A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Danocrine Side Effects, and Drug Interactions - Danazol
Danocrine Side Effects, and Drug Interactions - Danazol
SIDE EFFECTS
In general, the side effects associated with DANOCRINE therapy are attributable to the pharmacological activity of the drug; these effects may reflect DANOCRINE'S weak androgenic and anabolic activity and/or the gonadal suppression which results from therapy.
Androgenic/Anabolic Effects
Very Common
• acne (13%)
Common
• Weight gain (4%), seborrhoea (2%), hirsutism (5%), oedema (6%) and hair loss.
• Voice change (3%), which may take the form of hoarseness, sore throat or of instability or deepening of the pitch. (see WARNINGS)
Rare
• Hypertrophy of the clitoris, fluid retention.
Endocrine Effects
Common
• Menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhoea. Although cyclical bleeding and ovulation usually return within 60 - 90 days after discontinuation of DANOCRINE, persistent amenorrhoea has occasionally been reported.
• Flushing (6%), vaginal dryness and irritation (4%) and sweating (3%) may reflect lowering of oestrogen.
Uncommon
• Changes in breast size.
Very rare
• Abnormalities in semen volume, viscosity, sperm count and motility may occur in males receiving long-term therapy. Testicular atrophy may occur rarely.
Hepatic Effects
Uncommon
• Hepatic dysfunction, as evidenced by elevated serum enzymes and/or jaundice have been reported in patients receiving a daily dosage of DANOCRINE of 400mg or more.
Rare
• Cholestatic jaundice
• Hepatic adenoma
Very rare
• Peliosis hepatis
• Malignant hepatic tumour
Biochemical Abnormalities
• Alterations in values for laboratory tests may occur during danazol therapy including: CPK, glucose tolerance, glucagon, sex hormone binding globulin, other plasma proteins, raised SGOT, decreased PBI, blunted cyclical surges of LH, and induction of aminolevulinic acid (ALA) synthetase.
• Other events include reduction in thyroid binding globulin and T4, with increased uptake of T3 but without disturbance of thyroid stimulating hormone or of free thyroxine index.
• Total cholesterol and LDL cholesterol may increase and HDL cholesterol may decrease. A decrease in apolipoproteins AI and AII has been reported. (See WARNINGS). The following reactions have also been reported:
Allergic
• Uncommonly urticaria and pruritis and rarely nasal congestion;
Skin
Common
• Rashes (3%) (maculopapular, vesicular, papular, purpuric, petechial), sometimes associated with facial oedema, fever or sun sensitivity.
Very rare
• Skin pigmentation
• Stevens-Johnson syndrome, inflammatory erythematous nodules and erythema multiforme.
Gastrointestinal
Common
• Nausea (2%), vomiting, constipation, indigestion and gastroenteritis.
Rare
• pancreatitis.
Genitourinary
Very rare
• Haematuria
Musculoskeletal
Common
• Muscle cramps, muscle tremors, spasms or pains, fasiculation, arthralgia, joint lock-up, joint swelling and pain in back, neck or extremities.
Very rare
• carpal tunnel syndrome which may be secondary to fluid retention.
CNS
Common
• headache, emotional lability, irritability, nervousness, anxiety, changes in appetite and depression.
Rare
• weakness, faintness, dizziness, vertigo, fatigue, tremor and benign intracranial hypertension.
Very rare
• provocation of migraine.
• aggravation of epilepsy.
Reported but incidence unknown
• Paraesthesias, sleep disorders, chills, cataracts and rarely Guillian-Barre Syndrome.
Haematologic
Rare
• Increased red cell and platelet count.
• polycythemia, leucopenia and thrombocytopenia.
Very rare
• Reversible erythrocytosis and eosinophilia.
• Splenic peliosis*
Reported but incidence unknown
• leucocytosis
Cardiovascular
Rare
• elevation in blood pressure and exacerbation of existing hypertension, palpitation and tachycardia.*
• Thrombotic events have also been observed, including sagittal sinus and cerebrovascular thrombosis as well as arterial thrombosis.
• Cases of myocardial infarction have been reported.
Ophthalmic
Rare
• Visual disturbances such as blurring of vision and difficulty in focusing, difficulty in wearing contact lenses and refraction disorders requiring correction.*
Other
Common
• Increased insulin requirements in diabetic patients, changes in libido and pelvic pain.
Very rare
• Epigastric pain, interstitial pneumonitis
• Pleuritic pain
Reported but incidence unknown
• bleeding gums, fever, and Bartholin's cyst and rarely nipple discharge
Note |
very common |
> 1/10 (> 10%) |
common |
> 1/100 and < 1/10 (>1% and <10%) |
uncommon |
> 1/1000 and < 1/100 (>0.1% and <1.0%) |
rare |
> 1/10,000 and < 1/1000 (> 0.01% and < 0.1%) |
very rare |
< 1/10,000 (< 0.01%) |
DRUG INTERACTIONS
Warfarin
Prolongation of prothrombin time occurs in patients stabilised on warfarin.
Anticonvulsant Therapy
Therapy with danazol may reduce the plasma clearance of carbamazepine, increasing its elimination half-life and plasma concentration and, may affect responsiveness to this agent and to phenytoin.
Cyclosporin and tacrolimus
Danazol can increase the plasma levels of cyclosporin and tacrolimus.
Oral Contraceptives
Although no specific interaction has been recorded, it is recommended that oral contraceptives should not be used concurrently with danazol.
Antidiabetic Therapy
Danazol can cause insulin resistance.
Concomitant Steroids
It is likely that interactions between danazol and gonadal steroid therapy would occur.
Antihypertensives
Danazol can diminish the effectiveness of antihypertensive agents.*
Laboratory Tests
Danazol treatment may interfere with laboratory determinations of testosterone, androstenedione, dehydroepiandrosterone or plasma proteins.*
Instructions to be Given to Female Patients
Advise patients that ovulation and menses may cease. Patients should be advised that use of DANOCRINE during pregnancy may damage the foetus and that if pregnancy is suspected DANOCRINE should be stopped and a physician consulted. A non-hormonal method of contraception should be recommended. Therapy should begin during menstruation.
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