Fludrocortisone 21-Acetate (JAMP Fludrocortisone)

1. Health Canada Product Monograph — Fludrocortisone 21-Acetate

• Fludrocortisone is used as partial replacement therapy for primary and secondary adrenocortical insufficiency (Addison's disease).
• Fludrocortisone is used to treat salt-losing adrenogenital syndrome.
• Because of its strong sodium-retaining effect, fludrocortisone is not recommended for conditions outside these approved indications.

• There are no adequate, well-controlled studies of systemic corticosteroids, including fludrocortisone, in pregnant women.
• Use during pregnancy requires weighing the possible benefit to the mother against the potential risk to the fetus.
• Infants born to mothers who received substantial corticosteroid doses during pregnancy should be watched closely for signs of low adrenal hormone function.
• Any corticosteroid treatment during pregnancy should be documented in the infant's medical record.

• There are no adequate, well-controlled studies of fludrocortisone in breastfeeding women.
• Other systemic corticosteroids are known to pass into human milk in low amounts.
• Use during breastfeeding requires weighing the possible benefit to the mother against the potential risk to the nursing infant.

• No specific safety or efficacy data are available for patients 65 years of age and older.
• Age-related decline in kidney and liver function, and a higher rate of hypertension or heart disease, warrant closer monitoring in older adults.

• Health Canada has not authorized an indication for pediatric use, as no data were available for review.
• Growth and development should be observed carefully in infants and children who require prolonged corticosteroid therapy.
• Chronic corticosteroid use can interfere with growth in children.

• For Addison's disease, the usual oral dose is one 0.1 mg tablet once daily, though the dose may range from one tablet three times a week to two tablets (0.2 mg) once daily depending on individual needs.
• If treatment-related high blood pressure develops, the dose is reduced to 0.05 mg daily.
• Fludrocortisone is often given together with cortisone or hydrocortisone to complete adrenal hormone replacement.
• For salt-losing adrenogenital syndrome, the usual oral dose is one to two tablets (0.1 to 0.2 mg) once daily.
• The lowest dose that controls the condition should be used, with a gradual dose reduction made whenever possible.
• Grapefruit and grapefruit juice should be avoided during treatment, since they can raise fludrocortisone blood levels.
• Fludrocortisone should not be stopped abruptly; the dose should be tapered gradually over weeks to months.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• With chronic excessive dosing, signs include high blood pressure, fluid retention or swelling, low potassium, notable weight gain, and enlargement of the heart.
• These effects usually subside within several days after stopping the drug; treatment can then resume at a lower dose if still needed.
• Muscle weakness from excessive potassium loss may occur and can be treated with potassium supplements.
• Regular monitoring of blood pressure and electrolytes reduces the risk of complications from excessive dosing.
• For large, acute overdoses, treatment includes gastric lavage or induced vomiting along with routine supportive measures.
• Careful monitoring of electrolytes is essential, with attention to potassium replacement and limiting dietary sodium intake.

• Nausea may occur.
• Trouble sleeping (insomnia) may occur.
• Headache may occur.
• Dizziness or a spinning sensation (vertigo) may occur.
• Weight gain may occur.
• Fainting (syncope) may occur.
• Slow wound healing may occur.
• Darkening of the skin or nails may occur.
• Muscle cramps, spasms, or aches may occur.
• Irregular menstrual periods may occur.
• Abnormal hair growth may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Adrenal suppression can occur, with dizziness, nausea, vomiting, abdominal pain, weakness, fatigue, and headache.
• Severe allergic reactions, including anaphylaxis, can occur.
• Blood clots in the leg or arm can occur, with pain, redness, swelling, and warmth.
• Congestive heart failure can develop or worsen, with shortness of breath, fatigue, leg swelling, and a rapid or irregular heartbeat.
• Cushing's syndrome (excess cortisol effect) can develop, with a rounded face, rapid weight gain, easy bruising, thin skin, stretch marks, and muscle weakness.
• Diabetes or worsening blood sugar control can occur, with frequent urination and thirst.
• Significant fluid retention (edema) can occur.
• Eye problems, including cataracts, glaucoma, and a retinal condition called central serous chorioretinopathy, can occur.
• Bulging of the eyes (exophthalmos) can occur.
• High blood pressure can develop or worsen.
• Serious infections can be masked or worsened, since corticosteroids reduce the body's ability to fight infection.
• Mental health problems, including depression and thoughts of self-harm, can occur.
• Bone problems, including osteoporosis and fractures of the spine or long bones, can occur.
• A rare but serious increase in pressure around the brain (pseudotumour cerebri) has been reported, usually after stopping treatment.
• Life-threatening and fatal cases of pheochromocytoma crisis have been reported when systemic corticosteroids were given to patients with this adrenal tumour.
• Seek urgent medical attention for chest pain, sudden shortness of breath, signs of a severe allergic reaction, or thoughts of self-harm.

• Use with caution in patients with high blood pressure, congestive heart failure, or a tendency to form blood clots.
• Use with caution in patients with diabetes mellitus or Cushing's syndrome.
• Use with caution in patients with peptic ulcer disease, diverticulitis, ulcerative colitis, or recent intestinal surgery.
• Use with caution in patients with osteoporosis or risk factors for it, since corticosteroids increase calcium loss.
• Use with caution in patients with a seizure disorder or myasthenia gravis.
• Use with caution in patients with liver disease, since drug clearance is reduced.
• Use with caution in patients with kidney disease, including acute or chronic nephritis.
• Use with caution in patients with an underactive thyroid, which enhances corticosteroid effect.
• Use with caution in patients with a history of psychiatric illness, since mood and behavioural changes can occur or worsen.
• Use with caution in patients with eye conditions such as herpes simplex of the eye, glaucoma, or cataracts.
• Use with caution during periods of physical stress, such as surgery, trauma, or serious illness, when a temporarily higher dose may be needed.
• Avoid driving or operating machinery if dizziness, vision changes, or fatigue occur.
• This product contains lactose and is not recommended for patients with rare hereditary galactose intolerance or lactase deficiency.

• Contraindicated in patients with known hypersensitivity to fludrocortisone or to any ingredient in the formulation.
• Contraindicated in patients with a systemic fungal infection.
• Contraindicated for use with live or live-attenuated vaccines while the patient is receiving immunosuppressive corticosteroid doses.
• Contraindicated in patients with herpes simplex infection of the eye, except for short-term emergency use in acute sensitivity reactions.
• Contraindicated in patients with vaccinia or varicella (chickenpox) infection, except for short-term emergency use in acute sensitivity reactions.

• Anticholinesterase drugs used for myasthenia gravis may have reduced effect, and severe weakness may result, when combined with fludrocortisone.
• Neuromuscular-blocking (anticholinergic) agents used in anesthesia may have enhanced or reduced effect when combined with fludrocortisone.
• Oral anticoagulants such as warfarin may have their effect increased or decreased by fludrocortisone, requiring close monitoring.
• Fludrocortisone may reduce the effectiveness of antidiabetic medications by raising blood sugar, requiring dose adjustment.
• Fludrocortisone may reduce the effectiveness of antihypertensive medications.
• Cyclosporine and fludrocortisone may each increase the other's activity when used together.
• CYP3A4-inducing drugs, including carbamazepine, phenobarbital, phenytoin, and rifampin, can increase the clearance of fludrocortisone and reduce its effect.
• CYP3A4-inhibiting drugs, including clarithromycin, ketoconazole, itraconazole, isoniazid, and ritonavir, can raise fludrocortisone blood levels and increase side-effect risk; this combination should generally be avoided.
• Digoxin and other digitalis medicines combined with fludrocortisone increase the risk of irregular heart rhythm or digitalis toxicity due to low potassium.
• Estrogens, including in oral contraceptives, can raise fludrocortisone blood levels.
• NSAIDs, including acetylsalicylic acid (aspirin), combined with fludrocortisone increase the risk of stomach ulcers and gastrointestinal bleeding.
• Potassium-depleting drugs, including amphotericin B and diuretics, combined with fludrocortisone increase the risk of low blood potassium.
• Somatropin (growth hormone) effectiveness may be reduced by fludrocortisone.
• Thyroid medications can change the clearance rate of fludrocortisone, requiring dose adjustment.
• Vaccines may be less effective when given during fludrocortisone treatment.

• Fludrocortisone can be taken with or without food.
• Grapefruit and grapefruit juice must be avoided during treatment, since they can raise fludrocortisone blood levels and increase the risk of side effects.

• Fludrocortisone is usually taken once daily at a consistent time each day, with or without food; avoid grapefruit and grapefruit juice around dosing.

• Store between 2°C and 8°C (refrigerated), protected from moisture.
• Keep out of the reach and sight of children.

• Fludrocortisone (JAMP Fludrocortisone) is a synthetic mineralocorticoid used to replace a hormone the adrenal glands are not making enough of.
• Take it exactly as prescribed, at the same time each day, and never stop or change the dose without talking to your doctor.
• Watch for and report signs of high blood pressure, swelling, unusual weight gain, or muscle weakness, which can signal too much medication.
• Tell every healthcare provider that you take fludrocortisone before surgery, vaccination, or starting a new medicine.
• Seek urgent medical attention for chest pain, severe shortness of breath, or signs of a severe allergic reaction.