Pilocarpine Hydrochloride
Tablet, Film Coated · Oral, Ophthalmic
Uses
Pilocarpine Hydrochloride Tablets are indicated for 1) the treatment of symptoms of dry mouth from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck; and 2) the treatment of symptoms of dry mouth in patients with Sjogren's Syndrome.
Dosage and administration
Regardless of the indication, the starting dose in patients with moderate hepatic impairment should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency do not require dosage reductions. The use of pilocarpine in patients with severe hepatic insufficiency is not recommended. If needed, refer to the Hepatic Insufficiency subsection of the Precautions section of this label for definitions of mild, moderate and severe hepatic impairment. Head & Neck Cancer Patients: The recommended initial dose of Pilocarpine Hydrochloride Tablets is 5 mg taken three times a day. Dosage should be titrated according to therapeutic response and tolerance. The usual dosage range is up to 15-30 mg per day. (Not to exceed 10 mg per dose). Although early improvement may be realized, at least 12 weeks of uninterrupted therapy with Pilocarpine Hydrochloride Tablets may be necessary to assess whether a beneficial response will be achieved. The incidence of the most common adverse events increases with dose. The lowest dose that is tolerated and effective should be used for maintenance. Sjogren's Syndrome Patients: The recommended dose of Pilocarpine Hydrochloride Tablets is 5 mg taken four times a day. Efficacy was established by 6 weeks of use.
Contraindications
Pilocarpine Hydrochloride Tablets are contraindicated in patients with uncontrolled asthma, known hypersensitivity to pilocarpine, and when miosis is undesirable, e.g., in acute iritis and in narrow-angle (angle closure) glaucoma.
Warnings
Cardiovascular Disease: Patients with significant cardiovascular disease may be unable to compensate for transient changes in hemodynamics or rhythm induced by pilocarpine. Pulmonary edema has been reported as a complication of pilocarpine toxicity from high ocular doses given for acute angle-closure glaucoma. Pilocarpine should be administered with caution in and under close medical supervision of patients with significant cardiovascular disease. Ocular: Ocular formulations of pilocarpine have been reported to cause visual blurring which may result in decreased visual acuity, especially at night and in patients with central lens changes, and to cause impairment of depth perception. Caution should be advised while driving at night or performing hazardous activities in reduced lighting. Pulmonary Disease: Pilocarpine has been reported to increase airway resistance, bronchial smooth muscle tone, and bronchial secretions. Pilocarpine hydrochloride should be administered with caution to and under close medical supervision in patients with controlled asthma, chronic bronchitis, or chronic obstructive pulmonary disease requiring pharmacotherapy.
Precautions
General Pilocarpine toxicity is characterized by an exaggeration of its parasympathomimetic effects. These may include: headache, visual disturbance, lacrimation, sweating, respiratory distress, gastrointestinal spasm, nausea, vomiting, diarrhea, atrioventricular block, tachycardia, bradycardia, hypotension, hypertension, shock, mental confusion, cardiac arrhythmia, and tremors. The dose-related cardiovascular pharmacologic effects of pilocarpine include hypotension, hypertension, bradycardia, and tachycardia. Pilocarpine should be administered with caution to patients with known or suspected cholelithiasis or biliary tract disease.Contractions of the gallbladder or biliary smooth muscle could precipitate complications including cholecystitis, cholangitis, and biliary obstruction. Pilocarpine may increase ureteral smooth muscle tone and could theoretically precipitate renal colic (or "ureteral reflux"), particularly in patients with nephrolithiasis. Cholinergic agonists may have dose-related central nervous system effects. This should be considered when treating patients with underlying cognitive or psychiatric disturbances. Hepatic Insufficiency: Based on decreased plasma clearance observed in patients with moderate hepatic impairment, the starting dose in these patients should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency (Child-Pugh score of 5-6) do not require dosage reductions. To date, pharmacokinetic studies in subjects with severe hepatic impairment (Child-Pugh score of 10-15) have not been carried out. The use of pilocarpine in these patients is not recommended. Child-Pugh Scoring System for Hepatic Impairment Clinical and Biochemical Measurements Points Scored for Increasing Abnormality 1 2 3 Encephalopathy (grade)* None 1 and 2 3 and 4 Ascites Absent Slight Moderate Bilirubin (mg. per 100 ml.) 1-2 2-3 >3 Albumin (g. per 100 ml.) 3-5 2.8-3.5 <2.8 Prothrombin Time (sec. Prolonged) 1-4 4-6 >6 For Primary Biliary Cirrhosis:- Bilirubin (mg. per 100 ml.) 1-4 4-10 >10 * According to grading of Trey C, Burns D, and Saunders S. Treatment of hepatic coma by exchange blood transfusion. N Engl J Med. 1966; 274:473-481. Reference: Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Brit. J. Surg. 1973; 60:646-9. Information for Patients Patients should be informed that pilocarpine may cause visual disturbances, especially at night, that could impair their ability to drive safely. If a patient sweats excessively while taking pilocarpine hydrochloride and cannot drink enough liquid, the patient should consult a physician. Dehydration may develop. Drug Interactions Pilocarpine should be administered with caution to patients taking beta-adrenergic antagonists because of the possibility of conduction disturbances. Drugs with parasympathomimetic effects administered concurrently with pilocarpine would be expected to result in additive pharmacologic effects. Pilocarpine might antagonize the anticholinergic effects of drugs used concomitantly. These effects should be considered when anticholinergic properties may be contributing to the therapeutic effect of concomitant medication (e.g., atropine, inhaled ipratropium). While no formal drug interaction studies have been performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone. Carcinogenesis, Mutagenesis, Impairment of Fertility Lifetime oral carcinogenicity studies were conducted in CD-1 mice and Sprague-Dawley rats. Pilocarpine did not induce tumors in mice at any dosage studied (up to 30 mg/kg/day, which yielded a systemic exposure approximately 50 times larger than the maximum systemic exposure observed clinically). In rats, a dosage of 18 mg/kg/day, which yielded a systemic exposure approximately 100 times larger than the maximum systemic exposure observed clinically, resulted in a statistically significant increase in the incidence of benign pheochromocytomas in both males and females, and a statistically significant increase in the incidence of hepatocellular adenomas in female rats. The tumorigenicity observed in rats was observed only at a large multiple of the maximum labeled clinical dose, and may not be relevant to clinical use. No evidence that pilocarpine has the potential to cause genetic toxicity was obtained in a series of studies that included: 1) bacterial assays ( Salmonella and E. coli ) for reverse gene mutations; 2) an in vitro chromosome aberration assay in a Chinese hamster ovary cell line; 3) an in vivo chromosome aberration assay (micronucleus test) in mice; and 4) a primary DNA damage assay (unscheduled DNA synthesis) in rat hepatocyte primary cultures. Oral administration of pilocarpine to male and female rats at a dosage of 18 mg/kg/day, which yielded a systemic exposure approximately 100 times larger than the maximum systemic exposure observed clinically, resulted in impaired reproductive function, including reduced fertility, decreased sperm motility, and morphologic evidence of abnormal sperm. It is unclear whether the reduction in fertility was due to effects on male animals, female animals, or both males and females. In dogs, exposure to pilocarpine at a dosage of 3 mg/kg/day (approximately 3 times the maximum recommended human dose when compared on the basis of body surface area (mg/m 2 ) estimates) for six months resulted in evidence of impaired spermatogenesis. The data obtained in these studies suggest that pilocarpine may impair the fertility of male and female humans.
Side effects
Head & Neck Cancer Patients: In controlled studies, 217 patients received pilocarpine, of whom 68% were men and 32% were women. Race distribution was 91% Caucasian, 8% Black, and 1% of other origin. Mean age was approximately 58 years. The majority of patients were between 50 and 64 years (51%), 33% were 65 years and older and 16% were younger than 50 years of age. The most frequent adverse experiences associated with pilocarpine hydrochloride tablets were a consequence of the expected pharmacologic effects of pilocarpine. Adverse Event Pilocarpine HCl Placebo 10 mg t.i.d. 5 mg t.i.d. (t.i.d.) (30 mg/day) (15 mg/day) N=121 N=141 N=152 Sweating 68% 29% 9% Nausea 15 6 4 Rhinitis 14 5 7 Diarrhea 7 4 5 Chills 15 3 <1 Flushing 13 8 3 Urinary Frequency 12 9 7 Dizziness 12 5 4 Asthenia 12 6 3 In addition, the following adverse events (≥3% incidence) were reported at dosages of 15-30 mg/day in the controlled clinical trials: Adverse Event Pilocarpine HCl Placebo 5-10 mg t.i.d. (t.i.d.) (15-30 mg/day) N=212 N=152 Headache 11% 8% Dyspepsia 7 5 Lacrimation 6 8 Edema 5 4 Abdominal Pain 4 4 Amblyopia 4 2 Vomiting 4 1 Pharyngitis 3 8 Hypertension 3 1 The following events were reported with treated head and neck cancer patients at incidences of 1% to 2% at dosages of 7.5 to 30 mg/day: abnormal vision, conjunctivitis, dysphagia, epistaxis, myalgias, pruritus, rash, sinusitis, tachycardia, taste perversion, tremor, voice alteration. The following events were reported rarely in treated head and neck cancer patients (<1%): Causal relation is unknown. Body as a whole: body odor, hypothermia, mucous membrane abnormality Cardiovascular: bradycardia, ECG abnormality, palpitations, syncope Digestive: anorexia, increased appetite, esophagitis, gastrointestinal disorder, tongue disorder Hematologic: leukopenia, lymphadenopathy Nervous: anxiety, confusion, depression, abnormal dreams, hyperkinesia, hypesthesia, nervousness, paresthesias, speech disorder, twitching Respiratory: increased sputum, stridor, yawning Skin: seborrhea Special senses: deafness, eye pain, glaucoma Urogenital: dysuria, metrorrhagia, urinary impairment In long-term treatment were two patients with underlying cardiovascular disease of whom one experienced a myocardial infarct and another an episode of syncope. The association with drug is uncertain. Sjogren's Syndrome Patients: In controlled studies, 376 patients received pilocarpine, of whom 5% were men and 95% were women. Race distribution was 84% Caucasian, 9% Oriental, 3% Black, and 4% of other origin. Mean age was 55 years. The majority of patients were between 40 and 69 years (70%), 16% were 70 years and older and 14% were younger than 40 years of age. Of these patients, 161/629 (89/376 receiving pilocarpine) were over the age of 65 years. The adverse events reported by those over 65 years and those 65 years and younger were comparable except for notable trends for urinary frequency, diarrhea, and dizziness. The incidences of urinary frequency and diarrhea in the elderly were about double those of the non-elderly. The incidence of dizziness was about three times as high in the elderly as in the non-elderly. These adverse experiences were not considered to be serious. In the 2 placebo-controlled studies, the most common adverse events related to drug use were sweating, urinary frequency, chills, and vasodilatation (flushing). The most commonly reported reason for patient discontinuation of treatment was sweating. Expected pharmacologic effects of pilocarpine include the following adverse experiences associated with pilocarpine hydrochloride tablets: Adverse Event Pilocarpine HCl Placebo 5 mg q.i.d. (q.i.d.) (20 mg/day) N=255 N=253 Sweating 40% 7% Urinary Frequency 10 4 Nausea 9 9 Flushing 9 2 Rhinitis 7 8 Diarrhea 6 7 Chills 4 2 Increased Salivation 3 0 Asthenia 2 2 In addition, the following adverse events (≥3% incidence) were reported at dosages of 20 mg/day in the controlled clinical trials: Adverse Event Pilocarpine HCl Placebo 5 mg q.i.d. (q.i.d.) (20 mg/day) N=255 N=253 Headache 13% 19% Flu Syndrome 9 9 Dyspepsia 7 7 Dizziness 6 7 Pain 4 2 Sinusitis 4 5 Abdominal Pain 3 4 Vomiting 3 1 Pharyngitis 2 5 Rash 2 3 Infection 2 6 The following events were reported in Sjogren's patients at incidences of 1% to 2% at dosing of 20 mg/day: accidental injury, allergic reaction, back pain, blurred vision, constipation, increased cough, edema, epistaxis, face edema, fever, flatulence, glossitis, lab test abnormalities, including chemistry, hematology, and urinalysis, myalgia, palpitation, pruritus, somnolence, stomatitis, tachycardia, tinnitus, urinary incontinence, urinary tract infection, and vaginitis. The following events were reported rarely in treated Sjogren's patients (<1%) at dosing of 10-30 mg/day: Causal relation is unknown.
Drug interactions
Drug Interactions Pilocarpine should be administered with caution to patients taking beta-adrenergic antagonists because of the possibility of conduction disturbances. Drugs with parasympathomimetic effects administered concurrently with pilocarpine would be expected to result in additive pharmacologic effects. Pilocarpine might antagonize the anticholinergic effects of drugs used concomitantly. These effects should be considered when anticholinergic properties may be contributing to the therapeutic effect of concomitant medication (e.g., atropine, inhaled ipratropium). While no formal drug interaction studies have been performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone.
Pregnancy
Pregnancy Pregnancy:Teratogenic Effects Pilocarpine was associated with a reduction in the mean fetal body weight and an increase in the incidence of skeletal variations when given to pregnant rats at a dosage of 90 mg/kg/day (approximately 26 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area (mg/m 2 ) estimates). These effects may have been secondary to maternal toxicity. In another study, oral administration of pilocarpine to female rats during gestation and lactation at a dosage of 36 mg/kg/day (approximately 10 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area (mg/m 2 ) estimates) resulted in an increased incidence of stillbirths; decreased neonatal survival and reduced mean body weight of pups were observed at dosages of 18 mg/kg/day (approximately 5 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area (mg/m 2 ) estimates) and above. There are no adequate and well-controlled studies in pregnant women. Pilocarpine hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pediatric use
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Geriatric use
Geriatric Use Head and Neck Cancer Patients : In the placebo-controlled clinical trials (see Clinical Studies section) the mean age of patients was approximately 58 years (range 19 to 80). Of these patients, 97/369 (61/217 receiving pilocarpine) were over the age of 65 years. In the healthy volunteer studies, 15/150 subjects were over the age of 65 years. In both study populations, the adverse events reported by those over 65 years and those 65 years and younger were comparable. Of the 15 elderly volunteers (5 women, 10 men), the 5 women had higher C max's and AUC's than the men. (See Pharmacokinetics section.) Sjogren's Syndrome Patients: In the placebo-controlled clinical trials (See Clinical Studies section), the mean age of patients was approximately 55 years (range 21 to 85). The adverse events reported by those over 65 years and those 65 years and younger were comparable except for notable trends for urinary frequency, diarrhea, and dizziness (See ADVERSE REACTIONS section).
Description
Pilocarpine Hydrochloride Tablets contain pilocarpine hydrochloride, a cholinergic agonist for oral use. Pilocarpine hydrochloride is a hygroscopic, odorless, bitter tasting white crystal or powder which is soluble in water and alcohol and virtually insoluble in most non-polar solvents. Pilocarpine hydrochloride, with a chemical name of (3 S - cis )-2(3 H )-Furanone, 3-ethyldihydro-4-[(1 -methyl-1 H -imidazol-5-yl) methyl] monohydrochloride, has a molecular weight of 244.72. Each 5 mg Pilocarpine Hydrochloride Tablet for oral administration contains 5 mg of pilocarpine hydrochloride. Inactive ingredients in the tablet, the tablet's film coating, and polishing are: carnauba wax, hypromellose, microcrystalline cellulose, stearic acid, titanium dioxide and other ingredients. Each 7.5 mg Pilocarpine Hydrochloride Tablet for oral administration contains 7.5 mg of pilocarpine hydrochloride. Inactive ingredients in the tablet, the tablet's film coating, and polishing are: carnauba wax, hypromellose, microcrystalline cellulose, stearic acid, titanium dioxide, FD&C blue # 2 aluminum lake, and other ingredients. 2f444b6e-figure-01
How supplied
Pilocarpine Hydrochloride Tablets, 5 mg, are white, film coated, debossed round tablets, coded SAL 5. Each tablet contains 5 mg pilocarpine hydrochloride. They are supplied as follows: NDC 0228-2801-11 bottles of 100 with a child-resistant closure. Store up to 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). Pilocarpine Hydrochloride Tablets, 7.5 mg, are blue, film coated, debossed round tablets, coded SAL 7.5. Each tablet contains 7.5 mg pilocarpine hydrochloride. They are supplied as follows: NDC 0228-2837-11 bottles of 100 with a child-resistant closure. Store up to 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). Manufactured for: Teva Pharmaceuticals USA, Inc. Parsippany, NJ 07054 by: Patheon Inc. Ontario, Canada L5N 7K9 LF-121899-01 Revised - January 2021 2000013377
Patient information
Information for Patients Patients should be informed that pilocarpine may cause visual disturbances, especially at night, that could impair their ability to drive safely. If a patient sweats excessively while taking pilocarpine hydrochloride and cannot drink enough liquid, the patient should consult a physician. Dehydration may develop.
Label text from the FDA structured product label by Actavis Pharma, Inc. (revised Aug 31, 2021). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Pilocarpine Hydrochloride in 22 products
Pilocarpine Hydrochloride NDC products (22)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 69292-265 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | AMICI PHARMACEUTICALS LLC | ANDA |
| 69238-1747 | Pilocarpine Hydrochloride 40 mg/mL Solution/ Drops | Amneal Pharmaceuticals NY LLC | ANDA |
| 60219-5922 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1746 | Pilocarpine Hydrochloride 20 mg/mL Solution/ Drops | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1745 | Pilocarpine Hydrochloride 10 mg/mL Solution/ Drops | Amneal Pharmaceuticals NY LLC | ANDA |
| 59651-224 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 59651-225 | Pilocarpine Hydrochloride 7.5 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 50268-652 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | AvPAK | ANDA |
| 63629-2099 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 72162-1078 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 63629-8351 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 0527-1407 | Pilocarpine Hydrochloride 7.5 mg/1 Tablet, Film Coated | Lannett Company, Inc. | ANDA |
| 0527-1313 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | Lannett Company, Inc. | ANDA |
| 70069-181 | Pilocarpine Hydrochloride 10 mg/mL Solution/ Drops | Somerset Therapeutics, LLC | ANDA |
| 70069-191 | Pilocarpine Hydrochloride 20 mg/mL Solution/ Drops | Somerset Therapeutics, LLC | ANDA |
| 70069-201 | Pilocarpine Hydrochloride 40 mg/mL Solution/ Drops | Somerset Therapeutics, LLC | ANDA |
| 0228-2801 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | Actavis Pharma, Inc. | NDA AUTHORIZED GENERIC |
| 0228-2837 | Pilocarpine Hydrochloride 7.5 mg/1 Tablet, Film Coated | Actavis Pharma, Inc. | NDA AUTHORIZED GENERIC |
| 68084-928 | Pilocarpine Hydrochloride 5 mg/1 Tablet, Film Coated | American Health Packaging | NDA AUTHORIZED GENERIC |
| 61314-206 | Pilocarpine Hydrochloride 40 mg/mL Solution/ Drops | Sandoz Inc | NDA AUTHORIZED GENERIC |
| 61314-204 | Pilocarpine Hydrochloride 20 mg/mL Solution/ Drops | Sandoz Inc | NDA AUTHORIZED GENERIC |
| 61314-203 | Pilocarpine Hydrochloride 10 mg/mL Solution/ Drops | Sandoz Inc | NDA AUTHORIZED GENERIC |
Pilocarpine Hydrochloride recalls
- D-0679-2017 May 3, 2017 · Class III · Terminated
Failed Impurities/Degradation Specifications.
Frequently asked questions
What is Pilocarpine Hydrochloride used for?
Pilocarpine Hydrochloride Tablets are indicated for 1) the treatment of symptoms of dry mouth from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck; and 2) the treatment of symptoms of dry mouth in patients with Sjogren's Syndrome.
What are the side effects of Pilocarpine Hydrochloride?
Head & Neck Cancer Patients: In controlled studies, 217 patients received pilocarpine, of whom 68% were men and 32% were women. Race distribution was 91% Caucasian, 8% Black, and 1% of other origin. Mean age was approximately 58 years. The majority of patients were between 50 and 64 years (51%), 33% were 65 years and older and 16% were younger than 50 years of age. The most frequent adverse… See the full label for the complete list.
Who makes Pilocarpine Hydrochloride?
Pilocarpine Hydrochloride is listed by 10 labelers in the FDA NDC directory, including AMICI PHARMACEUTICALS LLC, Amneal Pharmaceuticals NY LLC, Aurobindo Pharma Limited, AvPAK.
Has Pilocarpine Hydrochloride been recalled?
The FDA enforcement database lists 1 recall for Pilocarpine Hydrochloride, most recently D-0679-2017 (class iii): Failed Impurities/Degradation Specifications.