Posology : מינונים

4.2 Posology and method of administration                                       or therapeutic use of an appropriate antihistamine and/or                    Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) or not known The therapy should be prescribed by a physician experienced in              paracetamol should be considered.                                            (cannot be estimated from the available data). Adverse reactions the management of HIV infection.                                                                                                                         identified from post-marketing experience are included in italics. Cidofovir administration is contraindicated in patients unable to
Before each administration of cidofovir, serum creatinine and               receive probenecid because of a clinically significant                       Adverse reactions possibly or probably related to cidofovir urine protein levels should be investigated. It must be                     hypersensitivity to the active substance or medicinal product or             based on clinical trial experience and post-marketing administered with oral probenecid and intravenous saline as                 to other sulfa containing medicines. Use of cidofovir without                surveillance
described below (see section 4.4 for appropriate                            concomitant probenecid has not been clinically investigated. A                System Organ Class            Adverse reactions
recommendations, and under section 6.6 for information on                   probenecid desensitisation program is not recommended for use.
obtaining probenecid).                                                                                                                                    Blood and lymphatic system disorders
In addition to probenecid, patients must receive a total of one
Posology                                                                    litre of 0.9% (normal) saline solution intravenously immediately              Very common                   Neutropenia
Adults:                                                                     prior to each infusion of cidofovir. Patients who can tolerate the            Nervous system disorders
Induction treatment. The recommended dose of cidofovir is                   additional fluid load may receive up to a total of 2 litres of 0.9%
Very common                   Headache
5 mg/kg body weight (given as an intravenous infusion at a                  saline intravenously with each dose of cidofovir. The first litre of
constant rate over 1 hour) administered once weekly for two                 saline solution should be infused over a 1 hour period immediately            Eye disorders
consecutive weeks.                                                          before the cidofovir infusion, and the second litre, if given,                Common                        Iritis, uveitis, hypotony of the eye infused over a 1-3 hour period beginning simultaneously with                                                (see section 4.4)
Maintenance treatment. Beginning two weeks after the
the cidofovir infusion or starting immediately after the infusion
completion of induction treatment, the recommended                                                                                                        Ear and labyrinth disorders
of cidofovir.
maintenance dose of cidofovir is 5 mg/kg body weight
Cidofovir therapy should be discontinued and intravenous                      Not known                     Hearing impaired
(given as an intravenous infusion at a constant rate over 1 hour)
administered once every two weeks. Suspension of maintenance                hydration is advised if serum creatinine increases by ≥ 44 μmol/l             Respiratory, thoracic and mediastinal disorders
treatment with cidofovir should be considered in accordance with            (≥ 0.5 mg/dl), or if persistent proteinuria ≥ 2+ develops. In patients
Common                        Dyspnea
local recommendations for the management of HIV infected                    exhibiting ≥ 2+ proteinuria, intravenous hydration should be
patients.                                                                   performed and the test repeated. If following hydration, a                    Gastrointestinal disorders
≥ 2+ proteinuria is still observed, cidofovir therapy should be               Very common                   Nausea, vomiting
discontinued. Continued administration of cidofovir to patients
Elderly population:                                                         with persistent ≥ 2+ proteinuria following intravenous hydration              Common                        Diarrhoea
The safety and efficacy of cidofovir have not been established for          may result in further evidence of proximal tubular injury,                    Not known                     Pancreatitis
the treatment of CMV disease in patients over 60 years of age.              including glycosuria, decreases in serum phosphate, uric acid
Since elderly individuals frequently have reduced glomerular                                                                                              Skin and subcutaneous tissue disorders
and bicarbonate, and elevations in serum creatinine.
function, particular attention should be paid to assessing renal                                                                                          Very common                   Alopecia, rash
Interruption, and possibly discontinuation, is required for
function before and during administration of the medicinal                  changes in renal function. For those patients who fully recover               Renal and urinary disorders
product.                                                                    from cidofovir associated renal toxicity, the benefits-risk balance           Very common                   Proteinuria, blood creatinine of reintroducing cidofovir has not yet been evaluated.                                                      increased (see section 4.4)
Renal insufficiency:
Common                        Renal failure
Renal insufficiency [creatinine clearance ≤ 55 ml/min or ≥ 2+               Patient monitoring
proteinuria (≥100 mg/dl)] is a contraindication for the use of                                                                                            Uncommon                      Fanconi syndrome acquired Proteinuria appears to be an early and sensitive indicator of
cidofovir (see sections 4.3 and 4.4).                                       cidofovir-induced nephrotoxicity. Patients receiving cidofovir                General disorders and administration site conditions must have their serum creatinine and urine protein levels                     Very common                   Asthenia, fever
Hepatic insufficiency:                                                      determined on specimens obtained within 24 hours prior to the
administration of each dose of cidofovir. Differential white blood            Common                        Chills
The safety and efficacy of cidofovir have not been established in
patients with hepatic disease and therefore it should be used with          cell counts should also be performed prior to each dose of
caution in this patient population.                                         cidofovir (see section 4.8).                                                 Reports of renal failure (plus events possibly caused by renal failure, e.g. blood creatinine increased, proteinuria, glycosuria)
Ocular events                                                                received during post-marketing surveillance include some which
Paediatric population:
were fatal. Cases of acute renal failure have been reported after
The safety and efficacy of cidofovir in children below 18 years of          Patients receiving cidofovir should be advised to have regular
only one or two doses of cidofovir.
age have not been established. No data are available. It is not             follow-up ophthalmologic examinations for possible occurrence
of uveitis/iritis and ocular hypotony. In case of uveitis/iritis             The finding of any glycosuria, proteinuria/aminoaciduria,
recommended for use in children below 18 years of age.
cidofovir should be discontinued if there is no response to                  hypouricemia, hypophosphatemia and/or hypokalemia,
treatment with a topical corticosteroid or the condition worsens,            should prompt for the consideration of cidofovir-related
Method of administration                                                                                                                                 Fanconi syndrome.
or if iritis/uveitis reoccurs after successful treatment.
Precautions to be taken before handling or administering the                                                                                             The following table lists adverse reactions possibly or probably medicinal product:                                                                                                                                       related to probenecid based on clinical trial experience: Other
Adequate precautions including the use of appropriate safety
equipment are recommended for the preparation, administration               Cidofovir should be considered a potential carcinogen in humans               System Organ Class            Adverse reactions
and disposal of cidofovir. The preparation of cidofovir reconstituted       (see section 5.3).                                                            Nervous system disorders
solution should be done in a laminar flow biological safety                 Caution should be applied when considering cidofovir treatment
Common                        Headache
cabinet. Personnel preparing the reconstituted solution should              of patients with diabetes mellitus due to the potential increased
wear surgical gloves, safety glasses and a closed front surgical-           risk of developing ocular hypotony.                                           Gastrointestinal disorders
type gown with knit cuffs. If cidofovir contacts the skin, wash             Male patients should be advised that cidofovir caused reduced                 Very common                   Nausea, vomiting
membranes and flush thoroughly with water (see section 6.6).                testes weight and hypospermia in animals. Although not                        Skin and subcutaneous tissue disorders
CIDOFOVIR RAZ 75mg/ml is for intravenous infusion only. The                 observed in clinical studies of cidofovir, such changes may
recommended dose, frequency, or infusion rate must not be                   occur in humans and cause infertility. Men should be advised to               Very common                   Rash
exceeded. It must be diluted in 100 millilitres 0.9% (normal) saline        practice barrier contraceptive methods during and for 3 months                General disorders and administration site conditions prior to administration. The entire volume should be infused                after treatment with cidofovir (see sections 4.6 and 5.3).
Very common                   Fever
intravenously into the patient at a constant rate over a period of
1 hour by use of a standard infusion pump. To minimise potential                                                                                          Common                        Asthenia, chills
Appropriate precautions should continue to be employed to
nephrotoxicity, oral probenecid and intravenous saline                      prevent transmission of HIV.
prehydration must be administered with each                                                                                                              In addition probenecid may also cause other adverse reactions CIDOFOVIR RAZ 75 mg/ml (see section 4.4).                                                                                                                including anorexia, gingival pain, flushing, alopecia, dizziness, Excipients
anaemia, and pollakiuria. Hypersensitivity reactions, with
This medicinal product contains approximately 2.5 mmol                       dermatitis, pruritus, urticaria and, rarely, anaphylaxis, and