1. INDICATION : ERECTILE DYSFUNCTION off-label marketing

2. INDICATION : HYPERTENSION off-label marketing

3. DOES THIS SOUND ABSURD ??? off-label marketing

4. off-label marketing PRESENTED BY : VIRENDRA KUMAR SEMESTER- I ROLL-NO : 32 MBA(PHARM)

5.

• Off-label use

• Off-label marketing

• Off-label prescription

• Off-label promotion

• Case studies

• Drugs commonly used off label

• FDAMA-1997

• Concluding remarks

off-label marketing

6.

• The FDA regulates the manufacture, labeling, and promotion of drugs

• • In the NDA, the applicant has to prove that the drug is safe and effective for various uses

• • • These uses become the labeled usesthe uses for which the tests have been conducted.

• • • Once a drug is approved by the FDA, various medical researchers and practictioners may discover that such drugs have other valid (off-label) uses.

off-label marketing

7.

• • The FDA does not regulate the practice of medicine

• • It is completely legal for physicians to prescribe pharmaceutical drugs for off-label uses, so long as what they are doing is not research

• • off-label use of pharmaceutical drugs could potentially subject doctors to liability for malpractice.

off-label marketing

8.

• Off-label prescription

• FDA regulations pro hibit DTC promotion & restrict physiciantargeted promotion

• Unproven off-label use may be costly and threaten patient safety

off-label marketing

9.

• FDA

• • focuses on market entry

• • historically maintained a hands-off approach

• Sometimes little market incentive to seek approval for additional indications:

• • older & generically available drugs

• • population size too small

• No alternatives exist: orphan drugs & pediatric

• Desire to broaden therapeutic alternatives:

• • failure of standard therapy

• • innovation seeking behavior

off-label marketing

10.

• Have a huge stake in off-label uses of their products

• • One source estimates that 40 percent of the prescriptions are off-label

• In general, drug manufacturers are not allowed by statute and the FDA to promote off-label uses for the products

• • Not allowed to advertise off-label uses

• • Not allowed to induce physicians to prescribe off-label uses

off-label marketing

11.

• Clinically Reasonable

• Well-known evidence based-therapy

• Supported by treatment guidelines

• Other drugs in class are indicated

• Cost-effective generic substitution

• Innovative approaches when standard therapies fail

• Concerns

• May not bear same degree of clinical or scientific scrutiny as labeled indications

• Inconclusive evidence:

• • contraindications

• • safe dose

• • ADRs

• Over use of unproven off-label therapies may be costly

off-label marketing

12.

• In general, doctors may prescribe a drug for unapproved uses

• In general, manufacturers may not promote unapproved uses.

• Benefits: some off-label uses are scientifically valid and provide tremendous benefits to patients, especially in areas of life-saving drugs

• Risks: no guarantee of scientific validity; unknown health risks; waste of public resources; certain side effects not justified

off-label marketing

13.

• Profit motive:

• -Clinical trials costly

• -Off-label sales can be significant

• -These factors can affect corporate judgment

• Off-label promotion relies on covert marketing techniques

• Before 1997, FDA allowed dissemination of information about off-label uses only when such information was solicited by the physician

off-label marketing

14. off-label marketing Figure 1. Proportion of Off-Label Prescribing by Functional Class

15. off-label marketing

16.

• In June 2004,Pfizer had paid $ 430 in fine and civil judgments

• Acc. To FDA ,the Parke Davis division of Warner Lambert (which was acquired by Pfizer in 2000) was aggressively marketing Neurontin for off-label uses.

off-label marketing

17.

• Neurontin (gabapentin) is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults with epilepsy, at doses ranging between 900 mg to 1800 mg per day

off-label marketing APPROVED INDICATION (between 1994 2001)

18.

• Alcohol Detoxification

• Amyotrophic Lateral Sclerosis

• Antidepressant-Induced Bruxism

• Anxiety Disorder; Panic Disorder; OCD

• Behavior Problems - Dementia-Related

• Bipolar Disorder; Mania

• Borderline Personality Disorder

• Brachioradial Pruritus

• Central Nervous System Disorders

• Charles Bonnet Syndrome

• Cluster Headache

• Cocaine Dependency

• Dystonia

• Essential Tremor

• Headache (SUNCT)

• Migraine Prophylaxis

• Multiple Sclerosis Complications

• Myalgias - Taxane Induced

• Neuropathic Cancer Pain

• Neuropathic Pain Syndromes

• Neuropathy - HIV-Related

• Nicotine Withdrawal

• Nystagmus

• Orthostatic Tremor

• Pain - Postpoliomyelitis Pain

• Pain - Reflex Sympathetic Dystrophy

• Partial Seizures - Monotherapy

• Phantom Limb Syndrome

• Restless Legs Syndrome

• Social Phobia

• Spasticity

off-label marketing

19. off-label marketing

20.

• Voicemail recordings

• Internal documents

• Vendor documents

• Data (IMS, Scott-Levin, Verispan, Medicaid)

• Witnesses (Sales people, doctors)

• Patent applications

off-label marketing

21.

• Medical Liaisons

• Consultant and advisory board meetings

• CMEs

• Dinner meetings and teleconferences

• Preceptorships

off-label marketing

22.

• Payments to physicians (~$ 50 million to 3,000 physicians)

• -Grants

• -Speaker fees

• -Honoraria

• -Paid vacations

• -Olympics tickets

• Ghostwritten articles

• Suppress negative information

off-label marketing

23.

• US Patent 5,084,479: Neuro-degenerative diseases (1990)

• US Patent 5,510,381: mania and bipolar disorder (1995)

• US Patent 5,792,796: anxiety and panic (1995)

• US Patent 6,242,488: pain (2000)

• US Patent 6,426,368: alcoholism (2001)

off-label marketing

24.

• Initial estimate for lifetime sales of Neurontin was $500 million

• Off-label marketing was successful: in 2003 use of Neurontin for unapproved uses accounted for nearly 90% of its sales

• Sales of Neurontin now exceed $2 billion annually

off-label marketing

25. off-label marketing PAIN (NEURONTIN V. DILANTIN)

26.

• Warner-Lambert pled guilty to two counts of violating the Food Drug & Cosmetic Act

• Warner-Lambert paid $430 million:

• -$152 million to settle federal civil False Claims Act liabilities

• -$38 million to settle its state civil liabilities to the fifty sates and fund remediation program

• -$240 million federal criminal fine

off-label marketing

27.

• Approximately 40% of all drug use is off-label

• 33% of all prescriptions in cancer treatment

• 81% of patients with AIDS receive at least one drug off-label

• 56% of all prescriptions for antidepressants

• Nearly all pediatric patients are prescribed drugs off-label

• Source: Tabarrok, 2000

off-label marketing

28.

• Otsuka American Pharmaceutical, the US unit of the Japanese drugmaker, agreed to pay more than $4 million to resolve allegations that it marketed the Abilify antipsychotic for off-label uses, according to the US Department of Justice .

• From 2002 through 2005, Otsuka knowingly promoted the sale and use of Abilify for pediatric use and to treat dementia-related psychosis, although at the time, the FDA had not approved the drug for use in geriatric patients, teenagers or children.

Pharma Blog - 2008 March 27 CASE-2 se 2

29.

• Botox example

• • 1989: FDA approved for facial neurological movement disorders

• • 2002: FDA approved to combat wrinkles and excessive underarm sweating

• • Currently, FDA approved for both

• • cosmetic and therapeutic uses

• Until 2002, it wasnt illegal from FDA to use Botox for wrinkles but it was prohibited to advertise it for wrinkles

off-label marketing

30.

• ASPIRIN (used off- label till 1998,to reduce the risk of heart attack)

• Viagra (off-label use for erectile dysfunction)

• Minoxidil (used off-label for hair growth)

off-label marketing

31.

• GABAPENTIN (anticonvulsant)

• 83%: 20% supp. / 80% no supp.

• AMITRIPTYLINE (psychiatric:tri-cyclic antidepressant) 79%: 25% supp. / 75% no supp.

• ISOSORBIDE MONONITRATE (cardiac: nitrate)

• 75%: 64% supp. / 36% no supp.

• DIGOXIN (cardiac: dysrythmia)

• 66%: 38% supp. / 62% no supp.

• RISPERIDONE (psychiatric: anti-psychotic)

• 66%: 1% supp. / 99+% no supp.

off-label marketing

32.

• ACTIQ By Cephalon, oral tarnsmucosal fentanyl citrate(OTFC) is used off-label to treat moderate to severe chronic, non-malignant pain even though it is FDA-approved solely for break-through pain in cancer patients.

• Bevacizumab (Avastin, Genentech/Roche) is a monoclonal antibody against vascular endothelial growth factor (VEGF). has been used against Age Related Macular Degeneration, but the evidence for its use is anecdotal.

off-label marketing

33.

• Carbamazepine , or Tegretol, has been used as a mood stabilizer and is accepted treatment for bipolar disorder .

• Methotrexate (MTX), approved for the treatment of choriocarcinoma, is frequently used for the medical treatment of an unruptured ectopic pregnancy. There is no FDA-approved drug for this purpose and there is little incentive to sponsor an unpatented drug such as MTX for FDA-approval.

off-label marketing

34.

• In 1997, Congress passed FDAMA allowing manufacturers to disseminate information about off-label uses to health care providers under certain circumstances

• FDAMA purports to liberalize the dissemination of information regarding off-label use to health care professionals, but the requirements for legally disseminating such information are burdensome

off-label marketing

35.

• Off-label marketing had benefited in past by unveil the unknown uses of drugs ,but at the same time ,case like Neurontin etc..shows that it has detrimental effect on people who were victims of Off-label marketing.

• Physicians need to understand their responsibility

• Current Indian scenario is totally different

off-label marketing

36. off-label marketing