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Table 4 Clinical relevance and management guidelines/monitoring parameters of most frequent potential drug–drug interactions in patients with malaria

From: Potential drug–drug interactions associated with adverse clinical outcomes and abnormal laboratory findings 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)
  1. BUN blood urea nitrogen, ALT alanine aminotransferase, ALP alkaline phosphatase, LFTs liver function tests, FBS fasting blood sugar
  2. aFrequencies are given in parenthesis and calculated among patients with respective interaction