When conventional medications, such as antibiotics (doxycycline, minocycline, and azithromycin) and topical vitamin A derivatives like adapalene, are ineffective in treating severe cystic or nodular acne, isotretinoin (Accutane, Claravis) is recommended.

Isotretinoin Uses:

• Severe recalcitrant nodular Acne:

  • Treatment for severe, resistant, nodular acne that is not responding to traditional medicine (including systemic antibiotics)

• Off Label Use of Isotretinoin in Adults:

  • Squamous cell skin cancer (prevention in high-risk patients)
  • Cutaneous T-cell lymphomas
  • Moderate Acne

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Isotretinoin Dose in Adults:

Isotretinoin Dose in the treatment of Severe Recalcitrant Nodular Acne:

• 1 mg per kg per day in 2 divided doses as tolerated after one month of 5 mg per kg per day in 2 divided doses. 
• Continue until you've administered 120 to 150 mg/kg cumulatively. 
• Authenticator's labelling: 
  • Current clinical practice might not be reflected in the dosing in the prescribed instructions. 
  • In two split dosages, 0.5 to 1 mg/kg/day. 
  • Adults who have a very severe illness, scarring, or trunk involvement may need to increase their dosage by up to 2 mg/kg/day, as tolerated.

Dose in the therapy of Squamous cell skin cancer, prevention in high-risk patients (off-label):

• Oral: Initial dosage is 0.25 mg/kg every other day for a month, followed by 0.25 mg/kg daily for a month, and finally 0.5 mg/kg daily.
• Depending on tolerance, adjust the dose as necessary; for severe skin cancer, higher doses could be more beneficial.
• To more clearly describe the function of isotretinoin in this situation, more information could be required.

Isotretinoin dose in the therapy of moderately severe Acne: Oral:

• Low-dose regimens:

  • For 24 weeks, take 0.25 to 0.4 mg per kilogramme every day.
  • 20 milligrammes per day for six months (between 0.3 and 0.4 mg/kg/day).

Dose in Cutaneous T-cell lymphomas (off-label):

• Oral: For 3 to 4 months, provide 1 mg/kg/day (split into two doses) together with interferon alfa-2b.
• If there is a response, the treatment may be continued for a further three months
• if the response persists after six months of therapy, isotretinoin and interferon alfa-2b may be administered at a 50% lower dose for a further three months, followed by interferon alfa-2b maintenance therapy.
• To more clearly characterise the function of isotretinoin in the treatment of this illness, more studies may be required.

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Isotretinoin Dose in Children:

Isotretinoin Dose in the treatment of severe recalcitrant nodular acne vulgaris:

• Children over 12 years and Adolescents:

  • For severe instances (including the trunk, nuchal area, lower back, buttocks, and thighs), greater dosages up to 2 mg/kg/day in two separate doses may be necessary.
  • Oral: 0.5 to 1 mg/kg/day in 2 divided doses.
  • Typically, the course of treatment lasts 15 to 20 weeks, or for as long as it takes the total number of cysts to reduce by 70%, whichever comes first.
  • An alternative reported strategy is to continue the course of treatment until a cumulative total of 120 mg/kg (for example, 1 mg/kg/day for 120 days).
  • To reduce early flare, an initial dosage of 0.5 mg/kg/day may be utilised.

Dose in the therapy of moderately severe acne vulgaris: 

• Adolescents and Children over 12 years of age:

  • Effectiveness has been demonstrated at doses of 20 mg/day (0.3 to 0.5 mg/kg/day) given continuously for 6 to 12 months, totaling 120 mg/kg.

Dose in the maintenance therapy of Neuroblastoma:

• Infants, Children, and Adolescents:

  • Oral: 80 mg/m2 per dose every 12 hrs for the final two weeks (14 days in a row) of a cycle of four weeks for a total of six cycles.

  • The first week of the four-week cycle is when the dinutuximab treatment is given.

  • Start following more chemotherapy or a transplant.

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Pregnancy Risk Factor X

• The medication and its metabolites may be found in foetal tissues after maternal usage.
• It is not advised if you are pregnant.
• Any foetus that is exposed while pregnant might possibly be harmed.
• It is hard to tell whether a foetus that was exposed was harmed.
• [Warning in Us Boxes] It should not be used by patients who are pregnant or may become pregnant.
• Severe birth abnormalities are quite likely. Even for brief periods of time, isotretinoin use can result in birth abnormalities.
• Premature births and spontaneous abortions are both often reported.
• Skull deformity, ear abnormalities (including anotia and micropinna), eye abnormalities, facial dysmorphia, and microphthalmia are among the known external abnormalities.
• CNS abnormalities are documented as cerebellar malformations, hydrocephalus and microcephaly.
• They also include cerebral abnormalities, cerebellar malformations, cerebellar malformations, hydrocephalus and cranial nerve deficiency.
• Thymus gland abnormalities; cardiovascular abnormalities; parathyroid hormone deficiencies.
• Birth abnormalities in the heart, parathyroid glands, brain, skull, and ears have been linked to isotretinoin.
• There are instances with IQs (intelligence quotients) below 85, with or without additional anomalies, according to reports.
• Sometimes, death occurs with some of the abnormalities that were previously observed.
• Patients who are exposed to the medication while pregnant must stop therapy right once, and they should be sent to an obstetrician-gynecologist with knowledge of reproductive toxicity for further testing and counselling.
• Patients with a childbearing potential need to be able and willing to follow the iPLEDGE(tm), pregnancy prevention program guidelines.
• Before beginning therapy, females with childbearing potential should have at least two negative pregnancy tests. Testing should be continued every month throughout therapy.
• Prior to beginning therapy, throughout the course of treatment, and for at least one month after it is over, you should utilise two types of contraception concurrently and regularly.
• Patients who are capable of having children shouldn't get pregnant while receiving treatment or within a month after quitting isotretinoin.
• After stopping the medication, patients who are capable of having children should take a pregnancy test within a month.
• Any pregnancies should be reported to the iPLEDGE(tm) program (www.ipledgeprogram.com or 866495-0654) and the FDA through MedWatch (800-FDA-1088).

Isotretinoin use during breastfeeding:

• It is unknown if breast milk contains isotretinoin.
• A case report describes drug-induced galactorrhea that manifests as the release of a greenish liquid out of the breasts.
• The manufacturer does not recommend breastfeeding due to the risk of serious adverse reactions in breastfed babies.

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Dose in Kidney Disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Isotretinoin Dose in Liver Disease:

• Hepatic impairment prior to treatment:
  • The manufacturer's labelling does not mention dose changes. 
• Hepatotoxicity when receiving treatment:
  • If normalisation of the liver enzymes does not happen quickly or if hepatitis is detected, stop taking the medication.

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Side Effects of Isotretinoin:

• Neuromuscular & skeletal:

  • Back pain

• Endocrine & metabolic:

  • Increased serum triglycerides

Less Common Side Effects of Isotretinoin:

• Ophthalmic:

  • Conjunctivitis
  • Blepharitis
  • Chalazion
  • Hordeolum

Side effects of Isotretinoin (Frequency not defined):

• Respiratory:

  • Bronchospasm
  • Dry Nose
  • Epistaxis
  • Granulomatosis With Polyangiitis
  • Respiratory Tract Infection
  • Voice Disorder
•  

• Cardiovascular:

  • Palpitations
  • Syncope
  • Cerebrovascular Accident
  • Chest Pain
  • Edema
  • Flushing
  • Tachycardia
  • Thrombosis

• Hypersensitivity:

  • Anaphylaxis
  • Hypersensitivity Reaction

• Central Nervous System:

  • Drowsiness
  • Malaise
  • Nervousness
  • Aggressive Behavior
  • Depression
  • Dizziness
  • Paresthesia
  • Pseudotumor Cerebri
  • Psychosis
  • Seizure
  • Emotional Lability
  • Fatigue
  • Headache
  • Insomnia
  • Lethargy
  • Suicidal Ideation
  • Vasculitis (Renal)
  • Violent Behavior

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Aspartate Aminotransferase
  • Hepatitis

• Dermatologic:

  • Diaphoresis
  • Eczema
  • Eruptive Xanthoma
  • Hypopigmentation
  • Nail Disease
  • Acne Fulminans
  • Allergic Skin Reaction
  • Alopecia
  • Cheilitis
  • Paronychia
  • Pruritus
  • Pyogenic Granuloma
  • Scaling Of Skin Of Feet
  • Skin Atrophy
  • Skin Photosensitivity
  • Facial Erythema
  • Hair Disease
  • Hirsutism
  • Hyperpigmentation
  • Skin Rash
  • Sunburn (Increased Susceptibility)
  • Superficial Peeling Of Palms
  • Xeroderma

• Endocrine & Metabolic:

  • Menstrual Disease
  • Weight Loss
  • Increased Lactate Dehydrogenase
  • Increased Serum Cholesterol
  • Increased Serum Glucose
  • Decreased HDL Cholesterol
  • Increased Gamma-Glutamyl Transferase
  • Hyperuricemia

• Infection:

  • Herpes Simplex Infection (Disseminated)
  • Infection

• Gastrointestinal:

  • Gastrointestinal Signs And Symptoms (Nonspecific)
  • Gingival Hemorrhage
  • Pancreatitis
  • Xerostomia
  • Gingivitis
  • Inflammatory Bowel Disease
  • Nausea
  • Colitis
  • Esophagitis
  • Esophageal Ulcer

• Genitourinary:

  • Genitourinary Disease (Nonspecific Findings)
  • Hematuria
  • Proteinuria
  • Pyuria

• Hematologic & Oncologic:

  • Anemia
  • Bruise
  • Lymphadenopathy
  • Neutropenia
  • Purpuric Disease
  • Thrombocytopenia

• Renal:

  • Glomerulonephritis

• Miscellaneous:

  • Wound Healing Impairment

• Neuromuscular & Skeletal:

  • Asthenia
  • Arthralgia
  • Arthritis
  • Bone Disease
  • Calcification Of Ligament
  • Calcification Of Tendon
  • Decreased Bone Mineral Density
  • Increased Creatine Phosphokinase In Blood Specimen
  • Myalgia
  • Premature Epiphyseal Closure
  • Skeletal Hyperostosis
  • Tendonitis

• Ophthalmic:

  • Cataract
  • Corneal Opacity
  • Keratitis
  • Night Blindness
  • Optic Neuritis
  • Photophobia
  • Vision Color Changes
  • Visual Disturbance

• Otic:

  • Auditory Impairment
  • Tinnitus

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Contraindications to Isotretinoin:

• Pregnancy or the possibility of becoming pregnant
• Allergy reactions to the drug, or any component thereof
• Hypersensitivity to parabens (Zenatane and vitamin A only)

Canadian labeling: Additional contraindications that are not found in the US labeling

• Breastfeeding
• Hyperlipidemia
• Concurrent tetracycline treatment
• Hepatic or renal impairment
• Hypervitaminosis A

Warnings and precautions

• Auditory impairment

  • It is possible to develop hearing impairment even after treatment has been stopped.
  • Stop using the treatment if you experience hearing loss or tinnitus.

• Loss of bone mineral density:

  • Reduced bone mineral density, osteoporosis, and osteopenia might result from it. Fracture healing has also been found to be delayed.
  • Patients with a genetic propensity for bone loss (e.g., age-related osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism) should be treated with caution, as should those with anorexia nervosa and those taking concurrent medications that may affect vitamin D metabolism or cause drug-induced osteoporosis or osteomalacia. These medications include systemic corticosteroids, anticonvulsants,
  • Patients may be more vulnerable to injuries from repetitive impact activities (like sports), which are known to increase the risk of hip growth plate injuries in late adolescence and early adulthood as well as spondylolisthesis, with or without pars fractures.

• Growth effects

  • It is a common treatment for skelet hyperostosis, premature epiphyseal closing of bones, and other conditions.

• Hematologic effects

  • There have been reports of agranulocytosis and, in rare circumstances, neutropenia.
  • Treatment should be stopped if there are clinically substantial reductions in white cell count.

• Dermatologic effects

  • For serious skin responses, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, keep an eye on the patient after post-marketing reports of the condition erythema multiflora.
  • Stop the therapy if there are any serious side effects.
•  

• Hepatic effects

  • It can result in clinical hepatitis when used. Elevations of mild to severe liver enzymes may also result from it. The dose might be changed to remedy this.
  • It is advised to cease taking all medications if you have a suspicion of having hepatitis.

• Hypersensitivity reactions

  • There have been occurrences of anaphylaxis as well as other allergic responses, such as severe allergic vasculitis and cutaneous reactions.
  • If you experience severe allergic reactions, discontinue treatment and seek medical advice.

• Inflammatory bowel disease

  • Inflammatory bowel disease has been identified in people who have no prior history of intestinal issues (including regional ileitis).
  • Stop the therapy as soon as severe diarrhoea, stomach discomfort, or rectal bleeding appears.
  • According to a statement from the American Academy of Dermatology, there is insufficient proof to link the use of isotretinoin with IBD.

• Musculoskeletal effects

  • There have been reports of musculoskeletal symptoms, including arthralgia.
  • Symptoms were generally mild to moderate and sometimes required discontinuation or reduction in therapy.
  • Sometimes, there is a temporary pain in the chest. Symptoms usually disappear after stopping therapy. However, in some cases, they persist.
  • Rhabdomyolysis has been associated with strenuous exercise, but it is rare.

• Ocular effects

  • The use of contact lenses has been linked to vision impairment, corneal opacities and decreased tolerance (due to dry eye), as well as decreased night vision.
  • Patients with visual impairments should stop receiving treatment.
  • Patients should be careful when operating machinery or driving at night.

• Pancreatitis

  • Acute pancreatitis can strike patients with increased or normal triglyceride levels. Rarely, there have been cases of deadly hemorrhagic pancreatitis.
  • Discontinue treatment if hypertriglyceridemia is not brought under control to an appropriate level or if pancreatitis symptoms appear.

• Photosensitivity

  • Avoid direct sunlight or ultraviolet rays.

• Diabetes:

  • Patients with diabetes mellitus should exercise caution because there have been reports of poor glucose control.
•  

• Pseudotumor cerebri:

  • Pseudotumor cerebri (benign inner hypertension) has been linked to retinoids, especially in children.
  • The risk may be increased by concurrent use of other drugs that have this effect (e.g. tetracyclines).
  • If papilledema develops, immediately stop and consult a neurologist.

• Psychiatric effects

  • These drugs can cause psychosis, depression, mood disturbance, suicidal ideation and suicide attempts.
  • Suicidal thoughts and indications of despair should be regularly watched in patients.
  • If you experience depression, mood disturbances, psychosis or aggression, discontinue therapy.
  • It may not be enough to stop treatment. Further evaluation may be required.
  • Patients with a history of psychiatric disorders should be cautious.

• Hypertriglyceridemia:

  • There have been reports of markedly elevated serum triglycerides.
  • Hypertriglyceridemia patients should exercise caution, as should those who are high risk (such as those with diabetes, obesity, or increasing alcohol use).
  • After discontinuation of therapy, the effects on cholesterol, HDL, and triglycerides were reversed.
  • Remind patients to restrict or stay away from ethanol. Triglyceride levels may rise as a result of excessive intake.

Isotretinoin: Drug Interaction

Risk Factor C (Monitor therapy)
Alcohol (Ethyl)	May intensify the negative or harmful effects of isotretinoin (Systemic). Particularly, there may be a higher chance of having elevated triglyceride concentrations.
Aminolevulinic Acid (Topical)	Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Topical).
Mipomersen	The hepatotoxic effects of Mipomersen may be enhanced by ISOtretinoin (Systemic).
Porfimer	The photosensitizing action of Porfimer may be enhanced by photosensitizing agents.
Verteporfin	.Verteporfin's photosensitizing action may be strengthened by photosensitizing agents.
Risk Factor D (Consider therapy modification)
Progestins (Contraceptive)	The therapeutic benefit of progestins may be diminished by retinoic acid derivatives (Contraceptive). Progesterone serum levels may be reduced by retinoic acid derivatives (Contraceptive). Treatment: Patients using retinoic acid derivatives should utilise two kinds of reliable contraception. Minipills that contain just microdosed progesterone and no oestrogen are regarded as ineffective forms of contraception.
Risk Factor X (Avoid combination)
Aminolevulinic Acid (Systemic)	Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Systemic).
Multivitamins/Fluoride (with ADE)	may intensify the negative or harmful effects of derivatives of retinoic acid.
Multivitamins/Minerals (with ADEK, Folate, Iron)	may intensify the negative or harmful effects of derivatives of retinoic acid.
Multivitamins/Minerals (with AE, No Iron)	may intensify the negative or harmful effects of derivatives of retinoic acid.
Tetracyclines	May intensify the negative or harmful effects of derivatives of retinoic acid. It is especially concerning when pseudotumor cerebri develops.
Vitamin A	May intensify the negative or harmful effects of derivatives of retinoic acid.

 

Monitoring parameters:

• Severe skin reactionsCBC with differential and platelet count
• Signs of depression, mood alteration, psychosis, and aggression
• Baseline sedimentation rate
• Glucose
• CPK
• Changes in vision

Liver function tests:

• Before beginning treatment, once every two weeks, or whenever the treatment's effectiveness has been determined.

Imipenem Cilastatin (Tienam)

• Prior to therapy and every week or two weeks until the effectiveness of the treatment has been determined.
• The test shouldn't be done less than 36 hours following ethanol ingestion.

Pregnancy test (for all patients of childbearing potential):

• Prior to starting treatment, a woman must have two negative tests with a sensitivity of at least 25 milliunits/mL (the second test must be carried out at least 19 days after the first and during the first five days of her menstrual period); monthly pregnancy tests must be negative before a prescription can be renewed and must be performed one month after stopping treatment (Absorica).

Monitor adherence while being utilised for oncology reasons.

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How to administer Isotretinoin?

Oral:

• Administer while eating (except Absorica, which may be taken without regard to meals).
• The manufacturer's labelling states that capsules should be consumed whole along with a full glass of drink; they should not be chewed or sucked on.
• If a patient is unable to swallow the capsule whole, an oral liquid may be made (see Temporarily Made); removing the medication from the capsule may cause esophageal irritation.
• It is not advised and has not been shown safe to take isotretinoin once a day.

Neuroblastoma (off-label use):

• In pharmacokinetic research, if patients were unable to swallow capsules whole, the end of the capsule was pierced or sliced, and capsule contents were extruded into ice cream or yoghurt; if the capsule is opened, contents must be taken right away to prevent deterioration.
• For further information, see Extemporaneously Prepared.

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Mechanism of action of Isotretinoin:

• When used to treat acne, it reduces the size and production of sebum.
• It is used to treat neuroblastoma.
• It decreases cell proliferation and induces differentiation.

Notification-

• Pharmacokinetic parameters for adolescents (13-15 years) are the same as those of adults.

Half-life elimination:

• Terminal: Parent drug: 21 hours;
• Metabolite: 21 to 24 hours

Absorption:

• Enhanced by a supper heavy in fat
• If Absorica is administered while the patient is fasting, it absorbs 83% more than Accutane. When consumed with meals that are heavy in fat, they are bioequivalent.

Metabolism:

• A significant metabolite produced by the liver via CYP2B6, 2C8, 2C9, and 3A4 is 4-oxoisotretinoin (active)

Excretion:

• Urine and feces (equal amounts)

Protein binding:

• 99% to 100% (primarily to albumin)

Time to peak, serum:

• 3 to 5 hours

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International Brand Names of Isotretinoin:

 

• Accutane Roche
• ALTI-Isotretinoin
• Clarus
• Epuris
• Accotin
• Acnal SC
• Absorica
• Zenatane
• Acnecur
• Acnelar
• Acnemin
• Absorica LD
• Amnesteem
• Claravis
• Myorisan
• Acnetrex
• Acnotin
• Acnova
• Atlacne
• Cosmin
• Curacne
• Curacne Ge
• Curakne
• Akinol
• Aknenormin
• Aknetin
• Aknil Gel
• Curatane
• Dercutane
• Dermatane
• Hyndriax
• Isocural
• Isocutan
• Isoface
• Isolve
• Isosupra
• Isotane
• Isotina
• Isotinon
• Atretin
• Ciscutan
• Claravis
• Contracne
• Isotren
• Isotret-Hexal
• Isotrex
• Isotrex Gel
• Isotroin
• LOAC SC
• Neotrex
• Netlook
• Nimegen
• Oratane
• Procuta Ge
• Reducar
• Reticap-5
• Retigel
• Roaccutan
• Roaccutane
• Roacnetan
• Roacta
• Roacutan
• Rocta
• Sotret
• Sotrexe
• Tretinex

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Isotretinoin Brand Names in Pakistan:

Isotretinoin Cream 0.5 mg in Pakistan
ACCUNATE	SAFE PHARMACEUTICAL (PVT) LTD.
ISO-BAN PLUS	LINEAR PHARMA

 

Isotretinoin Cream 0.05 %w/w in Pakistan
COSMIN	SAFFRON PHARMACEUTICAL COMPANY
ISONEX	SHROOQ PHARMACEUTICALS

 

Isotretinoin Gel 0.5 % in Pakistan
ISOTONE	BIOGEN PHARMA

 

Isotretinoin Gel 0.05 % in Pakistan
ISOMED	MEDERA PHARMACEUTICALS (PVT) LTD.

 

Isotretinoin Gel 0.05 %w/w in Pakistan
COSMUN	FESTEL LAB
ISO A	BROOKES PHARMACEUTICAL LABORATORIES (PAK.) LTD.
ISO-A	PEARL PHARMACEUTICALS
ISONEX	SHROOQ PHARMACEUTICALS
ISOTIN	Shaigan Pharmaceuticals (PVT) LTD
ISOTREX	GLAXOSMITHKLINE
ORANATE	PEARL PHARMACEUTICALS
TRETIDERM	DERMA TECHNO PAKISTAN

 

Isotretinoin Gel 0.05 % w/w in Pakistan
ISTEROL	VALOR PHARMACEUTICALS

 

Isotretinoin Gel 0.05 %w/w in Pakistan
ORATRAXIN	PEARL PHARMACEUTICALS

 

Isotretinoin Tablets 10 mg in Pakistan
ORIVER	TABROS PHARMA

 

Isotretinoin Tablets 20 mg in Pakistan
ACNOREN	GILLMAN PHARMACEUTICALS
ISOFACE TABLET	GENOME PHARMACEUTICALS (PVT) LTD
ORIVER	TABROS PHARMA
TREZO	GENERA PHARMACEUTICALS
TREZO	GENERA PHARMACEUTICALS

 

Isotretinoin Capsules 10 mg in Pakistan
ACNEWIN	WNS FIELD PHARMACEUTICALS
ACNO	PARAMOUNT PHARMACEUTICALS
ACNO	PARAMOUNT PHARMACEUTICALS
ACNOGEN	ROTEX MEDICA PAKISTAN (PVT) LTD
ACNOGEN	ROTEX MEDICA PAKISTAN (PVT) LTD
FREAC	WESTMED PHARM (PVT) LTD
ISO-A	PEARL PHARMACEUTICALS
ISOFACE	MEDISEARCH PHARMACAL(PVT) LTD
ISONEX	SHROOQ PHARMACEUTICALS
ISOTOP	PANACEA PHARMACEUTICALS
ISOZAM	VALOR PHARMACEUTICALS
ORATANE	PEARL PHARMACEUTICALS
RECUTE	SHAWAN PHARMACEUTICALS
RECUTE	SHAWAN PHARMACEUTICALS
ROACCUTANE	ROCHE PAKISTAN LTD.
SONION	SEMOS PHARMACEUTICALS (PVT) LTD.
SONION	SEMOS PHARMACEUTICALS (PVT) LTD.

 

Isotretinoin Capsules 20 mg in Pakistan
ACCURE	DERMAGEN PHARMA PAKISTAN (PVT) LIMITED
ACCUTANE	AIMS TRADERS
ACNETRAC	WARAFANA PHARMACEUTICALS
ACNETRAC	WARAFANA PHARMACEUTICALS
ACNETRAC	WARAFANA PHARMACEUTICALS
ACNEWIN	WNS FIELD PHARMACEUTICALS
ACNO	PARAMOUNT PHARMACEUTICALS
ACNO	PARAMOUNT PHARMACEUTICALS
ACNO	PARAMOUNT PHARMACEUTICALS
ACNOGEN	ROTEX MEDICA PAKISTAN (PVT) LTD
AKNEFIN	WISE PHARMACEUTICALS (PVT) LTD
ARYNOIN	PHARMA HEALTH PAKISTAN (PVT) LTD
BEFAST	WEBROS PHARMACEUTICALS
FREAC	WESTMED PHARM (PVT) LTD
ISO-A	PEARL PHARMACEUTICALS
ISODERM	CANDID PHARMACEUTICALS
ISODERM	CANDID PHARMACEUTICALS
ISOFACE	MEDISEARCH PHARMACAL(PVT) LTD
ISOLEX	AMBROSIA PHARMACEUTICALS
ISOLIT	GOODMAN LABORATORIES
ISOLIT	GOODMAN LABORATORIES
ISOMERA	MEDERA PHARMACEUTICALS (PVT) LTD.
ISONAS	DERMAGEN PHARMA PAKISTAN (PVT) LIMITED
ISONEX	SHROOQ PHARMACEUTICALS
ISOTOP	PANACEA PHARMACEUTICALS
ISOWAN–T	SWAN PHARMACEUTICALS(PVT) LTD
ISOZAM	VALOR PHARMACEUTICALS
ORATANE	PEARL PHARMACEUTICALS
RECUTANE	Remedy Pharmaceuticals (Pvt) Ltd
RECUTE	SHAWAN PHARMACEUTICALS
RECUTE	SHAWAN PHARMACEUTICALS
RESOFT	MERILINE PHARMACEUTICALS
ROACADVAN	ADVANCED PHARMACEUTICALS
ROACCUTANE	ROCHE PAKISTAN LTD.
SONION	SEMOS PHARMACEUTICALS (PVT) LTD.
SONION	SEMOS PHARMACEUTICALS (PVT) LTD.
SORETIN	HYGEIA PHARMACEUTICALS
TRESTON	AXIS PHARMACEUTICALS
VERION	FLORENCE FARMACEUTICALS (PVT) LTD