quinine sulfate

Available forms
Available by prescription only
Capsules: 200 mg, 260 mg, 325 mg
Tablets: 260 mg

Indications and dosages
 Prevention of malaria ◇. Adults: 325 mg P.O. b.i.d. Continue for 6 weeks after exposure. May be used with primaquine phosphate if Plasmodium ovale or P. vivax are endemic in the area.
 Malaria (chloroquine-resistant). Adults: 650 mg P.O. q 8 hours for 3 to 7 days, with 25 mg pyrimethamine q 12 hours for 3 days and 500 mg sulfadiazine q.i.d. for 5 days.
Children: 25 to 30 mg/kg daily P.O. divided into three doses for 3 to 7 days.
 Babesi microti infections along with clindamycin therapy ◇. Adults: 650 mg P.O. q 8 hours for 7 days.
Children: 25 mg/kg daily P.O. divided into three doses for 7 days.
 Nocturnal recumbency leg muscle cramps ◇. Adults: 200 to 300 mg P.O. h.s. Discontinue if leg cramps subside for several days to determine if continued therapy is needed.

Pharmacodynamics
Antimalarial action: Quinine intercalates into DNA, disrupting the parasite’s replication and transcription; it also depresses oxygen uptake and carbohydrate metabolism by parasite. Drug is active against asexual erythrocytic forms of Plasmodium falciparum, P. malariae, P. ovale, and P. vivax and is used for chloroquine-resistant malaria.
Skeletal muscle relaxant action: Quinine increases refractory period, decreases excitability of the motor end plate, and affects calcium distribution within muscle fibers.

Pharmacokinetics
Absorption: Almost completely absorbed.
Distribution: Distributed widely into the liver, lungs, kidneys, and spleen; CSF levels reach 2% to 5% of serum levels. Quinine is about 70% bound to plasma proteins and readily crosses the placental barrier.
Metabolism: Metabolized in the liver.
Excretion: Less than 5% is excreted unchanged in urine; small amounts of metabolites appear in feces, gastric juice, bile, saliva, and breast milk. Half-life is 7 to 21 hours in healthy or convalescing persons; it’s longer in patients with malaria. Urine acidification hastens elimination.

Contraindications and precautions
Contraindicated in pregnant patients, patients hypersensitive to drug, and patients with G6PD deficiency, optic neuritis, tinnitus, or history of blackwater fever or thrombocytopenic purpura with previous quinine ingestion.
  Use cautiously in patients with arrhythmias and in those taking sodium bicarbonate.

Interactions
Drug-drug. Acetazolamide, sodium bicarbonate: May increase quinine levels by decreasing urinary excretion. Monitor patient closely.
Aluminum-containing antacids: May delay or decrease quinine absorption. Avoid use together.
Cimetidine: Decreases clearance and increases half-life of quinine. Use together cautiously or switch to ranitidine.
Digitoxin, digoxin: Increases plasma levels of these drugs. Monitor levels closely.
Mefloquine: May cause additive cardiac effects. Don’t use together.
Neuromuscular blockers: May potentiate effects of these drugs. Monitor patient closely.
Warfarin: May potentiate action by depressing synthesis of vitamin K-dependent clotting factors. Monitor PT and INR closely.

Adverse reactions
CNS: severe headache, apprehension, excitement, confusion, delirium, syncope, hypothermia, vertigo, seizures (with toxic doses), fever.
CV: hypotension, CV collapse (with overdose or rapid I.V. administration), conduction disturbances.
EENT: altered color perception, photophobia, blurred vision, night blindness, amblyopia, scotoma, diplopia, mydriasis, optic atrophy, tinnitus, impaired hearing.
GI: epigastric distress, diarrhea, nausea, vomiting.
GU: renal tubular damage, anuria.
Hematologic: hemolytic anemia, thrombocytopenia, agranulocytosis, hypoprothrombinemia, thrombosis at infusion site.
Metabolic: hypoglycemia.
Respiratory: asthma, dyspnea.
Skin: rash, pruritus, flushing.
Other: facial edema.

Effects on lab test results
• May decrease blood glucose level.
• May decrease hemoglobin and hematocrit, PT, and platelet and granulocyte counts.

Overdose and treatment
Signs and symptoms of overdose include tinnitus, vertigo, headache, fever, rash, CV effects, GI distress (including vomiting), blindness, apprehension, confusion, and seizures.
 Treatment includes gastric lavage followed by supportive measures, which may include fluid and electrolyte replacement, artificial respiration, and stabilization of blood pressure and renal function.
 Anaphylactoid reactions may require epinephrine, corticosteroids, or antihistamines. Urinary acidification may increase elimination of quinine but will also augment renal obstruction. Hemodialysis or hemoperfusion may be helpful. Vasodilator therapy or stellate blockage may relieve visual disturbances.

Special considerations
• Administer quinine after meals to minimize gastric distress; don’t crush tablets because drug irritates gastric mucosa.
• Quinine is no longer used for acute malarial attack by P. vivax or for suppression of malaria from resistant organisms.
• Serum levels of 10 mcg/ml or more may confirm toxicity as the cause of tinnitus or hearing loss.
• Discontinue drug if signs of idiosyncrasy or toxicity occur.
• Drug falsely elevates urinary catecholamines and may interfere with 17-hydroxycorticosteroid and 17-ketogenic steroid tests.
Breast-feeding patients
• Before giving drug to breast-feeding woman, evaluate infant for possible G6PD deficiency.
Geriatric patients
• Use cautiously in patients with conduction disturbances.

Patient education
• Teach patient about adverse reactions and the need to report them immediately, especially tinnitus and hearing impairment.
• Tell patient to avoid concurrent use of antacids that contain aluminum because they may alter drug absorption.
• Instruct patient to keep drug out of reach of children.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use