses to an adult. There have been reports of methemoglobinemia, coma, and death in patients without life-threatening cyanide poisoning but who were treated with injection of sodium nitrite at dosages less than twice those recommended for the treatment of cyanide poisoning.

MANAGEMENT: Sodium nitrite should be used with caution in the presence of other methemoglobin-inducing drugs. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with sodium nitrite. Methemoglobin levels should be monitored and oxygen administered whenever possible. 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; anxiety; and confusion. In severe cases, patients may progress to central nervous system depression, stupor, seizures, acidosis, cardiac arrhythmias, syncope, and shock. 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%. If patient does not respond to administration of oxygen, clinically significant methemoglobinemia should be treated with methylene blue 1 to 2 mg/kg by slow intravenous injection over 5 minutes.

References (3)
  1. Coleman MD, Coleman NA (1996) "Drug-induced methaemoglobinaemia: treatment issues." Drug Saf, 14, p. 394-405
  2. (2012) "Product Information. Sodium Nitrite (sodium nitrite)." Hope Pharmaceuticals
  3. Rehman HU (2001) "Methemoglobinemia." West J Med, 175, p. 193-6

Drug and food interactions

Moderate

oxytetracycline food

Applies to: oxytetracycline / phenazopyridine / sulfamethizole

ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption. The calcium content in some foods can form nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals. Because oral tetracycline has caused rare cases of esophagitis and esophageal ulceration, patients should be advised to take tetracycline with a large glass of water while standing or sitting upright and to avoid laying down immediately afterwards.

References (5)
  1. (2001) "Product Information. Achromycin (tetracycline)." Lederle Laboratories
  2. (2001) "Product Information. Declomycin (demeclocycline)." Lederle Laboratories
  3. (2024) "Product Information. Pylera (bismuth subcitrate potassium/metronidazole/tetracycline)." Flynn Pharma Ltd
  4. (2025) "Product Information. Pylera (bismuth subcitrate potassium/metronidazole/tetracycline)." H2-Pharma LLC
  5. Laboratoires Juvise Pharmaceuticals (2025) Bismuth subcitrate potassium, metronidazole, tetracycline hydrochloride capsules (Pylera) - product monograph. https://pdf.hres.ca/dpd_pm/00076786.PDF
Moderate

oxytetracycline food

Applies to: oxytetracycline / phenazopyridine / sulfamethizole

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References (11)
  1. Neuvonen PJ (1976) "Interactions with the absorption of tetracyclines." Drugs, 11, p. 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R (1972) "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand, 191, p. 409-11
  3. Venho VM, Salonen RO, Mattila MJ (1978) "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol, 14, p. 277-80
  4. (2002) "Product Information. Minocin (minocycline)." Lederle Laboratories
  5. Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
  6. Bateman FJ (1970) "Effects of tetracyclines." Br Med J, 4, p. 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K (1970) "Interference of iron with the absorption of tetracyclines in man." Br Med J, 4, p. 532-4
  8. Greenberger NJ (1971) "Absorption of tetracyclines: interference by iron." Ann Intern Med, 74, p. 792-3
  9. Neuvonen PJ, Penttila O (1974) "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol, 7, p. 361-3
  10. (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
  11. (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


Report options

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.