Usage
Penicillamine is primarily prescribed for:
- Wilson’s Disease: A genetic disorder causing copper accumulation in the body.
- Cystinuria: A hereditary disorder characterized by excessive cystine in the urine, leading to kidney stones.
- Rheumatoid Arthritis: An autoimmune disease causing joint inflammation.
- Heavy Metal Poisoning (e.g., lead, arsenic): Penicillamine acts as a chelating agent, binding to heavy metals and facilitating their removal.
Pharmacological Classification: Chelating agent, disease-modifying antirheumatic drug (DMARD).
Mechanism of Action: Penicillamine works primarily by chelating copper, promoting its excretion in urine. It also reduces cystine levels in urine, preventing stone formation. In rheumatoid arthritis, its mechanism isn’t fully understood but might involve immunomodulatory effects.
Alternate Names
- D-Penicillamine
- (2S)-2-amino-3-methyl-3-sulfanylbutanoic acid
Brand Names: Cuprimine, Depen, D-Penamine
How It Works
Pharmacodynamics:
- Wilson’s Disease: Binds and removes excess copper.
- Cystinuria: Reduces cystine levels by forming a more soluble disulfide complex with cysteine.
- Rheumatoid Arthritis: May affect collagen synthesis, decrease T-cell activity, and scavenge free radicals, reducing inflammation.
Pharmacokinetics:
- Absorption: Administered orally; absorption is variable and reduced by food.
- Metabolism: Some hepatic metabolism occurs.
- Elimination: Primarily renal excretion; dosage adjustments are necessary in renal impairment.
Mode of Action: Penicillamine’s primary mode of action is through its copper and cystine chelating properties. It forms stable complexes with these substances, which are then readily excreted by the kidneys.
Receptor Binding/Enzyme Inhibition: Not a primary mechanism of action for this drug.
Elimination Pathways: Predominantly renal excretion as penicillamine-metal complexes or penicillamine-cysteine disulfide.
Dosage
Standard Dosage
Adults:
- Wilson’s Disease: 750-1500 mg/day in divided doses, taken on an empty stomach.
- Cystinuria: 1-4 g/day in divided doses, adjusted to maintain urinary cystine below 200 mg/L.
- Rheumatoid Arthritis: Initial: 125-250 mg/day, gradually increased to 500-750 mg/day as tolerated. Maximum: 1500 mg/day.
Children:
- Wilson’s Disease: 20 mg/kg/day divided BID or TID, taken 1 hour before meals.
- Cystinuria: 20-30 mg/kg/day divided BID or TID, taken 1 hour before meals.
- Rheumatoid Arthritis: 15-20 mg/kg/day, initial dose lower, gradually increased.
Special Cases:
- Elderly Patients: Start at a lower dose and titrate cautiously, monitoring for adverse effects. Dose reduction may be required due to age-related decline in renal function.
- Patients with Renal Impairment: Dosage adjustment is essential, avoiding use if creatinine clearance is below 50 mL/min.
- Patients with Hepatic Dysfunction: Caution is advised, but specific dosage adjustments are not well defined. Monitor liver function tests.
- Patients with Comorbid Conditions: Consider individual patient characteristics and potential drug interactions.
Clinical Use Cases
Penicillamine does not have a clinical indication for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Dosage must be adjusted based on the indication, patient response, tolerance, renal function, and the presence of other medical conditions.
Side Effects
Common Side Effects
- Anorexia
- Diarrhea
- Dysgeusia (altered taste)
- Nausea and vomiting
- Skin rash
- Proteinuria
Rare but Serious Side Effects
- Aplastic anemia
- Agranulocytosis
- Thrombocytopenia
- Goodpasture’s syndrome
- Pulmonary complications (e.g., pneumonitis, fibrosis)
- Hepatotoxicity
- Myasthenia gravis-like syndrome
- Nephrotic syndrome
- Optic neuritis
Long-Term Effects
Chronic complications can include kidney damage, bone marrow suppression, and skin changes (wrinkling, elastosis perforans serpiginosa).
Adverse Drug Reactions (ADR)
Serious ADRs include aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture’s syndrome, and severe allergic reactions. These require prompt discontinuation of the drug and supportive management.
Contraindications
- History of penicillamine-induced aplastic anemia or agranulocytosis.
- Penicillin allergy.
- Pregnancy (except for Wilson’s disease or specific cases of cystinuria when the benefits outweigh the risks).
- Breastfeeding.
- Renal insufficiency and rheumatoid arthritis (combined).
- Concurrent use with gold therapy, antimalarial drugs, or immunosuppressants.
Drug Interactions
- Digoxin: Penicillamine may decrease digoxin levels.
- Iron supplements: Reduce penicillamine absorption. Administer separately.
- Antacids: Reduce penicillamine absorption. Administer separately.
- Gold salts, antimalarials, immunosuppressants: Increased risk of serious hematologic and renal adverse reactions. Avoid concurrent use.
- Drugs that suppress bone marrow function: Increased risk of myelosuppression.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated except in specific cases). Penicillamine is teratogenic and can cause connective tissue disorders in the fetus.
- Breastfeeding: Contraindicated. Penicillamine is excreted in breast milk and can affect copper and zinc levels in infants.
Drug Profile Summary
- Mechanism of Action: Chelating agent, forming complexes with copper, cystine, and other heavy metals, facilitating their excretion. May have immunomodulatory effects in rheumatoid arthritis.
- Side Effects: Nausea, vomiting, diarrhea, dysgeusia, skin rash, proteinuria; rarely, aplastic anemia, agranulocytosis, Goodpasture’s syndrome.
- Contraindications: Penicillin allergy, history of penicillamine-related blood disorders, pregnancy (generally), breastfeeding, concurrent use with certain medications.
- Drug Interactions: Digoxin, iron, antacids, gold salts, antimalarials, immunosuppressants.
- Pregnancy & Breastfeeding: Contraindicated except in specific cases.
- Dosage: Varies depending on indication and patient factors. See detailed dosage guidelines above.
- Monitoring Parameters: Complete blood count, urinalysis, renal function tests, liver function tests, urinary copper levels (for Wilson’s disease), urinary cystine levels (for cystinuria).
Popular Combinations
Penicillamine is typically used as monotherapy. In Wilson’s disease, it might be combined with a low-copper diet. Pyridoxine (vitamin B6) supplementation may be given to prevent pyridoxine deficiency induced by penicillamine.
Precautions
- General Precautions: Monitor blood counts, renal function, and liver function regularly.
- Pregnant Women: Contraindicated except for specific cases. Discuss risks and benefits with the patient.
- Breastfeeding Mothers: Contraindicated. Advise against breastfeeding.
- Children & Elderly: Adjust dosage as needed. Closely monitor for side effects.
- Lifestyle Considerations: Alcohol may exacerbate side effects. Advise patients about potential driving impairment if side effects like dizziness occur.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Penicillamine?
A: Dosage varies based on the indication and patient factors. See detailed dosage guidelines above.
Q2: What are the common side effects of penicillamine?
A: Common side effects include altered taste, nausea, vomiting, diarrhea, loss of appetite, skin rash, and proteinuria.
A: Serious side effects include bone marrow suppression (aplastic anemia, agranulocytosis, thrombocytopenia), autoimmune reactions (Goodpasture’s syndrome, myasthenia gravis-like syndrome), and severe allergic reactions.
Q4: Can penicillamine be used during pregnancy?
A: Generally contraindicated due to its teratogenic effects. It can be used in Wilson’s disease when the potential benefits for the mother outweigh the risks to the fetus. Dosage reduction is crucial.
Q5: Is it safe to breastfeed while taking penicillamine?
A: No. Penicillamine is excreted in breast milk and can affect the infant. Breastfeeding is contraindicated.
Q6: How does penicillamine interact with other medications?
A: It can interact with various medications, including digoxin, iron supplements, antacids, gold salts, antimalarials, and immunosuppressants. Consult the drug interaction section for details.
Q7: How should penicillamine be administered?
A: Administer orally on an empty stomach, at least 1 hour before or 2-3 hours after meals. Avoid administering with other medications, food, or milk.
Q8: What monitoring parameters are important for patients on penicillamine?
A: Regularly monitor complete blood counts, renal function tests, liver function tests, urinalysis. In Wilson’s disease, monitor urinary copper levels, and in cystinuria, monitor urinary cystine levels.
Q9: What are the contraindications to using penicillamine?
A: Contraindications include penicillin allergy, history of penicillamine-related aplastic anemia or agranulocytosis, pregnancy (generally), breastfeeding, and concurrent use with certain medications like gold salts and antimalarials.
