**8. Drug interactions**

302 Psoriasis

in a large-scale trial (Krupp & Monka, 1990), whereas no increase in the incidence of lymphomas was noted in another large-scale trial (Paul et al., 2003). Significantly, psoriasis itself leads to chronic immunological overactivation, and to greater risks of lymphoma and

In 1252 patients with severe psoriasis, low-dosage cyclosporin (2.7–3.1 mg/kg/day) was associated with a 6-fold increase in cutaneous squamous cell carcinomas after up to 5 years' follow-up. The greatest risks of these nonmelanoma skin cancers were in patients treated with cyclosporin for >2 years, in patients previously exposed to PUVA, and in patients exposed to other immunosuppressants or methotrexate (Paul et al., 2003). In another large-scale study, 6/842 psoriatic patients (0.7%) developed premalignant or malignant skin lesions during cyclosporin therapy, but nearly all of these patients had received previous treatment with PUVA, ultraviolet B, or methotrexate (Krupp & Monka,

The current recommendation is that if phototherapy is considered in psoriatic patients, narrowband ultraviolet B should be the first choice; cyclosporin can then be reserved for future therapy, if necessary (Griffiths et al., 2004; Pathirana et al., 2009). Cyclosporin should not be used together with phototherapy, or immediately before or after PUVA (see section 5); in patients with a high total dose of PUVA, or with a history of squamous cell carcinoma or melanoma, cyclosporin should be avoided (Griffiths et al., 2004; Pathirana et

Numerous case reports exist of solid organ tumours developing during cyclosporin treatment in dermatology patients (Ryan et al., 2010). However, no increase in the incidence of solid organ tumours was noted in a study of 1252 psoriatic patients treated with cyclosporin (Paul et al., 2003), and although another large-scale study reported solid organ tumours in 5/842 patients (0.6%), the lead investigator considered any relationship between these tumours and cyclosporin to be unlikely (Krupp & Monka, 1990). Large case-control studies suggest that cyclosporin plus other immunosuppressive therapies may actually have immunoprotective effects against, and reduce the risks of, some tumour types (e.g. breast

Fatigue and influenza-like symptoms may occur in up to 20% of cyclosporin-treated patients (Table 2), and joint pain and muscle aches are also frequently reported (10–40% of patients)

Hyperbilirubinaemia manifests in up to one-third of cyclosporin recipients (Pathirana et al., 2009), but this effect is usually dose-related, and does not require further investigation if other liver function abnormalities are absent (Ryan et al., 2010). Transaminase elevations may also occur in up to one-third of cyclosporin-treated patients. If plasma bilirubin or

other malignancies than in the general population (Ryan et al., 2010).

**7.9.2 Nonmelanoma skin cancers** 

1990).

al., 2009).

**7.9.3 Solid organ tumours** 

and rectal cancers) (Ryan et al., 2010).

**7.10 Other side effects** 

(Pathirana et al., 2009).

Several drug interactions have been documented for cyclosporin, which is extensively metabolised by the CYP 3A system in the liver and small intestine. Some of the key interactions include the following: (Novartis Pharmaceuticals Corporation 2009; Ryan et al., 2010)

