Quinacrine

What is quinacrine?

Quinacrine is a derivative of quinine, synthesised from bark of the cinchona tree. It was extensively used as an antimalarial agent for millions of servicemen in the Pacific region during the 1940s. It was found to be well tolerated and has subsequently been used for the treatment of connective tissue diseases such as lupus erythematosus. However, due to yellowish skin changes that occur after long-term use, it is not used as commonly as hydroxychloroquine or chloroquine [1,2].

Quinacrine is also known as mepacrine and has the brand name Atabrine^TM.

Who uses quinacrine?

The use of quinacrine in dermatology has been mostly superseded by chloroquine and hydroxychloroquine [2]. Although it can be used alone, quinacrine is usually used in combination with hydroxychloroquine to boost response in recalcitrant inflammatory skin conditions such as:

• Discoid lupus erythematosus
• Subacute cutaneous lupus erythematosus
• Sarcoidosis
• Dermatomyositis.

Quinacrine may be preferred in patients at ocular risk or those with profound fatigue as it is a CNS stimulant [1]. It is also useful in those who are unable to tolerate chloroquine derivatives.

Discoid lupus erythematosus

Lupus pernio

Dermatomyositis

Tell me more about quinacrine

Mechanism of action

Quinacrine has been shown to have anti-proliferative, anti-inflammatory, anti-parasitic and anti-cancer effects [3].

Pharmacokinetics

Quinacrine is rapidly absorbed from the gastrointestinal tract following oral administration. The plasma concentration of quinacrine increases rapidly during the first week and equilibrates by the fourth week. Quinacrine is slowly excreted, mainly via the kidneys [1,3].

Dosing

Quinacrine is dispensed as 100 mg tablets.

The recommended maintenance dose is 100 mg daily orally, or alternate days in fair-skinned patients because of skin discolouration. The onset of action is 3–6 weeks, depending on the initial dose. If there has been no improvement after 8 weeks, then the quinacrine should be ceased [1].

It is often combined with hydroxychloroquine, when hydroxychloroquine alone is ineffective. For example, hydroxychloroquine 200–400 mg daily with 50–100 mg quinacrine every second day.

Quinacrine is an older medication and is no longer marketed in Australia but is available through the Special Access Scheme (SAS). It is not available in New Zealand.

What are the side effects and risks of quinacrine?

Quinacrine is generally well tolerated. Common minor adverse effects such as transient headache, gastrointestinal symptoms (eg, nausea, abdominal cramping, and diarrhoea), and dizziness, improve with time or a reduction in the dose [1,3]

Quinacrine commonly causes yellowing and bruise-like discolouration of the skin, oral mucosa, nails and sclera that is not related to liver injury. This discolouration is more prominent in fair skinned patients but is harmless and will fade when the treatment is stopped [1,3]. Dermatitis is another common skin complaint that resolves with discontinuation of the quinacrine [1].

Unlike chloroquine or hydroxychloroquine, quinacrine has a very low risk of retinal toxicity [4].

High doses of quinacrine, usually exceeding those used in dermatology, cause more serious side effects. These include corneal oedema (> 500 mg/d), neurological issues (1200 mg/d), liver toxicity, and aplastic anaemia [3]. Although the latter has rarely been reported in doses less than 300 mg/day, routine blood test monitoring is recommended. The aplastic anaemia is often preceded by a lichen planus-like rash.

Pregnancy and antimalarial medications

Quinacrine crosses into the placenta, therefore should not be given to pregnant women, or women planning a pregnancy.

Quinacrine is excreted in small amounts in breast milk. Although problems have not been reported, its use during breastfeeding should be avoided if possible.

Children and elderly patients

Children tolerate quinacrine less well than adults and it may cause vomiting due to its bitter taste.

Appropriate studies in elderly populations have not been performed. However, no geriatric–specific problems have been documented.

What are the contraindications with quinacrine?

Women planning a pregnancy, pregnant and lactating women should not take quinacrine.

Caution should be taken in:

• The use of quinacrine in children below 5 years of age
• Excessive alcohol consumption
• Patients with severe liver disease.