Table 4.
Clinical relevance and management guidelines/monitoring parameters of most frequent potential drug–drug interactions in patients with malaria
| Interactionsa | Dose categoriesa | Signs and symptomsa | Laboratory investigationsa | Management guidelines/monitoring parameters |
|---|---|---|---|---|
| Calcium containing products—Ceftriaxone (52) | High + high (4) | Fever (3), sepsis (1) | Elevated BUN (1), elevated serum creatinine (1), leukocytosis (2) | Avoid mixing or administering ceftriaxone concomitantly with calcium-containing IV solutions or infusions in the same IV administration line through a Y-site. Monitor for signs of nephrotoxicity, thrombosis, precipitates deposition in lungs, or decreased ceftriaxone effectiveness |
| High + low (5) | Fever (3) | Elevated BUN (3), leukocytosis (1) | ||
| Low + high (15) | Fever (4), cough (4), congested chest (2), chest pain (1), breathing difficulty (1) | Elevated BUN (5), elevated serum creatinine (5), leukocytosis (5) | ||
| Low + low (28) | Cough (6), fever (4), chest pain (3), orthopnea (2), tachypnea (1), wheezing (1) | Elevated BUN (5), elevated serum creatinine (7), leukocytosis (3) | ||
| Isoniazid–rifampin (10) | High + high (6) | Vomiting (1), body aches (1), left hypochondrium pain (1) | Elevated ALT (1), elevated ALP (2) | Monitor for signs and symptoms of hepatotoxicity such as jaundice, vomiting, fever, and anorexia. Also monitor baseline and periodic LFTs |
| Low + high (2) | Anaemia (1), pale (1), weakness (1), anorexia (1), body aches (1) | Elevated ALP (1) | ||
| Low + low (2) | Body aches (1), pale (1), weight loss (1), ascites (1), hepatomegaly (1), anorexia (1) | Elevated ALT (1), elevated ALP (2) | ||
| Pyrazinamide–rifampin (10) | High + high (6) | Vomiting (1), body aches (1), left hypochondrium pain (1) | Elevated ALT (1), elevated ALP (2) | Monitor for signs and symptoms of hepatotoxicity such as jaundice, vomiting, fever, and anorexia. Also monitor baseline and periodic LFTs |
| Low + high (2) | Anaemia (1), pale (1), weakness (1), anorexia (1), body aches (1) | Elevated ALP (1) | ||
| Low + low (2) | Body aches (1), pale (1), weight loss (1), ascites (1), hepatomegaly (1), anorexia (1) | Elevated ALT (1), elevated ALP (2) | ||
| Isoniazid–acetaminophen (9) | High + high (5) | Vomiting (1), body aches (1), left hypochondrium pain (1) | Elevated ALT (1), elevated ALP (1) | Monitor for signs and symptoms of hepatotoxicity such as jaundice, vomiting, fever, and anorexia. Also monitor baseline and periodic LFTs. Avoid concomitant administration of hepatotoxic drugs |
| Low + high (3) | Anorexia (2), pale (1), anaemia (1), vomiting (1), weakness (1), body aches (1), ascites (1), hepatomegaly (1) | Elevated ALT (1), elevated ALP (2) | ||
| Low + low (1) | Body aches (1), pale (1), weight loss (1) | Elevated ALP (1) | ||
| Prochlorperazine–quinine (8) | High + high (5) | Tachycardia (4), hypotension (3), hypertension (1) | Hypokalemia (1) | Monitor ECG and signs and symptoms of QT interval prolongation, specifically in patients at higher risk. Concomitant administration of QT interval prolonging drugs needs to be avoided |
| High + low (1) | Hypotension 1) | |||
| Low + low (2) | Hypotension (2), tachycardia (1), chest pain (1), confusion (1) | Hypokalemia (1) | ||
| Cefpodoxime–ranitidine (7) | Low + high (2) | Fever (1) | – | Administer cefpodoxime at least 2 h before ranitidine, or administer cefpodoxime with food. Monitor for improvement in patient condition |
| Low + low (5) | Fever (2), urosepsis (1) | Leukocytosis (3) | ||
| Metronidazole–quinine (6) | High + high (5) | Tachycardia (3), hypotension (3), hypertension (1), confusion (1), chest pain (1) | Hypokalemia (2) | Monitor ECG and signs and symptoms of QT interval prolongation, specifically in patients at higher risk. Concomitant administration of QT interval prolonging drugs needs to be avoided |
| Low + low (1) | Chest pain (1), tachycardia (1), hypotension (1) | – | ||
| Domperidone–ranitidine (6) | High + high (1) | Hypotension (1) | – | Monitoring for signs and symptoms of domperidone toxicity is suggested. Start domperidone at low dose then titrate gradually with caution. Discontinue domperidone if patient experiences syncope, palpitations, dizziness, or seizure. Also monitor ECG and signs and symptoms of prolonged QT interval |
| High + low (4) | Tachycardia (4), hypertension (3), headache (2), confusion (1), hypotension (1) | – | ||
| Low + high (1) | Tachycardia (1), hypotension (1) | – | ||
| Dexamethasone–rifampin (5) | High + high (3) | Irritable (3), hypertension (2), hypotension (1), fatigue (1), nausea (1), vomiting (1) | Elevated FBS (2) | Monitor for signs and symptoms of adrenal insufficiency. Adjust dose of dexamethasone, if given combine |
| Low + high (1) | Drowsiness (1), hypotension (1) | – | ||
| Low + low (1) | Vomiting (1), fever (1), hypotension (1) | – | ||
| Ciprofloxacin—metronidazole (5) | High + low (4) | Hypotension (3), tachycardia (2), hypertension (1), orthopnea (1), chest pain (1) | – | Monitor ECG and signs and symptoms of QT interval prolongation, specifically in patients at higher risk. Concomitant administration of QT interval prolonging drugs needs to be avoided |
| Low + low (1) | Dizziness (1), tachycardia (1) | Hypokalemia (1) |
BUN blood urea nitrogen, ALT alanine aminotransferase, ALP alkaline phosphatase, LFTs liver function tests, FBS fasting blood sugar
aFrequencies are given in parenthesis and calculated among patients with respective interaction