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Drug Interactions between oxytetracycline / phenazopyridine / sulfamethizole and Wycillin

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

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Interactions between your drugs

Major

phenazopyridine procaine penicillin

Applies to: oxytetracycline / phenazopyridine / sulfamethizole and Wycillin (procaine penicillin)

MONITOR CLOSELY: Coadministration of medications containing local anesthetics with other oxidizing agents that can also induce methemoglobinemia such as 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), cardiac or pulmonary disease, genetic predisposition, and glucose-6-phosphate dehydrogenase (G6PD) deficiency.

MANAGEMENT: Close monitoring for signs and symptoms of methemoglobinemia is recommended if medications containing local anesthetics must be used with other methemoglobin-inducing agents. Signs and symptoms of methemoglobinemia may occur immediately or hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia (e.g., cyanotic skin discoloration, abnormal blood coloration, 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.

References

  1. (2004) "Product Information. Penicillin G Procaine (penicillin)." Monarch Pharmaceuticals Inc
  2. (2009) "Product Information. Bicillin C-R 900/300 (benzathine penicillin-procaine penicillin)." Wyeth Laboratories
  3. (2009) "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc
  4. (2017) "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions
View all 4 references

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Major

sulfamethizole procaine penicillin

Applies to: oxytetracycline / phenazopyridine / sulfamethizole and Wycillin (procaine penicillin)

MONITOR CLOSELY: Coadministration of medications containing local anesthetics with other oxidizing agents that can also induce methemoglobinemia such as 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), cardiac or pulmonary disease, genetic predisposition, and glucose-6-phosphate dehydrogenase (G6PD) deficiency.

MANAGEMENT: Close monitoring for signs and symptoms of methemoglobinemia is recommended if medications containing local anesthetics must be used with other methemoglobin-inducing agents. Signs and symptoms of methemoglobinemia may occur immediately or hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia (e.g., cyanotic skin discoloration, abnormal blood coloration, 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.

References

  1. (2004) "Product Information. Penicillin G Procaine (penicillin)." Monarch Pharmaceuticals Inc
  2. (2009) "Product Information. Bicillin C-R 900/300 (benzathine penicillin-procaine penicillin)." Wyeth Laboratories
  3. (2009) "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc
  4. (2017) "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions
View all 4 references

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Moderate

oxytetracycline procaine penicillin

Applies to: oxytetracycline / phenazopyridine / sulfamethizole and Wycillin (procaine penicillin)

GENERALLY AVOID: Tetracyclines may reduce the effect of penicillins by inhibiting cellular protein synthesis which is necessary for cell wall synthesis inhibition by penicillins. Antagonism is more likely when low doses of either agent are administered. Therapeutic failure may result.

MANAGEMENT: This combination should be avoided if possible.

References

  1. Gunnison JB, Coleman VR, Jawetz E (1950) "Interference of aureomycin and of terramycin with action of penicillin in vitro." Proc Soc Exp Biol Med, 75, p. 549-52
  2. Lepper MH, Dowling HF (1951) "Treatment of pneumococcic meningitis with penicillin compared with penicillin plus aureomycin." Arch Intern Med, 88, p. 489-94
  3. Jawetz E (1975) "Synergism and antagonism among antimicrobial drugs: a personal perspective." West J Med, 123, p. 87-91
  4. Olsson RA, Kirby JC, Romansky MJ (1961) "Pneumococcal meningitis in the adult." Ann Intern Med, 55, p. 545-9
  5. (2001) "Product Information. Declomycin (demeclocycline)." Lederle Laboratories
  6. (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
View all 6 references

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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 of these foods forms nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals.

References

  1. (2001) "Product Information. Achromycin (tetracycline)." Lederle Laboratories
  2. (2001) "Product Information. Declomycin (demeclocycline)." Lederle Laboratories

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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

  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.
View all 11 references

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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.

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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.

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