 VITAMIN K:

 Generic Name: Phytonadione

 Dosage Form: Injection

 dose 1 at birth
 dose 2 usually three to five days later
 dose 3 in the fourth week, if the baby is fully breast fed. (Babies fed mainly by
formula do not need the third dose.)

 Mechanism of action:
o Phytonadione is readily absorbed following intramuscular administration. After
absorption, phytonadione is initially concentrated in the liver, but the concentration
declines rapidly. Very little vitamin K accumulates in tissues. Little is known about
the metabolic fate of vitamin K. Almost no free unmetabolized vitamin K appears in
bile or urine.
o The pharmacological action of vitamin K is related to its normal physiological
function, that is, to promote the hepatic biosynthesis of vitamin K dependent clotting
factors.
 Indications:
o Anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione
derivatives;
o Prophylaxis and therapy of hemorrhagic disease of the newborn
o Hypoprothrombinemia due to antibacterial therapy
o Hypoprothrombinemia secondary to factors limiting absorption or synthesis of
vitamin K, e.g., obstructive jaundice, biliary fistula, ulcerative colitis, celiac disease,
intestinal resection, cystic fibrosis of the pancreas, and regional enteritis
o Other drug-induced hypoprothrombinemia where it is definitely shown that the result
is due to interference with vitamin K metabolism, e.g., salicylates.

 Contraindication:
o Hypersensitivity to any component of this medication.

 Precaution:
o Pediatric Use
o Hemolysis
o Jaundice
o Hyperbilirubinemia in neonates, particularly those that are premature, may be related
to the dose of Vitamin K1 Injection. Therefore, the recommended dose should not be
exceeded

 Adverse reaction:
o Deaths have occurred after intravenous and intramuscular administration.
o Pain, swelling, and tenderness at the injection site may occur.
o The possibility of allergic sensitivity including an anaphylactoid reaction, should be
kept in mind.
o Infrequently, usually after repeated injection, erythematous, indurated, pruritic
plaques have occurred; rarely, these have progressed to scleroderma-like lesions that
have persisted for long periods. In other cases, these lesions have resembled erythema
perstans.
 o Hyperbilirubinemia has been observed in the newborn following administration of
phytonadione. This has occurred rarely and primarily with doses above those
recommended. 

 Dosage and Administration

o Whenever possible, Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP)
should be given by the subcutaneous route.
o When intravenous administration is considered unavoidable, the drug should be
injected very slowly, not exceeding 1 mg per minute.
o Protect from light at all times.
o Parenteral drug products should be inspected visually for particulate matter and
discoloration prior to administration, whenever solution and container permit.

 Directions for Dilution

o Vitamin K1 Injection may be diluted with 0.9% Sodium Chloride Injection, 5%
Dextrose Injection, or 5% Dextrose and Sodium Chloride Injection. Benzyl alcohol as
a preservative has been associated with toxicity in newborns.
o Therefore, all of the above diluents should be preservative-free. Other diluents should
not be used. When dilutions are indicated, administration should be started
immediately after mixture with the diluent, and unused portions of the dilution should
be discarded, as well as unused contents of the ampul.

 Prophylaxis of Hemorrhagic Disease of the Newborn

 The American Academy of Pediatrics recommends that vitamin K1 be given to the
newborn. A single intramuscular dose of Vitamin K1 Injection 0.5 to 1 mg within one
hour of birth is recommended.

 Treatment of Hemorrhagic Disease of the Newborn

 Empiric administration of vitamin K1 should not replace proper laboratory evaluation
of the coagulation mechanism. A prompt response (shortening of the prothrombin
time in 2 to 4 hours) following administration of vitamin K1 is usually diagnostic of
hemorrhagic disease of the newborn, and failure to respond indicates another
diagnosis or coagulation disorder.
 Vitamin K1 Injection 1 mg should be given either subcutaneously or intramuscularly.
Higher doses may be necessary if the mother has been receiving oral anticoagulants.
 Whole blood or component therapy may be indicated if bleeding is excessive. This
therapy, however, does not correct the underlying disorder and Vitamin K1 Injection
should be given concurrently.

Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) Summary of Dosage

Guidelines (See circular text for details)

Newborns Dosage
Hemorrhagic Disease of the Newborn
Prophylaxis 0.5 to 1 mg IM within 1 hour of birth

    Treatment 1 mg SC or IM
(Higher doses may be necessary if the mother
has been receiving oral anticoagulants)

Adults Initial Dosage

Anticoagulant-Induced 2.5 mg to 10 mg or
Prothrombin Deficiency up to 25 mg
(caused by coumarin or indanedione (rarely 50 mg)
derivatives)

Hypoprothrombinemia 2.5 mg to 25 mg or
Due to other causes more (rarely up to
(Antibiotics; Salicylates or other drugs; 50 mg)
Factors limiting absorption or synthesis)

 Side effects:
 Less common: -With menadiol or high doses of phytonadione in newborns

 Decreased appetite
 decreased movement or activity
 difficulty in breathing
 enlarged liver
 general body swelling
 irritability
 muscle stiffness
 paleness
 yellow eyes or skin
 Rare - With injection only
 Difficulty in swallowing
 fast or irregular breathing
 lightheadedness or fainting
 shortness of breath
 skin rash, hives and/or itching
 swelling of eyelids, face, or lips
 tightness in chest
 troubled breathing and/or wheezing
 Rare
 Blue color or flushing or redness of skin
 dizziness
 fast and/or weak heartbeat
 increased sweating
  low blood pressure (temporary)

Minor Side Effects

 Less common:

 Flushing of face
 redness, pain, or swelling at place of injection
 skin lesions at place of injection (rare)
 unusual taste
 CABERGOLIN:

 Generic: Cabergoline
 Form: oral tablet
 Strength: 0.5 mg

 Dosage for high prolactin levels

 Adult dosage (ages 18–64 years)
o Typical starting dosage: 0.25 mg taken twice per week.
o Maximum dosage: 1 mg twice per week.
 Child dosage (ages 0–17 years):
o This medication has not been studied in children. It should not be used in people
younger than 18 years.
 Senior dosage (ages 65 years and older)
o The kidneys and liver of older adults may not work as well as they used to. This can
cause body to process drugs more slowly. As a result, more of a drug stays in body for
a longer time. This raises risk of side effects.

 What is cabergoline?
 Cabergoline oral tablet is a prescription drug that’s only available as a generic drug.
There is no brand-name version available. Cabergoline only comes as a tablet take by
mouth.

 Why it's use?

 Cabergoline is used to treat high levels of prolactin in body. This happens when
pituitary gland makes extra prolactin.
 High prolactin levels may be caused by a hormone problem or by a tumor in pituitary
gland.
 High prolactin levels can cause changes in a woman’s ovulation, menstrual cycle, and
breast milk production.
 In men, high prolactin levels can affect reproduction and cause sexual issues.
 These include a decreased sex drive and not being able to get or keep an erection.

 How it works?
 Cabergoline belongs to a class of drugs called dopamine agonists.
 A class of drugs is a group of medications that work in a similar way.
 These drugs are often used to treat similar conditions.
 Dopamine is a chemical body makes.
 It prevents body from releasing prolactin.
 Cabergoline works by binding to dopamine receptors.
 This also keeps body from releasing prolactin, which helps decrease prolactin levels.

 Side effects:
 Cabergoline oral tablet can cause drowsiness as well as other side effects.
 More common side effects:
 Nausea
 Constipation
 Headache
 Dizziness
 Weakness or lack of energy
If these effects are mild, they may go away within a few days or a couple of
weeks. If they’re more severe or don’t go away, talk to doctor or pharmacist.

 Serious side effects:

 trouble breathing
 shortness of breath
 a cough that doesn’t go away
 chest pain that doesn’t go away
 stomach pain
 swelling in your legs, ankles, or feet

 Heart valve problems. Symptoms can include:

 swelling in your arms, legs, hands, or feet
 trouble breathing
 changes in your heart rhythm
 chest pain
 cough

Contraindications:
 Antipsychotic drugs such as haloperidol, thiothixene, chlorpromazine, and
prochlorperazine
 Antinausea drugs such as metoclopramide or promethazine
 Cabergoline warnings:
This drug comes with several warnings.
 Allergy warning:
 trouble breathing
 swelling of throat or tongue

 Warnings for people with certain health conditions

 For people with heart problems: If you have uncontrolled high blood pressure or heart
valve problems, you should not use this drug. It can make your condition worse. If
you have high blood pressure, ask your doctor if your blood pressure is under control.
 For people with history of tissue scarring: If you have a history of scarred tissue in
your lungs, heart, kidney, or abdomen (stomach area), you should not use this drug. It
can make your condition worse.
 For people with high blood pressure from pregnancy: If you’re currently pregnant and
have high blood pressure from your pregnancy, you should not use this drug. It can
make your condition worse.
 For people with liver problems: You may not be able to process this drug well. This
may increase the levels of the drug in your body and cause more side effects.

 Warnings for other groups:

 For pregnant women: Cabergoline is a category B pregnancy drug. That means two
things:
1. Research in animals has not shown a risk to the fetus when the mother takes the drug.
2. There aren’t enough studies done in humans to show if the drug poses a risk to the
fetus.
 For women who are breastfeeding: It isn’t known if this drug passes into breast milk.
If it does, it may cause side effects in a child who is breastfed. This drug may also
keep you from making breast milk. Talk to your doctor if you breastfeed your child.
You may need to decide whether to stop breastfeeding or stop taking this medication.
 For seniors: The kidneys and liver of older adults may not work as well as they used
to. This can cause your body to process drugs more slowly. As a result, more of a
drug stays in your body for a longer time. This raises your risk of side effects.
 For children: This medication has not been studied in children. It should not be used
in people younger than 18 years.

 HORMONAL THERAPY:
  ESTROGENS:

 They are naturally occurring steroidal sex hormones with 18 carbon atoms.
 They are produced in the body by the ovary, adrenal gland &by tha placenta during
pregnancy.
 Estradiol is the most active estrogen produced in the body.
 It is metabolized to form estrone & estriol mainly in the liver.
 Estradiol is 10 times more potent than estrogen & 25 times than estriol.
 Natural estrogens given orally are rapidly metabolized in the liver & so they are
ineffective.
 Synthetic compounds can be used orally & have replaced the natural Products.

Preparations for clinical use:

1) Conjugated estrogens: Premarin tablet 0.625mg,1.25mg 20mg/5ml injection.
2) Ehinyl estradiol: Lynoral 0.01mg, 0.05 mg tablet in oral pills :0.03 to 0.05mg with
different progestogens.
3) Estriol : Evalon 1.0 & 2.0 mg tablet.
4) Estradiol valerate: 10 mg/1 ml progynon depot l/M inj.
5) Estradiol benzoate: 1.0mg along with estradiol phenyl propionate & testosterone in
inj. Mixogen.
6) Dienestero : 0.01%topical cream for vaginal application.
7) Estradiol pellets: Subcutaneas implants 25, 50 100 mg.

Uses:
1. CONTRACEPTION: 20 OR 30 ug ethingl estradiol is commonly used in currently
available low dose & phasic pills.

2. MENOPAUSE :
a) Menopausal symptoms: To control hot flushes, sweating, depression, insomnia etc.
Lynoral 0.01 mg, premarin 0.625mg orevalon 2 mg daily for 3wks with one week rest
is advocated.
b) Postmenopausal osteoporosis: Estrogen is useful in prevention & treatment of
osteoporosis. Premarin 0.625mg tablet is given daily.
c) Senile vaginitis, dyspareunia: Dienosterol cream is used.
In recent times serms & tibolone are more used in menopausal patients.
3. D U B: High doses are required for the acute episode, while cyclical therapy by OC
pills or lynoral 0.05mg for 21days with progesterone added in last 7-10 days is
advised for at least 3 months.

4. Menstrual problems: Estrogens in OC pills are commonly used for

 Primary dysmenorrhoea
 Regularization of cycles
 Postponement or advancement of cycles.

5. Amenorrhoea:
  In primary & secondary amenorrhoea estrogen – progesterone challenge test for
investigating the cause & for cyclical therapy to have cyclical bleeding if necessary.

6. Endometriosis: OC pills as pseudo – pregnancy treatment.

7. Hypogonadism to stimulate secondary sexual characters.
8. Vulvovaginitis in young children.
9. Acne vulgaris & hirsuitsm.
10. Asherman syndrome after breaking the adhesions to stimulate the endomaterial
growth.

11. Low dose estrogen is used along with clomiphene in infertility cases to counter the
antiestrogenic effects on cervical mucous & endome triwn however there is no strong
scientific evidence.

Side effects:
 Nausea
 Vomiting
 Painful breast
 Water retention
 Weight gain
 Impaired glucose tolerance
 Growth of fibroid
 Breast Carcinoma
 Endometrial Carcinoma
 Gall bladder disease
 Thromboembolic disease
 Coronary disease
 Cerebrovascular disease
 DES syndrome

 PROGESTOGENS:

 Progesterone is a natural steroid with 21 carbon atoms.

 It is mainly produced by corpus luteum from the ovary & during pregnancy from
placenta. Adrenal contributes to very little amount.
 It is metabolized in liver.
 Natural micronized & synthetic progestogens are useful orally for clinical use.

Progestogens are dividend in 4 main groups :-

A. Natural Progesterone
B. Derivatives of Progesterone :
I. Derivatives of Progesterone (C-21) Pregnane progestogens:
o 17 alpha hydroxy progesterone caproate
o Medroxy progesterone acetate
o Chlormadinon acetate
 o Stereoisomer of progesterone – Dydrogesterone
II. Derivatives of 19 testosterone (C-18) :
(a) Oestrane steroids:
o Norethisterone
o Norethisterone acetate
o Norethynodrel
o Allylestrenol
(b) Gonane steroids:
o Norgestrel-dl-norgestrel
o Levonorgestrel
Newer Gonanes:
o Desogestrel
o Gestodene
o Norgestimate

Preparations for clinical use:

1. Progesterone: Natural micronized progesterone as 100,200,300 & 400mg soft capsule
or 50 & 100 mg I/M injection.
e.g. Susten, her NMP , Naturogest , Vageston.
2. 17 a HPC: Proluton depot 250-500 mg I/m injection.
3. Medroxy progesterone acetate : Modus, Meprate, Deviry tablets 5-10mg DMPA
injection 150 mg/ml
4. Dydrogesterone : Duphastone tablet 5mg.
5. Norethisterone : Primoute-N , Dubogen ,sysrone tablet 5mg.
6. Norethisterone Acetate : Regestrone tablet 5mg.
7. Lynestrenol : Orgametril tablet 5mg.
8. Norgestrel Levonorgestrel : In oral pills 0.5mg.
9. Allylestrenol : Gestanin, Fetugard , Gravidin 5mg tablets.

Uses:
 Contraception: Along with estrogen in oral pills different progestogens are used. Only
progestogens are used in minipill, injectable contraceptive & implants.
 DUB : Primolute-N , Regestrone , Orgametril , Meprate are used 10-20mg oral for 5-
10 days in acute episode & then after, in last 10-14 days of each cycle 5-10 mg per
day is given for 6 months.
 Infertility due to luteal phase defect : Natural micronized progesterone is used : It is
used through oral or vaginal route & I/M injections. Vaginal route is preferred unless
there is vaginal absorption & hepatic bypass it gives better blood levels & better
results.
o It is used in dose of 200 to 300 mg/day from 16th day of cycle for 10 days.
 Threatened abortion : Habitual abortion : As mentioned above. As compared to
synthetic progesterone natural micronized prog. has better bioavailability & minimal
side effects.
 Dysmenorrhoea : Duphastone 5mg twice or thrice a day from 5 th to 25th day of cycle.
Instead cyclical oral pills this may be given for 6 months.
 Premenstrual tension : Duphastone , Primolute-N , orgametril etc, 10mg bid from 15 th
to 26th day of cycle OR cyclical oral pills.
 Endometriosis : (a) With oral pills as psuedopregnancy treatment (b) Tablet Meprate
30mg per day for 6 months (c) Newer progestogen Gestrinone(R-2323) 2.5mg orally
twice weekly or Dienogest 2mg daily.
 Endometrial hyperplasia : Adenomatous hyperplasia : Oral pills for 6 months.
Atypical hyperplasia : Injection Depot provera 100mg/wk OR Injection proluton
500mg/wk.
 Endometrial carcinoma : For treatment of endometrial carcinoma large doses of
progesterone are used.
 Primary or secondary amenorrhoea : Progesterone challenge test – any of the
synthetic oral tablet is used 10mg for 5 days. OR Natural injection progesterone 50
mg I/m for 2 days.
 Postponement of menses : Any oral tablet is given 5 to 10 mg daily at least 4-6 days
before expected date. Menses can be safely postponed for maximum of 15 days.
Period starts 2 to 3 days after stopping the drug.
 Uterine hypoplasia – Proluton depot I/M is given after pretreatment with progynon ,
weekly I/M for 8 wks.
 Fibrocystic disease of breast: Provera , Dubogen 10-20 mg is used.
 Precocious puberty: MPA is found useful in the treatment of precocious puberty in
children.

Side Effects :
o Nausea
o Vomiting
o Diarrhoea
o Water retention
o Weight gain
o Break through bleeding
o Amenorrhoea
o Hypertension
o Musculinization of female fetus
o Deep vein thrombosis
o Pulmonary embolism