Quinacrine

Overview

Quinacrine is an antiprotozoal drug with activity against a variety of protozoans and helminths. In small animal medicine, newer, safer, or more effective agents have largely replaced its use, except as an alternative treatment for Giardia spp. or Trichomonas spp.

Quinacrine is absorbed well from the gastrointestinal tract and is distributed throughout the body. It is concentrated in the liver, spleen, lungs, and adrenal glands. The drug is metabolized slowly and eliminated primarily by the kidneys.

Mechanism of Action (MOA): The mechanism responsible for quinacrine’s antiprotozoal activity against Giardia spp. is not fully understood. Quinacrine binds to DNA by intercalation between adjacent base pairs, thereby inhibiting RNA transcription and translocation. It also interferes with electron transport and inhibits succinate oxidation and cholinesterase.

Indications

Quinacrine is used as an alternative or last-line antiprotozoal agent in dogs and cats; other drugs are preferred and used more often.

• Giardiasis: Alternative treatment for Giardia spp. infections in dogs and cats.
• Trichomoniasis: Alternative treatment for Trichomonas spp. infections.
• Coccidiosis (cats): Last-line treatment for susceptible Coccidia spp. infections.

Dosage (Reference)

Dog

Quinacrine is considered a last-line treatment option for Giardia spp. and other susceptible protozoal infections in dogs.

Cat

Quinacrine may be used as a last-line treatment option for Giardia spp. or Coccidia spp. infections in cats.

Warnings & Precautions

Quinacrine should be used cautiously in dogs and cats, particularly in patients with hepatic disease. Monitor for adverse effects; gastrointestinal and behavioral effects are reported in small animals.

• Hepatic dysfunction: Use with extreme caution in patients with hepatic dysfunction.
• Pregnancy and lactation: Safety has not been established in animals. Use only when the maternal benefits outweigh the potential risks to offspring.
• Reproductive findings: Quinacrine crosses the placenta and has been implicated in a case of renal agenesis and hydrocephalus in a human infant and, at high doses, in increased fetal death rates in rats; it enters maternal milk in only small amounts.
• Name confusion: Do not confuse quinacrine with quinidine; writing part of the name in capitals (tall-man lettering) on prescriptions reduces the risk of error.
• Relative contraindications: In people, quinacrine is relatively contraindicated in psychotic disorders, psoriasis, or porphyria, as it may exacerbate these conditions; relevance to dogs and cats is unknown.

Drug Interactions

The following drug interactions have been reported or are considered theoretically significant in patients receiving quinacrine. Concurrent use is not necessarily contraindicated, but the risks should be weighed and additional monitoring performed when appropriate.

• Ethanol: Quinacrine may cause a disulfiram-like reaction when used with alcohol.
• Hepatotoxic drugs (e.g., androgens, azole antifungals, estrogens, NSAIDs): Quinacrine concentrates in the liver and should be used cautiously with other hepatotoxic medications.
• Primaquine: Quinacrine increases the toxicity of primaquine; concurrent use is contraindicated; primaquine should also not be given within 3 months of quinacrine.

Side Effects & Overdose

Side Effects

Adverse effects are common in dogs and cats and primarily involve gastrointestinal, behavioral, and systemic reactions.

• Yellow discoloration: Benign yellowing of the skin and urine may occur and does not indicate jaundice.
• Gastrointestinal effects: Anorexia, nausea, diarrhea and cramps may occur during treatment; vomiting has been reported after oral administration.
• Behavioral changes: Abnormal behaviors such as fly biting and agitation have been reported.
• Lethargy: Decreased activity or lethargy may occur.
• Pruritus: Itching has been reported in some patients.
• Fever: Elevated body temperature may occur during treatment.
• Reported in people: Hypersensitivity reactions, hepatopathy, aplastic anemia, corneal edema and retinopathy have rarely been reported in people, mainly with high-dose, long-term use.

Overdose

The severity of quinacrine overdose is dose dependent. Clinical signs primarily involve the central nervous system, gastrointestinal tract, and cardiovascular system.

• CNS excitation: May occur with acute toxicity, including seizures.
• Gastrointestinal disturbances: May occur with acute toxicity.
• Vascular collapse: Severe overdose may result in circulatory compromise.
• Cardiac arrhythmias: Abnormal heart rhythms may occur with acute toxicity.
• Management: Treatment consists of gastrointestinal decontamination and supportive, symptomatic care.
• Enhanced elimination: Urinary acidification with ammonium chloride and forced diuresis with adequate fluid therapy may increase urinary excretion of the drug.
• Poison control: For a known or suspected overdose, consult a 24-hour poison control center that provides veterinary-specific information.

Key Notes

Practical clinical points that may help optimize the use of quinacrine in dogs and cats:

• Reserve therapy: Newer, safer, or more effective antiprotozoal agents have largely replaced quinacrine in small animal practice.
• Slow elimination: Quinacrine is eliminated slowly, with a reported half-life in people of 5 to 14 days, and significant amounts may still be detected in urine for up to 2 months after discontinuation.
• Tissue accumulation: The drug concentrates in the liver, spleen, lungs, and adrenal glands, and is highly bound to plasma proteins in people (80% to 90%).
• CNS penetration: Cerebrospinal-fluid concentrations reach only 1% to 5% of plasma concentrations.
• Bitter taste: Quinacrine has a very bitter taste and may be crushed and mixed with food to improve acceptance.
• Laboratory interference: Quinacrine may cause falsely elevated plasma and urine cortisol values due to interfering fluorescence.
• Urine discoloration: Acidic urine may develop a deep yellow color during treatment.
• Monitoring: Guidance is not uniform. One source follows fecal examinations, resolution of the clinical signs being treated, and adverse effects, while the other considers no specific monitoring necessary.
• Storage: Store tablets in a tight, light-resistant container at room temperature; quinacrine is not stable in solution for any length of time.
• First-line alternatives: Fenbendazole is considered a first-line treatment for giardiasis; metronidazole and tinidazole are preferred to quinacrine and are used more often.