Description: Quinacrine is an oral antiprotozoal agent used most commonly in the treatment of giardiasis. During World War II, quinacrine was effectively and widely used as an antimalarial agent. It also has been used in the treatment of cestodiasis. More recently, quinacrine has been replaced by other agents, such as praziquantel and chloroquine, in the treatment of malaria and cestodiasis. Quinacrine was introduced as an antimalarial in 1930. FDA approval is recorded in 1964. Production of quinacrine tablets was discontinued by the sole manufacturer in 1991, however, some pharmacies may compound quinacrine capsules from supplies of bulk powder. Mechanism of Action: The mechanism by which quinacrine exerts its antiprotozoal effect against Giardia is unknown. Quinacrine has no vermicidal activity against cestodes (tapeworms) but instead works on the head of the tapeworm. These actions cause the parasites to detach from the intestinal wall, and they are expelled from the GI tract due to normal GI peristalsis. Quinacrine is active against Diphyllobothrium latum (fish tapeworm), Dipylidium caninum (cat and dog tapeworm), Hymenolepis diminuta (rat tapeworm), H. nana (dwarf tapeworm), Taenia saginata (beef tapeworm), and T. solium (pork tapeworm). The antimalarial activity of quinacrine is also uncertain but is believed to be due either to the inhibition of hemoglobin digestion by the plasmodia or to the incorporation of quinacrine into DNA, which inhibits DNA metabolism in susceptible parasites. Quinacrine also has been used in patients with discoid lupus erythematosus†. Its effects are believed to be due to the drug's binding to nucleoproteins, which are able to suppress the lupus erythematosus cell factor. Pharmacokinetics: Quinacrine is administered orally. It is readily absorbed from the GI tract, with peak plasma levels occurring about 8 hours following oral administration. Quinacrine undergoes a high degree of protein binding in body tissues, especially the pancreas, lungs, bone marrow, spleen, liver, erythrocytes, and skeletal muscle. The drug concentrates primarily in the liver. Quinacrine is slowly metabolized and slowly excreted. Excretion of quinacrine occurs principally through the urine. Quinacrine may be detected in the urine up to 2 months after therapy has been discontinued. Small amounts of unaltered quinacrine are excreted in feces, sweat, milk, saliva, and bile.

ndications...Dosage The following organisms are generally considered susceptible to quinacrine in vitro: Diphyllobothrium latum; Dipylidium caninum; Giardia lamblia; Hymenolepis diminuta; Hymenolepis nana; Plasmodium falciparum; Plasmodium malariae; Plasmodium vivax; Taenia saginata; Taenia solium. For the treatment of cestodiasis caused by Taenia saginata, Taenia solium, or Diphyllobothrium latum: Oral dosage: Adults and children 14 years and over: Four doses of 200 mg PO given 10 minutes apart with 600 mg PO of sodium bicarbonate given with each dose. Children 11—14 years: 600 mg PO in 3—4 divided doses given 10 minutes apart with 300 mg PO of sodium bicarbonate given with each dose. Children 5—10 years: 400 mg PO in 3—4 divided doses given 10 minutes apart with 300 mg PO of sodium bicarbonate given with each dose. For the treatment of cestodiasis caused by Hymenolepis nana, Hymenolepis diminuta†, or Dipylidium caninum†: NOTE: On the night before receiving quinacrine, a dose of sodium sulfate dissolved in water should be given, one tablespoonful for adults and half a tablespoonful for children. Quinacrine doses should be followed by a sodium sulfate purge 1˝ hours later. Oral dosage: Adults and children 14 years and over: Initially, 900 mg PO in 3 doses, 20 minutes apart; then 100 mg tid for 3 days. Children 11—14 years: Initially, 400 mg PO in 3 doses, 20 minutes apart; then 100 mg PO tid for 3 days. Children 8—10 years: 300 mg PO in 3 doses, 20 minutes apart; then 100 mg PO bid for 3 days. Children 4—8 years: Initially, 200 mg PO in 3 doses, 20 minutes apart; then 100 mg PO after breakfast for 3 consecutive days. For the treatment of giardiasis: Oral dosage: Adults: 100 mg PO tid for 5—7 days. In patients with AIDS, the recommended dosage is 100 mg PO tid for 5 days.[518] Children: 7 mg/kg/day PO in 3 divided doses for 5 days. Maximum daily dose is 300 mg/day. For malaria: •for the treatment of acute malaria: Oral dosage: Adults and children 8 years and over: 200 mg PO with 1 g sodium bicarbonate every 6 hours for 5 doses; then 100 mg PO every 8 hours for 6 days. Maximum dose is 2.8 g in 7 days. Children 4—8 years: 200 mg PO every 8 hours; then 100 mg PO every 12 hours for 6 days. Children 1—4 years: 100 mg PO every 8 hours; then 100 mg daily for 6 days. •for the suppression of malaria: Oral dosage: Adults and children >= 8 years: 100 mg PO daily for 1—3 months. Children < 8 years: 50 mg PO daily for 1—3 months. Patients with renal impairment: No dosage adjustment needed. (Use with caution in severe renal impairment) †non-FDA-approved indication

Administration Oral Administration •Patient should be properly prepared before treatment of cestodiasis. A bland, nonfat, liquid or semisolid diet should be instituted at least one (1) day before treatment and a fast after the evening meal. •A saline cathartic and/or cleansing enema may be given prior to cestodiasis treatment. •Administration of sodium bicarbonate reduces nausea and vomiting.

Contraindications Quinacrine should be used with caution in patients with hepatic disease, other hepatotoxic drugs, or alcoholism because the drug concentrates in the liver. Quinacrine should be used with caution in patients with psoriasis and porphyria because it can exacerbate these conditions. Quinacrine is classified as pregnancy category C. Animal studies have revealed teratogenic effects in animals given high doses of quinacrine. The potential risk to the fetus must be weighed against the potential benefits of using quinacrine. Quinacrine is found in small amounts in the breast milk. There have been no reported problems in breast-feed infants. Quinacrine should be administered with caution to patients with renal disease with severe renal impairment, cardiac disease, G6PD deficiency (glucose 6-phosphate dehydrogenase deficiency), or to infants (under 1 year). Quinacrine should be used with caution in patients with a history of psychosis or in elderly patients (over 60 years) because the drug can cause a transient psychosis.

Interactions Quinacrine increases the toxicity of primaquine by displacing it from tissue binding sites, resulting in a significant increase in plasma primaquine levels. Quinacrine must be administered with caution in conjunction with hepatotoxic drugs because it concentrates in the liver. Quinacrine can affect ethanol metabolism by inhibiting aldehyde dehydrogenase. Accumulation of acetaldehyde can cause a minor disulfiram-like reaction. Cross-resistance can occur between quinacrine and chloroquine.

Adverse Reactions Large doses of quinacrine can produce adverse effects such as severe headache and GI disturbances including nausea/vomiting, abdominal pain or cramps, and mild diarrhea. Other adverse side effects during therapy with quinacrine include blood dyscrasias, hepatitis (and elevated hepatic enzymes), aplastic anemia, pancytopenia, fainting, seizures, and retinopathy. Small doses of quinacrine can cause mild headache, dizziness, and GI disturbances. Neuropsychiatric disturbances can manifest as nightmares, restlessness, confusion, anxiety, irritability, euphoria, aggressive behavior, nervousness, and emotional change. Transient toxic psychosis have been reported in some patients during therapy with quinacrine. Quinacrine temporarily imparts a yellow color to the urine and skin. Patients should be counseled regarding urine discoloration and/or skin discoloration. Other dermatologic reactions which occur less frequently include urticaria, black and blue skin and nail discoloration, exfoliative dermatitis, and contact dermatitis. Prolonged treatment for suppression of malaria can cause reversible corneal edema or deposits, manifested by visual halos, focusing difficulty, and blurred vision.

518. Smith PD, moderator. Gastrointestinal infections in AIDS. Ann Intern Med. 1992;116:63—77.

Quinacrine Atabrine® | Atarbine®