KWI-nine

Therapeutic Classification: antimalarials

• Chloroquine-resistant falciparum malaria (alone or with pyrimethamine and a sulfonamide or with a tetracycline; has also been used with clindamycin and mefloquine depending on origin of illness).

• Disrupts metabolism of the erythrocytic phase of Plasmodium falciparum.
• Increases the refractory period of skeletal muscle, increases the distribution of calcium within muscle fibers, decreases the excitability of motor end-plate regions, resulting in decreased response to repetitive nerve stimulation and acetylcholine.

• Death of P. falciparum.

Absorption: Rapidly and almost completely (80%) absorbed following oral administration.

Distribution: Varies with condition and patient; does not enter CSF well. Crosses the placenta and enters breast milk.

Protein Binding: >90% in patients with cerebral malaria, pregnant women, and children; 85–90% in patients with uncomplicated malaria; 70% in healthy adults.

Metabolism/Excretion: >80% metabolized by the liver; metabolites have less activity than quinine; metabolites excreted in urine. 20% excreted unchanged in urine. Excretion ↑ in acidic urine.

Half-life: 11 hr (↑ in patients with malaria).

(antimalarial blood levels)

Contraindicated in:

• Hypersensitivity to quinine, quinidine, or mefloquine
• History of previous serious adverse reaction to quinine including thrombotic thrombocytopenic purpura, thrombocytopenia, acute intravascular hemolysis, hemoglobinuria, or hemoglobinemia
• QTc prolongation or conditions predisposing to QTc prolongation including hypokalemia and bradycardia
• Concurrent use of Class IA or Class III antiarrhythmics, mefloquine, pimozide, or macrolide anti-infectives (↑ risk of arrhythmias)
• Myasthenia gravis
• Optic neuritis
• Severe hepatic impairment.

Use Cautiously in:

• Glucose–6–phosphate deficiency (↑ risk hemolysis)
• Recurrent or interrupted malaria therapy
• History of arrhythmias, especially QTc prolongation
• Atrial fibrillation/flutter (may cause paradoxical ↑ in ventricular response)
• Hypoglycemia
• History of thrombocytopenic purpura
• Mild or moderate hepatic impairment
• OB: Use only if potential maternal benefit justifies potential fetal risk; may ↑ risk of hypoglycemia in mother especially during 3rd trimester
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Children <16 yr (safety and effectiveness not established).

CV: PR interval prolongation, QT interval prolongation, TORSADES DE POINTES.

Derm: rash, STEVENS-JOHNSON SYNDROME.

Endo: hypoglycemia.

GI: abdominal cramps/pain, diarrhea, nausea, vomiting, hepatotoxicity.

GU: ↓fertility (males).

Hemat: bleeding, blood dyscrasias, hemolytic anemia, HEMOLYTIC UREMIC SYNDROME, THROMBOCYTOPENIA, THROMBOTIC THROMBOCYTOPENIC PUPURA.
Misc: cinchonism, (INCLUDING ANAPHYLAXIS AND FEVER)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• Concurrent use of Class IA antiarrhythmics (quinidine, procainamide, disopyramide, Class III antiarrhythmics, mefloquine, pimozide, or macrolide anti-infectives ↑ risk of arrhythmias and should be avoided.
• Antacids containing aluminum or magnesium↓ absorption; avoid concurrent use.
• Cimetidine, ketoconazole, ritonavir, tetracycline, theophylline, and erythromycin may ↑ levels; avoid concurrent use with erythromycin or ritonavir.
• Rifampin and rifabutin may ↓ levels; avoid concurrent use with rifampin.
• May ↑ effects of neuromuscular blocking agents.
• May ↑ risk of hemolytic, ototoxic, or neurotoxic reactions when used concurrently with agents sharing these toxicities.
• Concurrent use with mefloquine↑ risk of seizures and adverse cardiovascular reactions.
• Urinary alkalinizers including acetazolamide and sodium bicarbonate may ↑ blood levels.
• May ↑ levels of carbamazepine, phenobarbital, atorvastatin, simvastatin, lovastatin, desipramine, dextromethorphan, digoxin, and warfarin.
• Carbamazepine, phenobarbital, and phenytoin may ↓ levels.

• PO (Adults): 648 mg every 8 hr for 7 days.

(Generic available)

• Capsules: 200 mg; 300 mg; 324 mg;

• Malaria: Assess patient for improvement in signs and symptoms of condition daily during therapy.
• Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.

• Monitor for thrombocytopenia; usually resolved within a wk of discontinuation, but may cause a fatal hemorrhage if quinine is not discontinued.
  • May cause ↑ urinary 17-ketogenic steroids when metyrapone or Zimmerman method is used.

• Plasma quinine levels of >10 mcg/mL may cause tinnitus and impaired hearing.
  • Signs of toxicity or cinchonism include tinnitus, headache, nausea, and slightly disturbed vision; usually disappear rapidly upon discontinuing quinine.

• Do not confuse quinine with quinidine.
• PO: Administer with or after meals to minimize GI distress. Aluminum-containing antacids will decrease and delay absorption; avoid concurrent use.

• Instruct patient to take medication as directed and continue full course of therapy, even if feeling better. Take missed doses as soon as remembered, unless almost time for the next dose. If more than 4 hr has elapsed since missed dose, wait and take the next dose as scheduled. Do not double doses or take more than recommended. Advise patient to read the Patient Information leaflet prior to starting therapy and with each Rx refill.
• Review methods of minimizing exposure to mosquitoes with patients receiving quinine (use insect repellent, wear long-sleeved shirt and long trousers, use screen or netting).
• Quinine may cause visual changes. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• May cause diarrhea, nausea, stomach cramps or pain, vomiting, or ringing in the ears. Advise patient to notify health care professional promptly if these become pronounced.
• Advise patient to stop quinine and notify health care professional of any evidence of allergy (flushing, itching, rash, fever, facial swelling, stomach pain, difficult breathing, ringing in the ears, visual problems) or rash.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

• Improvement in signs and symptoms of malaria. Advise patient to contact health care professional if not feeling better within 1–2 days or if fever returns following therapy.

Qualaquin