Injection should be followed by a meal or snack containing carbohydrates within 30 minutes.
The preparations are administered subcutaneously in the thigh or abdominal wall. Subcutaneous injection into the abdominal wall results in faster absorption than from other injection sites.
Insulin suspensions are never to be administered intravenously.

Side Effects:

• Hypoglycemia, severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death.
• Symptoms of generalized hypersensitivity may include generalized skin rash, itching, sweating, gastrointestinal upset, angioneurotic edema, difficulties in breathing, palpitation, and reduction in blood pressure.
• Fast improvement in blood glucose control may be associated with a condition termed acute painful neuropathy, which is usually reversible. Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
• Injection site reactions (redness, swelling, itching, pain, and hematoma at the injection site) may occur during treatment with Insulin. Most reactions are transitory and disappear during continued treatment. Edema may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.

Precautions:
Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycemia. In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis which is potentially lethal.
Hypoglycemia may occur if the insulin dose is too high in relation to the Insulin requirement. If an adjustment is needed, it may occur with the first dose or during the first several weeks or months.
Patients whose blood glucose control is greatly improved e.g. by intensified insulin therapy may experience a change in their usual warning symptoms of hypoglycemia and should be advised accordingly.

Use in Pregnancy & Lactation:
There are no restrictions on the treatment of diabetes with Insulin during pregnancy as Insulin does not pass the placental barrier.
There are no restrictions on the treatment of diabetes with Insulin during lactation, as Insulin treatment of the nursing mother involves no risk to the baby. However, the Insulin dosage, diet, or both may need to be reduced.

Overdose:

• Insulins have no specific overdose definitions. However, hypoglycemia may develop over sequential stages:
• Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient constantly carry some sugar lumps, sweets, biscuits, or sugary fruit juice.
• Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously. Glucose must also be given i.v if the patient does not respond to glucagon within 10 to 15 minutes.
• Upon regaining consciousness administration of oral carbohydrates is recommended for the patient to prevent relapse.

Storage:
Store at 2°C to 8°C in a refrigerator. Do not freeze. Protect from light.

Contraindication:
There is no evidence available on contraindication but it may happen in patients who are hypersensitive to any of its ingredients.

Store at a cool and dry place, protect from light.

Ivermectin 6 Tablet: Each tablet contains Ivermectin USP 6 mg.

Description:
Ivermectin selectively binds and with high affinity to glutamate-gated chloride ion channels, which occur in invertebrate nerve and muscle cells leading to an increase in the permeability of cell membranes to chloride ions with hyperpolarization of the nerve or muscle cell and, ultimately, death of the parasite.

Dosage & Administration:

For Treatment (If COVIO Positive): 2 Tablets of Ivermectin 6 mg once daily for 5 days. (2+0+0 for 5 days).
For Prophylaxis: Single-dose as mentioned below to be taken on Day 1 & same dose on Day 7.

• Body Weight 15-24 kg: 1 Tablet of Ivermectin 3 mg
• Body Weight 25-35 kg: 1 Tablet of Ivermectin 6 mg
• Body Weight 36-50 kg: 1 Tablet of Ivermectin 6 mg + 1 Tablet of Ivermectin 3 mg
• Body Weight 51-65 kg: 2 Tablets of Ivermectin 6 mg
• Body Weight 66-79 kg: 2 Tablets of Ivermectin 6 mg + 1 Tablet of Ivermectin 3 mg
• Body Weight >80 kg: 3 Tablets of Ivermectin 6 mg

Strongyloidiasis: The recommended dosage of Ivermectin for the treatment of strongyloidiasis is a single oral dose designed to provide approximately 200 mcg/kg of body weight. Patients should take tablets on an empty stomach with water. In general, additional doses are not necessary. However, follow-up stool examinations should be performed to verify eradication of infection.

Dosage Guidelines for Ivermectin for Strongyloidiasis:

• Body Weight (kg) 15-24: Dose 3 mg/kg
• Body Weight (kg) 25-35: Dose 6 mg/kg
• Body Weight (kg) 36-50: Dose 9 mg/kg
• Body Weight (kg) 51-65: Dose 12 mg/kg
• Body Weight (kg) 66-79: Dose 15 mg/kg
• Body Weight (kg) >80: Dose 200 mcg/kg

Onchocerciasis: The recommended dosage of Ivermectin is a single oral dose designed to provide approximately 150 mcg of Ivermectin per kg of body weight on an empty stomach with water, the most commonly used dose interval is 12 months. For the treatment of individual patients, retreatment may be considered at intervals as short as 3 months.

Dosage Guidelines for Ivermectin for Onchocerciasis:

• Body Weight (kg) 15-25: Dose 3 mg/kg
• Body Weight (kg) 26-44: Dose 6 mg/kg
• Body Weight (kg) 45-64: Dose 9 mg/kg
• Body Weight (kg) 65-84: Dose 12 mg/kg
• Body Weight (kg) >85: Dose 150 mcg/kg

Interaction:
Post-marketing reports of increased INR (International Normalized Ratio) have been rarely reported when ivermectin was co-administered with warfarin.

Contraindications:
It is contraindicated in patients who are hypersensitive to any component of this product.

Side Effects:
Strongyloidiasis: In four clinical studies involving a total of 109 patients given either one or two doses of 170 to 200 mcg/kg of Ivermectin, the following adverse reactions were reported as possibly, probably, or definitely related to Ivermectin.

• Body as a whole: asthenia/fatigue (0.9%), abdominal pain (0.9%)
• Gastrointestinal: anorexia (0.9%), constipation (0.9%), diarrhea (1.8%), nausea (1.8%), vomiting (0.9%) Nervous System/Psychiatric: dizziness (2.8%), somnolence (0.9%), vertigo (0.9%), tremor (0.9%)
• Skin: pruritus (2.8%), rash (0.9%), and urticaria (0.9%).

Onchocerciasis: arthralgia/synovitis (19.3%), axillary lymph node enlargement and tenderness (11.0% and 4.4%, respectively), cervical lymph node enlargement and tenderness (5.3% and 1.2%, respectively), inguinal lymph node enlargement and tenderness (12.6% and 13.9%, respectively), other lymph node enlargement and tenderness (3.0% and 1.9%, respectively), pruritus (27.5%), skin involvement including edema, papular and pustular or frank urticarial rash (22.7%), and fever (22.6%), abnormal sensation in the eyes, eyelid edema, anterior uveitis, conjunctivitis, limbitis, keratitis, and chorioretinitis or choroiditis. These have rarely been severe or associated with loss of vision and have generally resolved without corticosteroid treatment. The following adverse reactions have been reported since the drug was registered overseas: hypotension (mainly orthostatic hypotension), worsening of bronchial asthma, toxic epidermal necrolysis, and Stevens-Johnson syndrome.

Pregnancy & Lactation:

• Pregnancy Category C. Ivermectin does not appear to be selectively fetotoxic to the developing fetus. There are, however, no adequate and well-controlled studies in pregnant women. Ivermectin should not be used during pregnancy since safety in pregnancy has not been established.
• Nursing Mothers: Ivermectin is excreted in human milk in low concentrations. Treatment of mothers who intend to breastfeed should only be undertaken when the risk of delayed treatment to the mother outweighs the possible risk to the newborn

Precautions & Warnings:
Historical data have shown that microfilaricidal drugs, such as diethylcarbamazine citrate (DEC-C), might cause cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction) and ophthalmological reactions in patients with onchocerciasis. These reactions are probably due to allergic and inflammatory responses to the death of microfilariae. Patients treated with Ivermectin for onchocerciasis may experience these reactions in addition to clinical adverse reactions possibly, probably, or definitely related to the drug itself. The treatment of severe Mazzotti reactions has not been subjected to controlled clinical trials. Oral hydration, recumbency, intravenous normal saline, and/or parenteral corticosteroids have been used to treat postural hypotension. Antihistamines and/or aspirin have been used for most mild to moderate cases. After treatment with microfilaricidal drugs, patients with hyperreactive onchodermatitis (sowda) may be more likely than others to experience severe adverse reactions, especially edema and aggravation of onchodermatitis. Rarely, patients with onchocerciasis who are also heavily infected with Loa loa may develop a serious or even fatal encephalopathy either spontaneously or following treatment with an effective microfilaricide. In these patients, the following adverse experiences have also been reported: back pain, conjunctival hemorrhage, dyspnea, urinary and/or fecal incontinence, difficulty in standing/walking, mental status changes, confusion, lethargy, stupor, or coma.

Use in Special Populations:

• Pediatric Use: Safety and effectiveness in pediatric patients weighing less than 15 kg have not been established.
• Geriatric Use: Clinical studies of Ivermectin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Storage:
Keep in a dry place, below 30°C. Protect from light. Keep out of the reach of children.

Therapeutic Class: Gastro-Intestinal Disorders (Bulk-forming laxatives, Herbal, and Nutraceuticals)

Ispaghula Husk and Mebeverine Hydrochloride are indicated for the treatment of all kinds of IBS such as IBS-C, IBS-D & IBS-A.

Indications:
Isotretinoin is indicated in severe forms of acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy.

Description:
Isotretinoin produces its effects through altering progress through the cell cycle, cell differentiation, survival, and apoptosis. These actions reduce sebum production, preventing the blockage of pores, and the growth of acne-causing bacteria. Isotretinoin and 4-oxo-isotretinoin both significantly reduce the production of sebum. Isotretinoin has little to no affinity for retinol-binding proteins (RBPs) and retinoic acid nuclear receptors (RARs). Tretinoin and 4-oxo-tretinoin bind to the RAR-γ receptor, which is suspected to be part of the action of acne treatment by isotretinoin. Isotretinoin induces apoptosis in sebocytes, leading to a decrease in sebum production. Isotretinoin also reduces the formation of comedones by reducing hyperkeratinization through an unknown mechanism. Isotretinoin does not directly kill bacteria but it does reduce the size of sebum ducts and makes the microenvironment less hospitable to acne-causing bacteria. It may also increase immune mechanisms and alter the chemotaxis of monocytes to reduce inflammation.

Dosage & Administration:
The capsules should be taken with food once or twice daily. Isotretinoin should only be prescribed by or under the supervision of physicians with expertise in the use of systemic retinoids for the treatment of severe acne and a full understanding of the risks of isotretinoin therapy and monitoring requirements.

• Adults including adolescents and the elderly: Isotretinoin therapy should be started at a dose of 0.5 mg/kg daily. The therapeutic response to isotretinoin and some of the adverse effects are dose-related and vary between patients. This necessitates individual dosage adjustment during therapy. For most patients, the dose ranges from 0.5-1.0 mg/kg per day. Long-term remission and relapse rates are more closely related to the total dose administered than to either duration of treatment or daily dose. It has been shown that no substantial additional benefit is to be expected beyond a cumulative treatment dose of 120-150 mg/kg. The duration of treatment will depend on the individual daily dose. A treatment course of 16-24 weeks is normally sufficient to achieve remission. In the majority of patients, complete clearing of the acne is obtained with a single treatment course. In the event of a definite relapse, a further course of Isotretinoin therapy may be considered using the same daily dose and cumulative treatment dose. As a further improvement of the acne can be observed up to 8 weeks after discontinuation of treatment, a further course of treatment should not be considered until at least this period has elapsed.
• Patients with severe renal insufficiency: In patients with severe renal insufficiency treatment should be started at a lower dose (e.g. 10 mg/day). The dose should then be increased up to 1 mg/kg/day or until the patient is receiving the maximum tolerated dose.
• Children: Isotretinoin is not indicated for the treatment of prepubertal acne and is not recommended in patients less than 12 years of age due to a lack of data on efficacy and safety.
• Patients with intolerance: In patients who show severe intolerance to the recommended dose, treatment may be continued at a lower dose with the consequences of a longer therapy duration and a higher risk of relapse. In order to achieve the maximum possible efficacy in these patients, the dose should normally be continued at the highest tolerated dose.

Interaction:
Additive adverse effects with Vit-A or its derivatives. Decreased efficacy of microdose progesterone (use 2 forms of contraception).Increased risk of local irritation with topical keratolytic or exfoliative anti-acne agents. Oxidizing agents (e.g. benzoyl peroxide) may reduce the efficacy of topical isotretinoin.

Contraindications:
Isotretinoin is contraindicated in women who are pregnant or breastfeeding. Isotretinoin is contraindicated in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met. Isotretinoin is also contraindicated in patients with hypersensitivity to Isotretinoin or to any of the excipients. Isotretinoin is also contraindicated in patients with hepatic insufficiency, with excessively elevated blood lipid values, with hypervitaminosis A, receiving concomitant treatment with tetracyclines.

This medicinal product is contraindicated in women of childbearing potential unless all of the following conditions of the Pregnancy Prevention Programme are met: She has severe acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy. She understands the teratogenic risk. She understands the need for rigorous follow-up, on a monthly basis. She understands and accepts the need for effective contraception, without interruption, 1 month before starting treatment, throughout the duration of treatment, and 1 month after the end of treatment. At least one and preferably two complementary forms of contraception including a barrier method should be used. Even if she has amenorrhea she must follow all of the advice on effective contraception. She should be capable of complying with effective contraceptive measures. She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy. She understands the need and accepts to undergo pregnancy testing before, during, and 5 weeks after the end of treatment. She has acknowledged that she has understood the hazards and necessary precautions associated with the use of Isotretinoin. These conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy. The prescriber must ensure that the patient complies with the conditions for pregnancy prevention as listed above, including confirmation that she has an adequate level of understanding. The patient has acknowledged the aforementioned conditions. The patient has used at least one and preferably two methods of effective contraception including a barrier method for at least 1 month prior to starting treatment and is continuing to use effective contraception throughout the treatment period and for at least 1 month after cessation of treatment. Negative pregnancy test results have been obtained before, during, and 5 weeks after the end of treatment. The dates and results of pregnancy tests should be documented.

Side Effects:
Some of the side effects associated with the use of Isotretinoin are dose-related. The side effects are generally reversible after altering the dose or discontinuation of treatment, however, some may persist after treatment has stopped. The following symptoms are the most commonly reported undesirable effects with isotretinoin: dryness of the skin, dryness of the mucosae e.g. of the lips (cheilitis), the nasal mucosa (epistaxis), and the eyes (conjunctivitis).

The incidence of the adverse events was calculated from pooled clinical trial data involving 824 patients and from post-marketing data. Frequency categories are defined as Very common (³1/10), Common (³1/100 to <1/10), Uncommon (³1/1,000 to <1/100), Rare (³1/10,000 to <1/1,000), Very rare (³1/10,000 to <1/1,000) and not known (cannot be estimated from the available data. Infections: Very Rare: Gram-positive (mucocutaneous) bacterial infection Blood and lymphatic system disorders: Very common: Anaemia, red blood cell sedimentation rate increased, thrombocytopenia, thrombocytosis; Common: Neutropenia; Very Rare: Lymphadenopathy Immune system disorders: Rare: Allergic skin reaction, anaphylactic reactions, hypersensitivity Metabolism and nutrition disorders: Very Rare: Diabetes mellitus, hyperuricaemia Psychiatric disorders: Rare: Depression, depression aggravated, aggressive tendencies, anxiety, mood alterations. Very Rare: Abnormal behaviour, psychotic disorder, suicidal ideation suicide attempt, suicide Nervous system disorders: Common: Headache; Very Rare: Benign intracranial hypertension, convulsions, drowsiness, dizziness Eye disorders: Very Common: Blepharitis, conjunctivitis, dry eye, eye irritation; Very Rare: Blurred vision, cataract, colour blindness (colour vision deficiencies), contact lens intolerance, corneal opacity, decreased night vision, keratitis, papilloedema (as a sign of benign intracranial hypertension), photophobia, visual disturbances. Ear and labyrinth disorders: Very Rare: Hearing impaired Vascular disorders: Very Rare: Vasculitis (for example Wegener's granulomatosis, allergic vasculitis) Respiratory, thoracic and mediastinal disorders: Common: Epistaxis, nasal dryness, nasopharyngitis, Very Rare: Bronchospasm (particularly in patients with asthma), hoarseness Gastrointestinal disorders: Very Rare: Colitis, ileitis, dry throat, gastrointestinal haemorrhage, haemorrhagic diarrhoea and inflammatory bowel disease, nausea, pancreatitis Hepatobiliary disorders: Very Common: Transaminase increased; Very rare: Hepatitis Skin and subcutaneous tissues disorders: Very Common: Pruritus, rash erythematous, dermatitis, cheilitis, dry skin, localised exfoliation, skin fragility (risk of frictional trauma), Rare: Alopecia, Very Rare: Acne fulminans, acne aggravated (acne flare), erythema (facial), exanthema, hair disorders, hirsutism, nail dystrophy, paronychia, photosensitivity reaction, pyogenic granuloma, skin hyperpigmentation, sweating increased. Musculoskeletal and connective tissue disorders: Very Common: Arthralgia, myalgia, back pain (particularly in children and adolescent patients), Very Rare: Arthritis, calcinosis (calcification of ligaments and tendons), epiphyses premature fusion, exostosis, (hyperostosis), reduced bone density, tendonitis. Renal and urinary disorders: Very Rare: Glomerulonephritis. General disorders and administration site conditions: Very Rare: Granulation tissue (increased formation of), malaise. Overdose Isotretinoin is a derivative of vitamin A. Although the acute toxicity of Isotretinoin is low, signs of hypervitaminosis A could appear in cases of accidental overdose. Manifestations of acute vitamin A toxicity include severe headache, nausea or vomiting, drowsiness, irritability, and pruritus. Signs and symptoms of accidental or deliberate overdosage with Isotretinoin would probably be similar. These symptoms would be expected to be reversible and to subside without the need for treatment. Pharmaceutical precautions Store in a cool and dry place protected from light.

Pregnancy & Lactation:
Pregnancy is an absolute contraindication to treatment with Isotretinoin. If pregnancy does occur in spite of these precautions during treatment with Isotretinoin or in the month following, there is a great risk of very severe and serious malformation of the foetus. The foetal malformations associated with exposure to Isotretinoin include central nervous system abnormalities (hydrocephalus, cerebellar malformation/abnormalities, microcephaly), facial dysmorphia, cleft palate, external ear abnormalities (absence of external ear, small or absent external auditory canals), eye abnormalities (microphthalmia), cardiovascular abnormalities (conotruncal malformations such as tetralogy of Fallot, transposition of great vessels, septal defects), thymus gland abnormality and parathyroid gland abnormalities. There is also an increased incidence of spontaneous abortion. If pregnancy occurs in a woman treated with isotretinoin, treatment must be stopped and the patient should be referred to a physician specialized or experienced in teratology for evaluation and advice. Isotretinoin is highly lipophilic, therefore the passage of isotretinoin into human milk is very likely. Due to the potential for adverse effects in the child exposed via mothers’ milk, the use of Isotretinoin is contraindicated in nursing mothers.

Precautions & Warnings:

• Contraception: Female patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception. As a minimum requirement, female patients at potential risk of pregnancy must use at least one effective method of contraception. Preferably the patient should use two complementary forms of contraception including a barrier method. Contraception should be continued for at least 1 month after stopping treatment with Isotretinoin, even in patients with amenorrhea.
• Pregnancy testing: According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25mIU/mL are recommended to be performed in the first 3 days of the menstrual cycle, as follows.
• Prior to starting therapy: In order to exclude the possibility of pregnancy prior to starting contraception, it is recommended that an initial medically supervised pregnancy test should be performed and its date and result recorded. In patients without regular menses, the timing of this pregnancy test should reflect the sexual activity of the patient and should be undertaken approximately 3 weeks after the patient last had unprotected sexual intercourse. The prescriber should educate the patient about contraception. A medically supervised pregnancy test should also be performed during the consultation when Isotretinoin is prescribed or in the 3 days prior to the visit to the prescriber and should have been delayed until the patient had been using effective contraception for at least 1 month. This test should ensure the patient is not pregnant when she starts treatment with Isotretinoin.
• Follow-up visits: Follow-up visits should be arranged at 28-day intervals. The need for repeated medically supervised pregnancy tests every month should be determined according to local practice including consideration of the patient’s sexual activity and recent menstrual history (abnormal menses, missed periods, or amenorrhea). Where indicated, follow-up pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber.
• End of treatment: Five weeks after stopping treatment, women should undergo a final pregnancy test to exclude pregnancy.
• Prescribing and dispensing restrictions: Prescriptions of Isotretinoin for women of childbearing potential should be limited to 30 days of treatment and continuation of treatment requires a new prescription. Ideally, pregnancy testing, issuing a prescription, and dispensing of Isotretinoin should occur on the same day. Dispensing of isotretinoin should occur within a maximum of 7 days of the prescription.
• Male patients: The available data suggest that the level of maternal exposure from the semen of the patients receiving Isotretinoin is not of a sufficient magnitude to be associated with the teratogenic effects of Isotretinoin. Male patients should be reminded that they must not share their medication with anyone, particularly not females.
• Additional precautions: Patients should be instructed never to give this medicinal product to another person, and to return any unused capsules to their pharmacist at the end of treatment. Patients should not donate blood during therapy and for 1 month following discontinuation of Isotretinoin because of the potential risk to the foetus of a pregnant transfusion recipient.
• Psychiatric disorders: Depression, depression aggravated, anxiety, aggressive tendencies, mood alterations, psychotic symptoms, and very rarely, suicidal ideation, suicide attempts, and suicide have been reported in patients treated with Isotretinoin. Particular care needs to be taken in patients with a history of depression and all patients should be monitored for signs of depression and referred for appropriate treatment if necessary. However, discontinuation of isotretinoin may be insufficient to alleviate symptoms, and therefore further psychiatric or psychological evaluation may be necessary.
• Skin and subcutaneous tissues disorders: Acute exacerbation of acne is occasionally seen during the initial period but this subsides with continued treatment, usually within 7-10 days, and usually does not require dose adjustment. Exposure to intense sunlight or to UV rays should be avoided. Where necessary a sun-protection product with a high protection factor of at least SPF 15 should be used. Aggressive chemical dermabrasion and cutaneous laser treatment should be avoided in patients on Isotretinoin for a period of 5-6 months after the end of the treatment because of the risk of hypertrophic scarring in atypical areas and more rarely post-inflammatory hyper or hypopigmentation in treated areas. Wax depilation should be avoided in patients on Isotretinoin for at least a period of 6 months after treatment because of the risk of epidermal stripping. Concurrent administration of isotretinoin with topical keratolytic or exfoliative anti-acne agents should be avoided as local irritation may increase. Patients should be advised to use a skin moisturizing ointment or cream and a lip balm from the start of treatment as isotretinoin is likely to cause dryness of the skin and lips. There have been post-marketing reports of severe skin reactions (e.g. erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN)) associated with Isotretinoin use. As these events may be difficult to distinguish from other skin reactions that may occur, patients should be advised of the signs and symptoms and monitored closely for severe skin reactions. If a severe skin reaction is suspected, Isotretinoin treatment should be discontinued. Allergic reactions: Anaphylactic reactions have been rarely reported, in some cases after previous topical exposure to retinoids. Allergic cutaneous reactions are reported infrequently. Serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement have been reported. Severe allergic reactions necessitate interruption of therapy and careful monitoring.
• Eye disorders: Dry eyes, corneal opacities, decreased night vision, and keratitis usually resolve after discontinuation of therapy. Dry eyes can be helped by the application of a lubricating eye ointment or by the application of tear replacement therapy. Intolerance to contact lenses may occur which may necessitate the patient to wear glasses during treatment. Decreased night vision has also been reported and the onset in some patients was sudden. Withdrawal of Isotretinoin may be necessary.
• Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, and increased serum creatine phosphokinase values have been reported in patients receiving Isotretinoin, particularly in those undertaking vigorous physical activity. Bone changes including premature epiphyseal closure, hyperostosis, and calcification of tendons and ligaments have occurred after several years of administration at very high doses for treating disorders of keratinization. The dose levels, duration of treatment, and total cumulative dose in these patients generally far exceeded those recommended for the treatment of acne.
• Benign intracranial hypertension: Cases of benign intracranial hypertension have been reported, some of which involved concomitant use of tetracyclines. Signs and symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances, and papilloedema. Patients who develop benign intracranial hypertension should discontinue Isotretinoin immediately.
• Hepatobiliary disorders: Liver enzymes should be checked before treatment, 1 month after the start of treatment, and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated. Transient and reversible increases in liver transaminases have been reported. In many cases, these changes have been within the normal range and values have returned to baseline levels during treatment. However, in the event of persistent clinically relevant elevation of transaminase levels, reduction of the dose or discontinuation of treatment should be considered.
• Renal insufficiency: Renal insufficiency and renal failure do not affect the pharmacokinetics of Isotretinoin. Therefore, Isotretinoin can be given to patients with renal insufficiency. However, it is recommended that patients are started on a low dose and titrated up to the maximum tolerated dose.
• Lipid Metabolism: Serum lipids (fasting values) should be checked before treatment, 1 month after the start of treatment, and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated. Elevated serum lipid values usually return to normal on reduction of the dose or discontinuation of treatment and may also respond to dietary measures. Isotretinoin has been associated with an increase in plasma triglyceride levels. Isotretinoin should be discontinued if hypertriglyceridaemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur. Levels in excess of 800mg/dL or 9mmol/L are sometimes associated with acute pancreatitis, which may be fatal.
• Gastrointestinal disorders: Isotretinoin has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. Patients experiencing severe (hemorrhagic) diarrhoea should discontinue Isotretinoin immediately.
• High-Risk Patients: In patients with diabetes, obesity, alcoholism, or a lipid metabolism disorder undergoing treatment with Isotretinoin, more frequent checks of serum values for lipids and/or blood glucose may be necessary. Elevated fasting blood sugars have been reported, and new cases of diabetes have been diagnosed during Isotretinoin therapy.

Storage:
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.