Fung, JJ

Jain, AB

Parks, P

Shapiro, R

Starzl, TE

Todo, S

PubMed

Jain, A

Name not available

The side effects of FK 506 in humans

D-Scholarship@Pitt

The Side Effects of FK 506 in Humans /07t) R. Shapiro, J.J. Fung, A.B. Jain, P. Parks, S. Todo, and T.E. Starzl AN important question about FK 506 concerns the nature and extent of any side effects associated with its clinical use. Because the issues of renal and metabolic effects are addressed in other papers, the discussion here will focus on patient symptoms associated with intrave-nous and oral FK 506. Since the experience in primarily treated and rescue patients has been so different, the two groups will be described separately. Most of the side effects are associated with intravenous FK 506; taken orally, the drug is associated with few or no symptoms. PRIMARY FK 506 GROUP Of 31 patients undergoing liver transplantation and treated primarily with FK 506 and low-dose steroids, 42% had no reported or observable side effects associated with intra-venous FK 506, and 87% had no symptoms with oral FK 506 (Table I). The most common side effects noted with intravenous FK 506 were mild nausea and headache; each symptom was seen in 32% of the patients. No patient in the primary group required antiemetic or analgesic therapy. A curious sensation of warmth or hyperesthesia, either sys-temic or localized to the extremities, was noted in 23% of patients receiving intravenous FK 506; this effect was not seen with the oral form of the drug. A possible variation of this symptom was circumoral numbness and tingling asso-ciated with each intravenous dose; this was seen in three patients (10%), and disappeared with conversion to oral FK 506. Unusual side effects included tremors, seen in two Table 1. Side Effects In 31 Patients Treated Primarily With FK506 Side Etlects IV(%) PO(%) Headache 32 6 Nausea 32 0 Sensetion of warmth! hyperesthesia 23 0 Circumoral numb-ness, tingling 10 0 Tremors 6 3 Abdominal pain 3 0 Chest pain 3 0 Flushing 3 0 Itching 3 0 Vomiting 3 0 Insomnia 0 10 Sensation of racing 0 6 Hair loss 0 3 Increasad hair growth 0 3 No symptoms 42 87 patients (6%). Itching, flushing, abdominal pain (without clinical sequelae), vomiting. and chest pain (without elec-trocardiographic changes) were each seen in one patient (3%). Generally, most symptoms began about 30 minutes after the beginning of the intravenous dose and lasted for about 1 hour after the completion of the infusion. Only four patients (13%) had any symptoms associated with oral FK 506. Three patients (10%) complained of insomnia, and this problem disappeared when the dose of FK 506 was reduced. Two patients (6%) noted headache, and two patients had a sensation of "racing." Tremors, hair loss, and excessive hair growth were each seen in one patient (3%). In general. the few symptoms associated with oral FK 506 were of minor significance and tended to disappear following dose reduction. RESCUE FK 506 GROUP Thirty-one patients receiving FK 506 as rescue therapy after liver or kidney transplantation were studied. The rescue protocol called for both intravenous CyA and FK 506 to be administered on successive days. The greatest number and· the only significant side effects were seen during this conversion to intravenous FK 506 (Table 2), when patients had therapeutic blood levels ofCyA. Every patient in the rescue group had one or more symptoms associated with intravenous FK 506. Seventy-seven per-cent had headaches of varying severity; during the period of the trial in which combined intravenous Cy A and FK 506 were given, most patients needed no analgesic ther-apy. while the first few patients actually required narcot-ics. Nausea was also a common side effect and was seen in 65% of patients; again. antiemetics were only required in the first few patients who had received high doses of intravenous CyA and FK 506. Vomiting or diarrhea were less common and were seen in 35% of patients. The sensation of warmth or hyperesthesia was seen in 61% of the patients receiving intravenous FK 506 as rescue therapy. Less common side effects were flushing or itch-ing, seen in 16% of the patients, and tremors, noted in 13% From the Department of Surgery, University Health Center of Pittsburgh, University of Pittsburgh; and the Veterans Administra-tion Medical Center, Pittsburgh, PA. Supported by research grants from the Veterans Administration and Project Grant No. OK 29961 from the National Institutes of Health, Bethesda, MD. Address reprint requests to T.E. Starzl, MD, PhD, Department of Surgery, 3601 Fifth Avenue, Falk Clinic 5C, Pittsburgh, PA 15213. © 1990 by Appleton & Lange 0041-1345190/$3.00/ + 0 Transplantation Proceedings, Vol 22, No 1, Suppl 1 (February), 1990: pp 35-36 35 36 Table 2. Side Eftecta In 31 Patients Trellted with FK 506 aa Rescue Therepy Side Effects IV(%) PO(%) Headache n 6 Nausea 65 10 Sensation of warmth! hyperesthesia 61 0 Diarrhea 35 6 Vomiting 35 10 Flushing 16 0 Itching 16 0 Tremors 13 0 Anxiety 10 0 Chest pain 10 0 Rash 10 0 Anorexia 6 6 Shortness of breath 6 0 Abdominal cramping 3 0 Abdominal pain 3 0 Blurred vision 3 0 Fatigue 3 0 Night sweats 3 0 Photophobia 3 0 Hair loss 0 6 No symptoms 0 74 of patients. There were a number of side effects noted less frequently. These included rash (10%), chest pain (10%; without electrocardiographic changes or creatine phos-phokinase-MB enzyme elevations), acute anxiety (10%), SHAPIRO, FUNG, JAIN ET AL anorexia (6%), shortness of breath (6%; without clinical sequelae), abdominal pain or cramping (6%), night sweats (3%), fatigue (3%), photophobia (3%), and blurred vision (3%). After conversion to oral FK 506 and elimination of Cy A, the range and frequency of side effects declined markedly. Nausea and vomiting were seen episodically in 10% of patients; headaches, diarrhea, anorexia, and a question of hair loss were each seen in 6%. These side effects were sporadic and disappeared within a few weeks. Seventy-four percent of the rescue patients had no side effects after conversion to oral FK 506. DISCUSSION FK 506 has relatively few side effects in primarily treated patients. The symptoms thus far have been minor and have been seen for the most part only after intravenous admin-istration of the drug. The most common side effects were headache, nausea, vomiting, and flushing. A significantly higher incidence of these side effects was noted in the rescue group receiving intravenous FK 506, and this, plus the other adverse interactions described elsewhere in this symposium, makes us recommend for fresh cases that FK 506 and Cy A not be used together. 

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The side effects of FK 506 in humans

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