NOVARTIS EXHIBIT 2169
`Par v Novartis, IPR 2016-00084
`Page 1 of 4
`
`

`
`NOVARTIS EXHIBIT 2169
`Par v Novartis, IPR 2016-00084
`Page 2 of 4
`
`

`
`1102
`
`Hollister-Stier—Cont.
`
`CHLO-AMINE: As with any drug, if you are pregnant or
`nursing a baby, seek the advice of a health professional be-
`fore using this product.
`Patients should not drive or operate machinery after taking
`Chlo-Amine. Drowsiness, dizziness, blurred vision, dry
`mouth and gastrointestinal upsets may occur. Keep out of
`reach of children.
`The asthmatic patient should take the chloropheniramine
`maleate tablets with caution.
`LIMITED WARRANTY: A number of factors beyond our
`control could reduce the efficacy of this product or even re-
`sult in an ill effect following its use. These include storage
`and handling of the product after it leaves our hands, diagno-
`sis, dosage, method of administration and biological differ-
`ences in individual patients. Because of these factors, it is
`important that this product be stored properly and that the
`directions be followed carefully during use.
`The foregoing statement is made in lieu of any other war-
`ranty, express or implied, including any warranty of mer-
`chantability or fitness. Representatives of the Company are
`not authorized to vary the terms of this warranty or the con-
`tents of any printed labeling for this product except by
`printed notice from the Company's Spokane, WA office. The
`prescriber and user of this product must accept the terms
`hereof.
`Epinephrine Mfg. by: Wyeth Laboratories, Inc.,
`Philadelphia, PA 19101
`Pkgd. and Dist by:
`Miles Inc.
`Hollister- Pharmaceutical Division
`Stier Spokane, WA 99207 USA
`Phys: 471103 M02 10/88 © 1988 Miles Inc.
`Cr. Ref. 471104
`
`ICI Pharma
`A Business Unit of ICI Americas Inc.
`WILMINGTON. OE 19897 USA
`
`NOLVADEX® 10 mg Tablets
`[nol'va-dex"]
`(tamoxifen citrate)
`
`&
`
`DESCRIPTION
`NOLVADEX® (tamoxifen citrate) tablets for oral adminis-
`tration contain 15.2 mg of tamoxifen citrate, which is equiva-
`lent to 10 mg of tamoxifen. It is a nonsteroidal antiestrogen.
`Chemically, NOLVADEX is the trans-isomer of a triphenyl-
`ethylene derivative. The chemical name is (Z) 2-[4-
`(l^diphenyl-1-butenyl) phenoxy]-N, N-dimethylethan-
`amine 2-hydroxy-l,2,3-propanetricarboxylate (1:1).
`Tamoxifen citrate has a molecular weight of 563.62, the pKa'
`is 8.85, the equilibrium solubility in water at 3TC is
`0.5 mg/mL and in 0.02 N HC1 at STC, it is 0.2 mg/mL.
`NOLVADEX is intended only for oral administration; the
`tablets should be protected from heat and light.
`Inactive ingredients: carboxymethylcellulose calcium, mag-
`nesium stearate, mannitol, starch.
`CLINICAL PHARMACOLOGY
`NOLVADEX is a nonsteroidal agent which has demon-
`strated potent antiestrogenic properties in animal test sys-
`tems. The antiestrogenic effects may be related to its ability
`to compete with estrogen for binding sites in target tissues
`such as breast. Tamoxifen inhibits the induction of rat mam-
`mary carcinoma induced by dimethylbenzanthracene
`(DMBA) and causes the regression of already established
`DMBA-induced tumors. In this rat model, tamoxifen appears
`to exert its antitumor effects by binding to estrogen
`receptors.
`In cytosols derived from human breast adenocarcinomas,
`tamoxifen competes with estradiol for estrogen receptor
`protein. Preliminary pharmacokinetics in women using
`radiolabeled tamoxifen has shown that most of the radioac-
`tivity is slowly excreted in the feces, with only small
`amounts appearing in urine. The drug is excreted mainly as
`conjugates, with unchanged drug and hydroxylated metabo-
`lites accounting for 30% of the total.
`Blood levels of total radioactivity following single oral doses
`of approximately 0.3 mg/kg reached peak values of 0.06-0.14
`ug/mL at 4-7 hours after dosing, with only 20%-30% of the
`drug present as tamoxifen. There was an initial half-life of
`7-14 hours with secondary peaks four or more days later.
`The prolongation of blood levels and fecal excretion is be-
`lieved to be due to enterohepatic circulation.
`Two studies (Hubay and NSABP B-09) demonstrated an im-
`proved disease-free survival following radical or modified
`radical mastectomy in postmenopausal women or women 50
`years of age or older with surgically curable breast cancer
`with positive axillary nodes when NOLVADEX was added to
`adjuvant cytotoxic chemotherapy. In the Hubay study,
`
`Physicians' Desk Reference®
`NOLVADEX was added to "low-dose" CMF (cyclophospha-
`mide, methotrexate and fluorouracil). In the NSABP B-09
`study, NOLVADEX was added to melphalan [L-phenylala-
`nine mustard (P)] and fluorouracil (F).
`Tumor hormone receptors may help predict which patients
`will benefit from the adjuvant therapy, but not all breast
`cancer adjuvant NOLVADEX studies have shown a clear
`relationship between hormone receptor status and treat-
`ment effect. In the Hubay study, patients with a positive
`(more than 3 fmol) estrogen receptor were more likely to
`benefit. In the NSABP B-09 study in women age 50-59 years,
`only women with both estrogen and progesterone receptor
`levels 10 fmol or greater clearly benefited, while there was a
`nonstatistically significant trend toward adverse effect in
`women with both estrogen and progesterone receptor levels
`less than 10 fmol. In women age 60-70 years, there was a
`trend toward a beneficial effect of NOLVADEX without
`any clear relationship to estrogen or progesterone receptor
`status.
`Three prospective studies (ECOG-1178, Toronto, NATO)
`using NOLVADEX adjuvantly as a single agent demon-
`strated an improved disease-free survival following total
`mastectomy and axillary dissection for postmenopausal
`women with positive axillary nodes compared to placebo/no
`treatment controls. The NATO study also demonstrated an
`overall survival benefit.
`One prospective, double-blind, randomized study (NSABP-
`14) demonstrated a significant improvement in disease-free
`survival for NOLVADEX compared to placebo when used
`adjuvantly following total mastectomy and axillary dissec-
`tion or segmental resection, axillary dissection, and breast
`radiation in women with axillary node-negative breast can-
`cer whose tumors were estrogen receptor positive (> 10
`fmol/mg cytosol protein). The benefit was apparent in both
`women under age 50 and those aged 50 years or more. One
`additional randomized study (NATO) demonstrated im-
`proved disease-free survival for NOLVADEX compared to no
`adjuvant therapy following total mastectomy and axillary
`dissection in postmenopausal women with axillary node-
`negative breast cancer. In this study, the benefits of
`NOLVADEX appeared to be independent of estrogen recep-
`tor status.
`Three prospective, randomized studies (Ingle, Pritchard,
`Buchanan) compared NOLVADEX to • ovarian ablation
`(oophorectomy or ovarian irradiation) in premenopausal
`women with advanced breast cancer. Although the objective
`response rate, time to treatment failure, and survival were
`similar with both treatments, the limited patient accrual
`prevented a demonstration of equivalence. In an overview
`analysis of survival data from the three studies, the hazard
`ratio for death (NOLVADEX/ovarian ablation) was 1.00
`with two-sided 95% confidence intervals of 0.73 to 1.37. Ele-
`vated serum and plasma estrogens have been observed in
`premenopausal women receiving NOLVADEX. However,
`the data from the randomized studies do not suggest an ad-
`verse effect. A limited number of premenopausal patients
`with disease progression during NOLVADEX therapy re-
`sponded to subsequent ovarian ablation.
`INDICATIONS AND USAGE
`Adjuvant Therapy: NOLVADEX is effective in delaying
`recurrence following total mastectomy and axillary dissec-
`tion or segmental mastectomy, axillary dissection, and
`breast irradiation in women with axillary node-negative
`breast cancer. Data are insufficient to predict which women
`are most likely to benefit and to determine if NOLVADEX
`provides any benefit in women with tumors less than 1 cm.
`NOLVADEX is effective in delaying recurrence following
`total mastectomy and axillary dissection in postmenopausal
`women with breast cancer (Tis, N^ Mo). In some
`NOLVADEX adjuvant studies, most of the benefit to date
`has been in the subgroup with 4 or more positive axillary
`nodes.
`The estrogen and progesterone receptor values may help to
`predict whether adjuvant NOLVADEX therapy is likely to
`be beneficial.
`Therapy for Advanced Disease: NOLVADEX is effective in
`the treatment of metastatic breast cancer in women. In pre-
`menopausal women with metastatic breast cancer,
`NOLVADEX is an alternative to oophorectomy or ovarian
`irradiation. Available evidence indicates that patients whose
`tumors are estrogen receptor positive are more likely to ben-
`efit from NOLVADEX therapy.
`CONTRAINDICATIONS
`NOLVADEX is contraindicated in patients with known hy-
`persensitivity to the drug.
`WARNINGS
`Visual disturbance including cornea! changes, cataracts and
`retinopathy have been reported in patients receiving
`NOLVADEX.
`As with other additive hormonal therapy (estrogens and
`androgens), hypercalcemia has been reported in some breast
`cancer patients with bone metastases within a few weeks of
`starting treatment with NOLVADEX. If hypercalcemia does
`
`Consult 1992 Supplements for revisions
`
`occur, appropriate measures should be taken and, if severe,
`NOLVADEX should be discontinued.
`A small number of cases of endometrial hyperplasia and
`endometrial polyps have been reported in association with
`NOLVADEX treatment. A definitive relationship to
`NOLVADEX therapy has not been established.
`In a'single large randomized trial in Sweden of adjuvant
`tamoxifen 40 mg/day for 2-5 years, an increased incidence of
`endometrial cancer was noted. Thirteen of 931 tamoxifen
`treated patients versus 2 of 915 controls developed cancer of
`the body of the uterus [RR = 6.4 (1.4 - 28), P <0.01]. How-
`ever, in a review of more than 12,000 patients entered into
`twelve other large ongoing adjuvant studies (including
`NSABP B-14) in which patients have received NOLVADEX
`20-40 mg/day for periods of 1-5+ years versus control, no
`increased incidence of cancer of the uterus was seen.
`In the same Swedish trial, the incidence of second primary
`breast tumors was reduced in the tamoxifen arm (P <0.05).
`In the NSABP B-14 trial in which patients were randomized
`to NOLVADEX 20 mg/day for 5 years versus placebo, the
`incidence of second primary breast cancers is also reduced.
`Pregnancy Category D: NOLVADEX may cause fetal harm
`when administered to a pregnant woman. Individuals should
`not become pregnant while taking NOLVADEX and should
`use barrier or nonhormonal contraceptive measures. Effects
`on reproductive functions are expected from the antiestro-
`genic properties of the drug. In reproductive studies in rats
`at dose levels equal to or below the human dose, nonterato-
`genic developmental skeletal changes were seen and were
`found to be reversible. In addition, in fertility studies in rats
`and in teratology studies in rabbits using doses at or below
`those used in humans, a lower incidence of embryo implanta-
`tion and a higher incidence of fetal death or retarded in utero
`growth were observed, with slower learning behavior in
`some rat pups. The impairment of learning behavior did not
`achieve statistical significance in one study, and, in another
`study where significance was reported, this was by compar-
`ing dosed animals with controls of another study. Several
`pregnant marmosets were dosed during organogenesis or in
`the last half of pregnancy. No deformations were seen, and
`although the dose was high enough to terminate pregnancy
`in some animala, those that did maintain pregnancy showed
`no evidence of teratogenic malformations. There are no ade-
`quate and well-controlled studies in pregnant women. There
`have been reports of spontaneous abortions, birth defects,
`fetal deaths, and vaginal bleeding. If this drug is used during
`pregnancy or the patient becomes pregnant while taking this
`drug, the patient should be apprised of the potential hazard
`to the fetus.
`PRECAUTIONS
`General: NOLVADEX should be used cautiously in pa-
`tients with existing leukopenia or thrombocytopenia. Obser-
`vations of leukopenia and thrombocytopenia occasionally
`have been made, but it is uncertain if these effects are due to
`NOLVADEX therapy. Transient decreases in platelet
`counts, usually to 50,000-100,000/mm3, infrequently lower,
`have been occasionally reported in patients taking
`NOLVADEX for breast cancer. No hemorrhagic tendency
`has been recorded, and the platelet counts returned to
`normal levels even though treatment with NOLVADEX
`continued.
`Information for Patients: Women taking NOLVADEX
`should be instructed to report abnormal vaginal bleeding
`which should be promptly investigated.
`Laboratory Tests: Periodic complete blood counts, includ-
`ing platelet counts, may be appropriate.
`Drug Interactions: When NOLVADEX is used in combina-
`tion with coumarin-type anticoagulants, a significant in-
`crease in anticoagulant effect may occur. Where such coad-
`ministration exists, careful monitoring of the patient's pro-
`thrombin time is recommended.
`Drug/Laboratory Testing Interactions: During postmarket-
`ing surveillance, T4 elevations were reported for a few post-
`menopausal patients which may be explained by increases in
`thyroid-binding globulin. These elevations were not accom-
`panied by clinical hyperthyroidism.
`Variations in the karyopyknotic index on vaginal smears
`and various degrees of estrogen effect on Pap smears have
`been infrequently seen in postmenopausal patients given
`NOLVADEX.
`In the postmarketing experience with NOLVADEX, infre-
`quent cases of hyperlipidemias have been reported. Periodic
`monitoring of plasma triglycerides and'cholesterol may be
`indicated in patients with pre-existing hyperlipidemias.
`Carcinogenesis: A conventional carcinogenesis study in
`rats, (doses of 5, 20, and 35 mg/kg/day for up to 2 years) re-
`vealed hepatocellular carcinoma at all doses, and the inci-
`dence of these tumors was significantly greater among
`rats given 20 or 35 mg/kg/day (69%) than those given
`5 mg/kg/day (14%). The incidence of these tumors in rats
`given 5 mg/kg/day (29.5 mg/m2) was significantly greater
`than in controls.
`In addition, preliminary data from 2 independent reports of
`6-month studies in rats reveal liver tumors which in one
`study are classified as malignant.
`
`NPC02233833
`
`NOVARTIS EXHIBIT 2169
`Par v Novartis, IPR 2016-00084
`Page 3 of 4
`
`

`
`Consult 1992 Supplements for revisions
`
`Physicians' Desk Reference®
`NSABP B-14 STUDY
`
`No. of Patients (%)
`
`Adverse Effect
`
`Hot flashes
`Fluid retention
`Vaginal discharge
`Irregular menses
`Nausea
`Skin rash
`Diarrhea
`Vomiting
`Phlebitis
`Thrombocytopenia*
`Leukopenia"
`
`NOLVADEX
`(n= 1376)
`
`787
`339
`330
`264
`2S5
`180
`106
`25
`16
`10
`7
`
`(57)
`(26)
`(24)
`(19)
`(19)
`(13)
`(8)
`(2)
`(1)
`(1)
`(1)
`
`Placebo
`(n=1396)
`
`666
`326
`160
`203
`236
`150
`129
`16
`2
`4
`10
`
`(41)
`(23)
`(12)
`(15)
`(17)
`(11)
`(9)
`(1)
`(<1)
`(<1)
`(1)
`
`'Defined as a platelet count of < 100,000/mm3
`"Defined as a white blood cell count of <3000/mm3
`
`Endocrine changes in immature and mature mice were in-
`vestigated in a 13-month study. Granulosa cell ovarian tu-
`mors and interstitial cell testicular tumors were found in
`mice receiving NOLVADEX, but not in the controls.
`Mutagenesls: No genotoxic potential has been found in a
`battery of in vivo and in vitro tests with pro- and eukaryotic
`test systems with drug metabolizing systems present.
`Impairment of Fertility: Fertility in female rats was de-
`creased following administration of 0.04 mg/kg for two
`weeks prior to mating through day 7 of pregnancy. There
`was a decreased number of implantations, and all fetuses
`were found dead.
`Following administration to rats of 0.16 mg/kg from days
`7-17 of pregnancy, there were increased numbers of fetal
`deaths. Administration of 0.125 mg/kg to rabbits during
`days 6-18 of pregnancy resulted in abortion or premature
`delivery. Fetal deaths occurred at higher doses. There were
`no teratogenic changes in either rat or rabbit segment II
`studies. Several pregnant marmosets were dosed with 10
`mg/kg/day either during organogenesis or in the last half of
`pregnancy. No deformations were Been, and although the
`dose was high enough to terminate pregnancy in some ani-
`mals, those that did maintain pregnancy showed no evidence
`of teratogenic malformations. Bats given 0.16 mg/kg from
`day 17 of pregnancy to 1 day before weaning demonstrated
`increased numbers of dead pups at parturition. It was re-
`ported that some rat pups showed slower learning behavior,
`but this did not achieve statistical significance in one study,
`and in another study where significance was reported, this
`was obtained by comparing dosed pnimala with controls of
`another study.
`The recommended daily human dose of 20-40 mg corre-
`sponds to 0.4-0.8 mg/kg for an average 50 kg woman.
`Pregnancy Category D: See WARNINGS.
`Nursing Mothers: It is not known whether this drug is ex-
`creted in human milk. Because many drugs are excreted in
`human milk and because of the potential for serious adverse
`reactions in nursing infants from NOLVADEX, a decision
`should be made whether to discontinue nursing or to discon-
`tinue the drug, taking into account the importance of the
`drug to the mother.
`
`ADVERSE REACTIONS
`Adverse reactions to NOLVADEX are relatively mild and
`rarely severe enough to require discontinuation of treat-
`ment. If adverse reactions are severe, it is sometimes possible
`to control them by a simple reduction of dosage without loss
`of control of the disease.
`
`In patients treated with NOLVADEX for metastatic breast
`cancer, the most frequent adverse reactions to NOLVADEX
`are hot flashes and nausea and/or vomiting. These may oc-
`cur in up to one-fourth of patients.
`Less frequently reported adverse reactions are vaginal bleed-
`ing, vaginal discharge, menstrual irregularities and skin
`rash. Usually these have not been of sufficient severity to
`require dosage reduction or discontinuation of treatment.
`Increased bone and tumor pain and, also, local disease flare
`have occurred, which are sometimes associated with a good
`tumor response. Patients with increased bone pain may re-
`quire additional analgesics. Patients with soft tissue disease
`may have sudden increases in the size of preexisting lesions,
`sometimes associated with marked erythema within and
`surrounding the lesions and/or the development of new le-
`sions. When they occur, the bone pain or disease flare are
`seen shortly after starting NOLVADEX and generally sub-
`side rapidly.
`Other adverse reactions which are seen infrequently are
`hypercalcemia, peripheral edema, distaste for food, pruritus
`vulvae, depression, dizziness, light-headedness and head-
`ache.
`There have been infrequent reports of thromboembolic
`events occurring during NOLVADEX therapy. Since for
`cancer patients in general an increased incidence of throm-
`boembolic events is known to occur, a causal relationship to
`NOLVADEX remains conjectural. An increased incidence
`has been reported when cytotoxic agents are combined with
`NOLVADEX.
`Ovarian cysts have been observed in a small number of pre-
`menopausal patients with advanced breast cancer who have
`been treated with NOLVADEX.
`Continued clinical studies have resulted in further informa-
`tion which better indicates the incidence of adverse reactions
`with NOLVADEX as compared to placebo.
`In the ongoing NSABP study B-14, patients with axillary
`node-negative breast cancer were randomized to 5 years of
`NOLVADEX or placebo following primary surgery. The re-
`ported adverse effects are tabulated below (mean follow-up of
`29 months). The incidence of hot flashes (57% v 41%), vagi-
`nal discharge (24% v 12%), and irregular menses (19% v
`15%) were higher with NOLVADEX compared with placebo.
`The incidence of all other adverse effects were similar in the
`two treatment groups with the exception of thromboembolic
`events (phlebitis), which although rare, were more common
`with NOLVADEX than with placebo. [See table above.]
`In the Eastern Cooperative Oncology Group (ECOG) adju-
`vant breast cancer trial, NOLVADEX or placebo was admin-
`
`Adverse Reactions*
`
`Flush
`Amenorrhea
`Altered Menses
`Oligomenorrhea
`Bone Pain
`Menstrual Disorder
`Nausea
`Cough/Coughing
`Edema
`Fatigue
`Musculoskeletal Pain
`Pain
`Ovarian Cystfs)
`Depression
`Abdominal Cramps
`Anorexia
`
`* Some patients had more than one adverse reaction.
`
`NOLVADEX
`All Effects
`Number of Patients (%)
`n= = 104
`
`OVARIAN ABLATION
`All Effects
`Number of Patients (%)
`n= 100
`
`34
`17
`13
`9
`6
`6
`5
`4
`4
`4
`3
`3
`3
`2
`1
`1
`
`(32.7)
`(16.3)
`(12.6)
`(8.7)
`(5.7)
`(5.7)
`(4.8)
`(3.8)
`(3.8)
`(3.8)
`(2.8)
`(2.8)
`(2.8)
`(1.9)
`(1)
`(1)
`
`46
`69
`5
`1
`6
`
`0
`4
`2
`2
`2
`2
`
`(46)
`(69)
`(6)
`(1)
`(6)
`(4)
`' (4)
`(1)
`(1)
`(1)
`(0)
`(4)
`(2)
`(2)
`(2)
`(2)
`
`1103
`
`istered for 2 years to patients following mastectomy. When
`compared to placebo, NOLVADEX showed a significantly
`higher incidence of hot flashes (19% versus 8% for placebo).
`The incidence of all other adverse reactions was similar in
`the 2 treatment groups with the exception of thrombocytope-
`nia where the incidence for NOLVADEX was 10% versus
`3% for placebo, an observation of borderline statistical
`significance.
`In other adjuvant studies, Toronto and NOLVADEX Adju-
`vant Trial Organization (NATO), patients received either
`NOLVADEX or no therapy. In the Toronto study, hot flashes
`and nausea and/or vomiting were observed in 29% and 19%
`of patients, respectively, for NOLVADEX versus 1% and 0%
`in the untreated group. In the NATO trial, hot flashes, nau-
`sea and/or vomiting and vaginal bleeding were reported in
`2.8%, 2.1%, and 2.0% of patients, respectively, for
`NOLVADEX versus 0.2% for each in the untreated group.
`The following table summarizes the incidence of adverse
`reactions reported at a frequency of 2% or greater from clini-
`cal trials (Ingle, Pritchard, Buchanan) which compared
`NOLVADEX therapy to ovarian ablation in premenopausal
`patients with metastatic breast cancer.
`[See table below.]
`OVERDOSAGE
`Acute overdosage in humans has not been reported. Signs
`observed at the highest doses following studies to determine
`LDgo in animals were respiratory difficulties and convul-
`sions. No specific treatment for overdosage is known; treat-
`ment must be symptomatic.
`DOSAGE AND ADMINISTRATION
`One or two 10 mg tablets twice a day (morning and evening).
`In three single agent adjuvant studies, one 10 mg
`NOLVADEX tablet was administered two (ECOG and
`NATO) or three (Toronto) times a day for two years (see Clin-
`cial Pharmacology). In the ongoing NSABP study B-14, one
`10 mg NOLVADEX tablet is being given twice a day for five
`years. The optimal duration of adjuvant therapy is not
`known.
`HOW SUPPLIED
`Tablets containing tamoxifen as the citrate in an amount
`equivalent to 10 mg of tamoxifen (round, biconvex, uncoated,
`white tablet identified with NOLVADEX 600 debossed on
`one side and a cameo debossed on the other side) are supplied
`in bottles of 60 tablets and 250 tablets. Protect from heat and
`light. NDC 03100600.
`
`Rev Z 05/90
`
`ICIPharma
`A business unit of ICI Americas Inc.
`Wilmington, DE 19897 USA
`Shown in Product Identification Section, page 412
`
`SORBITRATE®
`[sorb 'i-trate ]
`(Isosorbide Dinitrate)
`
`5
`
`DESCRD?TION
`SORBITRATE® (isosorbide dinitrate), an organic nitrate, is
`a vasodilator with effects on both arteries and veins. SORBI-
`TRATE is available as:
`SORBITRATE® SUBLINGUAL
`2.6 mg Sublingual Tablet Each tablet contains 2.5 mg of
`isosorbide dinitrate.
`Inactive ingredients: com starch, lactose (hydrous), magne-
`sium stearate, pregelatinized'starch.
`6 mg Sublingual Tablet Each tablet contains 5 mg of isosor-
`bide dinitrate.
`Inactive ingredients: com starch, lactose (hydrous), magne-
`sium stearate, pregelatinized starch, Red 7.
`10 mg Sublingual Tablet. Each tablet contains 10 mg of
`isosorbide dinitrate.
`Inactive ingredients: corn starch, lactose (hydrous), magne-
`sium stearate, Yellow 10.
`SORBITRATE® CHEW ABLE
`5 mg Chewable Tablet. Each tablet contains 5 mg of isosor-
`bide dinitrate.
`Inactive ingredients: Blue 1, confectioner's sugar, corn
`starch, flavor, hydrogenated vegetable oil, magnesium stea-
`rate, mannitol, povidone, Yellow 10.
`10 mg Chewable Tablet. Each tablet contains 10 mg of iso-
`sorbide dinitrate.
`Inactive ingredients: confectioner's sugar, corn starch,
`flavor, hydrogenated vegetable oil, magnesium stearate,
`mannitol, povidone, Yellow 10.
`SORBITRATE® ORAL
`5 mg Oral Tablet. Each tablet contains 5 mg of isosorbide
`dinitrate.
`Inactive ingredients: Blue 1, com starch, lactose (hydrous),
`magnesium stearate, pregelatinized starch, Yellow 10.
`
`Continued on next page
`
`NPC02233834
`
`NOVARTIS EXHIBIT 2169
`Par v Novartis, IPR 2016-00084
`Page 4 of 4