Evoxac (cevimeline)

Cevimeline works on the same principle as pilocarpine: stimulating the remaining functional salivary and lacrimal gland cells to produce more moisture. However, cevimeline is more selective for the M1 and M3 muscarinic receptors that are most abundant on salivary glands, rather than activating all muscarinic receptor subtypes equally.

This selectivity may provide two advantages: stronger stimulation of saliva production and fewer off-target effects like sweating (which is driven primarily by M2/M3 receptors on sweat glands). Patients who experience excessive sweating with pilocarpine sometimes tolerate cevimeline better.

Like pilocarpine, cevimeline is a symptomatic treatment only. It does not address the underlying autoimmune destruction of glands and must be taken continuously to maintain its effect.

Evoxac is the brand name for cevimeline hydrochloride, an oral capsule approved by the FDA in January 2000 to treat dry mouth in people with Sjogren's syndrome.

About the disease: Sjogren's syndrome is an autoimmune disease in which the immune system attacks the glands that make saliva and tears.

Capsule: Each white capsule contains 30 mg of cevimeline and is marked EVOXAC on the cap.

Maker and generics: The brand is marketed by Cosette Pharmaceuticals, and generic cevimeline capsules are also available.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Cevimeline is approved for 1 use: treating the symptoms of dry mouth in people with Sjogren's syndrome.

Symptom treatment only: It helps the glands you still have make more saliva but does not slow the underlying autoimmune damage. It must be taken continuously to keep working.

Other uses: Any other use, such as dry mouth from radiation or from other medicines, is outside the FDA-approved label.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Cevimeline is a cholinergic agonist, meaning it mimics acetylcholine, the nerve signal that tells glands to secrete.

Receptors: It binds to muscarinic receptors, the docking sites on salivary and sweat glands and on smooth muscle in the gut and bladder.

Effect: Stimulating those receptors on the salivary glands increases saliva production.

Selectivity: It is more selective for the M1 and M3 receptor types that are most abundant on salivary glands, which is why it may cause less sweating than older drugs that activate all muscarinic receptor types equally.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Cevimeline is a muscarinic agonist, also described as a cholinergic agonist or a secretagogue (a drug that stimulates secretion).

Approved secretagogues: It is 1 of 2 FDA-approved oral secretagogues for Sjogren's dry mouth, the other being pilocarpine.

Selectivity: Within the class it is considered selective for the M1 and M3 muscarinic receptor subtypes.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

The chemical name is cis-2'-methylspiro{1-azabicyclo[2.2.2]octane-3,5'-[1,3]oxathiolane} hydrochloride, hydrate (2:1).

Why spiro: A spiro compound is one in which 2 rings share a single atom, like 2 hoops joined at 1 point; in cevimeline a quinuclidine ring (the azabicyclo-octane) and an oxathiolane ring share 1 carbon.

Formula and weight: Its formula is C10H17NOS.HCl with a half molecule of water, and its molecular weight is 244.79.

Appearance: It is a white to off-white crystalline powder that dissolves readily in water.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

The recommended dose is 1 capsule of 30 mg taken 3 times a day.

Higher doses: The label says there is not enough safety information to support doses above 30 mg 3 times a day, and no evidence that higher doses work better.

With food: Taking it with food slows absorption, delaying the peak blood level from about 1.5 hours to about 2.9 hours and lowering it by 17.3%.

How to take: Swallow the capsule with water, and drink extra water if the drug makes you sweat heavily, since dehydration can develop.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Effects on saliva typically begin within 60 to 90 minutes and last about 4 to 6 hours, which is why it is dosed 3 times a day.

Peak level: After a single 30 mg capsule, cevimeline reaches its peak blood level in about 1.5 to 2 hours.

Half-life: The drug's half-life (the time for the blood level to fall by half) is about 5 hours, and it does not build up in the body with repeated dosing.

Elimination: Most of it leaves the body in the urine within 24 hours.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

The most common side effect tied to its gland-stimulating action is excessive sweating, followed by nausea and runny nose.

Trial size: In the Sjogren's trials, 533 people took cevimeline 30 mg 3 times a day and 164 took placebo.

Gland-related effects: Excessive sweating (18.7% vs 2.4% on placebo), nausea (13.8% vs 7.9%), runny nose (11.2% vs 5.4%), diarrhea (10.3% vs 10.3%) and excessive saliva (2.2% vs 0.6%).

Other common events: Reported in at least 3% of people on cevimeline were headache (14.4%, which was lower than the 20.1% on placebo), sinus infection (12.3%), upper respiratory infection (11.4%), indigestion (7.8%), abdominal pain (7.6%), urinary tract infection (6.1%), cough (6.1%) and vomiting (4.6%).

Stopping and other reports: In the placebo-controlled US studies, 14.6% of people stopped cevimeline because of side effects. Blurred vision, especially at night, and gallbladder inflammation (cholecystitis) have also been reported.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Evoxac should not be taken by anyone with uncontrolled asthma, by anyone who has had an allergic reaction to cevimeline, or by people in whom a constricted pupil would be harmful, such as those with acute iritis (inflammation of the colored part of the eye) or narrow-angle glaucoma.

Heart conditions: The label says it should be used with caution and close medical supervision in people with a history of angina or heart attack, because it can change heart rhythm or rate.

Lung conditions: The same caution applies to people with controlled asthma, chronic bronchitis or COPD, because it can tighten the airways.

Kidney stones or gallstones: People with a history of either should also use it with caution, since it can make the gallbladder and ureters contract.

Pregnancy and breastfeeding: There are no well-controlled studies in pregnant women, and it is not known whether it passes into breast milk.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Yes.

Beta blockers: The label advises caution because of a possible effect on the heart's electrical conduction.

Nervous system drugs: Other drugs that stimulate the parasympathetic nervous system can add to cevimeline's effects, and cevimeline can cancel out the drying effect of anticholinergic drugs taken on purpose.

Liver enzymes: Cevimeline is broken down by the liver enzymes CYP2D6 and CYP3A4, so medicines that block those enzymes can raise its levels, and people with low CYP2D6 activity may be at higher risk of side effects.

What to do: Give your doctor and pharmacist a full list of what you take.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

The main alternative is pilocarpine, the other oral secretagogue approved for Sjogren's dry mouth.

Pilocarpine: It acts on a broader range of muscarinic receptors and tends to cause more sweating.

Symptom relief only: Both drugs only relieve symptoms, and disease-modifying treatments for Sjogren's remain in clinical development.

Switching: People who sweat too much on pilocarpine sometimes tolerate cevimeline better, so switching between the 2 is something to discuss with your doctor.

If neither works: If you cannot take either because of uncontrolled asthma, narrow-angle glaucoma or heart disease, your rheumatologist or dentist can talk through other ways to manage dry mouth.

Both stimulate saliva production.

Cevimeline: Evoxac is more selective for salivary gland receptors (M1/M3), which may cause less sweating than pilocarpine.

Pilocarpine: It acts on a broader range of receptors.

Disease effect: Neither modifies the underlying disease.

In the placebo-controlled trials, cevimeline improved dry mouth symptoms and measured saliva flow, though one study found higher saliva flow without a significant difference in patient ratings.

First trial: In a 6-week placebo-controlled trial of 75 people, 76% of those taking cevimeline 30 mg 3 times a day said their dry mouth was better, compared with 35% on placebo.

Second trial: In a 12-week trial of 197 people, the 30 mg dose again produced a statistically significant improvement in dry mouth symptoms and in measured saliva flow, while a 15 mg dose improved saliva flow but not symptoms.

Third trial: In a second 12-week trial of 212 people, saliva flow rose significantly but patient ratings did not differ significantly, partly because the placebo response was high in that study.

Patient reviews: Trial Friend does not collect patient reviews, so the trial ratings above are the best available measure of how people felt on the drug.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Yes, generic cevimeline hydrochloride 30 mg capsules are available from several companies.

Cost: The FDA label does not list a price, and Trial Friend does not have a verified cost figure; what you pay depends on your insurance, your pharmacy and whether the brand or the generic is dispensed.

Assistance: No manufacturer assistance program is listed for Evoxac on Trial Friend, so ask your pharmacist about the generic and any discount options.

Cevimeline was developed by Daiichi Sankyo under the code SNI-2011 and received FDA approval in January 2000.

Current brand owner: The Evoxac brand is now marketed by Cosette Pharmaceuticals, Inc. of South Plainfield, New Jersey, and the current label was issued in February 2022.

Generics: Generic versions are made by several other companies.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07

Store the capsules at room temperature, 77°F (25°C), with short trips between 59°F and 86°F (15°C to 30°C) allowed.

Packaging: Evoxac is supplied in child-resistant bottles of 100 capsules.

Keep away from children: Keep the bottle closed and out of reach of children, since an overdose can cause exaggerated effects such as sweating, vomiting, slow or fast heartbeat, low blood pressure and confusion.

Source: FDA label for Evoxac, DailyMed, effective 2022-09-07