DFP- and DFX-related adverse effects and their management
| Adverse events . | Incidence in core trials, % . | Monitoring and management . |
|---|---|---|
| DFP-related | ||
| Gastrointestinal (nausea, vomiting, and abdominal pain) | 33 in first y | Mild: continue drug or reduce dose. If severe, discontinue drug temporarily and restart at lower dose. Try liquid formation. 5% of patients discontinue drug permanently. |
| Neutropenia (neutrophils < 1.5 × 109/L) | 8.5 | Monitor blood count weekly for first year, fortnightly in second and subsequent years. Stop drugs for a few weeks. Rechallenge and continue drug if neutrophils at safe level of > 1.5 × 109/L. |
| Agranulocytosis (neutrophils < 0.5 × 109/L) | 1 | Stop drug, treat with intravenous antibiotics if febrile. Give G-CSF if neutropenia prolonged and/or febrile. |
| Rise in transaminases | 7 | Continue to monitor without stopping drug. Enzymes usually fall to normal. If persistently raised > 2 times ULN ( ∼ 1% of patients), discontinue drug. |
| Arthropathy | 3.9-41 | Related to degree of iron overload in some series. Stop drug temporarily and restart at lower dose. ∼ 2% of patients stop drug permanently because of arthropathy. |
| Zinc deficiency | Rare: mainly in diabetes | Give zinc supplements. |
| DFX-related* | ||
| Gastrointestinal | ||
| Diarrhea | 8.8 | Patients should take an antidiarrheal for up to 2 days and keep hydrated. DFX could be taken in the evening rather than the morning. Products, such as Lactaid (if the patient is lactose intolerant) or probiotics (acidophilus or lactobacillus), could be added to the diet. |
| Abdominal pain | 5.0 | Patients should sip water or other clear fluids, and avoid solid food for the first few hours. Avoid narcotic pain medications and nonsteroidal anti-inflammatory drugs. DFX could be taken in the evening rather than the morning. |
| Nausea/vomiting | 14.3 | Patients should drink small, steady amounts of clear liquids, such as electrolyte solutions, and keep hydrated. |
| Skin rash | ||
| Mild to moderate | 4.3 | Likely to resolve spontaneously. DFX should be continued without dose adjustment. |
| Severe | 0.4 | DFX should be interrupted and reintroduced at a lower dose. Patients should take low-dose oral steroids for a short period of time. |
| Renal changes | 36 | Serum creatinine levels should be assessed in duplicate before therapy, then monthly. If patients have additional renal risk factors, serum creatinine levels should be monitored weekly for the first month or after modification of DFX therapy, then monthly. |
| > 33% above pretreatment values at 2 consecutive visits (not attributed to other causes) | 11 | DFX dose should be reduced by 10 mg/kg. |
| Progressive increases beyond the ULN | 0 | DFX should be interrupted, then reinitiated at a lower dose followed by gradual dose escalation if the clinical benefit outweighs the potential risks. |
| Pediatrics, > 33% above pretreatment values and above the age-appropriate ULN at 2 consecutive visits | 11 | DFX dose should be reduced by 10 mg/kg. |
| Changes in liver function (elevation in transaminases) | 2 | Liver function should be monitored monthly. After any severe or persistent elevations in serum transaminase levels, dose modifications should be considered. DFX therapy can be cautiously reintroduced once transaminase levels return to baseline. |
| Auditory and ocular alterations | < 1 | Auditory and ophthalmic function should be tested before initiating therapy and annually thereafter. |
| Adverse events . | Incidence in core trials, % . | Monitoring and management . |
|---|---|---|
| DFP-related | ||
| Gastrointestinal (nausea, vomiting, and abdominal pain) | 33 in first y | Mild: continue drug or reduce dose. If severe, discontinue drug temporarily and restart at lower dose. Try liquid formation. 5% of patients discontinue drug permanently. |
| Neutropenia (neutrophils < 1.5 × 109/L) | 8.5 | Monitor blood count weekly for first year, fortnightly in second and subsequent years. Stop drugs for a few weeks. Rechallenge and continue drug if neutrophils at safe level of > 1.5 × 109/L. |
| Agranulocytosis (neutrophils < 0.5 × 109/L) | 1 | Stop drug, treat with intravenous antibiotics if febrile. Give G-CSF if neutropenia prolonged and/or febrile. |
| Rise in transaminases | 7 | Continue to monitor without stopping drug. Enzymes usually fall to normal. If persistently raised > 2 times ULN ( ∼ 1% of patients), discontinue drug. |
| Arthropathy | 3.9-41 | Related to degree of iron overload in some series. Stop drug temporarily and restart at lower dose. ∼ 2% of patients stop drug permanently because of arthropathy. |
| Zinc deficiency | Rare: mainly in diabetes | Give zinc supplements. |
| DFX-related* | ||
| Gastrointestinal | ||
| Diarrhea | 8.8 | Patients should take an antidiarrheal for up to 2 days and keep hydrated. DFX could be taken in the evening rather than the morning. Products, such as Lactaid (if the patient is lactose intolerant) or probiotics (acidophilus or lactobacillus), could be added to the diet. |
| Abdominal pain | 5.0 | Patients should sip water or other clear fluids, and avoid solid food for the first few hours. Avoid narcotic pain medications and nonsteroidal anti-inflammatory drugs. DFX could be taken in the evening rather than the morning. |
| Nausea/vomiting | 14.3 | Patients should drink small, steady amounts of clear liquids, such as electrolyte solutions, and keep hydrated. |
| Skin rash | ||
| Mild to moderate | 4.3 | Likely to resolve spontaneously. DFX should be continued without dose adjustment. |
| Severe | 0.4 | DFX should be interrupted and reintroduced at a lower dose. Patients should take low-dose oral steroids for a short period of time. |
| Renal changes | 36 | Serum creatinine levels should be assessed in duplicate before therapy, then monthly. If patients have additional renal risk factors, serum creatinine levels should be monitored weekly for the first month or after modification of DFX therapy, then monthly. |
| > 33% above pretreatment values at 2 consecutive visits (not attributed to other causes) | 11 | DFX dose should be reduced by 10 mg/kg. |
| Progressive increases beyond the ULN | 0 | DFX should be interrupted, then reinitiated at a lower dose followed by gradual dose escalation if the clinical benefit outweighs the potential risks. |
| Pediatrics, > 33% above pretreatment values and above the age-appropriate ULN at 2 consecutive visits | 11 | DFX dose should be reduced by 10 mg/kg. |
| Changes in liver function (elevation in transaminases) | 2 | Liver function should be monitored monthly. After any severe or persistent elevations in serum transaminase levels, dose modifications should be considered. DFX therapy can be cautiously reintroduced once transaminase levels return to baseline. |
| Auditory and ocular alterations | < 1 | Auditory and ophthalmic function should be tested before initiating therapy and annually thereafter. |
ULN indicates upper limits of normal.
Data from Vichinsky.81