quinine sulfate

Action

Unknown. Thought to interfere with DNA synthesis by increasing pH in intracellular organelles of susceptible parasites.

Availability

Capsules: 324 mg

Indications and dosages

➣ Uncomplicated Plasmodium falciparum malaria

Adults and children age 16 and older: 648 mg (two capsules) P.O. q 8 hours for 7 days

Dosage adjustment

• Severe chronic renal impairment

Contraindications

• Hypersensitivity to drug (including but not limited to thrombocytopenia, idiopathic thrombocytopenia purpura, thrombocytopenic purpura, hemolytic uremic syndrome, blackwater fever), mefloquine, quinidine

• G6PD deficiency

• Optic neuritis

• Tinnitus

• Prolonged QT interval

• Myasthenia gravis

Precautions

Use cautiously in:

• renal or hepatic impairment

• hypoglycemia

• concurrent use of digoxin and drugs known to prolong QT interval, including Class IA antiarrhythmics (such as disopyramide, procainamide, quinidine) and Class III antiarrhythmics (such as amiodarone, dofetilide, sotalol)

• concurrent use of antacids, rifampin, ritonavir, neuromuscular blockers, macrolide anti-infectives, CYP3A4 substrates, including astemizole, cisapride, terfenadine (not available in U.S.), pimozide, halofantrine, quinidine (avoid use)

• pregnant or breastfeeding patients.

• children younger than age 16 (safety and efficacy of capsules not established).

Administration

• Give with or without food.

Adverse reactions

CNS: headache, vertigo, syncope, apprehension, restlessness, excitement, confusion, delirium, dizziness, seizures

CV: angina, vasculitis, cardiac rhythm or conduction disturbances

EENT: diplopia, amblyopia, blurred vision, scotoma, abnormal color perception, photophobia, night blindness, mydriasis, optic atrophy, hearing loss, tinnitus

GI: nausea, vomiting, diarrhea, abdominal cramps, epigastric pain, dysphagia

GU: hemolytic uremic syndrome Hematologic: hemolytic anemia, hypoprothrombinemia, acute hemolysis, thrombocytopenic purpura, agranulocytosis

Hepatic: hepatotoxicity

Metabolic: hypothermia, hypoglycemia

Respiratory: asthma

Skin: rash, pruritus, photosensitivity, flushing, diaphoresis

Other: cinchonism, facial edema, hypersensitivity reactions including fever and hemolytic uremic syndrome

Interactions

Drug-drug. Aminophylline, theophylline: increased quinine mean area under the curve (AUC) and C_max.

Antacids: delayed or decreased quinine absorption

Atorvastatin, other HMG-CoA reductase inhibitors that are CYP3A4 substrates: increased risk of myopathy

Cimetidine: decreased metabolism and increased effects of quinine

Class IA, Class III antiarrhythmics: increased risk of ECG abnormalities, including prolonged QT interval

CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin): decreased quinine plasma concentration and increased carbamazepine, phenobarbital, and phenytoin AUC and C_max

CYP3A4 inducers or inhibitors, CYP3A4 and CYP2D6 substrates: decreased efficacy and increased adverse effects of these drugs

Digoxin: increased digoxin blood level

Other antimalarials including halofantrine, mefloquine: increased risk of seizures, ECG abnormalities, and cardiac arrest

Neuromuscular blockers: increased effects of these drugs, leading to respiratory difficulty

Rifampin: increased metabolism and decreased effects of quinine

Ritonavir: increased quinine mean AUC, C_max, and elimination half-life

Succinylcholine: delayed succinylcholine metabolism

Tetracycline: increased quinine mean plasma concentration

Urinary alkalizers (such as acetazol-amide, sodium bicarbonate): increased quinine blood level and risk of toxicity

Warfarin: increased warfarin effects, increased risk of bleeding

Drug-diagnostic tests. Urinary 17-ketogenic steroids: elevated levels

Patient monitoring

Monitor for signs and symptoms of hypersensitivity reaction, including fever and hemolytic uremic syndrome. Discontinue drug if signs or symptoms of hypersensitivity occur.

• Stay alert for signs and symptoms of cinchonism, including tinnitus, headache, nausea, and visual disturbances.

Assess for bleeding tendency, arrhythmias, and hepatotoxicity.

• Monitor CBC, renal and liver function tests, and quinine and glucose levels.

Patient teaching

• Tell patient he may take with or without food.

Teach patient to recognize and immediately report signs and symptoms of cinchonism, cardiac arrhythmias, nephrotoxicity, and hepatotoxicity.

Instruct patient to report unusual bleeding or bruising.

• Tell female patient to discuss pregnancy or breastfeeding with prescriber before taking drug.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.