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Drug Interactions between Bethaprim Pediatric and Kaletra

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

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Interactions between your drugs

Moderate

sulfamethoxazole ritonavir

Applies to: Bethaprim Pediatric (sulfamethoxazole / trimethoprim) and Kaletra (lopinavir / ritonavir)

MONITOR: A disulfiram-like reaction has been reported in two patients who consumed alcohol while taking sulfamethoxazole-trimethoprim DS every 12 hours, although a causal relationship has not been established. The mechanism of interaction is unknown. Both ritonavir oral solution and lopinavir-ritonavir oral solution contain a substantial amount of alcohol (greater than 40% by volume), which, theoretically, can produce a disulfiram-like reaction when coadministered with sulfamethoxazole-trimethoprim. Pharmacokinetically, coadministration of ritonavir (500 mg every 12 hours) and sulfamethoxazole-trimethoprim (single 800mg-160 mg dose) has resulted in a 20% decrease in the area under the plasma concentration-time curve (AUC) of sulfamethoxazole and a 20% increase in the AUC of trimethoprim. The plasma level of ritonavir was not affected. These alterations are unlikely to be of clinical significance, thus dosage adjustments should not be necessary.

MANAGEMENT: Until further information is available, it may be advisable to avoid using ritonavir oral solution and lopinavir-ritonavir oral solution with sulfamethoxazole-trimethoprim. Patients who are prescribed the combination should be alerted to the potential of a disulfiram reaction, which may include symptoms such as flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  2. Heelon MW, White M "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
  3. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

trimethoprim ritonavir

Applies to: Bethaprim Pediatric (sulfamethoxazole / trimethoprim) and Kaletra (lopinavir / ritonavir)

MONITOR: A disulfiram-like reaction has been reported in two patients who consumed alcohol while taking sulfamethoxazole-trimethoprim DS every 12 hours, although a causal relationship has not been established. The mechanism of interaction is unknown. Both ritonavir oral solution and lopinavir-ritonavir oral solution contain a substantial amount of alcohol (greater than 40% by volume), which, theoretically, can produce a disulfiram-like reaction when coadministered with sulfamethoxazole-trimethoprim. Pharmacokinetically, coadministration of ritonavir (500 mg every 12 hours) and sulfamethoxazole-trimethoprim (single 800mg-160 mg dose) has resulted in a 20% decrease in the area under the plasma concentration-time curve (AUC) of sulfamethoxazole and a 20% increase in the AUC of trimethoprim. The plasma level of ritonavir was not affected. These alterations are unlikely to be of clinical significance, thus dosage adjustments should not be necessary.

MANAGEMENT: Until further information is available, it may be advisable to avoid using ritonavir oral solution and lopinavir-ritonavir oral solution with sulfamethoxazole-trimethoprim. Patients who are prescribed the combination should be alerted to the potential of a disulfiram reaction, which may include symptoms such as flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  2. Heelon MW, White M "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
  3. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical PROD (2001):

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Minor

sulfamethoxazole lopinavir

Applies to: Bethaprim Pediatric (sulfamethoxazole / trimethoprim) and Kaletra (lopinavir / ritonavir)

Limited data suggest that sulfamethoxazole-trimethoprim (SMX-TMP) may rarely prolong the QT interval of the electrocardiogram. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. There have been isolated reports of QT prolongation and ventricular arrhythmias occurring in patients treated with SMX-TMP intravenously. However, a causal relationship has not been established, and the risk of clinically significant QT prolongation is unlikely at recommended dosages of SMX-TMP. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Wiener I, Rubin D, Martinez E, et al. "QT prolongation and paroxysmal ventricular tachycardia occurring during fever following trimethoprim-sulfamethoxazole administration." Mt Sinai J Med 48 (1981): 53-5
  2. Crouch MA, Limon L, Cassano AT "Clinical relevance and management of drug-related QT interval prolongation." Pharmacotherapy 23 (2003): 881-908
  3. Lopez JA, Harold JG, Rosenthal MC, Oseran DS, Schapira JN, Peter T "QT prolongation and torsades de pointes after administration of trimethoprin-sulfamethoxazole." Am J Cardiol 59 (1987): 376-7
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Darpo B "Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes." Eur Heart J Suppl 3(Suppl K) (2001): K70-80
View all 7 references

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Drug and food interactions

Moderate

ritonavir food

Applies to: Kaletra (lopinavir / ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

lopinavir food

Applies to: Kaletra (lopinavir / ritonavir)

ADJUST DOSING INTERVAL: Food significantly increases the bioavailability of lopinavir from the oral solution formulation of lopinavir-ritonavir. Relative to fasting, administration of lopinavir-ritonavir oral solution with a moderate-fat meal (500 to 682 Kcal; 23% to 25% calories from fat) increased lopinavir peak plasma concentration (Cmax) and systemic exposure (AUC) by 54% and 80%, respectively, whereas administration with a high-fat meal (872 Kcal; 56% from fat) increased lopinavir Cmax and AUC by 56% and 130%, respectively. No clinically significant changes in Cmax and AUC were observed following administration of lopinavir-ritonavir tablets under fed conditions versus fasted conditions. Relative to fasting, administration of a single 400 mg-100 mg dose (two 200 mg-50 mg tablets) with a moderate-fat meal (558 Kcal; 24.1% calories from fat) increased lopinavir Cmax and AUC by 17.6% and 26.9%, respectively, while administration with a high-fat meal (998 Kcal; 51.3% from fat) increased lopinavir AUC by 18.9% but not Cmax. Relative to fasting, ritonavir Cmax and AUC also increased by 4.9% and 14.9%, respectively, with the moderate-fat meal and 10.3% and 23.9%, respectively, with the high-fat meal.

MANAGEMENT: Lopinavir-ritonavir oral solution should be taken with meals to enhance bioavailability and minimize pharmacokinetic variability. Lopinavir-ritonavir tablets may be taken without regard to meals.

References

  1. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

sulfamethoxazole food

Applies to: Bethaprim Pediatric (sulfamethoxazole / trimethoprim)

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References

  1. Heelon MW, White M "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother 64 (2020): e02167-19

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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.