Which of the two medications—Ciplox TZ (ciprofloxacin and tinidazole) or Combiflam (ibuprofen and paracetamol)—is most likely responsible for the acute angio‑edema (itching and swelling of the lips and eyelids) that occurred within an hour, given the patient’s known ketorolac allergy?

Acute Angioedema: Identifying the Culprit Medication

Given the patient's known ketorolac allergy and the acute onset of angioedema (lip and eyelid swelling with itching) within one hour of taking both medications, Combiflam (containing ibuprofen, an NSAID) is the most likely culprit due to cross-reactivity between NSAIDs, and this medication should be immediately discontinued. 1, 2, 3

Immediate Clinical Action

Stop both medications immediately and treat the acute allergic reaction now. 1, 4

• Administer an antihistamine (such as diphenhydramine) for symptomatic relief of the angioedema 4, 5
• Monitor closely for progression to airway involvement (tongue, larynx, or pharyngeal swelling), which would constitute a life-threatening emergency requiring epinephrine 0.2-0.5 mg IM and potential airway intervention 6, 4, 5
• The rapid onset within one hour strongly suggests an IgE-mediated Type I hypersensitivity reaction, which can progress to anaphylaxis 7, 2

Why Combiflam (Ibuprofen) Is the Primary Suspect

NSAIDs demonstrate well-documented cross-reactivity, and patients allergic to one NSAID (ketorolac in this case) are at significant risk for reactions to other NSAIDs including ibuprofen. 2, 3

• Angioedema with or without urticaria is a recognized manifestation of NSAID hypersensitivity, with leukotrienes playing a particular mediator role 2
• The timing (within one hour) fits the typical presentation of IgE-mediated allergic angioedema to NSAIDs 7, 2
• Ketorolac and ibuprofen are both cyclooxygenase-1 (COX-1) inhibitors, making cross-reactivity highly probable 2

Why Ciplox TZ (Ciprofloxacin/Tinidazole) Is Less Likely But Not Excluded

While fluoroquinolones can cause serious allergic reactions, the clinical pattern here points more strongly to the NSAID. 1

• Ciprofloxacin can cause severe allergic reactions including hives, swelling of lips/tongue/face, and throat tightness, typically requiring immediate discontinuation 1
• However, the patient's documented ketorolac allergy and the known cross-reactivity pattern among NSAIDs makes Combiflam the more probable cause 2, 3
• Fluoroquinolone allergies are less common than NSAID allergies in patients with prior NSAID sensitivity 1, 3

Definitive Diagnosis Strategy

To definitively identify the causative agent, perform the following after the acute reaction resolves:

• Document this reaction thoroughly as a potential NSAID allergy in the medical record, noting the temporal relationship and clinical presentation 7
• Refer to an allergist for formal evaluation with skin testing (prick test) once the acute reaction has completely resolved (typically 4-6 weeks later) 4, 7
• Measure serum tryptase levels during the acute reaction if possible, as elevation supports mast cell degranulation in IgE-mediated reactions 3
• Never rechallenge with either medication without supervised allergy testing, as subsequent reactions can be more severe 7, 1

Critical Pitfalls to Avoid

Do not assume this is a minor reaction - angioedema involving the lips and eyelids can rapidly progress to life-threatening laryngeal edema. 4, 5

• Do not give the patient another NSAID (including aspirin, naproxen, diclofenac, or any COX inhibitor) without formal allergy evaluation, as cross-reactivity is common 2, 3
• Do not rely solely on antihistamines - have epinephrine immediately available and monitor for at least 4-6 hours for progression, as biphasic reactions can occur 6, 5
• Do not dismiss the ciprofloxacin entirely - document avoidance of both drug classes until formal testing clarifies the specific culprit 1, 3

Future Medication Management

For pain/fever management: Use paracetamol (acetaminophen) alone, which is present in Combiflam but is generally safe in NSAID-allergic patients. 2

For infections: If fluoroquinolones need to be avoided pending allergy testing, consider alternative antibiotic classes (beta-lactams, macrolides) based on the specific infection and local resistance patterns. 1

Provide the patient with:

• An allergy alert card documenting "possible NSAID allergy (ibuprofen/ketorolac) and possible ciprofloxacin allergy" 3
• Clear instructions to avoid all NSAIDs until formal allergy evaluation 2, 3
• Emergency action plan with antihistamines and instructions to seek immediate care if swelling recurs or worsens 6, 4