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 HCI | Placebo |
| 10 mg t.i.d. | 5 mg t.i.d. | (t.i.d.) |
| (30mg/day) | (15mg/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 in 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 HCI | 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, vaginitis.
The following events were reported rarely in treated Sjogren's patients (<1%) at dosing of 10-30 mg/day: Causal relation is unknown.
Body as a whole: chest pain, cyst, death, moniliasis, neck pain, neck rigidity, photosensitivity reaction
Cardiovascular: angina pectoris, arrhythmia, ECG abnormality, hypotension, hypertension, intracranial hemorrhage, migraine, myocardial infarction
Digestive: anorexia, bilirubinemia, cholelithiasis, colitis, dry mouth, eructation, gastritis, gastroenteritis, gastrointestinal disorder, gingivitis, hepatitis, abnormal liver function tests, melena, nausea & vomiting, pancreatitis, parotid gland enlargement, salivary gland enlargement, sputum increased, taste loss, tongue disorder, tooth disorder
Hematologic: hematuria, lymphadenopathy, abnormal platelets, thrombocythemia, `thrombocytopenia, thrombosis, abnormal WBC
Metabolic and Nutritional: peripheral edema, hypoglycemia
Musculoskeletal: arthralgia, arthritis, bone disorder, spontaneous bone fracture, pathological fracture, myasthenia, tendon disorder, tenosynovitis
Nervous: aphasia, confusion, depression, abnormal dreams, emotional lability, hyperkinesia, hypesthesia, insomnia, leg cramps, nervousness, paresthesias, abnormal thinking, tremor
Respiratory: bronchitis, dyspnea, hiccup, laryngismus, laryngitis, pneumonia, viral infection, voice alteration
Skin: alopecia, contact dermatitis, dry skin, eczema, erythema nodosum, exfoliative dermatitis, herpes simplex, skin ulcer, vesiculobullous rash
Special senses: cataract, conjunctivitis, dry eyes, ear disorder, ear pain, eye disorder, eye hemorrhage, glaucoma, lacrimation disorder, retinal disorder, taste perversion, abnormal vision
Urogenital: breast pain, dysuria, mastitis, menorrhagia, metrorrhagia, ovarian disorder, pyuria, salpingitis, urethral pain, urinary urgency, vaginal hemorrhage, vaginal moniliasis
The following adverse experiences have been reported rarely with ocular pilocarpine: A-V block, agitation, ciliary congestion, confusion, delusion, depression, dermatitis, middle ear disturbance, eyelid twitching, malignant glaucoma, iris cysts, macular hole, shock, and visual hallucination.
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