Table 7.
Clinical relevance, dose considerations, and monitoring/management guidelines of top-10 pDDIs in patients with pneumonia
| Interactionsa | Dose categoriesa | Signs and symptoms and Laboratory abnormalitiesb | Patients: n (%c) | Monitoring/management guidelines |
|---|---|---|---|---|
| Aspirin – Furosemide (40) | Low + Low (21) | Increased BUN | 14 (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 creatinine | 10 (47.6) | |||
| Hyponatremia | 7 (33.3) | |||
| Hypertension | 6 (28.6) | |||
| Dyspnea | 6 (28.6) | |||
| Confusion | 5 (23.8) | |||
| Drowsiness | 4 (19) | |||
| Edema | 2 (9.5) | |||
| Hypokalemia | 2 (9.5) | |||
| Hyperchloremia | 1 (4.8) | |||
| Orthopnea | 1 (4.8) | |||
| Chest pain | 1 (4.8) | |||
| Nausea | 1 (4.8) | |||
| Coma | 1 (4.8) | |||
| Low + High (19) | Increased BUN | 16 (84.2) | ||
| Hypertension | 13 (68.4) | |||
| Increased serum creatinine | 11 (57.9) | |||
| Dyspnea | 7 (36.8) | |||
| Hyperchloremia | 6 (31.6) | |||
| Chest pain | 5 (26.3) | |||
| Orthopnea | 5 (26.3) | |||
| Edema | 5 (26.3) | |||
| Confusion | 4 (21) | |||
| Hypokalemia | 4 (21) | |||
| Hyponatremia | 4 (21) | |||
| Drowsiness | 2 (10.5) | |||
| Hypernatremia | 1 (5.3) | |||
| Hyperkalemia | 1 (5.3) | |||
| Nausea | 1 (5.3) | |||
| Furosemide – Hydrocortisone (39) | High + High (11) | Fever | 7 (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. |
| Tachycardia | 5 (45.4) | |||
| Constipation | 5 (45.4) | |||
| Confusion | 4 (36.4) | |||
| Irregular heart rate | 3 (27.3) | |||
| Hypokalemia | 2 (18.2) | |||
| Vomiting | 1 (9.1) | |||
| High + Low (11) | Fever | 5 (45.4) | ||
| Confusion | 4 (36.4) | |||
| Constipation | 3 (27.3) | |||
| Hypokalemia | 3 (27.3) | |||
| Tachycardia | 2 (18.2) | |||
| Irregular heart rate | 1 (9.1) | |||
| Low + High (11) | Fever | 7 (63.6) | ||
| Tachycardia | 4 (36.4) | |||
| Constipation | 3 (27.3) | |||
| Hypokalemia | 3 (27.3) | |||
| Irregular heart rate | 3 (27.3) | |||
| Nausea | 2 (18.2) | |||
| Confusion | 1 (9.1) | |||
| Low + Low (6) | Fever | 4 (66.7) | ||
| Tachycardia | 4 (66.7) | |||
| Hypokalemia | 3 (50) | |||
| Irregular heart rate | 2 (33.3) | |||
| Vomiting | 1 (16.7) | |||
| Aspirin – Clopidogrel (37) | High + Low (2) | Bradycardia | 1 (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. |
| Hypotension | 1 (50) | |||
| Low + Low (35) | Hypotension | 14 (40) | ||
| Tachycardia | 9 (26) | |||
| Increased APTT | 9 (26) | |||
| Drowsiness | 7 (20) | |||
| Increased PT | 7 (20) | |||
| Weakness | 6 (17.1) | |||
| Increased INR | 5 (14.3) | |||
| Decreased platelets | 4 (11.4) | |||
| Palpitations | 1 (2.9) | |||
| Bradycardia | 1 (2.9) | |||
| Aspirin – Insulin (33) | Low + High (27) | Tachycardia | 11 (41) | Monitoring of patient’s blood glucose and clinical signs of hypoglycemia is suggested. Adjust the dose of insulin if necessary. |
| Loss of consciousness | 7 (26) | |||
| Drowsiness | 5 (18.5) | |||
| Pale | 3 (11.1) | |||
| Confusion | 2 (7.4) | |||
| Decreased FBS | 2 (7.4) | |||
| Irritability | 1 (3.7) | |||
| Seizures | 1 (3.7) | |||
| Palpitations | 1 (3.7) | |||
| Low + Low (5) | Pale | 1 (20) | ||
| Tachycardia | 1 (20) | |||
| High + Low (1) | Confusion | 1 (100) | ||
| Isoniazid – Rifampin (33) | Low + Low (27) | Fever | 22 (81.5) | Monitoring of hepatotoxicity (jaundice, vomiting, fever, anorexia, and LFTs) is advised. |
| Anorexia | 12 (44.4) | |||
| Increased ALP | 9 (33.3) | |||
| Vomiting | 6 (22.2) | |||
| Pale | 5 (18.5) | |||
| Anemia | 3 (11.1) | |||
| Weight loss | 2 (7.4) | |||
| Weakness | 2 (7.4) | |||
| Increased ALT | 2 (7.4) | |||
| Increased serum bilirubin | 2 (7.4) | |||
| Epigastric pain | 1 (3.7) | |||
| Hepatic encephalopathy | 1 (3.7) | |||
| Tiredness | 1 (3.7) | |||
| High + High (6) | Fever | 6 (100) | ||
| Increased ALP | 3 (50) | |||
|
Anorexia Epigastric pain |
2 (33.3) | |||
| 1 (16.7) | ||||
| Weight loss | 1 (16.7) | |||
| Pale | 1 (16.7) | |||
| Increased ALT | 1 (16.7) | |||
| Increased serum bilirubin | 1 (16.7) | |||
| Calcium containing products – Ceftriaxone (33) | Low + Low (19) | Fever | 11 (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 BUN | 10 (52.6) | |||
| Cough | 9 (47.4) | |||
| Increased serum bilirubin | 7 (36.8) | |||
| Leukocytosis | 7 (36.8) | |||
| Chest pain | 2 (10.5) | |||
| Low + High (7) | Cough | 4 (57.1) | ||
| Fever | 3 (42.8) | |||
| Increased BUN | 3 (42.8) | |||
| Increased serum bilirubin | 3 (42.8) | |||
| Leukocytosis | 2 (28.6) | |||
| Chest pain | 1 (14.3) | |||
| High + Low (5) | Fever | 4 (80) | ||
| Increased BUN | 2 (40) | |||
| Increased serum bilirubin | 2 (40) | |||
| Leukocytosis | 2 (40) | |||
| Chest pain | 2 (40) | |||
| Cough | 1 (20) | |||
| Sepsis | 1 (20) | |||
| High + High (2) | Increased BUN | 2 (100) | ||
| Increased serum bilirubin | 2 (100) | |||
| Leukocytosis | 2 (100) | |||
| Pyrazinamide – Rifampin (32) | Low + Low (28) | Fever | 23 (82.1) | Monitoring of LFTs during treatment is recommended. |
| Anorexia | 13 (46.4) | |||
| Increased ALP | 10 (35.7) | |||
| Vomiting | 6 (21.4) | |||
| Pale | 5 (17.8) | |||
|
Anemia Increased serum bilirubin |
3 (10.7) | |||
| 2 (7.1) | ||||
| Weakness | 2 (7.1) | |||
| Weight loss | 2 (7.1) | |||
| Increased ALT | 1 (3.6) | |||
| Epigastric pain | 1 (3.6) | |||
| Hepatic encephalopathy | 1 (3.6) | |||
| Tiredness | 1 (3.6) | |||
| High + High (4) | Fever | 4 (100) | ||
| Increased ALP | 2 (50) | |||
| Anorexia | 1 (25) | |||
| Epigastric pain | 1 (25) | |||
| Increased ALT | 1 (25) | |||
| Increased serum bilirubin | 1 (25) | |||
| Aspirin – Ramipril (28) | Low + Low (21) | Increased BUN | 18 (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 creatinine | 12 (57.1) | |||
| Hypertension | 9 (42.8) | |||
| Tachycardia | 8 (38.1) | |||
| Confused | 3 (14.3) | |||
| Hypokalemia | 3 (14.3) | |||
| Chest pain | 2 (9.5) | |||
| Headache | 1 (4.7) | |||
| Irregular heart rate | 1 (4.7) | |||
| Low + High (7) | Hypertension | 5 (71.4) | ||
| Increased BUN | 3 (42.8) | |||
| Increased serum creatinine | 3 (42.8) | |||
| Tachycardia | 2 (28.6) | |||
| Chest pain | 1 (14.3) | |||
| Hyperkalemia | 1 (14.3) | |||
| Albuterol – Furosemide (28) | High + High (9) | Tachycardia | 4 (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. |
| Constipation | 4 (44.4) | |||
| Fever | 3 (33.3) | |||
| Hypokalemia | 3 (33.3) | |||
| Confusion | 2 (22.2) | |||
| Vomiting | 1 (11.1) | |||
| Dehydration | 1 (11.1) | |||
| High + Low (17) | Constipation | 4 (23.5) | ||
| Tachycardia | 4 (23.5) | |||
| Hypokalemia | 4 (23.5) | |||
| Confusion | 3 (17.6) | |||
| Vomiting | 2 (11.7) | |||
| Fatigue | 2 (11.7) | |||
| Weakness | 2 (11.7) | |||
| Fever | 1 (5.9) | |||
| Low + High (1) | Constipation | 1 (100) | ||
| Low + Low (1) | Constipation | 1 (100) | ||
| Aspirin – Bisoprolol (23) | Low + Low (14) | Hypertension | 7 (50) | Patients’ blood pressure and hemodynamic parameters should be monitored. |
| Tachycardia | 4 (28.5) | |||
| Chest pain | 3 (21.4) | |||
| Irregular heart rate | 2 (14.3) | |||
| Headache | 2 (14.3) | |||
| Restless | 1 (7.1) | |||
| Drowsiness | 1 (7.1) | |||
| Low + High (7) | Hypertension | 6 (85.7) | ||
| Tachycardia | 6 (85.7) | |||
| Chest pain | 3 (42.8) | |||
| Irregular heart rate | 2 (28.6) | |||
| High + High (1) | Irregular heart rate | 1 (100) | ||
| Headache | 1 (100) | |||
| Hypertension | 1 (100) | |||
| Tachycardia | 1 (100) | |||
| High + Low (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
aFrequencies were given in round brackets
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
cPercentages were calculated based on dose categories