|
Product
Anti-asthmatic Products (Aerocort Inhaler)
|
Fertomid (Clomiphene Citrate Tablets)
|
|
| |
|
Fertomid
Clomiphene Citrate Tablets
FERTOMID - 50
Each uncoated tablet contains
Clomiphene Citrate BP 50 mg
DOSAGE FORM
Tablets for oral use
PHARMACOLOGY
Pharmacodynamics
Clomiphene citrate is an orally administered nonsteroidal agent which stimulates ovulation in a high percentage of appropriately selected anovulatory women, and improves sperm count and motility in men by inhibition of the negative feedback to the hypothalamus and anterior pituitary. It has no progestational, androgenic, or antiandrogenic effects and does not appear to interfere with pituitary - adrenal or pituitary - thyroid functions.
|
Pharmacokinetics
Orally administered 14 C labelled clomiphene citrate was readily absorbed when administered to humans. Cumulative excretion of the 14 C label by way of urine and faeces averaged about 50% of the oral dose after 5 days in 6 subjects, with mean urinary excretion of 7.8% and mean faecal excretion of 42.4%. A mean rate of excretion of 0.73% per day of the 14 C dose after 31 days to 35 days and 0.45% per day of the 14 C dose after 42 days to 45 days was seen in faecal and urine samples collected from 6 subjects for 14 to 53 days after clomiphene citrate 14 C administration. The remaining drug/metabolites may be slowly excreted from a sequestered enterohepatic recirculation pool.
INDICATIONS
Female Infertility
For induction of ovulation in patients with persistent ovulatory dysfunction who desire pregnancy. Fertomid can be used to make an irregularly ovulating woman ovulate regularly. The fertile period can be known in advance and coitus can thus be timed accordingly. Impediments to achieving pregnancy must be excluded or adequately treated before beginning Fertomid tablets.
In women having a menstrual cycle with a short luteal phase, pregnancy may not occur in spite of ovulation and fertilization. Fertomid rectifies this by increasing the levels of progesterone.
Other Gynaecological Disorders
Fertomid is useful in the treatment of oligomenorrhoea, dysfunctional uterine bleeding, amenorrhoea, post pill amenorrhoea, Stein Leventhal syndrome (polycystic ovarian disease), and Chiari Frommel syndrome.
Male infertility
Fertomid increases spermatogenesis and is useful in oligospermia and asthenospermia.
DOSAGE AND ADMINISTRATION
Female Infertility
One tablet of Fertomid-50 is taken daily for five days starting on the fifth day of the menstrual cycle. If ovulation does not appear to have occurred, a second course of two tablets of Fertomid-50 daily (in a single dose) for five days should be given starting from the fifth day of the next cycle.
A third treatment cycle may follow, with dosage regimens that are similar to the second.
An interval of 30 days should be maintained between consecutive courses.
In amenorrhoeic patients, the regimen is identical, but treatment can be started on any day.
Male Infertility
A dose of one tablet of Fertomid-25 daily for 25 days followed by a rest period of five days for three months.
CONTRAINDICATIONS
• Liver disease or history of liver dysfunction
• Abnormal bleeding of undetermined origin
• Patients with neoplastic diseases of the genital tract
•
As the drug may adversely affect the human foetus, it is absolutely contraindicated in pregnancy.
WARNINGS AND PRECAUTIONS
Causes of infertility other than ovarian dysfunction should be excluded before the start of treatment.
Hyperstimulation of the ovary, with excessive ovarian enlargement, may occur rarely. Patients undergoing therapy with clomiphene, particularly those with polycystic ovary syndrome, should receive the lowest possible doses to minimise ovarian enlargement or cyst formation. The patient should be instructed to report any abdominal or pelvic pain and should be evaluated for the presence of ovarian cysts before each cycle of treatment. Pelvic examination, which should be carried out with care, will reveal the diagnosis. The dose of Clomifene should be reduced. Further courses should not be given until the ovaries have returned to pre-treatment size.
The incidence of multiple pregnancy is increased when conception takes place during a Clomiphene-stimulated cycle.
In order to avoid inadvertent administration of clomiphene in early pregnancy, the basal body temperature should be monitored. In the absence of expected menses, a sensitive pregnancy test should be performed and only if negative should the patient be given the course of clomiphene.
Clomiphene should be used with caution:
• n patients with uterine fibroids, because of the risk of further enlargement of the fibroids
• n patients suffering from mental depression, because of the risk of exacerbation
• In patients with or susceptible to thrombophlebitis.
Clomiphene therapy should be withdrawn if the patient experiences visual disturbances and a full ophthalmologic examination should be performed.
Long-term cyclic therapy with clomiphene citrate is not recommended.
Patients should be advised that blurring or other visual symptoms might occasionally occur during therapy with clomiphene citrate . Patients should be warned that visual symptoms might render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting. If the patient has any visual symptoms, treatment should be discontinued and complete ophthalmologic evaluation carried out.
Drug Interactions
Drug interactions with clomiphene citrate have not been documented.
Pregnancy
Pregnancy Category X – Contraindicated
To avoid inadvertent clomiphene citrate administration during early pregnancy, careful pelvic examination must be done prior to each course of therapy, the basal body temperature must be recorded throughout all treatment cycles, and the patient should be carefully observed to determine whether ovulation occurs . If pregnancy or the presence of an ovarian cyst is suspected, subsequent therapy should be delayed until a correct diagnosis has been made.
Multiple Pregnancies
There is an increased chance of multiple pregnancies when conception occurs in relationship to clomiphene citrate therapy.
Ovarian Cyst
Pelvic examination is necessary prior to start of and before each subsequent course of clomiphene citrate . Clomiphene citrate should not be given in the presence of an ovarian cyst (including endometriosis involving the ovary).
Ovarian Enlargement
Pelvic examination is advised before each course of clomiphene citrate to exclude abnormal ovarian enlargement. Maximal enlargement of the ovary occurs several days after completion of the course. Patients who complain of pelvic pain should be examined with care. If ovarian enlargement occurs, subsequent courses of clomiphene citrate should be postponed till the ovaries have returned to their pretreatment size. It is important that the lowest dose of clomiphene citrate consistent with expectation of good results be used.
A lower dosage or a shorter duration of treatment is recommended in case unusual sensitivity to pituitary gonadotrophins is suspected as in some patients with polycystic ovaries.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term toxicity study in animals has not been performed to evaluate the carcinogenic or mutagenic potential of clomiphene citrate.
Ovarian Cancer
Prolonged use of clomiphene citrate may increase the risk of a borderline or invasive ovarian tumour .
Endometrial Carcinoma
Patients in later reproductive life have a greater tendency to endometrial carcinoma as well as a higher incidence of anovulatory disorders. Dilatation and curettage should always be done for diagnosis before starting clomiphene citrate therapy in such patients. If abnormal bleeding is present, full diagnostic measures are mandatory.
Lactation
It is not known whether clomiphene is distributed into breast milk. However, the drug may suppress lactation.
UNDESIRABLE EFFECTS
In Females
Side effects are dose related. The most common side effects are abdominal discomfort (distension, bloating, pain or tenderness), ovarian enlargement and visual blurring. The vasomotor symptoms resembling menopausal hot flushes are usually severe and disappear soon after treatment is discontinued.
Rare instances of massive ovarian enlargement and rupture of luteal cyst with haemoperitoneum have been reported.
Other less frequently reported symptoms include nausea, vomiting, increased nervous tension, depression, fatigue, dizziness, insomnia, headache, breast tenderness, heavier menses, intermenstrual spotting, weight gain, urticaria, allergic dermatitis, increased urinary frequencies and moderate reversible hair loss. When given continuously for prolonged period, clomiphene citrate may interfere with cholesterol synthesis.
» » » Postmarketing surveillance
Dermatologic : Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum, hypertrichosis, pruritus.
Central Nervous System : Migraine, headache, paresthesia, seizure, stroke, syncope
Psychiatric : Anxiety, irritability, mood changes, psychosis
Visual Disorders : Abnormal accommodation, cataract, eye pain, macular edema, optic neuritis, photopsia, posterior vitreous detachment, retinal haemorrhage, retinal thrombosis, retinal vascular spasm, temporary loss of vision
Cardiovascular : Arrhythmia, chest pain, edema, hypertension, palpitation, phlebitis, pulmonary embolism, shortness of breath, tachycardia, thrombophlebitis
Musculoskeletal : Arthralgia, back pain, myalgia
Hepatic : Transaminases increased, hepatitis
Neoplasms : Liver (hepatic hemangiosarcoma, liver cell adenoma, hepatocellular carcinoma); breast (fibrocystic disease, breast carcinoma); endometrium (endometrial carcinoma); nervous system (astrocytoma, pituitary tumour, prolactinoma, neurofibromatosis, glioblastoma multiforme, brain abcess); ovary (luteoma of pregnancy, dermoid cyst of the ovary, ovarian carcinoma); trophoblastic (hydatiform mole, choriocarcinoma); miscellaneous (melanoma, myeloma, perianal cysts, renal cell carcinoma, Hodgkin`s lymphoma, tongue carcinoma, bladder carcinoma); and neoplasms of offspring (neuroectodermal tumour, thyroid tumour, hepatoblastoma, lymphocytic leukaemia)
Genitourinary : Endometriosis, ovarian cyst (ovarian enlargement or cysts could, as such, be complicated by adnexal torsion), ovarian hemorrhage, tubal pregnancy, uterine haemorrhage
Body as a Whole: Fever, tinnitus, weakness
Other : Leukocytosis, thyroid disorder
Foetal/Neonatal Anomalies
Delayed development; abnormal bone development including skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia), foot, and joints; tissue malformations including imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, renal agenesis and dysgenesis, and malformations of the eye and lens (cataract), ear, lung, heart (ventricular septal defect and tetralogy of Fallot), and genitalia; as well as dwarfism, deafness, mental retardation, chromosomal disorders, and neural tube defects (including anencephaly).
In Males
Testicular tumours and gynaecomastia have been reported in males using clomiphene. The cause and effect relationship between reports of testicular tumours and the administration of clomiphene citrate is not known.
OVERDOSAGE
Toxic effects accompanying acute overdosage of clomiphene citrate have not been reported. Signs and symptoms of overdosage as a result of the use of more than the recommended dose during clomiphene citrate therapy include nausea , vomiting, vasomotor flushes, visual blurring, spots or flashes, scotomata, ovarian enlargement with pelvic or abdominal pain.
USERS INSTRUCTIONS
◊ Do not use this medicine if you have had an allergic reaction to Clomifene, are pregnant (or think you might be pregnant), or if you have liver disease, cysts on the ovaries, enlarged ovaries, or unusual vaginal bleeding.
◊ Take this medicine exactly as your doctor ordered.
◊ Your doctor will tell you how much to take and when to start.
◊ Take your medicine at the same time every day.
◊ You should be checked for pregnancy or ovulation by your doctor between treatments.
◊ You may need to take and record your basal body temperature every day, ask your doctor.
◊ If you miss a dose, take the missed dose as soon as you remember.
◊ Tell your doctor if you have missed any doses, because this may affect your treatment. Ask your doctor or pharmacist before taking any other medicine, including over-the-counter products.
STORAGE AND HANDLING INSTRUCTIONS
Store below 30°C, Protect from light.
PACKAGING INFORMATION
FERTOMID-25
Packing: Carton containing 10 blister strips of 10 tablets each.
Pack size: Blister strip of 10 tablets.
FERTOMID-50
Packing: Carton containing 1 blister strip of 10 tablets each. Pack
ing: Carton containing 10 blister strips of 10 tablets each.
Pack size: Blister strip of 10 tablets.
FERTOMID-100
Packing: Carton containing 10 blister strips of 5 tablets each.
Pack size: Blister strip of 5 tablets.
Presentation:
FERTOMID-50 ..............................10 tablets in a blister pack.
|
|
