Tacrolimus headache

Ahn AH, Berman BD, Dillon WP. Spontaneous intracranial hypotension-hypovolemia associated with tacrolimus. Headache 2010 50(8) 1386-9. 

The principal adverse reactions of tacrolimus are tremor, headache, diarrhea, hypertension, nausea, and renal dysfunction. Other reactions may include insomnia, paresthesia, constipation, anorexia, vomiting, anemia, leukocytosis, thrombocytopenia, hyperglycemia, dyspnea, pruritus, rash, abdominal pain, fever, asthenia, back pain,... 

Toxicities of the PSIs can include profound myelosuppression (especially thrombocytopenia), hepatotoxicity, diarrhea, hypertriglyceridemia, pneumonitis, and headache. Because nephrotoxicity is of major concern when administering calcineurin inhibitors, there is interest in increased early use of PSIs since renal toxicity is less common with these agents. However, increased use in stem cell transplantation regimens as graft-versus-host disease prophylaxis, particularly when combined with tacrolimus, has revealed an increased incidence of hemolytic-uremic syndrome. 

Adverse Effects. Common side effects of tacrolimus include gastrointestinal disturbances (cramps, nausea, diarrhea, constipation), weakness, fever, and skin rashes and itching. More serious problems include renal and central nervous system (CNS) toxicity (headache, anxiety, nervousness, seizures).41 Tacrolimus is also associated with problems with glucose metabolism (hyperglycemia, glucose intolerance), and can cause diabetes mellitus in certain individuals.73... 

Tacrolimus, an immunosuppressant that inhibits T-cell activation, is a useful alternative in severe recalcitrant psoriasis. Although it is not FDA approved for this indication, patients have received oral doses of 0.05 mg/kg daily, with increases up to 0.15 mg/kg daily, depending on results. Adverse effects include diarrhea, nausea, paresthesias, hypertension, tremor, and insomnia. Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can he administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral fohc acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

When neurological symptoms occur in patients taking tacrolimus they are very similar to those seen in patients taking ciclosporin, with more frequent insomnia, tremor, and headaches, but a similar rate of severe neurological adverse effects, such as acute psychosis, peripheral neuropathy, seizures, encephalopathy, coma, and paralysis. Persistent speech disorders (dysarthria, apraxia, expressive aphasia, akinetic mutism), and visual blurring can also occur (SEDA-21, 391) (SEDA-22, 420) (24). 

In 631 adult patients with moderate to severe atopic dermatitis enrolled in a randomized, double-blind, multicenter comparison of tacrolimus (0.03% or 0.1%) with a vehicle applied twice-daily for 12 weeks, the most common adverse events were skin burning, erythema, and pruritus (83). Others were flu-like symptoms and headache. Withdrawal was required in 50 patients because of adverse events, twice as many as in the vehicle group. There was pruritus in 30 patients, skin burning in 19, skin erythema in 12, and skin infections in two. Skin burning and pruritus have consistently been observed with tacrolimus ointment, typically during the first days of treatment, reducing in incidence within the first week they tend to be mild or moderate. 

Nephrotoxicity, neurotoxicity (tremor, headache, motor disturbances, seizures), G1 complaints, hypertension, hyperkalemia, hyperglycemia, and diabetes are all associated with tacrolimus use. As with cyclosporine, nephrotoxicity is limiting. Tacrolimus has a negative effect on pancreatic islet beta cells, and glucose intolerance and diabetes melli-tus are well-recognized complications of tacrolimus-based immunosuppression. As with other immunosuppressive agents, there is an increased risk of secondary tumors and opportunistic infections. Notably, tacrolimus does not adversely affect uric acid or LDL cholesterol. 

Nephrotoxicity, neurotoxicity (tremor, headache, motor disturbances, seizures), GI complaints, hypertension, hyperkalemia, hyperglycemia, and diabetes are all associated with tacrolimus use. 

A kidney transplant patient taking prednisone, azathioprine and tacrolimus 5 mg daily for 2 years experienced headache, confusion and grey areas in her vision within one week of starting nefazodone 50 mg twice daily in place of sertraline, for depression. Her serum creatinine had risen from 132 to 195 micromol/Land her trough tacrolimus level was greater than 30 nanograms/niL. Nefazodone was replaced by sertraline, and tacrolimus was withheld for 4 days. Signs oftacrolimus-induced neurotoxicity disappeared within 36 hours and serum creatinine and tacrolimus levels returned to pretreatment levels within 2 weeks. ... 

Intracranial hypotension/hypovolemia associated with tacrolimus has been described in a 50-year-old woman who took tacrolimus for 2 weeks [141 ]. Tacrolimus was replaced by mycophenolate mofetil, and her headaches resolved completely within 2 months. 

---