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Bromocriptine (parlodel ® )

Bromocriptine mesylate is a dopamine receptor agonist, which activates postsynaptic dopamine receptors. The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor (thought to be dopamine); in the corpus striatum the dopaminergic neurons are involved in the control of motor function. Clinically, bromocriptine significantly reduces plasma levels of prolactin in patients with physiologically elevated prolactin as well as in patients with hyperprolactinemia. The inhibition of physiological lactation as well as galactorrhea in pathological hyperprolactinemic states is obtained at dose levels that do not affect secretion of other tropic hormones from the anterior pituitary. Experiments have demonstrated that bromocriptine induces long lasting stereotyped behavior in rodents and turning behavior in rats having unilateral lesions in the substantia nigra. These actions, characteristic of those produced by dopamine, are inhibited by dopamine antagonists and suggest a direct action of bromocriptine on striatal dopamine receptors.

Bromocriptine mesylate is a nonhormonal, nonestrogenic agent that inhibits the secretion of prolactin in humans, with little or no effect on other pituitary hormones, except in patients with acromegaly, where it lowers elevated blood levels of growth hormone in the majority of patients.

In about 75% of cases of amenorrhea and galactorrhea, bromocriptine therapy suppresses the galactorrhea completely, or almost completely, and reinitiates normal ovulatory menstrual cycles.

Menses are usually reinitiated prior to complete suppression of galactorrhea; the time for this on average is 6 to 8 weeks. However, some patients respond within a few days, and others may take up to 8 months.

Galactorrhea may take longer to control depending on the degree of stimulation of the mammary tissue prior to therapy. At least a 75% reduction in secretion is usually observed after 8 to 12 weeks. Some patients may fail to respond even after 12 months of therapy.

In many acromegalic patients, bromocriptine produces a prompt and sustained reduction in circulating levels of serum growth hormone.

Bromocriptine mesylate produces its therapeutic effect in the treatment of Parkinson's disease, a clinical condition characterized by a progressive deficiency in dopamine synthesis in the substantia nigra, by directly stimulating the dopamine receptors in the corpus striatum. In contrast, levodopa exerts its therapeutic effect only after conversion to dopamine by the neurons of the substantia nigra, which are known to be numerically diminished in this patient population

Hyperprolactinemia-Associated Dysfunctions
Bromocriptine mesylate tablets and capsules are indicated for the treatment of dysfunctions associated with hyperprolactinemia including amenorrhea with or without galactorrhea, infertility or hypogonadism. Bromocriptine treatment is indicated in patients with prolactin-secreting adenomas, which may be the basic underlying endocrinopathy contributing to the above clinical presentations. Reduction in tumor size has been demonstrated in both male and female patients with macroadenomas. In cases where adenectomy is elected, a course of bromocriptine therapy may be used to reduce the tumor mass prior to surgery.

Bromocriptine mesylate tablet and capsule therapy is indicated in the treatment of acromegaly. Bromocriptine therapy, alone or as adjunctive therapy with pituitary irradiation or surgery, reduces serum growth hormone by 50% or more in approximately half of patients treated, although not usually to normal levels.

Since the effects of external pituitary radiation may not become maximal for several years, adjunctive therapy with bromocriptine offers potential benefit before the effects of irradiation are manifested.

Parkinson's Disease
Bromocriptine mesylate tablets or capsules are indicated in the treatment of the signs and symptoms of idiopathic or postencephalitic Parkinson's disease. As adjunctive treatment to levodopa (alone or with a peripheral decarboxylase inhibitor), bromocriptine therapy may provide additional therapeutic benefits in those patients who are currently maintained on optimal dosages of levodopa, those who are beginning to deteriorate (develop tolerance) to levodopa therapy, and those who are experiencing "end of dose failure" on levodopa therapy. Bromocriptine therapy may permit a reduction of the maintenance dose of levodopa and, thus may ameliorate the occurrence and/or severity of adverse reactions associated with long-term levodopa therapy such as abnormal involuntary movements (e.g., dyskinesias) and the marked swings in motor function ("on-off" phenomenon). Continued efficacy of bromocriptine therapy during treatment of more than 2 years has not been established.

Data are insufficient to evaluate potential benefit from treating newly diagnosed Parkinson's disease with bromocriptine. Studies have shown, however, significantly more adverse reactions (notably nausea, hallucinations, confusion and hypotension) in bromocriptine treated patients than in levodopa/carbidopa treated patients. Patients unresponsive to levodopa are poor candidates for bromocriptine therapy

DOSING - Adults:
Parkinsonism: 1.25 mg 2 times/day, increased by 2.5 mg/day in 2- to 4-week intervals (usual dose range is 30-90 mg/day in 3 divided doses), though elderly patients can usually be managed on lower doses

Neuroleptic malignant syndrome: 2.5-5 mg 3 times/day

Hyperprolactinemia: 2.5 mg 2-3 times/day

Acromegaly: Initial: 1.25-2.5 mg increasing as necessary every 3-7 days; usual dose: 20-30 mg/day

Prolactin-secreting adenomas: Initial: 1.25-2.5 mg/day; may be increased as tolerated every 2-7 days until optimal response (range: 2.5-15 mg/day)

Supplied: Capsule: 5 mg. Tablet: 2.5 mg

Cabergoline  (dostinex ® )

Long acting dopamine receptor agonist with a high affinity for D2 receptor.

Dosing (Adults): Hyperprolactinemic disorders: Initial dose: 0.25 mg orally twice weekly. The dose may be increased by 0.25 mg twice weekly up to a maximum of 1 mg twice weekly according to the patient's serum prolactin level. Dosage increases should not occur more rapidly than every 4 weeks. Once a normal serum prolactin level is maintained for 6 months, the dose may be discontinued and prolactin levels monitored to determine if cabergoline is still required. The durability of efficacy beyond 24 months of therapy has not been established.

Supplied: 0.5 mg tab.

Calcitonin (calcimar ® )

Calcitonin acts primarily on bone, but direct renal effects and actions on the gastrointestinal tract are also recognized. Calcitonin-salmon appears to have actions essentially identical to calcitonins of mammalian origin, but its potency per mg is greater and it has a longer duration of action. The actions of calcitonin on bone and its role in normal human bone physiology are still incompletely understood.

Miacalcin® (calcitonin-salmon) Injection, Synthetic is indicated for the treatment of symptomatic Paget’s disease of bone, for the treatment of hypercalcemia, and for the treatment of postmenopausal osteoporosis.

Paget’s Disease: At the present time, effectiveness has been demonstrated principally in patients with moderate to severe disease characterized by polyostotic involvement with elevated serum alkaline phosphatase and urinary hydroxyproline excretion.

In these patients, the biochemical abnormalities were substantially improved (more than 30% reduction) in about 2/3 of patients studied, and bone pain was improved in a similar fraction. A small number of documented instances of reversal of neurologic deficits has occurred, including improvement in the basilar compression syndrome, and improvement of spinal cord and spinal nerve lesions. At present, there is too little experience to predict the likelihood of improvement of any given neurologic lesion. Hearing loss, the most common neurologic lesion of Paget’s disease, is improved infrequently (4 of 29 patients studied audiometrically).

Patients with increased cardiac output due to extensive Paget’s disease have had measured decreases in cardiac output while receiving calcitonin. The number of treated patients in this category is still too small to predict how likely such a result will be.

The large majority of patients with localized, especially monostotic disease do not develop symptoms and most patients with mild symptoms can be managed with analgesics. There is no evidence that the prophylactic use of calcitonin is beneficial in asymptomatic patients, although treatment may be considered in exceptional circumstances in which there is extensive involvement of the skull or spinal cord with the possibility of irreversible neurologic damage. In these instances, treatment would be based on the demonstrated effect of calcitonin on Pagetic bone, rather than on clinical studies in the patient population in question.

Hypercalcemia: Miacalcin Injection is indicated for early treatment of hypercalcemic emergencies, along with other appropriate agents, when a rapid decrease in serum calcium is required, until more specific treatment of the underlying disease can be accomplished. It may also be added to existing therapeutic regimens for hypercalcemia such as intravenous fluids and furosemide, oral phosphate or corticosteroids, or other agents.

Postmenopausal Osteoporosis: Miacalcin Injection is indicated for the treatment of postmenopausal osteoporosis in females greater than 5 years postmenopause with low bone mass relative to healthy premenopausal females. Miacalcin Injection should be reserved for patients who refuse or cannot tolerate estrogens or in whom estrogens are contraindicated. Use of Miacalcin Injection is recommended in conjunction with adequate calcium and vitamin D intake to prevent the progressive loss of bone mass. No evidence currently exists to indicate whether or not Miacalcin Injection decreases the risk of vertebral crush fractures or spinal deformity. A recent controlled study, which was discontinued prior to completion because of questions regarding its design and implementation, failed to demonstrate any benefit of salmon calcitonin on fracture rate. No adequate controlled trials have examined the effect of salmon calcitonin injection on vertebral bone mineral density beyond 1 year of treatment. Two placebo-controlled studies with salmon calcitonin have shown an increase in total body calcium at 1 year, followed by a trend to decreasing total body calcium (still above baseline) at 2 years. The minimum effective dose of Miacalcin Injection for prevention of vertebral bone mineral density loss has not been established. It has been suggested that those postmenopausal patients having increased rates of bone turnover may be more likely to respond to anti-resorptive agents such as Miacalcin Injection.

Clinical allergy to synthetic calcitonin-salmon

DOSING - Adults:
Paget's disease: I.M., SubQ: Initial: 100 units/day; maintenance: 50 units/day or 50-100 units every 1-3 days

Hypercalcemia: Initial: I.M., SubQ: 4 units/kg every 12 hours; may increase up to 8 units/kg every 12 hours to a maximum of every 6 hours

Osteogenesis imperfecta: I.M., SubQ: 2 units/kg 3 times/week

Postmenopausal osteoporosis:
I.M., SubQ: 100 units/day
Intranasal: 200 units (1 spray)/day

Injection, solution, calcitonin-salmon: 200 int. units/mL (2 mL)
Solution, nasal spray, calcitonin-salmon: 200 int. units/0.09 mL (3.7 mL) [contains benzalkonium chloride]

Cosyntropin (cortrosyn ®)

CORTROSYN™ (cosyntropin) for Injection exhibits the full corticosteroidogenic activity of natural ACTH. Various studies have shown that the biologic activity of ACTH resides in the N-terminal portion of the molecule and that the 1 – 20 amino acid residue is the minimal sequence retaining full activity. Partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residues. For example, the decrement from 20 to 19 results in a 70% loss of potency.

The pharmacologic profile of CORTROSYN™ is similar to that of purified natural ACTH. It has been established that 0.25 mg of CORTROSYN™ will stimulate the adrenal cortex maximally and to the same extent as 25 units of natural ACTH. This dose of CORTROSYN™ will produce maximal secretion of 17-OH corticosteroids, 17- ketosteroids and / or 17 - ketogenic steroids.

The extra-adrenal effects which natural ACTH and CORTROSYN™ have in common include increased melanotropic activity, increased growth hormone secretion and an adipokinetic effect. These are considered to be without physiological or clinical significance.

Animal, human and synthetic ACTH (1–39) which all contain 39 amino acids exhibit similar immunologic activity. This activity resides in the C-terminal portion of the molecule and the 22–39 amino acid residues exhibit the greatest degree of antigenicity. In contrast, synthetic polypeptides containing 1–19 or fewer amino acids have no detectable immunologic activity. Those containing 1–26, 1–24 or 1–23 amino acids have very little immunologic although full biologic activity. This property of CORTROSYN™ assumes added importance in view of the known antigenicity of natural ACTH

CORTROSYN™ (cosyntropin) for Injection is intended for use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency. Because of its rapid effect on the adrenal cortex it may be utilized to perform a 30-minute test of adrenal function (plasma cortisol response) as an office or outpatient procedure, using only 2 venipunctures.

Severe hypofunction of the pituitary - adrenal axis is usually associated with subnormal plasma cortisol values but a low basal level is not per se evidence of adrenal insufficiency and does not suffice to make the diagnosis. Many patients with proven insufficiency will have normal basal levels and will develop signs of insufficiency only when stressed. For this reason a criterion which should be used in establishing the diagnosis is the failure to respond to adequate corticotropin stimulation. When presumptive adrenal insufficiency is diagnosed by a subnormal CORTROSYN™ test, further studies are indicated to determine if it is primary or secondary.

Primary adrenal insufficiency (Addison's disease) is the result of an intrinsic disease process, such as tuberculosis within the gland. The production of adrenocortical hormones is deficient despite high ACTH levels (feedback mechanism). Secondary or relative insufficiency arises as the result of defective production of ACTH leading in turn to disuse atrophy of the adrenal cortex. It is commonly seen, for example, as result of corticosteroid therapy, Sheehan's syndrome and pituitary tumors or ablation.

The differentiation of both types is based on the premise that a primarily defective gland cannot be stimulated by ACTH whereas a secondarily defective gland is potentially functional and will respond to adequate stimulation with ACTH. Patients selected for further study as the result of a subnormal CORTROSYN™ test should be given a 3 or 4 day course of treatment with Repository Corticotropin Injection USP and then retested. Suggested doses are 40 USP units twice daily for 4 days or 60 USP units twice daily for 3 days. Under these conditions little or no increase in plasma cortisol levels will be seen in Addison's disease whereas higher or even normal levels will be seen in cases with secondary adrenal insufficiency

Dosing (Adults):
IM: Reconstitute 0.25 mg (250 mcg) with 1mL NS and inject intramuscularly. OR
IV: Dilute in 2 to 5 mL of saline and give over a 2-minute period.
The usual normal response in most cases is an approximate doubling of the basal level, provided that the basal level does not exceed the normal range.

Diagnosis of adrenocortical insufficiency: IM, IV (over 2 minutes): Peak plasma cortisol concentrations usually occur 45-60 minutes after cosyntropin administration: 0.25 to 0.75 mg. Note: When greater cortisol stimulation is needed, an I.V. infusion may be used: 0.25 mg administered at 0.04 mg/hour over 6 hours.
Normal response: Many patients with normal adrenal function, however, do not respond to the expected degree so that the following criteria have been established to denote a normal response:

1. The control plasma cortisol level should exceed 5 micrograms/100 mL.
2. The 30-minute level should show an increment of at least 7 micrograms/100 mL above the basal level.
3. The 30-minute level should exceed 18 micrograms/100 mL.

Monitoring: Plasma cortisol levels usually peak about 45 to 60 minutes after an injection of CORTROSYN and some prefer the 60-minute interval for testing for this reason. While it is true that the 60-minute values are usually higher than the 30-minute values, the difference may not be significant enough in most cases to outweigh the disadvantage of a longer testing period. If the 60-minute test period is used, the criterion for a normal response is an approximate doubling of the basal plasma cortisol value.

Supplied: Inj (powder for reconstitution): 0.25 mg

Desmopressin  (ddavp ®) 


DDAVP Injection 4 mcg/mL contains as active substance, desmopressin acetate, a synthetic analogue of the natural hormone arginine vasopressin. One mL (4 mcg) of DDAVP (desmopressin acetate) solution has an antidiuretic activity of about 16 IU; 1 mcg of DDAVP is equivalent to 4 IU. DDAVP has been shown to be more potent than arginine vasopressin in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand's disease Type I.

Dose-response studies were performed in healthy persons, using doses of 0.1 to 0.4 mcg/kg body weight, infused over a 10-minute period. Maximal dose response occurred at 0.3 to 0.4 mcg/kg. The response to DDAVP of factor VIII activity and plasminogen activator is dose-related, with maximal plasma levels of 300 to 400 percent of initial concentrations obtained after infusion of 0.4 mcg/kg body weight. The increase is rapid and evident within 30 minutes, reaching a maximum at a point ranging from 90 minutes to two hours. The factor VIII related antigen and ristocetin cofactor activity were also increased to a smaller degree, but still are dose-dependent.

  1. The biphasic half-lives of DDAVP were 7.8 and 75.5 minutes for the fast and slow phases, respectively, compared with 2.5 and 14.5 minutes for lysine vasopressin, another form of the hormone. As a result, DDAVP provides a prompt onset of antidiuretic action with a long duration after each administration.
  2. The change in structure of arginine vasopressin to DDAVP has resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle.
  3. When administered by injection, DDAVP has an antidiuretic effect about ten times that of an equivalent dose administered intranasally.
  4. The bioavailability of the subcutaneous route of administration was determined qualitatively using urine output data. The exact fraction of drug absorbed by that route of administration has not been quantitatively determined.
  5. The percentage increase of factor VIII levels in patients with mild hemophilia A and von Willebrand's disease was not significantly different from that observed in normal healthy individuals when treated with 0.3 mcg/kg of DDAVP infused over 10 minutes.
  6. Plasminogen activator activity increases rapidly after DDAVP infusion, but there has been no clinically significant fibrinolysis in patients treated with DDAVP.
  7. The effect of repeated DDAVP administration when doses were given every 12 to 24 hours has generally shown a gradual diminution of the factor VIII activity increase noted with a single dose. The initial response is reproducible in any particular patient if there are 2 or 3 days between administrations

Children >/= 12 years and Adults:
Diabetes insipidus:
I.V., SubQ: 2-4 mcg/day (0.5-1 mL) in 2 divided doses or 1 /10 of the maintenance intranasal dose

Intranasal (using 100 mcg/mL nasal solution): 10-40 mcg/day (0.1-0.4 mL) divided 1-3 times/day; adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover. Note: The nasal spray pump can only deliver doses of 10 mcg (0.1 mL) or multiples of 10 mcg (0.1 mL); if doses other than this are needed, the rhinal tube delivery system is preferred.

Oral: Initial: 0.05 mg twice daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis (range: 0.1-1.2 mg divided 2-3 times/day)

Hemophilia A and mild to moderate von Willebrand disease (type I):
I.V.: 0.3 mcg/kg by slow infusion, begin 30 minutes before procedure

IIntranasal: Using high concentration spray (1.5 mg/mL): <50 kg: 150 mcg (1 spray); >50 kg: 300 mcg (1 spray each nostril); repeat use is determined by the patient's clinical condition and laboratory work; if using preoperatively, administer 2 hours before surgery

Decrease bleeding following cardiac bypass: 0.3 mcg/kg ivpb.

Provide short term protection for uremic hemorrhagic tendency: 0.3 mcg/kg ivpb q8h x 2 doses (diminishing response).

Greatly enhanced ADH activity. Less vasopressor activity.
Longer DOA. (Synthetic analog of vasopressin-posterior pituitary hormone).
ADH activity : Pressor activity [DDAVP: 2000-4000: 1 Vasopressin: 1:1]


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Endocrine / Other