Drug highlight: Pilocarpine
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0973-1075.30247
Source of Support: None, Conflict of Interest: None
Indications: Xerostomia (dry mouth) after radiation for head and neck cancer, dry mouth (and dry eyes) in Sj φgren's syndrome and drug-induced dry mouth.
Contra-indications: Intestinal or urinary obstruction, or where increased intestinal or urinary tract motility could be harmful (e.g., after recent surgery); uncontrolled asthma, chronic obstructive pulmonary diseases (COPD) or cardiovascular disease; acute iritis.
Pilocarpine is a parasympathomimetic (predominantly muscarinic) drug with mild b-adrenergic activity which stimulates secretion from exocrine glands, including salivary glands. The prophylactic use of pilocarpine 5 mg q.d.s. in patients receiving head and neck radiation (starting simultaneously and continuing for 4-6 weeks after the radiation is completed) has been shown to reduce the decrease in unstimulated salivary flow,, and to actually increase it in about 1/4 of patients., Despite this objective improvement, a large placebo-controlled trial (n=245) failed to show symptomatic benefit., On the other hand, about 50% of patients with dry mouth several weeks or months after radiation will respond to pilocarpine although benefit may take 3 months to become apparent., Thus, failure to demonstrate symptomatic benefit from prophylactic use may relate to a too short a treatment period or the presence of concurrent problems, e.g., mucositis.
About 90% of patients with drug-induced dry mouth respond to pilocarpine with benefit seen immediately. In a controlled study, 1/2 of the patients preferred pilocarpine (because it was more effective) and 1/2 preferred mucin-based artificial saliva (mainly because it was a spray and not a tablet). Undesirable effects were much more common in patients receiving pilocarpine (84% vs. 22%), which resulted in 1/4 of the patients withdrawing from the study.
Cheaper alternatives to pilocarpine, e.g., bethanechol are used at some centres.,,,
Bio-availability 96% PO.
Onset of action 20 min (drug-induced dry mouth); up to 3 months (after radiation).
Time to peak plasma concentration 1h.
Plasma halflife 1h.
Duration of action 3-5h.
Pilocarpine may antagonize the effects of antimuscarinic drugs, e.g., inhaled ipratropium bromide. Concurrent use with b-adrenergic antagonists (b-blockers) may cause cardiac conduction disturbances.
Cognitive or psychiatric disorder, epilepsy, Parkinsonism More Details, narrow-angle glaucoma. Miosis may affect vision and driving ability. Cardiovascular disease (changes in haemodynamics or heart rhythm), hyperthyroidism, asthma and COPD (increased bronchial smooth muscle tone, airway resistance and bronchial secretions). Peptic ulcer (increased acid secretion), gallstones or biliary tract disease (increased biliary smooth muscle contraction). Moderate-severe liver impairment (reduce dose). Renal impairment (insufficient human data on metabolism and excretion), kidney stones (potential for renal colic). Increased sweating may exacerbate dehydration in patients unable to drink sufficient fluids.
For full list, see manufacturer's summary of product characteristics.
Very common: (>10%): headache, flu-like syndrome, urinary frequency, sweating.
Common: (<10%, >1%): dizziness, asthenia, chills, blurred vision, eye pain, conjunctivitis, flushing, palpitations, hypertension (following initial hypotension), rhinitis, abdominal pain, dyspepsia, nausea, vomiting, diarrhoea or constipation, rash, pruritus.
In drug-induced dry mouth the effective dose is generally 5 mg ter die sumendus (three times a day) (t.d.s.) or less, whereas after radiation the effective dose is generally 5-10 mg t.d.s.:
It is cheaper to give pilocarpine eyedrops PO than to prescribe tablets, e.g., pilocarpine 4% 2-3 drops t.d.s. = 4-6 mg. Maximum cost/month about Rs. 300, whereas tablets would cost Rs. 600.
If bethanechol is used instead for drug-induced dry mouth:
Undesirable effects are similar to pilocarpine but generally less severe, either because the equivalent dose is less or the muscarinic receptor binding pattern of bethanechol is different.
Pilomax® (Sun Pharma)
Tablets 5 mg, 28 days @ 5 mg t.d.s. = Rs. 600.
Eyedrops 4% (40 mg/1 ml), 5 ml lasts 11-16 days @ 2-3 drops t.d.s = Rs. 105.