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Table 7 Clinical relevance, dose considerations, and monitoring/management guidelines of top-10 pDDIs in patients with pneumonia

From: Potential drug-drug interactions among pneumonia patients: do these matter in clinical perspectives?

InteractionsaDose categoriesaSigns and symptoms and Laboratory abnormalitiesbPatients: n (%c)Monitoring/management guidelines
Aspirin – Furosemide (40)Low + Low (21)Increased BUN14 (66.7)Monitoring of aspirin toxicity and renal function. Response of diuretic should be checked mainly anti-hypertensive effects. High doses are generally not recommended. Alternative may be considered where possible.
Increased serum creatinine10 (47.6)
Hyponatremia7 (33.3)
Hypertension6 (28.6)
Dyspnea6 (28.6)
Confusion5 (23.8)
Drowsiness4 (19)
Edema2 (9.5)
Hypokalemia2 (9.5)
Hyperchloremia1 (4.8)
Orthopnea1 (4.8)
Chest pain1 (4.8)
Nausea1 (4.8)
Coma1 (4.8)
Low + High (19)Increased BUN16 (84.2)
Hypertension13 (68.4)
Increased serum creatinine11 (57.9)
Dyspnea7 (36.8)
Hyperchloremia6 (31.6)
Chest pain5 (26.3)
Orthopnea5 (26.3)
Edema5 (26.3)
Confusion4 (21)
Hypokalemia4 (21)
Hyponatremia4 (21)
Drowsiness2 (10.5)
Hypernatremia1 (5.3)
Hyperkalemia1 (5.3)
Nausea1 (5.3)
Furosemide – Hydrocortisone (39)High + High (11)Fever7 (63.6)Serum potassium level and cardiovascular status should be monitored, especially if co-administered. Patients should be advised to inform their physician if they experience potential signs/symptoms of hypokalemia such as constipation, numbness, myalgia, abdominal pain, fatigue, tingling, weakness, irregular heartbeat, muscle cramps, and palpitation.
Tachycardia5 (45.4)
Constipation5 (45.4)
Confusion4 (36.4)
Irregular heart rate3 (27.3)
Hypokalemia2 (18.2)
Vomiting1 (9.1)
High + Low (11)Fever5 (45.4)
Confusion4 (36.4)
Constipation3 (27.3)
Hypokalemia3 (27.3)
Tachycardia2 (18.2)
Irregular heart rate1 (9.1)
Low + High (11)Fever7 (63.6)
Tachycardia4 (36.4)
Constipation3 (27.3)
Hypokalemia3 (27.3)
Irregular heart rate3 (27.3)
Nausea2 (18.2)
Confusion1 (9.1)
Low + Low (6)Fever4 (66.7)
Tachycardia4 (66.7)
Hypokalemia3 (50)
Irregular heart rate2 (33.3)
Vomiting1 (16.7)
Aspirin – Clopidogrel (37)High + Low (2)Bradycardia1 (50)Monitor patients’ platelets counts and any sign of bleeding. If an adverse effect is noted, the following options may be considered: (a) Decrease the dose of aspirin (b) GIT protection through proton pump inhibitors and patient should be educated about non-prescribed use of analgesics.
Hypotension1 (50)
Low + Low (35)Hypotension14 (40)
Tachycardia9 (26)
Increased APTT9 (26)
Drowsiness7 (20)
Increased PT7 (20)
Weakness6 (17.1)
Increased INR5 (14.3)
Decreased platelets4 (11.4)
Palpitations1 (2.9)
Bradycardia1 (2.9)
Aspirin – Insulin (33)Low + High (27)Tachycardia11 (41)Monitoring of patient’s blood glucose and clinical signs of hypoglycemia is suggested. Adjust the dose of insulin if necessary.
Loss of consciousness7 (26)
Drowsiness5 (18.5)
Pale3 (11.1)
Confusion2 (7.4)
Decreased FBS2 (7.4)
Irritability1 (3.7)
Seizures1 (3.7)
Palpitations1 (3.7)
Low + Low (5)Pale1 (20)
Tachycardia1 (20)
High + Low (1)Confusion1 (100)
Isoniazid – Rifampin (33)Low + Low (27)Fever22 (81.5)Monitoring of hepatotoxicity (jaundice, vomiting, fever, anorexia, and LFTs) is advised.
Anorexia12 (44.4)
Increased ALP9 (33.3)
Vomiting6 (22.2)
Pale5 (18.5)
Anemia3 (11.1)
Weight loss2 (7.4)
Weakness2 (7.4)
Increased ALT2 (7.4)
Increased serum bilirubin2 (7.4)
Epigastric pain1 (3.7)
Hepatic encephalopathy1 (3.7)
Tiredness1 (3.7)
High + High (6)Fever6 (100)
Increased ALP3 (50)
Anorexia
Epigastric pain
2 (33.3)
1 (16.7)
Weight loss1 (16.7)
Pale1 (16.7)
Increased ALT1 (16.7)
Increased serum bilirubin1 (16.7)
Calcium containing products – Ceftriaxone (33)Low + Low (19)Fever11 (57.9)Ceftriaxone should not be mixed or administered concomitantly with calcium-containing intravenous preparations in the same intravenous administration line. Monitor patient for signs of nephrotoxicity or decreased ceftriaxone effectiveness.
Increased BUN10 (52.6)
Cough9 (47.4)
Increased serum bilirubin7 (36.8)
Leukocytosis7 (36.8)
Chest pain2 (10.5)
Low + High (7)Cough4 (57.1)
Fever3 (42.8)
Increased BUN3 (42.8)
Increased serum bilirubin3 (42.8)
Leukocytosis2 (28.6)
Chest pain1 (14.3)
High + Low (5)Fever4 (80)
Increased BUN2 (40)
Increased serum bilirubin2 (40)
Leukocytosis2 (40)
Chest pain2 (40)
Cough1 (20)
Sepsis1 (20)
High + High (2)Increased BUN2 (100)
Increased serum bilirubin2 (100)
Leukocytosis2 (100)
Pyrazinamide – Rifampin (32)Low + Low (28)Fever23 (82.1)Monitoring of LFTs during treatment is recommended.
Anorexia13 (46.4)
Increased ALP10 (35.7)
Vomiting6 (21.4)
Pale5 (17.8)
Anemia
Increased serum bilirubin
3 (10.7)
2 (7.1)
Weakness2 (7.1)
Weight loss2 (7.1)
Increased ALT1 (3.6)
Epigastric pain1 (3.6)
Hepatic encephalopathy1 (3.6)
Tiredness1 (3.6)
High + High (4)Fever4 (100)
Increased ALP2 (50)
Anorexia1 (25)
Epigastric pain1 (25)
Increased ALT1 (25)
Increased serum bilirubin1 (25)
Aspirin – Ramipril (28)Low + Low (21)Increased BUN18 (85.7)Monitor patients’ blood pressure, hemodynamic parameters, and renal function. Incase of an adverse event, consider the following: (a) replace ACE inhibitors with angiotensin receptor blockers (b) an alternative non-aspirin antiplatelet agent (c) aspirin dosage less than 100 mg per day.
Increased serum creatinine12 (57.1)
Hypertension9 (42.8)
Tachycardia8 (38.1)
Confused3 (14.3)
Hypokalemia3 (14.3)
Chest pain2 (9.5)
Headache1 (4.7)
Irregular heart rate1 (4.7)
Low + High (7)Hypertension5 (71.4)
Increased BUN3 (42.8)
Increased serum creatinine3 (42.8)
Tachycardia2 (28.6)
Chest pain1 (14.3)
Hyperkalemia1 (14.3)
Albuterol – Furosemide (28)High + High (9)Tachycardia4 (44.4)Potassium balance and cardiovascular status should be monitored, especially if the beta-2 agonist is administered by nebulizer or systemically. Patients should be advised to inform their physician if they experience potential signs/symptoms of hypokalemia such as constipation, numbness, myalgia, abdominal pain, fatigue, tingling, weakness, irregular heartbeat, muscle cramps, and palpitation.
Constipation4 (44.4)
Fever3 (33.3)
Hypokalemia3 (33.3)
Confusion2 (22.2)
Vomiting1 (11.1)
Dehydration1 (11.1)
High + Low (17)Constipation4 (23.5)
Tachycardia4 (23.5)
Hypokalemia4 (23.5)
Confusion3 (17.6)
Vomiting2 (11.7)
Fatigue2 (11.7)
Weakness2 (11.7)
Fever1 (5.9)
Low + High (1)Constipation1 (100)
Low + Low (1)Constipation1 (100)
Aspirin – Bisoprolol (23)Low + Low (14)Hypertension7 (50)Patients’ blood pressure and hemodynamic parameters should be monitored.
Tachycardia4 (28.5)
Chest pain3 (21.4)
Irregular heart rate2 (14.3)
Headache2 (14.3)
Restless1 (7.1)
Drowsiness1 (7.1)
Low + High (7)Hypertension6 (85.7)
Tachycardia6 (85.7)
Chest pain3 (42.8)
Irregular heart rate2 (28.6)
High + High (1)Irregular heart rate1 (100)
Headache1 (100)
Hypertension1 (100)
Tachycardia1 (100)
High + Low (1)
  1. ALT Alanine Aminotransferase, ACE Angiotensin Converting Enzyme, ALP Alkaline Phosphatase, APTT Activated Partial Thromboplastin Time, BUN Blood Urea Nitrogen, FBS Fasting Blood Sugar, GIT Gastrointestinal Tract, HbA1c Glycated hemoglobin (A1c), INR International Normalized Ratio, LFTs Liver Function Tests, PT Prothrombin Time, RBS Random Blood Sugar
  2. aFrequencies were given in round brackets
  3. bAdverse outcomes were defined as follows, increased blood urea nitrogen (BUN): BUN ≤20 mg/dL; increased serum creatinine: serum creatinine > 1.06 mg/dL; hypernatremia: serum sodium > 145 mmol/L; hyponatremia: serum sodium < 135 mmol/L; hyperkalemia: serum potassium > 5.5 mmol/L; hypokalemia: serum potassium < 3.5 mmol/L; hyperchloremia: serum chloride > 105 mmol/L; hypertension: systolic blood pressure (BP) > 130 mmHg and/or diastolic BP > 90 mmHg; hypotension: systolic BP < 80 mmHg and/or diastolic BP < 50 mmHg; tachycardia: heart rate > 100 beats/min; bradycardia: heart rate < 70 beats/min; increased activated partial thromboplastin time (APTT): APTT > 35.5 s; increased prothrombin time (PT): PT > 15.5 s; increased international normalized ratio (INR): INR > 1.2; decreased platelets: platelets count < 150,000/μL; hypoglycemia: random blood sugar < 80 mg/dL or fasting blood sugar < 70 mg/dL; increased alkaline phosphatase: > 126 U/L; increased serum bilirubin: > 1 mg/dL; increased alanine aminotransferase: > 59 U/L (male), > 36 U/L (female); leukocytosis: total leukocyte count > 11,000/μL
  4. cPercentages were calculated based on dose categories