Pilocarpine hydrochloride 5 mg Tablet, Film Coated — NDC 68084-928-25 (Billing 68084-0928-25)

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.

ADVERSE REACTIONS 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 P… [Excerpted — this section continues on DailyMed.]

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.

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) 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. 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 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… [Excerpted — this section continues on DailyMed.]